Devices and assemblies for directed transport, microscopy, and directed discharge of tissue grafts or implants

Abstract

The invention provides a device for reliable support and / or transport of a tissue graft or implant, which allows for precise microscopic investigation and / or evaluation and quality control of the tissue graft or implant during handling and prior to introduction into a living being. The body of the device is a sleeve or tube housing having a rectangular shape with preferably rounded edges and two opposite openings of different size and shape. The first opening is circular in shape with a diameter suitable for connection to a tube or syringe nozzle. The second opening has an elliptical, circular, lenticular or rectangular shape, preferably with rounded edges in the case of a rectangular shape, the shape of the second opening being small enough to be inserted into a small surgical incision. The transparency of the device body and the preferably circular, rectangular shape allow for microscopic examination of the tissue graft or implant within the device and fixation of the position of the tissue graft or implant during transport and implantation. The elliptical, circular, lenticular or preferably rounded rectangular inner shape of the second opening ensures correct positioning of the tissue graft or implant during surgical implantation, thereby preventing problems such as loss of orientation of the tissue graft or implant. The invention also provides an assembly for loading, storing and / or transporting a tissue graft or implant comprising a device according to the invention. The invention also provides a washing assembly and a method for preparing a tissue graft or implant.

Description

TECHNICAL FIELD

[0001] The present invention provides a device for reliable support and / or transport of tissue grafts or implants, which allows for precise microscopic investigation and / or evaluation and quality control of tissue grafts or implants during handling and prior to introduction into a living being. The main body of the device is a sleeve or tube housing a rectangular shape with preferably rounded edges and two opposite openings of different sizes and shapes. The first opening is circular with a diameter suitable for connection to a tube or syringe nozzle. The second opening has an elliptical, circular, lenticular or rectangular shape, preferably with rounded edges, the shape of the second opening being small enough to be inserted into a small surgical incision. The transparency of the device main body and the preferably circular, rectangular shape allow for microscopic examination of the tissue graft or implant within the device and fixation of the position of the tissue graft or implant during transport and implantation. The elliptical, circular, lenticular or preferably rounded rectangular inner shape of the second opening ensures correct positioning of the tissue graft or implant during surgical implantation, thereby preventing problems such as loss of orientation of the tissue graft or implant. The present invention further provides an assembly for loading, storing and / or transporting tissue grafts or implants comprising a device according to the invention. The present invention further provides a washing assembly and a method for preparing tissue grafts or implants. BACKGROUND

[0002] The human cornea is one of the most transplanted tissues. Penetrating keratoplasty (PK), introduced more than 100 years ago, is a surgery that implants the entire cornea, including all layers of the cornea (epithelium, Bowman's membrane, stroma, posterior limiting membrane and endothelial cell layer) [1, 2]. The initial success rate of this surgical technique is about 80-90%, but due to geometric differences between the donor and recipient eye, patients recover slowly and complete visual recovery is rare. In addition, long-term monitoring of patients shows a high likelihood of graft failure, with more than 50% of patients requiring a second transplant within 10 years of the surgery [1].

[0003] Endothelial keratoplasty (EK) methods do not require the entire cornea to be transplanted. Therefore, the EK method is the most widely used today [2]. Correspondingly, EK techniques, including the transplantation of only the thin stromal layer of the cornea with the posterior limiting membrane and endothelial cell layer (Descemet's stripping endothelial keratoplasty [DSEK] or Descemet's automated endothelial keratoplasty [DSAEK]) have been developed as an alternative to PK [3]. These techniques are significantly better in terms of patient satisfaction and visual recovery compared to PK treatment. Nevertheless, these techniques still contain a high incidence of defects in the recovery of vision and significant long-term graft rejection (15-25%) caused by the stromal part of the implant [4, 5].

[0004] In the last decade, new endothelial keratoplasty techniques have been developed that include only the posterior elastic lamina and endothelial cell layer (Descemet Membrane Endothelial Keratoplasty [DMEK] and Pre-Descemet Endothelial Keratoplasty [PDEK]) with slightly thicker grafts [6, 7]. Advantages of these techniques include very rapid patient recovery with almost complete visual recovery within a few weeks postoperatively. Since there is no stroma, the recipient's eye has almost no visual defects that are affected by geometric differences between the donor and recipient eyes. In other words, it is likely that only DMEK and PDEK can provide almost complete visual recovery within a few weeks postoperatively, while patients of conventional DSEK / DSAEK and PK can never fully recover to complete vision due to the geometric inefficiency of these implants. Furthermore, the rate of graft rejection for DMEK / PDEK surgery is very low (<5%) compared to PK and DSEK / DSAEK surgery [3, 5, 8-12]. DMEK and PDEK are currently considered the most promising keratoplasty surgeries and are rapidly rising as the preferred keratoplasty technique worldwide.

[0005] It has been reported that the recently established ultra-thin (ut-)DSEK / DSAEK or nano-thin (nt-)DSEK / DSAEK techniques have similar benefits as their thicknesses can be only a few microns larger than DMEK and PDEK implants

[13] . Similar to DMEK / PDEK organization, compared to conventional DSEK / DSAEK and PK, the implantation of ut- / nt-DSEK / DSAEK implants / grafts significantly improves postoperative visual outcomes in shorter recovery times and reduces the rate of graft rejection

[14] . Despite these benefits, DMEK / PDEK and ut- / nt-DSEK / DSAEK techniques pose challenges in graft handling as the extreme graft fragility (for tissue integrity and cell number) limits the handling and delivery of the grafts. The delivery in a beaker filled with culture medium as initially suggested often results in graft damage

[13] . The grafts are easily damaged during preparation or surgery by simply touching the metal instruments. Current state-of-the-art methods suggest handling the grafts by water flow ("touchless") or instrument manipulation at the periphery of the graft where damage is less important for later visual recovery [15-17]. The fragility of the grafts requires additional quality control by the eye / tissue bank after preparation and by the surgeon during surgery. However, their benefits in application have led to a steady increase in surgeries, which in some hospitals has already exceeded 50% of the keratoplasty cases

[18] .

[0006] The success of the transplantation surgery depends to a large extent on the prevalence and quality (tissue integrity and cell count) of the grafts / implants provided from the donor to the patient

[18] . The prevalence of the grafts is entirely controlled by the tissue bank, which recovers more than 25% of the implants due to bacterial and fungal contamination and certain types of cancer and infectious diseases of the donor

[18] . Quality control of the grafts in terms of tissue integrity and cell count can theoretically be performed in the tissue / eye bank and in the operating room (surgical theater). However, the current medical standards

[19] require the tissue / eye bank to perform such quality assurance via specular microscopy and slit lamp examination. However, there is an increasing need to assess the implants in the surgical theater prior to implantation to prevent implant failure

[20] due to the high likelihood of transport-related damage of the current transport solutions.

[0007] One of the key features of thin EK tissues is the correct graft orientation (apical-basal polarity of the corneal endothelial cell layer ["top and bottom"]) to ensure graft functionality. Ensuring the correct graft orientation is a big problem for the surgeon

[20] , who in case of loss of graft orientation has to return the implant to the eye bank as it cannot be determined in the surgical theater. Damage related to the handling of the ut- / nt-DSEK / DSAEK and DMEK / PDEK implants during transport and surgery and loss of implant orientation during surgery often require repeating the transplantation procedure. To cope with these challenges, new graft handling, assessment, delivery, and transplantation methods have to be developed.

[0008] DMEK can be prepared by the surgeon in the surgical theater. This neglects the transport problem but significantly increases the surgery time and reduces the quality of the implant as the surgical theater is usually not designed for such procedures. The increasing popularity of the ultra-thin EK graft / implant procedures and their difficult preparation in the surgical theater requires improved, user-friendly solutions for tissue transport and assistance of the surgeon during implantation from the tissue / eye bank (e.g. for DMEK / PDEK and ut- / nt-DSEK / DSAEK).

[0009] The "pre-dissection" method is an alternative handling and delivery technique of DMEK tissue, where the corneal endothelial layer is completely cut but only partially dissected (removed) from the corneal stroma [22, 23]. In this safe method of DMEK graft delivery to the operating room, the tissue graft or implant is set in a liquid medium filled beaker. In the context of this document, the term "culture medium" refers to a liquid nutrient combination of the necessary ingredients to maintain cell viability during the implant storage, evaluation and / or transportation process. However, the main disadvantage of this technique is that the final dissection of the graft from the corneal stroma has to be done by the surgeon in the operating room. This way, the likelihood of graft failure increases due to incorrect (non-standardized) tissue handling and loss of graft orientation during surgery.

[0010] To solve this problem, tissue banks prepare "pre-dissected and pre-loaded" DMEK and DSAEK tissues, which are delivered to the operating room by means of a special device assembly, where the main part is a tissue / graft implant syringe, such as the Straiko Modified Jones tube [24, 25], an intraocular lens tube shell

[26] or the Geuder DMEK injector

[27] . The use of these "pre-dissected and pre-loaded" tissue / graft implants both reduces the surgery time and the various complications that arise in the operating room in case of a failed tissue preparation during surgery.

[0011] However, "pre-dissected and pre-loaded" tissue / graft implants require an additional level of quality assurance in the operating room, as the integrity of the implant as well as the cell properties should be evaluated before implantation to prevent graft failure. Current "pre-dissected and pre-loaded" tissue preparation solutions perform a post-handling evaluation of the implant / graft by the tissue / eye bank via precision microscopy methods, such as specular microscopy, slit lamp examination, optical microscopy and / or optical coherence tomography. Currently, this evaluation requires a significant amount of time (up to 45 minutes) in the eye bank quality control facility, as it is difficult to obtain good microscopic images of the corneal tissue within the current delivery devices

[28] . The application of this method in the operating room is not available before implantation, as the current containers and / or assemblies for pre-dissected and pre-loaded tissue transportation and implantation are not designed for precision microscopy methods and due to the round shape of the tissue / graft implant syringes, this results in various light reflection artefacts. Therefore, there is still a great need to create a transportation device that can both safely inject the graft implant into the living body and visualize the graft using precision microscopy. Preferably, this device also applies as a tissue graft / implant syringe, which would allow minimal handling of the tissue before implantation to address the fragility of such tissue grafts / implants.

[0012] Recently, a new corneal endothelial layer handling technique, commonly referred to as "endothelium in" or "tri-folded" DMEK, was introduced. In this technique, the implant is manually folded into an "envelope" shape during the dissection process, with the endothelial cell layer facing itself, as opposed to the natural implant roll ("endothelium out")

[26] . Notably, this process does not cause excessive corneal endothelial cell damage

[29] . If transferred into solution as a free-floating tissue, the implant will unfold within a few minutes to reach its natural "endothelium out" fold. However, a few minutes are enough to insert the "endothelium in" / "tri-folded" DMEK implant envelope into a syringe, thus preventing the implant from "opening" as the walls of the syringe will fix the implant in the folded "endothelium in" / tri-folded" position. Insertion of this implant into the patient's eye will cause the implant to open into its natural shape, thus allowing for rapid positioning and attachment to the patient's corneal endothelium without the need for extensive implant manipulation. The "endothelium in" / "tri-folded" corneal layer implantation technique has been found to be superior to the conventional "endothelium out" method as it significantly reduces the surgery time and the implant manipulation in the operating room

[29] . It also does not require prior training of the eye surgeon as the implant will open by itself, thus reducing possible surgical errors. On the other hand, the position of the implant in the syringe is crucial for the success of the surgery and requires continuous control of the implant orientation in the syringe by the eye bank technician. A wrong orientation of the implant during surgery can lead to its termination and implant failure. The orientation control during the "endothelium in" / "tri-folded" corneal layer implantation process requires the application of a "pulling" technique as the implant is moved from the syringe into the eye by a surgical microforceps, similar to the DSEK / DSAEK procedure

[26] . Due to the size and thickness of the implant, the use of a surgical microforceps to "pull" a DSEK / DSAEK implant is acceptable, but would cause damage to the thinner "endothelium in" / "tri-folded" DMEK. In principle, a "endothelium in" / "tri-folded" DMEK tissue could be injected as conveniently as an "endothelium out" DMEK implant. However, the current symmetrical / circular DMEK syringes (e.g. Geuder DMEK syringe or Straiko Modified Jones tube) do not allow for the control and maintenance of the orientation of the "endothelium in" / "tri-folded" DMEK, thus necessitating some new solutions.

[0013] Independent of the application technique, the storage, evaluation / quality control, transportation and injection of the implant requires a variety of protocols according to governmental regulations. First, the implant should be stored and transported in an approved, defined volume of a liquid medium which is much larger than the volume of the syringe. Second, the cell density / quality of the implant has to be determined after the last operational step, i.e. after the tissue is loaded into the storage / transportation device. Third, the implant has to be washed with balanced salt solution (BSS) before injection, because the composition of the liquid transfer medium should not enter the patient's eye. The term "BSS" includes buffered saline solutions, such as Hank's BSS, Earle's BSS, table salt solution, Alsever's salt solution, phosphate buffered saline (PBS), Tris buffered saline (TBS), Puck's salt solution, Gey's salt solution, Ringer's salt solution, Simm's salt solution and related buffered salt solutions. These regulations lead to the use of a syringe as part of the assembly which includes a container with a corresponding volume of the liquid medium which can fix the syringe in place for transportation and storage. Unfortunately, these syringes are not designed for the precise microscopic / tissue quality assurance method, because they are circular and cause various light reflection artifacts after the final assembly within the storage / transportation container. Furthermore, it is strongly recommended to perform tests for e.g. fungal infections by drawing a sample of the surrounding liquid medium next to the tissue graft or implant in order to prevent any false negative results

[30] . This means that the liquid medium should be drawn directly within the device containing the tissue graft or implant which is already placed within the assembly of the device for transportation and / or storage. This is currently not possible, e.g. when using the Geuder DMEK syringe with two closed caps

[30] . It is also beneficial in this case to use a storage / transportation container with two openings, wherein one opening is suitable for inserting the syringe holder including the syringe and the second opening is suitable for directly drawing the liquid medium from within the device. This prevents any additional handling or repositioning of the syringe within the assembly of the device for transportation and / or storage. Furthermore, protocols and devices are required which allow the flushing of the implant with BSS before injection into the living body without damaging or expelling the implant from the syringe. Therefore, the innovation of the syringe development has to include the description of a storage / transportation container as well as a washing and staining accessory / protocol for the implant within the syringe. SUMMARY

[0014] It is an object of the present invention to eliminate the disadvantages in the prior art and to minimize the loss of tissue grafts or implants due to damage of the cellular material by handling the tissue grafts or implants or due to loss of orientation of the tissue grafts or implants.

[0015] The object of the present invention is achieved by providing a device, an assembly for loading a tissue graft or implant into a device, an assembly for transporting and / or storing a tissue graft or implant within a device, located within a transport container, a washing and staining assembly and a method for preparing a tissue graft or implant as described below.

[0016] In one embodiment, the present invention provides a device for reliable support and / or storage and / or transportation of a tissue graft or implant, which allows for precise microscopic investigation and / or evaluation / quality control of the tissue graft or implant during handling and prior to introduction into a living body. The main body of the device is a sleeve or tube housing a rectangular shape, preferably with rounded edges, and two opposite openings of different sizes and shapes. The first opening is circular, with a diameter suitable for connection to a tube or syringe nozzle. The second opening has an elliptical, circular, lenticular or rectangular shape, preferably with rounded edges in the case of a rectangular shape, and the shape of the second opening is small enough to be inserted into a small surgical incision. The shape of the inner hollow compartment of the device, in particular for the second opening, can (but is not necessarily) different from the outer shape of the device. The transparency of the device main body and the preferably circular, rectangular shape allow for microscopic examination of the tissue graft or implant within the device and fixation of the position of the tissue graft or implant during delivery and implantation. The elliptical, circular, lenticular or preferably rounded rectangular inner shape of the second opening ensures correct positioning of the tissue graft or implant during surgical implantation, thus preventing problems such as loss of orientation of the tissue graft or implant. The elliptical, circular, lenticular or rounded rectangular outer shape of the second opening also reduces tissue tension and the corresponding damage to the surgical incision, as it ensures good closure of the wound when the device is located in the eye.

[0017] The present invention also provides an assembly for loading, storing and / or transporting a tissue graft or implant comprising a device according to the present invention. The present invention also provides a washing assembly and a method for preparing a tissue graft or implant.

[0018] In a preferred embodiment of the present invention, the assembly further comprises a device holder. Advantageously, this embodiment enables reliable transportation of the device with the tissue graft or implant, maintaining the orientation of the tissue graft or implant stable. Furthermore, the assembly is suitable for the application of microscopic examination techniques of the tissue graft or implant when the tissue graft or implant is located within the device and the device holder is placed within a storage / transport container. In addition, the assembly comprising the device holder is suitable for the sterile packaging, evaluation and quality control of the tissue graft or implant and transportation and / or storage.

[0019] Furthermore, the present application provides a washing assembly for washing and staining a tissue graft or implant within a device according to the present application. The washing assembly according to the present application is easy to use and omits unnecessary handling of the tissue graft or implant.

[0020] Furthermore, a method for preparing a tissue graft or implant using a device according to the present application is provided. The method allows for loading a tissue graft or implant within a device according to the present application, for applying evaluation and quality control techniques to the tissue graft or implant within the transport and / or storage device, before the tissue graft or implant is expelled from the device, and for washing and staining the tissue graft or implant.

[0021] In particular, ultra-thin tissue grafts or implants for ophthalmic interventions, such as DMEK, PDEK and ultra-thin- / nano-thin-DSEK / DSAEK or related grafts or implants (e.g. "endothelium-in" / "triple-fold" corneal grafts or implants) benefit from the present application and are therefore preferably used with the present application.

[0022] The present application enables quality control of tissue grafts or implants in eye banks as well as in the operating room by microscopic methods, thereby minimizing handling of the tissue grafts or implants. Furthermore, the orientation of the tissue grafts or implants can be controlled during the preparation, evaluation, storage, transport and expulsion process, which makes the present application particularly suitable for "endothelium-in" / "triple-fold" and "endothelium-out" corneal tissue grafts or implants.

[0023] The present application provides a device and assembly which is suitable for the storage and / or transport of tissue grafts or implants and which is also suitable for the injection of tissue grafts or implants into a living body, which facilitates the microscopic evaluation and / or examination of the tissue grafts or implants within the device, which can be located within the assembly. More specifically, the present application relates to the storage, handling, transport, observation and / or evaluation of corneal tissue samples, in particular samples for ophthalmic interventions, after preparation / handling and / or before transplantation into a living body. DETAILED DESCRIPTION

[0024] The present invention provides an optically transparent device which can be used for fast and precise microscopic investigation for quality control and to ensure correct orientation ("top and bottom") of tissue grafts or grafts and / or implants during handling and transportation and / or storage and / or storage of these tissue grafts or implants during introduction into a living being. The device according to the present invention is suitable for reliably supporting tissue grafts or implants during evaluation, storage and / or transportation. Suitable tissue grafts or implants are for example DMEK, PDEK and ultra- / nano-thin-DSEK / DSAEK grafts, or related grafts or implants. In particular, the present invention has a clear benefit for handling "endothelium-in" / "triple-fold" corneal grafts or implants.

[0025] The engineered properties of the device allow for microscopic analysis of the implant and fixation of the orientation during preparation, evaluation, storage, transportation and implantation, which simplifies the work of the technical control personnel during handling and preparation of the implant and the work of the surgeon during the implantation process.

[0026] Device

[0027] In a first aspect, the present invention provides a hollow device for reliable support during storage and / or transportation of tissue grafts or implants, comprising:

[0028] • a first opening,

[0029] • a main body,

[0030] • a conical region, and

[0031] • a second opening,

[0032] wherein the first opening has a circular shape and a funnel-like design configured to enable connection of a tube or a syringe, the main body is transparent and has a rectangular shape, the conical region is transparent and has an elliptical, circular, lenticular or rectangular shape, wherein the main body comprises at least two flat and parallel opposing positions. The funnel-like design means that the diameter of the opening slightly increases towards the rim. This configuration allows for precise evaluation and quality control of the tissue graft or implant within the device. Furthermore, the orientation of the tissue graft or implant within the device remains unchanged during evaluation, storage and / or transportation. The device is transparent for microscopic purposes and is set according to the usage regulations in clinical practice.

[0033] The terms "position" and "surface" are used synonymously throughout the description.

[0034] The first opening has a circular shape with an inner diameter which is suitable for connection with a tube and / or a syringe nozzle, which provides a connection and a smooth transition between the rounded rectangular shape of the device body and the circular shape of the syringe and / or tube. In one embodiment of the application, the first opening has an inner diameter which is suitable for connection with a tube and / or a syringe nozzle having a luer slip connection or a luer lock connection (according to ISO 80369). In a preferred embodiment, the inner diameter of the first opening is in the range of 3 mm to 6 mm, preferably in the range of 4 mm to 5 mm. In a preferred embodiment of the application, due to the funnel-like design of the first opening of the device, its size is sufficient for gently taking up a tissue graft or implant.

[0035] The body of the device is a sleeve or a tube housing which ensures a stable positioning of the implant during the microscopic evaluation, storage and transportation. The body preferably comprises at least two flat and parallel opposite sides. In a preferred embodiment of the application, the body has a rounded rectangular shape. By "rounded rectangular shape" is meant a rectangle with rounded edges. Further preferably, the body is composed of a transparent material.

[0036] The conical region connects the device body and the second opening and is also the region where the tissue graft is placed before injection. The conical region has an elliptical, circular, lenticular or rectangular shape, in the case of a rectangular shape preferably with rounded edges. In one embodiment of the application, the conical region comprises at least two flat opposite positions similar to the body. In one embodiment of the application, the inner wall and the outer wall of the conical region have the same shape. In another embodiment of the application, the outer wall of the conical region can have a different shape than the inner wall.

[0037] In a preferred embodiment of the application, the conical region is composed of a transparent material and comprises a rectangular shape with rounded edges. The transparency of the device body and the conical region, the rounded rectangular shape and the flat opposite sides allow a microscopic examination of the tissue graft or implant within the device and fix the orientation of the tissue graft or implant during the entire delivery and implantation process. When transporting a tissue graft or implant using prior art devices, a microscopic examination (such as specular microscopy, slit lamp examination, optical microscopy and optical coherence tomography) is difficult to perform due to various light reflection artifacts caused by the (purely circular) shape of these devices. Therefore, the device according to the application advantageously comprises flat opposite sides and a rounded rectangular shape, wherein light reflection artifacts and tissue graft or implant tension are minimized. Thus, the area of the body is particularly suitable for microscopic examination and, in case the conical region also has a rounded rectangular shape, the conical region also provides the above-mentioned advantages for microscopic examination.

[0038] Preferably, for the tapered region, the distance between the top and bottom walls of its inner hollow compartment and its outer shape are smaller compared to the main body. Advantageously, this configuration prevents the tissue graft or implant from being undesirably released through the second opening during evaluation, storage and / or transportation when the tissue graft or implant is located within the main body of the device. Secondly, this configuration provides the option to seal only the first opening of the device with the lid for transportation of the tissue graft or implant while the second opening remains open. The tapering of the main body towards the tapered region and / or the second opening of the device is sufficient to ensure that the tissue graft or implant is stably placed within the main body of the device without slipping out even with exceptionally high shear forces during evaluation, storage and / or transportation. This allows free oxygen / nutrient exchange between the liquid within the device and the surrounding liquid (e.g. nutrient medium) during transportation. In the context of this document, the term "culture medium" refers to a liquid nutrient composition of the required ingredients to maintain cell viability during implant storage, evaluation and / or transportation. Because of the defined non-interaction or modification of the medium by the proposed device and the medium not altering the characteristics of the device, any medium used in the state of the art / clinical practice can be used. Furthermore, this provides the possibility to sample the surrounding solution (e.g. nutrient medium) next to the tissue graft or implant when it is located within the device, e.g. for fungal infection testing, with a reduced likelihood of false negative results compared to the devices of the prior art

[30] .

[0039] The device comprises a second opening opposite to the first opening, wherein both openings have similar size and shape or, preferably, different size and shape.

[0040] The second opening is sided for the expulsion of the tissue graft or implant. In a preferred embodiment, the second opening has an elliptical, circular, lenticular or rounded rectangular shape which is preferably small enough to be inserted into a small surgical incision (2.4 mm to 3.0 mm incision width). In one embodiment of the present invention, the outer wall of the second opening has the same shape as the inner wall. In another embodiment, the outer wall of the second opening can have a different shape than the inner wall.

[0041] The elliptical, circular, lenticular or rounded rectangular inner shape of the second opening allows to maintain the orientation of the tissue graft or implant during the expulsion of the tissue graft or implant from the device during surgical implantation, thereby preventing the problem of loss of orientation of the tissue graft or implant.

[0042] Furthermore, in one embodiment of the present application, the second opening preferably comprises a small chamfered shaped opening, which is suitable for implant surgery insertion and incision wound sealing. The engineered chamfered shape of the second opening firstly ensures easy insertion of the device into the surgical incision and secondly provides implant support during implantation. For insertion of the tissue graft or implant, the longer wing of the chamfered portion preferably faces the bottom (positioned towards the posterior chamber of the eye) to ensure implant injection into the anterior chamber of the eye.

[0043] The conical region and the oval, circular, lenticular or rounded rectangular shape of the second opening also reduces tissue tension and the corresponding damage during device insertion, as the wound of the small surgical incision (2.4 mm to 3.0 mm incision width) is better sealed.

[0044] In one embodiment of the present application, the inner hollow compartments of the device (body, conical region and second opening) are identical to the outer shape of these compartments of the device. In another embodiment, the inner hollow compartments of the conical region and the second opening of the device can be different in shape from the outer shape of these compartments of the device. The advantage of this is to ensure stable orientation of the tissue within the device and optimal performance in terms of microscopic research and optimal functionality during the surgical procedure (for example wound closure of the surgical incision when inserting the device). Thus, in one embodiment of the present application, the inner shape of the conical region and the second opening is rounded rectangular, while the outer shape is oval.

[0045] The various components of the device according to the present application can have different dimensions. In one embodiment, the diameter of the inner hollow compartment of the first opening is between 2 mm and 10 mm, preferably between 3 mm and 8 mm, more preferably between 3 mm and 6 mm, most preferably between 4 mm and 5 mm.

[0046] In one embodiment of the present application, the distance between the top wall and the bottom wall of the inner hollow compartment of the body, which are flat and parallel to each other, is between 1 mm and 5 mm, preferably between 1.5 mm and 4 mm, more preferably between 2 mm and 3 mm.

[0047] According to the present application, the distance between the top wall and the bottom wall of the inner hollow compartment of the conical region is between 0.5 mm and 4 mm, preferably between 0.8 mm and 2 mm, more preferably between 1 mm and 2 mm.

[0048] In one embodiment, the distance between the top wall and the bottom wall of the inner hollow compartment of the second opening is equal to the distance between the top wall and the bottom wall of the inner hollow compartment of the conical region. In another embodiment of the present application, the distance between the top wall and the bottom wall of the inner hollow compartment of the second opening is smaller than the distance between the top wall and the bottom wall of the inner hollow compartment of the conical region.

[0049] According to the present application, the body has a constant wall thickness. The wall thickness is between 0.1 mm to 1.0 mm, preferably between 0.1 mm to 0.8 mm, more preferably between 0.1 mm to 0.6 mm or between 0.2 mm to 0.4 mm. Most preferably, the wall thickness is 0.3 mm.

[0050] The wall thickness of the tapered region and the second opening can vary and depends on the overall shape and / or the difference between the shape of the outer wall and the inner wall of the tapered region and the second opening. In case the second opening has the same shape as the tapered region, the wall thickness is constant. In this case, the wall thickness is between 0.1 mm to 1.0 mm, preferably between 0.1 mm to 0.8 mm, more preferably between 0.1 mm to 0.6 mm or between 0.2 mm to 0.4 mm. Most preferably, the wall thickness is 0.25 mm.

[0051] In another embodiment, the overall length of the device is between 20 mm to 100 mm, preferably between 20 mm to 75 mm, more preferably between 25 mm to 50 mm, most preferably between 30 mm to 40 mm.

[0052] The shape and dimensions of the device according to the present application also allow for an insertion of the tissue graft or implant in an oriented manner, as the inner shape of the device prevents a rotation of the tissue graft or implant within the device, even during a forward or backward movement along the inner hollow compartment of the device (for example, during a repositioning of the graft after transport for implantation, which will be described later), thus ensuring an oriented stability of the tissue graft or implant. This is particularly beneficial for the application of an “endothelium-in” / “triple-fold” DMEK implant, as it allows to maintain the orientation of the implant during a direct injection into the living body, without the need to use surgical forceps as in the conventional “pull-through” technique.

[0053] Conventional DMEK injectors are usually made of borate glass, as the device surface is thus preferably smooth to prevent damaging the implant during injection. However, the use of glass has some obvious drawbacks, as glass is very fragile and can easily break not only during tissue transport but also during surgery. More preferably, the injector tip is also small to fit into a small surgical incision (2.4 mm to 3.0 mm incision width), which requires the use of an injector with a thin glass wall. This aggravates the likelihood of damage / breakage of the device.

[0054] However, in one embodiment of the present application, the device is made of glass, preferably borate glass.

[0055] To overcome the above-mentioned drawbacks of devices made of glass, in a more preferred embodiment of the present application, the device is made of a transparent plastic that is more robust than glass but exhibits similar transparency. This type of glass is hereinafter referred to as "glass-like plastic". Furthermore, the wall thickness of the plastic can be much thinner than any glass (e.g. via injection molding or 3D printing) and is not at risk of breaking during the surgical procedure, which opens up new possibilities for creating smaller incisions on the patient's eye than with conventional devices. The transparency of the device enables evaluation and quality control of tissue implants or grafts by precision microscopy methods such as specular microscopy, slit lamp examination, optical microscopy and optical coherence tomography. In a most preferred embodiment, the plastic used for the preparation of the device according to the present application is highly transparent. According to the present application, the refractive index (ri) is in the range of ri = 1.30 to ri = 1.71, preferably in the range of ri = 1.30 to ri = 1.65, most preferably in the range of ri = 1.30 to ri = 1.60, which is similar to the ri of balanced salt solution (BSS, about 1.33 to 1.34 at 20°C and about 600 nm), which can be used for the loading, evaluation and / or storage of tissue grafts within the device. The term "BSS" includes buffered saline solutions, e.g. Hank's BSS, Earle's BSS, Tyrode's salt solution, Alsever's salt solution, phosphate buffered saline (PBS), Tris buffered saline (TBS), Puck's salt solution, Gey's salt solution, Ringer's salt solution, Simm's salt solution and related buffered salt solutions. Plastic compositions, e.g. combinations, mixtures, blends or copolymers of two or more plastics, can also be used to manufacture the device of the present application. Plastic compositions suitable for the device of the present application due to compliance with these requirements are listed in Table 1. In an embodiment of the present application, the device is made of a material listed in Table 1. In a preferred embodiment, the device is made of polyacrylate, polycarbonate or polystyrene.

[0056] Furthermore, there are specific coatings available to make the plastic surface smoother than borate glass. Both hydrophobic and hydrophilic coatings can be used to make the surface smooth.

[0057] In an embodiment of the present application, the inner surface of the device comprises a coating, wherein the coating can be a hydrophobic coating or a hydrophilic coating.

[0058] Hydrophobic coatings make the surface smooth and create strong surface tension, preventing the implant from "touching" the surface in solution, which is very convenient for "endothelium-out" DMEK and PDEK tissue grafts or implants. Hydrophobic coatings suitable for the device of the present application are listed in Table 2. In an embodiment of the present application, the inner surface of the device comprises a hydrophobic coating, a coating blend, a coating mixture or other combinations of hydrophobic coatings selected from Table 2.

[0059] In a preferred embodiment of the application, the inner surface of the device comprises a hydrophobic coating selected from the group comprising acrylate, organosiloxane, silane, epoxy, polymer, molybdenum disulfide, molybdenum disulfide / graphite, tungsten disulfide or graphite, preferably selected from the group comprising polymer, organosiloxane, silane, acrylate or epoxy.

[0060] The hydrophilic coating makes the surface slippery, in addition to acting as a lubricant, making the implant easier to slide over the surface. Thus, the hydrophilic coating is most suitable for implants that push against the surface of the inner compartment of the device, such as "endothelium-in" / "triple-fold" DMEK and ultra- / nano-thin-DSEK / DSAEK tissue grafts or implants. Hydrophilic coatings suitable for use in the device of the application are listed in Table 3. In an embodiment of the application, the inner surface of the device comprises a hydrophilic coating selected from the group comprising a hydrophilic coating, coating blend, coating mixture or other combination of hydrophilic coatings from Table 3.

[0061] In a preferred embodiment of the application, the inner surface of the device comprises a hydrophilic coating selected from the group comprising any hydrophilic polymer / hydrogel, preferably selected from the group comprising a coating comprising poly(ethylene glycol), poly(acrylate), poly(methacrylate) or a UV / light sensitive polymer.

[0062] A third method of changing the contact angle between a liquid and a solid surface is the use of millimeter-scale patterns as well as micro- or nano-structured surface patterns or a combination thereof (e.g. nano-micro structures

[31] ). Millimeter-scale patterns, if aligned with the injection / ejection direction of the graft, can control the orientation of the graft, while nano-scale surface patterns are known to increase the hydrophobicity of the surface [31, 32]. The use of micro-patterns is considered the best option as it combines the advantages of millimeter- and nano-scale patterns and can be produced by injection molding. The combination of micro- and nano-structured patterns allows, on the one hand, to maintain a clear microscopic visibility of the implant within the device for quality control, and on the other hand, to minimize the interaction of the implant with the syringe. This modification is particularly advantageous for "endothelium-in" / "triple-fold" implantation techniques, as less interaction with the inner walls of the device allows for easier ejection of the implant (without the need for additional instruments such as "pulling" techniques). Surface patterning can be combined with the coatings described above for optimal performance.

[0063] The benefit of surface patterning is that the contact area of the tissue graft or implant is reduced to less contact points compared to a flat surface. Thus, less tissue graft or implant surface interaction leads to less respective damage caused during loading, evaluation, storage and / or transportation of the tissue graft or implant as well as during expulsion from the device. It is important that the surface pattern does not interfere with the microscope procedure during the evaluation process (e.g. the special arrangement and size of the pattern should not widely scatter light during the microscope examination). Due to these circumstances, micro-structuring patterning and its combination with nano-structuring patterning is considered to be the most beneficial of all specified patterning types.

[0064] Thus, in one embodiment of the present application, the inner surface of the device comprises a surface pattern to increase the hydrophobicity and / or to reduce the contact area between the tissue graft or implant and the inner surface of the device, which surface pattern is a surface pattern of micro- and / or nano-structures (combination e.g. nano-micro-structures) in the range of 100 nm to 20 000 nm (0.1 pm to 20 pm), preferably in the range of 300 nm to 5000 nm (0.3 pm to 5 pm), more preferably in the range of 500 nm to 2500 nm (0.5 pm to 2.5 pm).

[0065] In one embodiment of the present application, the inner surface of the device comprises a surface pattern in combination with a hydrophobic or hydrophilic coating as described above.

[0066] The use of the "glass-like plastic" with the respective coating or surface pattern for implant preparation, storage, transportation and injection is safer than glass as it does not break; and it is more efficient as it can be designed specifically for implants. Together with the engineered shape of the device described above, it provides significant advantages in terms of efficiency and respective safety of the implantation procedure of tissue grafts and implants, in particular for all major types of endothelial keratoplasty (EK) tissue grafts and implants.

[0067] In one embodiment, the device of the present application further comprises a lid for the first opening and / or a lid for the second opening. In one most preferred embodiment, the present application comprises only one lid.

[0068] For storage and / or transportation and evaluation of the tissue, the device can be closed via applying a lid at the first opening and a lid at the second opening or via applying only one lid at the first opening. According to the present application, the lids have to remain tight enough to prevent the tissue graft or implant from sliding out of the device. At the same time, for the purpose of the microscope examination, the lids are configured such that at least the device body, preferably the device body and the conical region, remain uncovered.

[0069] Therefore, the present invention provides a device having a cover at the first opening and a cover at the second opening or only one cover at the first opening, wherein the cover is configured such that at least the body of the device, preferably the body of the device and the conical region of the device, remains uncovered.

[0070] The cover should be removable in a smooth and gentle manner. The design of the cover depends on the design of the opening of the device that should be closed. Since there are multiple combinations of the size and geometry of the first opening and the second opening according to the present invention, the design of the cover has to be adopted to the design of the selected device.

[0071] Therefore, the present invention provides a device, wherein the design of the cover for the first opening is adopted to the design of the first opening of the device and / or the design of the cover for the second opening of the device is adopted to the design of the second opening of the device.

[0072] The cover for closing the first opening and / or the second opening of the device can be made of any hard or soft plastic, for example selected from the group consisting of polypropylene (PP), polystyrene (PS), polyamide (PA), polyether ketone (PEK), polyether ether ketone (PEEK), poly(methyl methacrylate) (PMMA), polyethylene (PE), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyphthalamide (PPA), polyphenylene sulfide (PPS), polyamide-imide (PAI), polyphenylsulfone (PPSU), polyethersulfone (PES), polysulfone (PSU), polycarbonate (PC), acrylonitrile butadiene styrene (ABS), styrene-acrylonitrile copolymer (SAN) or polyvinyl chloride (PVC), rubber, silicone, macroporous material, glass and suitable mixtures or combinations thereof.

[0073] During transport and evaluation, the device is stored in a liquid transport medium. In order to ensure an adequate supply of oxygen and nutrients to the tissue graft or implant (located inside the device), solvent exchange between the inner hollow compartment of the device and the solution surrounding the device has to be ensured. Therefore, in one embodiment of the present invention, at least one cover is permeable.

[0074] Permeability can be ensured via the use of small pores in the closing cover, the use of a mesh, a membrane or a macroporous material or a related permeable material within the cover. In one embodiment of the present invention, the cover closing the first opening of the device is permeable. In one embodiment of the present invention, the cover closing the second opening of the device is permeable. In another embodiment, the covers closing the first and second openings of the device are permeable.

[0075] In a most preferred embodiment of the present application, only one cover closing device is present at the first opening. In this case, the exchange of solvent between the hollow compartment inside the device and the solution surrounding the device can be achieved via the second opening, thus ensuring an adequate supply of oxygen and nutrients to the tissue graft or implant (located inside the device). Therefore, if only the first opening is closed by a cover, this cover can be, but does not have to be, permeable. Thus, in a preferred embodiment of the present application, the device comprises a cover for the first opening of the device.

[0076] Assembly for loading, storage and transportation of tissue grafts or implants

[0077] The separate device is not suitable for successful loading of tissue grafts or implants into the device, additional tools and accessories are required. Therefore, in a second aspect, the present application relates to an assembly for loading tissue grafts or implants, comprising a device according to the present application, at least one syringe, a tube and at least one cover for closing at least one opening of the device. Preferably, the tissue graft or implant loading assembly is set up according to the usage regulations in clinical practice.

[0078] Advantageously, in all embodiments of the assembly for loading, storage and transportation of tissue grafts or implants, at least the main body of the device is not covered, thus it can be used for microscopic examination and / or macroscopic evaluation of the tissue graft or implant.

[0079] For the loading process of the tissue, the device is preferably connected to a tissue loading accessory. The tissue loading accessory can be, for example, a laboratory / culture dish containing the tissue graft or implant in a suitable liquid medium (e.g. BSS). Thus, the second opening of the device is connected via an additional tool to a standard syringe for the loading of the tissue. By standard syringe is meant a syringe that can be, for example, connected to a luer slip or luer lock connector. According to the present application, the additional tool can be a tube.

[0080] Thus, in an embodiment of the present application, there is provided an assembly for loading, short-term (< 24 hours) storage and / or transportation of tissue grafts or implants, comprising:

[0081] • a device according to the first aspect of the present application,

[0082] • at least one syringe,

[0083] • a tube, and

[0084] • at least one cover.

[0085] The tube is preferably made of a flexible material. In an embodiment of the present application, the tube is preferably made of a material selected from rubber, silicone, latex or related flexible materials.

[0086] The inner diameter of the tube is adjusted to be slightly smaller than the outer dimension of the second opening, e.g. at most 10% or 20% smaller, to ensure a tight seal when attached. The tube preferably has an inner diameter between 1 mm and 4 mm, more preferably between 2 mm and 3 mm or 10% smaller. In a most preferred embodiment of the application, the inner diameter of the tube is 2 mm or 10% smaller than 2 mm.

[0087] The length of the tube is adjusted to be long enough to facilitate handling, but short enough to prevent the tube from being excessively bent, which would affect smooth handling. The length of the tube is preferably between 50 mm and 150 mm, more preferably between 70 mm and 130 mm, even more preferably between 80 mm and 105 mm. In a most preferred embodiment of the application, the length of the tube is 95 mm. However, to facilitate the user, the tube can be manually shortened (e.g. using scissors, a scalpel or similar tool) to the desired length.

[0088] The tube according to the application can be directly attached to a standard syringe, e.g. by a luer lock or luer slip structure, or attached to a standard syringe by a standard tube connector. A standard tube connector is e.g. a luer connector. Such a standard connector can be made of any soft or hard plastic, e.g. a material selected from the group consisting of polypropylene (PP), polystyrene (PS), polyamide (PA), polyether ketone (PEK), polyether ether ketone (PEEK), poly(meth) methacrylate (PMMA), polyethylene (PE), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyphthalamide (PPA), polyphenylene sulfide (PPS), polyamide-imide (PAI), polyphenylsulfone (PPSU), polyethersulfone (PES), polysulfone (PSU), polycarbonate (PC), acrylonitrile butadiene styrene (ABS), styrene-acrylonitrile copolymer (SAN) or polyvinyl chloride (PVC).

[0089] Thus, in one embodiment of the application, there is provided an assembly for loading, short-term (<24 hours) storage and / or transport of a tissue graft or implant, comprising:

[0090] • a device according to the first aspect of the application,

[0091] • at least one syringe,

[0092] • a tube, wherein one side of the tube has a luer lock or luer slip connector, and

[0093] • at least one cap.

[0094] The device is designed such that the loading of a thin tissue graft or implant (e.g. DMEK / PDEK, ultra- / nano-thin-DSEK / DSAEK grafts and any related grafts or implants) can be performed from the first opening. This opening is not only suitable for direct attachment to a syringe nozzle and / or tube, but due to its funnel-like design (the diameter of the opening slightly increases towards the rim), its size is also suitable for gently taking up a tissue graft or implant.

[0095] To load a tissue graft or implant into the device, a tube is attached to the second opening by attaching one end of the tube to the second opening and the other end of the tube (including a luer lock connector or a luer slip connector) is attached to a syringe, e.g. preferably filled with BSS or a liquid nutrient medium, is connected to the second opening of the device. Subsequently, the syringe plunger is moved to expel excess air from the device and the tube. There should be no air bubbles within the device and the tube. As an example for the loading of a DMEK tissue, the first opening of the device is gently placed over the tissue graft or implant (present within a lab dish / culture dish containing the tissue graft or implant in a suitable liquid medium, e.g. BSS) without touching the tissue graft or implant and the syringe plunger is moved to upload the tissue graft or implant into the device by using a hydrodynamic flow.

[0096] To directly introduce the tissue graft or implant into a living body, the tissue graft or implant can be partially positioned within the conical region of the device, which can be referred to as the “injection position”. In this position, the tissue graft or implant is partially rolled up or slightly compressed, which ensures a stable positioning within the device. To directly introduce the tissue graft into a living body, another syringe filled with liquid, e.g. BSS, can be directly connected to the first opening of the device. Alternatively, the tissue graft or implant can also be fully positioned within the conical region for the “injection position”. However, this increases the likelihood of an undesired slippage of the tissue graft or implant out of the device during attachment of the syringe to the first opening of the device, as in this case there is not much space left towards the second opening of the device. Therefore, preferably, the tissue graft or implant is partially positioned within the conical region of the device for the “injection position”.

[0097] Now, the tube at the second opening can be gently removed together with the syringe, the device is ready for the expulsion of the tissue graft or implant. Alternatively, the assembly comprising the device with the tissue graft or implant, two syringes each attached to the first and second opening of the device (for the second opening via the tube and the syringe connector) can be used for gentle internal transport and / or storage, e.g. from a tissue preparation facility to an operating room, if these facilities are located within the same building.

[0098] For evaluation, storage and / or transport, the tissue graft or implant can be placed inside the body of the device, which can be referred to as "transport position". For reliable transport, the tube at the second opening of the device is gently removed and at least one opening of the device is sealed by a cap, preferably the first opening is sealed by a suitable cap. Alternatively, a suitable cap seals the first and the second opening. The properties of the suitable cap are as described above.

[0099] The device loaded with the tissue graft or implant has to be transported in a liquid medium with a volume of at least 20 ml, which is far beyond the inner volume of the device itself. Therefore, in one embodiment of the present application, the assembly for loading, storing and / or transporting the tissue graft or implant further comprises a transport device. Preferably, the transport device is arranged according to the regulations of use in clinical practice.

[0100] Currently, only few transport devices are available in the art. The Straiko Modified Jones tube [24, 25] suggests transport in an observation chamber similar to that used for whole corneal tissue transport and the Geuder syringe

[27] suggests transport in a standard container, which means a standard tissue culture flask. Both transport devices are also suitable for the transport of the device of the present application. Therefore, in one embodiment of the present application, the storage / transport device comprises an observation chamber as described in [24, 25] or a standard tissue culture flask as described in

[27] .

[0101] In a preferred embodiment of the present application, the storage / transport device is a device holder, which is suitable to be positioned inside a container. Such a container can be a standard tissue culture flask, a tissue culture flask with two openings or a similar container, e.g. an observation chamber as described in [24, 25]. Standard tissue culture flasks are commonly used in research and clinical cell and tissue applications and are also suitable for tissue evaluation via a precision microscope. Alternatively, the container can be a tissue culture flask with two openings, wherein one opening is suitable for insertion of the device holder comprising the device and the second opening is suitable for direct aspiration of the liquid medium from inside the device (e.g. for fungal testing).

[0102] According to the present application, the device holder comprises:

[0103] • a round neck with a holding structure,

[0104] • a finger-like structure attached to an oval platform with a cavity, and

[0105] • a bent strip column.

[0106] The device holder according to the present application is suitable to be positioned inside a container, e.g. a standard tissue culture flask or a tissue culture flask with two openings.

[0107] The fingertip-like structure according to the present application holds the device tightly. Thus, the fingertip-like structure has a cavity which is shaped to match the size of the device for easy assembly and gentle removal of the device. Advantageously, the fingertip-like structure is made of a plastic which has a slight elasticity, for example a plastic selected from the group consisting of polypropylene (PP), polyamide (PA), polyether ketone (PEK), polyether ether ketone (PEEK), poly(methyl methacrylate) (PMMA), polyethylene (PE), polyethylene terephthalate (PET) or a plastic blend, a plastic mixture, a copolymer or another combination of the aforementioned plastics, preferably a plastic selected from the group consisting of PP, PA, PE or PMMA. This allows the fingertip-like structure to be used as a "clip" during insertion of the device. Furthermore, the shape of the fingertip-like structure fixes the orientation / position of the device during transport. In particular, this can prevent the device from rotating. The fingertip-like structure is attached on an oval holding structure comprising the cavity, which is preferably made of the same material as the fingertip-like structure and is a strong support for the fingertip-like structure. The cavity is designed not to obscure the body, preferably not to obscure the body and the conical region of the device which serve as a microscopy area. Thus, if the device holder is inserted into a container, for example a standard tissue culture flask or a tissue culture flask with two openings, the tissue graft or implant loaded into the device can be easily examined from the top and the bottom of the standard tissue culture flask or the tissue culture flask with two openings.

[0108] The oval holding structure with the fingertip-like structure is attached to a warped strip column, which is shaped to match the bottom of a standard tissue culture flask or a tissue culture flask with two openings. The warped strip column is advantageously made of plastic, preferably of the same material as the fingertip-like structure and the oval holding structure with the cavity.

[0109] The warped strip column is attached to a round neck, which on the one hand allows insertion into a standard tissue culture flask or a tissue culture flask with two openings and on the other hand abuts against the neck of a standard tissue culture flask or against one neck of a tissue culture flask with two openings. This can prevent movement of the entire transport device within a standard tissue culture flask or a tissue culture flask with two openings. The round neck has a holding structure in the center which allows handling with tweezers and / or the fingers of the end user in order to reliably and easily insert and remove the device holder from a standard tissue culture flask or a tissue culture flask with two openings. The outer dimensions of the device holder are designed such that one end of the warped strip column touches the bottom of a standard tissue culture flask or a tissue culture flask with two openings, while the other end with the round neck is in the neck of a standard tissue culture flask or in one neck of a tissue culture flask with two openings and touches the closing lid of a standard tissue culture flask or one closing lid of a standard tissue culture flask with two openings when the standard tissue culture flask or the tissue culture flask with two openings is closed.

[0110] In a preferred embodiment of the present application, the device holder is made of plastic, preferably selected from the group consisting of polypropylene (PP), polyamide (PA), polyether ketone (PEK), polyether ether ketone (PEEK), poly(methyl methacrylate) (PMMA), polyethylene (PE), polyethylene terephthalate (PET) or plastic blends, plastic mixtures, copolymers or other combinations of the aforementioned plastics, more preferably selected from the group consisting of PP, PA, PE or PMMA. In a most preferred embodiment, the device holder is made of plastic in one piece, e.g. via injection molding or 3D printing.

[0111] In an embodiment of the present application, the round neck, the holding structure, the finger-like structure attached to the oval platform with a cavity and the bent strip column can be made of different plastics, preferably selected from the group consisting of polypropylene (PP), polyamide (PA), polyether ketone (PEK), polyether ether ketone (PEEK), poly(methyl methacrylate) (PMMA), polyethylene (PE), polyethylene terephthalate (PET) or plastic blends, plastic mixtures, copolymers or other combinations of the aforementioned plastics, more preferably selected from the group consisting of PP, PA, PE or PMMA.

[0112] The features of the device holder according to the present application prevent any movement of the device holder within a standard tissue culture flask or a tissue culture flask with two openings. The shape of the round neck prevents horizontal movement of the device holder within a standard tissue culture flask or a tissue culture flask with two openings, the shape of the bent strip column prevents any rotation or turning of the device holder within a standard tissue culture flask or a tissue culture flask with two openings. Since the device according to the present application is held tightly by the finger-like structure of the device holder, the device holder fixes the absolute positioning of the device within a standard tissue culture flask or a tissue culture flask with two openings. Thus, rotation or horizontal movement of the device and the tissue graft or implant within the device is prevented. The device holder according to the present application ensures that the device and the tissue graft or implant within the device remain in place during storage and / or transport. This is beneficial, for example, during transport prior to surgery, since graft preparation is performed by a skilled staff in an eye / tissue bank.

[0113] Advantageously, the device holder according to the present application allows for visual inspection control of the tissue graft or implant within the device and within the standard tissue culture flask or the tissue culture flask with two openings at the same time. The device holder also allows for efficient examination of the tissue graft or implant by different microscopic methods (tissue quality control), such as specular microscopy, slit lamp examination, optical microscopy and optical coherence tomography. This is based on the transparency of the standard tissue culture flask (or the tissue culture flask with two openings) and its common use under the microscope and the reliable position of the device comprising the tissue graft or implant, in which the flat surface of the body and the conical region of the device face the top and bottom of the standard tissue culture flask or the bottom of the tissue culture flask with two openings. The cost-effectiveness of the present invention is also good, as it allows the use of commercially available standard tissue culture flasks, the device holder can be made in one piece from plastic, for example via injection molding or 3D printing. Furthermore, the device holder has the advantage that the device can be put in and removed very reliably at the same time, which can even be done by untrained personnel.

[0114] Washing assembly

[0115] Furthermore, a washing assembly for washing and staining a tissue graft or implant within a device (e.g. implanted into an eye) prior to its discharge is provided. According to the present invention, the washing assembly comprises a macroporous material, a device according to the present invention, at least one syringe, optionally at least one cap and either a double-way extension line or a three-way cock valve, which can both comprise a hose. Preferably, the washing assembly is set up according to the usage regulations in clinical practice.

[0116] Advantageously, in all embodiments of the washing assembly, at least the body of the device is not covered, thus available for microscopic examination and / or macroscopic assessment of the tissue graft or implant.

[0117] Since the tissue graft or implant is transported in a liquid nutrient medium as described above, it has to be at least washed with BSS and / or stained with trypan blue and washed with BSS before injection into a living body. Trypan blue is a dye used for better visualization of tissue grafts or implants, in particular for ophthalmic interventions. It is therefore suitable for quality control of tissue grafts and implants. Due to cytotoxicity issues, tissue grafts or implants should not be exposed to trypan blue and BSS for a long time, so tissue grafts or implants are usually stained and washed just before implantation. Staining and washing is a complex procedure as it should be done without damaging the tissue graft or implant. Staining and washing is most preferably performed in the device transporting the tissue graft or implant to reduce handling of the tissue graft or implant that can lead to orientation disorders, loss or damage of the tissue graft or implant. Currently, this requires advanced training of the surgeon. However, sometimes undesired release of the tissue graft or implant from the transport device leads to the need to reinsert it into the device, which is both time consuming and damaging to the cells

[13] .

[0118] The present application therefore also provides an assembly for gentle and reliable washing of a tissue graft or implant. The washing assembly comprises:

[0119] • a macroporous material,

[0120] • a device according to the first aspect of the application or a similar conventional device,

[0121] • at least one syringe,

[0122] • optionally at least one cap,

[0123] • optionally at least one tube clamp,

[0124] • a double-bore extension line or a three-bore stopcock, wherein both optionally comprise a hose.

[0125] In one embodiment of the present application, the washing assembly comprises a macroporous material to control the liquid flow during washing of a tissue graft or implant. Due to the interconnected pores, the macroporous material allows liquid flow if a force is applied, but generally prevents liquid flow in steady state. In other words, when the second opening of the device faces the macroporous material, liquid entering the device from the first opening can pass through the device, but any large object, e.g. a tissue graft or implant, cannot escape. Due to the simplicity of the operation, even inexperienced staff can quickly and reliably stain and wash a tissue graft or implant with this assembly. Importantly, liquid cannot escape from the macroporous material unless an external force is applied, so the liquid medium and subsequent staining solution do not return to the device ("sponge effect") that holds the tissue graft or implant clean. This is similar to a sponge, where water in the sponge can only be removed when the sponge is compressed. Importantly, washing with macroporous material does not compromise the viability of the transplanted tissue graft or implant, e.g. human corneal endothelial cells.

[0126] In one embodiment of the present application, the macroporous material is embedded in a stable container. The macroporous material can be unsecured or secured to the stable container, e.g. by surface functionalization, application of a special surface topography, glue, sutures or special tactile / geometry of the container.

[0127] In another embodiment of the present application, the macroporous material is provided without any kind of container.

[0128] The macroporous material can have any possible geometry, preferably the macroporous material has at least one flat surface. The minimum thickness of the macroporous material depends on its overall volume. Preferably, the shape of the macroporous material is a cylinder with a diameter between 1 cm and 5 cm and a height between 0.3 cm and 3 cm (volume approximately 0.25 ml to 58 ml). This has the advantage that the second opening of the device can be pressed against the flat surface of the macroporous material, ensuring a tight connection.

[0129] Since the second opening of the device can have different shapes and geometries as described above (e.g. oval, circular, lenticular or rounded rectangular shape), in a more preferred embodiment of the present application, one surface of the macroporous material is adapted to the shape and geometry of the second opening of the device. The advantage of this embodiment is that a very tight connection between the macroporous material and the second opening of the device is easily achieved.

[0130] The macroporous material suitable for the cleaning assembly of the present application has interconnected pores with a porosity comprised between 10 pm and 600 pm, preferably between 10 pm and 400 pm, more preferably between 30 pm and 300 pm. The macroporous material advantageously has a low bulk stiffness and a high stability when compressed, which makes the handling easier during the cleaning and dyeing process according to the present application. Moreover, thanks to the "sponge effect" of the above-mentioned macroporous material, it allows to easily lift the device.

[0131] According to the present application, the macroporous material can be made of any type of suitable material, including natural sponges, foams, pure synthetic or biopolymers, synthetic or biopolymer blends, rubbers, any combination of the above and similar sponge-like materials. In a preferred embodiment of the present application, the macroporous material is made of synthetic or biopolymers, for example polyvinyl alcohol-based or cellulose-based sponges. These materials are advantageous in that they are readily available since they are widely used in medical devices (even implantable devices) and have already been certified for medical use, with very high sterility levels.

[0132] Moreover, the macroporous material can be prepared according to any of the developed techniques [33-35], including porogen leaching [36, 37], gas foaming [38, 39], phase separation [40, 41], electrospinning

[42] and freeze-gelation in aqueous media [43-45].

[0133] The macroporous material according to the present application has a low bulk stiffness and a high mechanical stability when compressed. These characteristics allow the material to be easily handled and allow a gentle geometrical adaptation to the shape of the second opening of the device. The macroporous material has a "cushioning effect", which allows to gently clean and dye the tissue grafts and implants inside the device, without applying any mechanical force during the dyeing and cleaning procedure that could compromise the integrity of the tissue grafts or implants.

[0134] Furthermore, the cleaning assembly comprises a double-bore extension line or a three-way stopcock. Both can be made of hard or soft plastic (e.g. selected from the group consisting of polypropylene (PP), polystyrene (PS), polyamide (PA), polyether ketone (PEK), polyether ether ketone (PEEK), poly(methyl methacrylate) (PMMA), polyethylene (PE), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyphthalamide (PPA), polyphenylene sulfide (PPS), polyamide-imide (PAI), polyphenylsulfone (PPSU), polyethersulfone (PES), polysulfone (PSU), polycarbonate (PC), acrylonitrile butadiene styrene (ABS), styrene-acrylonitrile copolymer (SAN) or polyvinyl chloride (PVC)), rubber, silicone, glass and suitable combinations thereof, and both can comprise a hose. The tube can be made of a material selected from the group consisting of rubber, silicone, latex or related flexible materials.

[0135] The length of the tube is adjusted to be long enough to facilitate handling, but short enough to prevent the tube from being excessively bent, which would affect smooth handling. The length of the tube is preferably between 100 mm and 200 mm, more preferably between 120 mm and 180 mm, even more preferably between 140 mm and 160 mm. In a very preferred embodiment of the application, the length of the tube is 150 mm.

[0136] In an embodiment of the application, the cleaning assembly further comprises a tube clamp and a closure cap for the end of the device and the double-bore extension line or the three-way stopcock. The tube clamp can be used to interrupt the flow in the tube used in the cleaning assembly. The cap is suitable for closing the open end of the double-bore extension line or the three-way stopcock. The closure cap for the device can be used to close the second opening of the device during and / or after cleaning and dyeing and / or to close the first opening of the device after disconnecting the device from the double-bore extension line or the three-way stopcock. In the case of a permeable closure cap, the cap can remain on the second opening of the device even during the cleaning and dyeing procedure.

[0137] According to the application, the double-bore extension line and the three-way stopcock are preferably equipped with a connection for connecting the device and a connection for connecting a syringe. In an embodiment of the application, the double-bore extension line and the three-way stopcock are preferably equipped with a hose with a male connection for attaching to the device via the first opening. The male connection is preferably a luer lock connection or a luer slip connection. The double-bore extension line and the three-way stopcock both have two further connections, which are preferably female connections. The female connections are preferably luer lock connections or luer slip connections. The female connections are suitable for connecting a conventional (e.g. luer lock or luer slip) syringe. The connection to the female connection can also, but need not, be equipped with a tube and / or a cap.

[0138] The cleaning set according to the application further comprises a syringe, which can be connected to the double-barrelled extension line or to the three-way stopcock. In one embodiment of the application, the cleaning set according to the application comprises two syringes, wherein one syringe, for example filled with BSS, can be connected to one of the female connections of the double-barrelled extension line or of the three-way stopcock, and the other syringe, for example filled with trypan blue staining solution, can be connected to the other female connection of the double-barrelled extension line or of the three-way stopcock.

[0139] According to the application, the cleaning set can comprise any similar conventional device instead of the device according to the application. In principle, similar conventional devices are devices suitable for carrying tissue grafts or implants. Such conventional devices are, for example, the Straiko Modified Jones tube [24, 25], the intraocular lens capsule

[26] or the Geuder DMEK injector

[27] .

[0140] Method for preparing a tissue graft or implant

[0141] In a fourth aspect, the present application provides a method for preparing a tissue graft or implant for injection into a living being using the device according to the application.

[0142] The method for cleaning a tissue graft or implant with the aid of the cleaning set is described in the context of the method for preparing a tissue graft or implant. Accordingly, the present application provides a method for preparing a tissue graft or implant using the device according to the application, comprising the following steps:

[0143] a) providing a tissue graft or implant,

[0144] b) loading the tissue graft or implant into the device,

[0145] c) sealing the device with at least one cap,

[0146] d) evaluating and quality-controlling the tissue graft or implant within the device, which is preferably placed within a storage / transport container with the aid of the device holder according to the application (for example for long-distance transport outside the tissue bank),

[0147] e) transporting the device with the tissue graft or implant, preferably using the device holder according to the application within a storage / transport container (for example for long-distance transport outside the tissue bank),

[0148] f) optionally evaluating and quality-controlling the tissue graft or implant within the device,

[0149] g) cleaning and staining the tissue graft or implant within the device.

[0150] According to the method of the present application, a tissue implant or graft is provided, which is preferably a tissue graft or implant suitable for DMEK, PDEK, ultra- / nano-thin-DSEK or DSAEK technology or any related technology.

[0151] The tissue graft or implant is loaded into the device according to the present application. Thus, the device is attached to a tissue loading accessory. The tissue loading accessory can be, for example, a lab dish / culture dish containing the tissue graft or implant in a suitable liquid medium, such as BSS. Further steps of tissue graft or implant loading are described in the "Assembly for loading, storage and transport of tissue grafts or implants" section of the present application.

[0152] For evaluation, storage and / or transport, the tissue graft or implant can be placed within the main body of the device, which can be referred to as "transport position". For reliable transport, at least one opening of the device is sealed by a lid, preferably the first opening and the second opening are sealed by suitable lids. The characteristics of suitable lids are described above.

[0153] According to the method of the present application, the device loaded with the tissue graft or implant is transported to the desired location. According to one embodiment of the present application, this is carried out by using a transport device according to the present application. Most preferably, a transport device is used which comprises a device holder according to the present application. Thus, the device is fixed in the device holder and the device holder is positioned in a container, such as a standard tissue culture flask or a tissue culture flask with two openings, which is dimensioned to be fillable with at least 20 ml of a suitable liquid medium, leaving at most 1-2 ml of air or preferably less air within the transport assembly.

[0154] Thus, in one embodiment of the present application, the device is transported within the device holder within a container, such as a standard tissue culture flask or a tissue culture flask with two openings. According to the method of the present application, the evaluation and quality control of the tissue graft or implant is carried out within the device. Thus, if a transport device is used which has a device holder according to the present application, the device can stay within the transport device and even within the container, such as a standard tissue culture flask or a tissue culture flask with two openings. According to the present application, the main body and the tapered region of the device are suitable for performing the above-mentioned precision microscopy techniques, such as specular microscopy, slit lamp examination, optical microscopy and optical coherence tomography.

[0155] Thus, the evaluation and quality control of the tissue graft or implant can be carried out during the entire method according to the present application. Because the device is suitable for microscopic examination and / or macroscopic evaluation of the tissue graft or implant at any time as long as at least the main body of the device is not covered.

[0156] It is particularly advantageous that the evaluation and quality control can be performed with the device containing the tissue graft or implant within the transport device and within the container, e.g. a standard tissue culture flask or a tissue culture flask with two openings, since additional handling of the tissue graft or implant is avoided. Thus, possible damage to the tissue graft or implant is minimized.

[0157] Before use / implantation, the tissue graft or implant has to be washed and preferably stained. According to the present application, this is preferably performed using the washing assembly provided by the present application and as described above. In other words, in one embodiment of the present application, step g) is performed while the tissue graft or implant is located within the device. Thus, if the lid at the second opening of the device is not liquid permeable, the device is removed from the transport device and the closure lid is removed at least from the first opening and optionally from the second opening of the device.

[0158] Before staining and washing of the tissue, one syringe filled with BSS is connected to one female connection of the double-barrelled extension line or the three-way stopcock and one syringe filled with staining solution, e.g. trypan blue, is connected to the other female connection. The volume of the syringe filled with BSS is preferably larger than the volume of the second syringe filled with staining solution. In one embodiment of the present application, the volume of the syringe filled with BSS is between 5 ml and 10 ml and the volume of the syringe filled with staining solution is between 1 ml and 4 ml.

[0159] For removing air from the assembly, in case of a double-barrelled extension line equipped with tubes at both female connections, the clamp at the position of the syringe filled with staining solution is kept open, while the other clamp at the outlet position of the syringe filled with BSS closes the tube completely. For a three-way stopcock, the position of the tap is adjusted such that the syringe filled with BSS and the male connection outlet are connected, while the position of the syringe filled with staining solution remains closed.

[0160] First, the tube connected to the syringe filled with staining solution is flushed completely with staining solution. The staining solution must not enter the male connection of the assembly, since this step is only for removing air.

[0161] Next, a thorough air removal and flushing of the assembly with BSS solution is required. In case of a double-barrelled extension line equipped with tubes at both female connections, the clamp at the position of the syringe filled with staining solution closes the tube completely, while the other clamp at the outlet position of the syringe filled with BSS remains open. For a three-way stopcock, the position of the tap is adjusted such that the syringe filled with BSS and the male connection outlet are connected, while the position of the syringe filled with staining solution remains closed.

[0162] Now, by pushing the plunger of the syringe filled with BSS, the assembly is completely flushed with BSS. No air should remain in the assembly and no staining solution should flow out of the male connector of the assembly. Fourth, the device containing the tissue graft or implant is connected to the male connector of the double-barrelled extension line or the three-way stopcock via the first opening and placed into a lab dish / culture dish filled with BSS to prevent air from seeping into the device.

[0163] To reduce the possibility of the tissue graft or implant to slide out of the device, the second opening of the device can be closed with a liquid-permeable cap or can be placed on / in a macroporous material from the washing assembly during the entire staining and washing procedure. Now, the liquid transport medium can be flushed out of the device before staining by gently pushing the plunger of the syringe filled with BSS, if applicable. Alternatively, the staining of the tissue graft or implant can be performed without prior washing with a BSS solution.

[0164] To this end, in case of a double-barrelled extension line equipped with tubes at both female connectors, the clamp at the position of the syringe filled with BSS is fully closed, while the other clamp at the outlet position of the syringe filled with staining solution remains open. For a three-way stopcock, the position of the tap is adjusted such that the syringe filled with staining solution and the male connector outlet are connected, while the position of the syringe filled with BSS remains closed.

[0165] Now, by pushing the plunger of the syringe filled with staining solution, the staining solution is gently added to the tissue graft or implant in the device and left for at least 1-2 minutes for sufficient staining. Prolonged staining will result in increased cell damage. After staining, in case of a double-barrelled extension line equipped with tubes at both female connectors, the clamp at the position of the syringe filled with staining solution is fully closed, while the other clamp at the outlet position of the syringe filled with BSS remains open. For a three-way stopcock, the position of the tap is adjusted such that the syringe filled with BSS and the male connector outlet are connected, while the position of the syringe filled with staining solution remains closed.

[0166] Finally, by pushing the plunger of the syringe filled with BSS, the device is completely flushed with BSS. The solution in the device should be clear and no staining solution should remain.

[0167] Now, the device and the corresponding (washed and / or stained and washed) tissue graft or implant is ready for implantation into a living body. To this end, the device can be kept in the washing assembly before insertion into the living body to save time and to reduce the likelihood of the tissue graft or implant slipping out of the device. Alternatively, the device can be gently removed from the washing assembly before insertion into the living body and the first opening of the device can be connected to a regular (e.g. luer lock or luer slip) syringe filled with BSS, which is described above in the loading procedure for tissue transplantation or implantation. In case a cap connected to the second opening of the device is used during the staining and washing procedure, the cap can remain connected to the device to reduce the likelihood of the tissue graft or implant slipping out of the device, but has to be removed immediately before implantation into the living body.

[0168] Upon application of hydrodynamic pressure, e.g. via a syringe, the tissue graft or implant can be gently washed without being "pushed out" of the device. This can be performed without extensive manipulation of the surgeon and without application of forceps or any other surgical device. Gentle and slow plunger movement of the syringe will prevent the tissue graft or implant from slipping.

[0169] However, in case the tissue graft or implant moves within the device during the staining and washing procedure, the tissue graft or implant can be repositioned within the device by gently pulling the plunger of the respective syringe at the female connector position of the washing assembly. It is important that no air enters the device during repositioning of the graft within the device.

[0170] By pushing the plunger of the BSS-filled syringe, the tissue graft or implant can be released out of the device. In the same way, the tissue graft or implant can be injected into a living body. For insertion of the tissue graft or implant, e.g. for ophthalmic interventions, the longer wing of the chamfered portion of the second opening of the device preferably faces the bottom (positioned towards the posterior chamber of the eye) to ensure injection of the implant into the anterior chamber of the eye.

[0171] Due to the inner shape and dimensions of the device according to the present invention, the release or implantation of the tissue graft or implant is performed in an oriented manner. Even during forward or backward movement along the inner hollow compartment of the device (e.g. during repositioning of the graft after transportation for implantation as described above), the preferably rounded rectangular inner shape of the device prevents the tissue graft or implant from turning within the device, thereby ensuring oriented stability of the tissue graft or implant during the entire period from tissue loading into the device to release of the tissue from the device.

[0172] According to the description, the present invention relates to the following items:

[0173] 1. A device for the safe support, storage and / or transport of a tissue graft or implant, comprising:

[0174] • a first opening,

[0175] • a main body,

[0176] • a tapered region, and

[0177] • a second opening,

[0178] wherein the main body is transparent and has a rectangular shape, the tapered region is transparent and has an elliptical, circular, lenticular or rectangular shape, wherein the main body comprises at least two flat and parallel opposite positions.

[0179] 2. The device according to item 1, wherein the first opening has a circular shape and a funnel design configured to be connectable with a tube or a syringe.

[0180] 3. The device according to any one of items 1 to 2, wherein the second opening has an elliptical, circular, lenticular or rounded rectangular shape.

[0181] 4. The device according to any one of items 1 to 3, wherein the outer wall of the second opening has a different shape than the inner wall.

[0182] 5. The device according to any one of items 1 to 4, wherein the outer wall of the tapered region has a different shape than the inner wall.

[0183] 6. The device according to any one of items 1 to 5, wherein the device comprises a first opening having an inner diameter between 3 mm and 6 mm, preferably between 4 mm and 5 mm.

[0184] 7. The device according to any one of items 1 to 6, wherein the device comprises a main body having a distance between the flat and parallel top and bottom walls of the interior between 1 mm and 5 mm, preferably between 1.5 mm and 4 mm, more preferably between 2 mm and 3 mm.

[0185] 8. The device according to any one of items 1 to 7, wherein the device comprises a tapered region and a second opening having a distance between the top and bottom walls of the interior between 0.8 mm and 2 mm, preferably between 1 mm and 2 mm.

[0186] 9. The device according to any one of items 1 to 8, wherein the device has a total length in the range of 25 mm to 50 mm, preferably in the range of 30 mm to 40 mm.

[0187] 10. The device according to any one of items 1 to 9, wherein the device is composed of glass, preferably borate glass.

[0188] 11. The device according to any one of items 1 to 9, wherein the device is composed of plastic, wherein the plastic is transparent and has a refractive index (ri) in the range of ri = 1.30 to ri = 1.71, preferably in the range of ri = 1.30 to ri = 1.65, most preferably in the range of ri = 1.30 to ri = 1.60, the refractive index of the plastic being similar to the refractive index ri = 1.33 to ri = 1.34 of balanced salt solutions (BSS), such as Hank's BSS, Earle's BSS, Tyrode's salt solution, Alsever's salt solution, phosphate buffered saline (PBS), Tris buffered saline (TBS), Puck's salt solution, Gey's salt solution, Ringer's salt solution, Simm's salt solution and related buffered salt solutions (at 20 °C).

[0189] 12. The device according to item 11, wherein the device is composed of polyacrylate, polycarbonate or polystyrene.

[0190] 13. The device according to any one of items 10 to 12, wherein the inner surface of the device comprises:

[0191] • a hydrophobic coating selected from a coating comprising acrylate, organosiloxane, silane, epoxy, polymer, molybdenum disulfide, molybdenum disulfide / graphite, tungsten disulfide or graphite, preferably selected from a coating comprising polymer, organosiloxane, silane, acrylate or epoxy; or

[0192] • a hydrophilic coating selected from a coating comprising any hydrophilic polymer / hydrogel, preferably selected from a coating comprising poly(ethylene glycol), poly(acrylate), poly(methacrylate) or UV / photo-sensitive polymer.

[0193] 14. The device according to any one of items 10 to 12, wherein the inner surface of the device comprises a surface pattern, the surface pattern being a micro- or nano-structured surface pattern or a combination thereof (e.g. nano-micro-structured) in the range of 100 nm to 20,000 nm, preferably in the range of 300 nm to 5,000 nm, more preferably in the range of 500 nm to 2,500 nm.

[0194] 15. The device according to any one of items 1 to 14, wherein the device further comprises a lid for the first opening and / or a lid for the second opening.

[0195] 16. The device according to item 15, wherein the cover is configured such that at least the body of the device, preferably the body of the device and the tapered region of the device, remains uncovered.

[0196] 17. The device according to any one of items 15 to 16, wherein the design of the cover for the first opening is adopted to the design of the first opening of the device and / or the design of the cover for the second opening of the device is adopted to the design of the second opening of the device.

[0197] 18. The device according to any one of items 15 to 17, wherein the cover consists of a material selected from the group consisting of hard or soft plastic, such as polypropylene (PP), polystyrene (PS), polyamide (PA), polyether ketone (PEK), polyether ether ketone (PEEK), polymethyl methacrylate (PMMA), polyethylene (PE), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyphthalamide (PPA), polyphenylene sulfide (PPS), polyamide-imide (PAI), polyphenylsulfone (PPSU), polyethersulfone (PES), polysulfone (PSU), polycarbonate (PC), acrylonitrile butadiene styrene (ABS), styrene-acrylonitrile copolymer (SAN) or polyvinyl chloride (PVC), rubber, silicone, macroporous material, glass and possible combinations thereof.

[0198] 19. The device according to any one of items 15 to 18, wherein the cover is permeable.

[0199] 20. The device according to item 19, wherein the cover comprises a small pore, a network, a membrane or a macroporous material or other permeable material.

[0200] 21. An assembly for loading, storing and transporting a tissue graft or implant, comprising

[0201] • the device according to any one of items 1 to 20,

[0202] • at least one syringe,

[0203] • a tube, and

[0204] • at least one cover.

[0205] 22. The assembly according to item 21, wherein the tube consists of a flexible material, preferably selected from rubber, silicone, latex or related flexible materials.

[0206] 23. The assembly according to any of items 21 to 22, wherein the inner diameter of the tube is up to 10% or 20% smaller than the size of the second opening of the device to ensure a tight seal when attached, and the tube has a length preferably between 50 mm to 150 mm, more preferably between 70 mm to 130 mm, even more preferably between 80 mm to 105 mm, most preferably a length of 95 mm.

[0207] 24. The assembly according to any of items 21 to 23, wherein the tube has a luer lock connection, a luer slip connection or a luer connection on one side, wherein the connection is composed of a material selected from hard or soft plastic, such as polypropylene (PP), polystyrene (PS), polyamide (PA), polyether ketone (PEK), polyether ether ketone (PEEK), polymethyl methacrylate (PMMA), polyethylene (PE), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyphthalamide (PPA), polyphenylene sulfide (PPS), polyamide-imide (PAI), polyphenylsulfone (PPSU), polyethersulfone (PES), polysulfone (PSU), polycarbonate (PC), acrylonitrile butadiene styrene (ABS), styrene-acrylonitrile (SAN) or polyvinyl chloride (PVC).

[0208] 25. The assembly according to item 21, wherein the assembly further comprises a transport device.

[0209] 26. The assembly according to item 25, wherein the transport device is a device holder comprising:

[0210] • a round neck with a holding structure,

[0211] • a fingertip-like structure attached to an oval platform with a cavity, and

[0212] • a bent strip,

[0213] The device holder is suitable for placement inside a container, such as a standard tissue culture flask or a tissue culture flask with two openings.

[0214] 27. The assembly according to item 26, wherein the fingertip-like structure comprises a cavity shaped to match the side of the device.

[0215] 28. The assembly according to any of items 26 to 27, wherein the fingertip-like structure and oval platform do not optically interfere with the body and the conical region of the device.

[0216] 29. The assembly according to any one of items 26 to 28, wherein the overall dimensions of the device holder are configured such that one end of the bent-up post is in contact with the bottom of a standard tissue culture flask or with the bottom of a tissue culture flask having two openings, the other end having the round neck protruding into the neck of a standard tissue culture flask or into one neck of a tissue culture flask having two openings and in contact with the closure cap of a standard tissue culture flask or with one cap of a tissue culture flask having two openings when closed.

[0217] 30. The assembly according to any one of items 26 to 29, wherein the components of the device holder are composed of a plastic selected from the group consisting of polypropylene (PP), polyamide (PA), polyether ketone (PEK), polyether ether ketone (PEEK), poly(methyl methacrylate) (PMMA), polyethylene (PE), polyethylene terephthalate (PET), preferably from the group consisting of PP, PA, PE or PMMA.

[0218] 31. The assembly according to any one of items 26 to 30, wherein the device holder is a one-piece holder, for example produced by injection molding or 3D printing.

[0219] 32. A washing assembly for washing and staining a tissue graft or implant, comprising:

[0220] • a macroporous material,

[0221] • a device according to any one of items 1 to 20 or a similar conventional device,

[0222] • at least one syringe,

[0223] • optionally at least one cap,

[0224] • optionally at least one tube clamp, and

[0225] • a double-bore extension line or a three-way stopcock, wherein both optionally comprise a hose.

[0226] 33. The washing assembly according to item 32, wherein the double pass extension line or the three-way stopcock valve is composed of a material selected from the group consisting of hard or soft plastic, such as polypropylene (PP), polystyrene (PS), polyamide (PA), polyether ketone (PEK), polyether ether ketone (PEEK), polymethyl methacrylate (PMMA), polyethylene (PE), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyphthalamide (PPA), polyphenylene sulfide (PPS), polyamide-imide (PAI), polyphenylsulfone (PPSU), polyethersulfone (PES), polysulfone (PSU), polycarbonate (PC), acrylonitrile butadiene styrene (ABS), styrene-acrylonitrile copolymer (SAN) or polyvinyl chloride (PVC), silicone, glass and possible combinations thereof.

[0227] 34. The washing assembly according to any one of items 32 to 33, wherein the macroporous material has at least one flat surface.

[0228] 35. The washing assembly according to any one of items 32 to 34, wherein the macroporous material closes the second opening of the device and is adapted to the shape of the second opening of the device.

[0229] 36. The washing assembly according to any one of items 32 to 35, wherein the macroporous material comprises interconnected pores and a porosity comprised between 10 pm and 600 pm, preferably between 10 pm and 400 pm, more preferably between 30 pm and 300 pm.

[0230] 37. The washing assembly according to any one of items 32 to 36, wherein the macroporous material is composed of a material selected from the group consisting of natural sponges, foams, pure synthetic or biopolymers, synthetic or biopolymer blends, rubbers and combinations thereof and sponge-like materials.

[0231] 38. The washing assembly according to any one of items 36 to 37, wherein the macroporous material is composed of a synthetic or biopolymer, such as a poly(vinyl alcohol)-based or cellulose-based sponge.

[0232] 39. The washing assembly according to any one of items 32 to 38, wherein the macroporous material is embedded within a stable container.

[0233] 40. A method for preparing a tissue graft or implant using a device according to any one of items 1 to 20, comprising the steps of:

[0234] a) providing a tissue graft or implant,

[0235] b) loading the tissue graft or implant into the device,

[0236] c) sealing the device with at least one lid,

[0237] d) performing an evaluation and quality control of the tissue graft or implant within the device,

[0238] e) shipping the device with the tissue graft or implant,

[0239] f) optionally performing an evaluation and quality control of the tissue graft or implant within the device,

[0240] g) performing a cleaning and staining of the tissue graft or implant within the device.

[0241] 41. The method according to item 40, wherein the device is shipped within a device holder.

[0242] 42. The method according to any one of items 40 to 41, wherein the device is shipped within a device holder within a container, such as a standard tissue culture flask or a tissue culture flask with two openings.

[0243] 43. The method according to any one of items 40 to 42, wherein the evaluation and quality control of the tissue graft or implant is performed with the device containing the tissue graft or implant within the shipping device and within a container, such as a standard tissue culture flask or a tissue culture flask with two openings.

[0244] 44. The method according to any one of items 40 to 43, wherein the cleaning and staining of the tissue graft or implant is performed with the cleaning assembly when the tissue graft or implant is located within the device.

[0245] Table

[0246] The present application is further described below by means of 3 tables, wherein,

[0247] Table 1: shows plastic components suitable for use in the device, wherein any of the listed plastics, plastic blends, plastic mixtures, copolymers or other combinations of the listed plastics can be used,

[0248] Table 2: shows hydrophobic coatings for use in the interior compartment of the device, wherein any of the listed coatings, coating blends, coating mixtures or other combinations of the listed coatings can be used,

[0249] Table 3: shows hydrophilic coatings for use in the interior compartment of the device, wherein any of the listed coatings, coating blends, coating mixtures or other combinations of the listed coatings can be used.

[0250] Table 1:

[0251]

[0252]

[0253]

[0254]

[0255]

[0256]

[0257]

[0258]

[0259]

[0260]

[0261]

[0262]

[0263]

[0264]

[0265]

[0266] Table 2:

[0267]

[0268]

[0269] Table 3:

[0270] BRIEF DESCRIPTION OF DRAWINGS

[0271] In the following, the application is explained in further detail by means of 11 figures, in which

[0272] Figure 1 : shows different designs of the device;

[0273] Figure 2 : shows a cross-section of the device;

[0274] Figure 3 : shows components for loading, storing and / or transporting an assembly of tissue grafts or implants;

[0275] Figure 4 : shows the process of loading a tissue graft or implant into the device;

[0276] Figure 5 : shows different positioning of a tissue graft or implant within the device;

[0277] Figure 6 : shows the preparation of the device (short-term transport assembly) loaded with a tissue graft or implant intended to be introduced directly into a living body;

[0278] Figure 7 : shows different caps for closing the first and second openings of the device;

[0279] Figure 8A and Figure 8B : shows possible designs of the device holder from different perspectives, as well as a tissue culture flask with two openings;

[0280] Figure 9 : shows the use of macroporous material as part of the assembly for washing and / or staining a tissue graft or implant;

[0281] Figure 10 : shows the release of a tissue graft or implant from the device;

[0282] Figure 11 : shows the use of a double-pass extension line or a three-way stopcock valve for a washing assembly for washing and / or staining a tissue graft or implant.

[0283] Figure 1 Three different possible designs of the device according to the invention are shown (labeled A, B and C). Each design is shown from the outside, from the front and transparently drawn so that the inner walls can be seen, and some of the internal compartments and the dimensions of the external compartments are shown. In all designs, the first opening (1), the main body (2), the tapered region (3) and the second opening (4) are shown. The outer wall dimensions of the main body are labeled with the letter (a) and more closely described in the front view with the letters (d) and (e), the outer wall dimensions of the tapered region are labeled with the letter (a) and more closely described in the front view with the letters (f) and (g). For all the designs shown, the main body (2) has the same dimensions and shape, but can also be different according to the invention. The dimensions of the inner wall of the tapered region are labeled with the letter (c) and more specifically described in the front view with the letters (h) and (i). The table below summarizes the labels used.

[0284]

[0285]

[0286] Design A shows the second opening (4) with its inner wall comprising a rounded rectangular shape with two flat opposite walls, while the outer wall has an elliptical shape. This figure clearly shows the flat and parallel opposite sides of the body (2), so that the body (2) has the following dimensions: d = 3.7 mm and e = 2.7 mm. Due to the elliptical outer shape, the tapered region (3) is slightly smaller compared to the body (2) to better fit into the surgical incision as described above. Figure 1 The tapered region (3) of the device (10) shown in design A has the following dimensions: f = 3.7 mm and g = 2.6 mm. The inner hollow compartment of the tapered region (3) has a rounded rectangular shape, which is more closely described by the dimensions h = 0.3 mm and i = 0.7 mm.

[0287] Design B shows the second opening (4) with its inner and outer walls having an elliptical shape. The body (2) with its flat and parallel opposite walls has the same dimensions (d) and (e) as design A. The dimensions of the tapered region are: f = 3.4 mm, g = 2.5 mm and h = 0.3 mm. The use of an elliptical shape for the inner wall of the tapered region compared to design A has the advantage that the tissue graft or implant is more smoothly expelled through the second opening of the design B of the device.

[0288] Design C shows another device (10) according to the present invention. The body (2) with its flat and parallel opposite walls has the same dimensions (d) and (e) as design A. The thickness of the tapered region (3) is different from designs A and B, decreasing linearly until it remains constant at the second opening. At the smallest cross-section, the tapered region has the following dimensions: f = 2.5 mm, g = 1.8 mm and h = 0.3 mm, and the inner and outer walls of the tapered region (3) have a rounded rectangular shape. The second opening (4) also has a rounded rectangular shape.

[0289] All designs allow for tissue grafting or implant injection in small surgical incisions (2.4 mm to 3.0 mm incision width) as described above.

[0290] Figure 2 A cross-section of the device (10) is shown. The dimensions of the inner hollow compartment of the body (2) and the tapered region (3) are denoted with the letters (m) and (n). In addition, the dimensions of the inner hollow compartment of the first opening (1) are denoted with the letter (k). According to the present invention, the first opening (1) can have a dimension (k) between 3 mm and 6 mm. The body (2) can have a dimension (m) between 1 mm and 5 mm, and the tapered region (3) can have a dimension (n) between 0.8 mm and 2 mm. The total length (l) of the device (10) is between 25 mm and 50 mm.

[0291] Figure 3 (A) toFigure 3 (E) shows the components used to load, store and transport the assembly of tissue grafts or implants. Figure 3 (A) shows a tube (5) with a luer slip connector (6) included in one embodiment of the present invention. Figure 3 (B) shows the connection of the tube (5) to the syringe (8) via the luer lock connector (7). In Figure 3 (C) and Figure 3 (D) it can be seen that the second opening (4) of the device (10) is connected to the tube (5). To load the tissue grafts or implants (11) into the device (10), the second opening (4) of the device (10) is connected to the tube (5) and the tube (5) is connected to the syringe (8), for example via the luer slip connector (6) connection Figure 3 (E).

[0292] Figure 4 (A) to (C) show the process of loading tissue grafts or implants into the device. To load the tissue grafts or implants (11) into the device (10), the syringe (8), for example preferably filled with balanced salt solution or liquid nutrient medium, is connected to the second opening (4) of the device (10) by connecting one end of the tube (5) to the second opening (4) and connecting the other end of the tube (5) to the syringe (8) via the luer lock connector (7). Subsequently, the syringe plunger is moved to expel excess air from the device (10) and the tube (5), no air bubbles should remain in the device (10) and the tube (5) Figure 4 (A).

[0293] To load the tissue grafts or implants (11) into the device (10), the device (10) is connected to a laboratory / culture dish (9) containing the tissue grafts or implants (11) in a suitable liquid medium, for example BSS or nutrient medium. The loading is performed starting from the first opening (1), which is large enough to gently suck in the tissue grafts or implants (11) due to its funnel-like design (the diameter of the opening increases slightly towards the edge). Thus, without touching the tissue grafts or implants (11), the first opening (1) of the device (10) is gently placed over the tissue grafts or implants (11) and the syringe plunger is moved to upload the tissue grafts or implants (11) into the device (10) using fluid dynamics flow Figure 4 (B) and Figure 4 (C).

[0294] For storage and / or transport and evaluation, the tissue grafts or implants (11) are located within the main body (2) of the device (10), which can be referred to as the "transport position" Figure 4 (C) and Figure 5(A)). For direct introduction of the tissue graft or implant (11) into e.g. a living body, the tissue graft or implant (11) can be positioned partly within the conical region (3) of the device (10), which can be referred to as "injection position" Figure 5 (B)). In this position, the tissue graft or implant (11) is partly rolled up / slightly compressed, which ensures its stable positioning within the device (10), e.g. for attaching a syringe (8 or 12) filled with BSS at the first opening (1) of the device (10) Figure 6 (A)). The tissue graft or implant (11) can also be positioned completely within the conical region (3) for "injection position". However, this increases the likelihood of undesired slippage of the tissue graft or implant (11) out of the device (10) during connection of the syringe (8 or 12) at the first opening (1) of the device (10), as in such a case there is not much space left towards the second opening (4) of the device (10).

[0295] Figure 6 (A) to Figure 6 (C) shows the preparation of a device (10) loaded with a tissue graft or implant (11) intended for direct introduction into a living body. After loading the tissue graft or implant (11) into the device (10), a second syringe (12) filled with a liquid, e.g. a balanced salt solution or a nutrient medium, is directly connected to the first opening (1) of the device (10). At this point, the tube (5) connected to the second opening (4) and the syringe (8) used for loading the device (10) are still connected Figure 6 (A)). After connecting the second syringe (12) to the first opening Figure 6 (B)), the tube (5) is disconnected from the syringe (8) Figure 6 (C)) and the device is ready to expel the tissue graft or implant (11), e.g. for injection into a living body.

[0296] According to the present invention, different kinds of caps are suitable for closing the first opening (1) and the second opening (4) of the device (10). Figure 7 (A) to Figure 7 (D) shows some suitable caps. As Figure 7 (A) and Figure 7 (C) show, a first cap (13, 15) closes the first opening (1) and a second cap (14) closes the second opening (4). In both embodiments, the main body (2) is not covered and can be used for microscopic examination and / or macroscopic assessment of the tissue graft or implant (11). At least one of the caps used is permeable to allow exchange of oxygen and nutrients during transport and / or storage of the tissue graft or implant (11) within the device (10). Further embodiments of the present invention are shown in Figure 7(B) and Figure 7 The first opening (1) is still closed by the first cap (13, 15) and the second opening (4) is closed by a luer slip connection (6) equipped with a short flexible tube (5), which can be of the same material as the tube (5) used to load the tissue. Figure 3 The advantage of these embodiments is that not only the body (2) is unobstructed, but also the conical region (3) is unobstructed, so both parts of the device (10) are available for microscopic and / or macroscopic evaluation of the tissue graft or implant (11).

[0297] For reliable storage and / or transport of the device (10) with the tissue graft or implant (11), the present invention also provides a device holder (20) as shown in Fig. 8(A). The device holder comprises a fingertip-like structure with an elliptical holding structure having a cavity (16), wherein the fingertip-like structure has a cavity with a shape matching the side of the device (10) for easy assembly and gentle removal of the device (10) and for holding the device (10). Furthermore, the shape of the fingertip-like structure comprising the elliptical holding structure with the cavity (16) ensures the orientation / position of the device (10) during storage and / or transport. In particular, it can prevent the device (10) from rotating. The fingertip-like structure comprising the elliptical holding structure with the cavity (16) does not interfere with the body (2) and the tapered region (3) of the device (10), so that the body (2) and the tapered region (3) are still available as a microscopy region. The fingertip-like structure comprising the elliptical holding structure with the cavity (16) is attached to a bent strip post (17) which is attached to a round neck (18) which on the one hand allows insertion into a standard tissue culture flask or a tissue culture flask (40) with two openings and on the other hand abuts against the neck of a standard tissue culture flask or one neck of a tissue culture flask (40) with two openings. This can prevent movement of the entire transport device within a standard tissue culture flask or a tissue culture flask (40) with two openings. The round neck (18) has a holding structure (19) in the center which allows manipulation with forceps and / or the fingers of the end user in order to remove the device holder (20) from a standard tissue culture flask or from a tissue culture flask (40) with two openings. The overall dimensions of the device holder (20) are such that one end of the bent strip post (17) touches the bottom of a standard tissue culture flask or of a tissue culture flask (40) with two openings, while the other end with the round neck (18) is at the neck of a standard tissue culture flask or one neck of a tissue culture flask (40) with two openings and touches the closing cap of a standard tissue culture flask or one closing cap of a tissue culture flask (40) with two openings when the standard tissue culture flask or the tissue culture flask (40) with two openings is closed. Fig. 8(B) shows a tissue culture flask (40) with two openings which is suitable for being inserted by the device holder (20) comprising the device (10). The design of the tissue culture flask (40) with two openings allows direct aspiration of the medium in the device (10) from one opening (43) (e.g. for fungal tests), while the other opening (44) can be used for insertion of the device holder (20) comprising the device (10).Screw caps (41, 42) on both necks (43, 44) ensure a tight and leak-proof seal (11) of the tissue culture flask with two openings (40) during storage and / or transport and evaluation of tissue grafts or implants within the device (10), which is preferably held within the tissue culture flask with two openings (40) together with the device holder (20).

[0298] Figure 9 (A) to Figure 9 (F) shows the use of macroporous material (21) for washing and staining. The first opening (1) of the device (10) is connected to a syringe (12) and the second opening (4) of the device (10) is positioned above the macroporous material (21) Figure 9 (A) and Figure 9 (B)). In one embodiment, the device (10) is pressed against the macroporous material (21) Figure 9 (C) and Figure 9 (D)), thus providing a tight connection between the macroporous material (21) and the second opening (4). In another embodiment, the device (10) is pressed against the macroporous material (21) Figure 9 (E) and Figure 9 (F)) so that a tighter connection is provided. The macroporous material (21) has a size large enough to absorb the solution pressed out from the device (e.g. sponge) and the device (10) does not burst from the bottom of the macroporous material (21).

[0299] Figure 10 (A) to Figure 10 (C) shows the release of the tissue graft or implant (11) from the device (10) by pushing the syringe (8 or 12) connected to the first opening (1). The syringe (8 or 12) is not shown. The tissue graft or implant is gently moved in a directed manner by a fluid dynamic flow. First, the tissue graft or implant (11) is located within the conical region (3) of the device (10) ("injection position", Figure 10 (A)). By pushing the plunger of the syringe (8 or 12), the tissue graft or implant (11) slides out of the second opening (4) of the device (10) Figure 10 (B)) and finally leaves the device (10) Figure 10 (C).

[0300] Furthermore, the washing assembly comprises a double-bore extension line (31) or a three-bore tap (32), both comprising a hose (33, 34) with a male connection (preferably a Luer lock connection or a Luer slip connection) (26), as Figure 11The cleaning assembly further comprises a tube clamp (27, 28) and a closure cap (22, 23) for the female end (24, 25) of the double-barrelled extension line (31) or the three-way stopcock (32) in one embodiment of the application. The tube clamp (27, 28) can be used to interrupt the flow in the tubes (29, 30) used in the cleaning assembly.

[0301] The double-barrelled extension line (31) or the three-way stopcock (32) has a hose (34, 33) comprising a male connection (26) for connecting the device (10). The male connection (26) is preferably a luer lock connection or a luer slip connection. The double-barrelled extension line (31) or the three-way stopcock (32) both have two further connections, preferably female connections (24, 25). The female connections (24, 25) are preferably luer lock connections or luer slip connections. The female connections (24, 25) are suitable for connecting a conventional syringe (8) or (12) and can optionally be closed with a cap (22, 23). As Figure 11 shown, the connection to the female connections (24, 25) is in the case of the double-barrelled extension line (31) with tubes (29, 30) attached, while the three-way stopcock (32) has no tubes connected to the female connections (24, 25). However, the tubes (29, 30) are not necessarily required.

[0302] For cleaning and staining of a tissue graft or implant (11), a syringe (8) filled with balanced salt solution (BSS) is attached to one female connection (24) of the double-barrelled extension line (31) or the three-way stopcock (32) and another syringe (12) filled with a staining solution, for example trypan blue, is connected to the other female connection (25). The volume of the syringe (8) filled with BSS is preferably greater than the volume of the second syringe (12) filled with the staining solution. Figure 11 The syringes (8 or 12) are not shown in

[0303] The use of the assembly shown in Figure 11 is described in detail below.

[0304] To remove air from the assembly, in the case of the double-barrelled extension line (31), the clamp (28) of the tube (30) at the position (25) with the syringe (12) filled with the staining solution is left open, while the other clamp (27) at the position (24) of the syringe outlet filled with BSS completely closes the tube (29). For the three-way stopcock (32), the position of the tap is adjusted so that the syringe (12) filled with the staining solution at the position (25) and the male connection (26) outlet are connected, while the position (24) with the syringe filled with BSS remains closed.

[0305] First, the tubing (30) and the position (25) connected to the syringe (12) filled with the staining solution are flushed completely with the staining solution. The staining solution must not enter the male connector (26) of the assembly (31, 32) as this step is only used to remove air.

[0306] Next, a thorough air removal and flushing of the assembly with BSS solution is required. In case of a double-barreled extension line (31), the clamp (28) at the position (25) of the tubing (30) with the syringe (12) filled with the staining solution is closed completely, while the other clamp (27) at the tubing (29) of the outlet position (24) of the syringe (8) filled with BSS remains open. For the three-way stopcock (32), the tap position is adjusted so that the syringe (8) filled with BSS at the position (24) and the male connector (26) outlet are connected, while the position (25) of the syringe (12) filled with the staining solution remains closed.

[0307] Now, the assembly is completely flushed with BSS by pushing the plunger of the syringe (8) filled with BSS. No air should remain in the assembly and no staining solution should flow out of the male connector of the assembly. Fourth, the device (10) containing the tissue graft or implant (11) is connected via the first opening (1) to the male connector (26) of the double-barreled extension line (31) or the three-way stopcock (32) and is placed into the BSS-filled lab dish / petri dish (9, not shown) to prevent air from seeping into the device (10). Figure 11

[0308] To reduce the possibility of the tissue graft or implant (11) to slide out of the device (10), the second opening (4) of the device (10) can be closed with a lid (13, 14, 15) or can be placed on / into the macroporous material (21) from the flushing assembly during the entire staining and washing process. If applicable, the liquid transport medium can now be flushed out of the device (10) before staining by gently pushing the plunger of the syringe (8) filled with BSS at the position (24). Alternatively, the staining of the tissue graft or implant (11) can be performed without prior washing with BSS solution.

[0309] Now, in case of a double-barreled extension line (31), the clamp (27) at the position (24) of the tubing (29) with the syringe (8) filled with BSS is closed completely, while the other clamp (28) at the tubing (30) of the outlet position (25) of the syringe (12) filled with the staining solution remains open. For the three-way stopcock (32), the tap position is adjusted so that the syringe (12) filled with the staining solution at the position (25) and the male connector (26) outlet are connected, while the position (24) of the syringe (8) filled with BSS remains closed.​

[0310] Now, by pushing the plunger of the syringe (12) filled with the staining solution, the staining solution is gently added to the tissue graft or implant (11) in the device (10) and left for at least 1-2 minutes for adequate staining. Prolonged staining can lead to increased cell damage. After staining, in case of a double pass extension line, the clamp (28) at the position (25) of the syringe (12) with the staining solution is fully closed to the tube (30), while the other clamp (27) to the tube (29) at the outlet position (24) of the syringe (8) filled with BSS remains open. For a three-way stopcock (32), the position of the tap is adjusted so that the syringe (8) filled with BSS at the position (24) and the male connector (26) outlet are connected, while the position (25) of the syringe (12) with the staining solution remains closed.

[0311] Finally, by pushing the plunger of the syringe (8) filled with BSS, the device (10) is completely flushed with BSS. The solution in the device (10) should be completely transparent and no staining solution should remain. Now, the device (10) and the corresponding tissue graft or implant (11) are ready for the ejection of the tissue graft or implant (11), in particular for the injection of the tissue graft or implant (11) into a living being.

[0312] List of reference signs

[0313] 1 first opening

[0314] 2 body

[0315] 3 conical region

[0316] 4 second opening

[0317] 5 tube

[0318] 6 luer slip connector

[0319] 7 luer lock connector

[0320] 8 syringe

[0321] 9 labware / petri dish

[0322] 10 device

[0323] 11 tissue graft or implant

[0324] 12 syringe

[0325] 13 lid

[0326] 14 lid

[0327] 15 lid

[0328] 16 fingertip-like structure comprising an elliptical platform with a cavity

[0329] 17 bent-up post

[0330] 18 round neck

[0331] 19 retention structure

[0332] 20 device holder

[0333] 21 macroporous material

[0334] 22 cap

[0335] 23 cap

[0336] 24 female connector

[0337] 25 female connector

[0338] 26 male connector

[0339] 27 tube clamp

[0340] 28 tube clamp

[0341] 29 tube

[0342] 30 tube

[0343] 31 double-bore extension line

[0344] 32 three-way stopcock

[0345] 33 tube

[0346] 34 tube

[0347] 40 tissue culture flask with two openings

[0348] 41 screw cap

[0349] 42 screw cap

[0350] 43 threaded neck

[0351] 44 threaded neck

[0352] References

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[0354] [2] Price M O & Price F W, Clin Exp Ophthalmol. 2010; 38, 128-140

[0355] [3] Hamzaoglu E C, et al. Ophthalmology. 2015 122; 11, 2193-2199

[0356] [4] Uchino Y, et al. Cornea. 2011; 30: 287-290

[0357] [5] Li S, et al. PLoS ONE. 2017; 12(12): e0182275

[0358] [6] Melles G R, et al. Cornea. 2002; 21: 415-418

[0359] [7] Melles G R, et al. Cornea. 2006; 25: 987-990

[0360] [8] Anshu A, et al. Ophthalmology. 2012; 119: 536-540

[0361] [9] Tourtas T, et al. Am J Ophthalmol. 2012; 153: 1082-1090

[0362]

[10] Guerra F P, et al. Ophthalmology. 2011; 118: 2368-2373

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[11] Guerra F P, et al. Cornea. 2011; 30: 1382-1386

[0364]

[12] Ham L, et al. Arch Ophthalmol. 2009; 127: 252-255

[0365]

[13] 57 th annual Eye Bank Association of America meeting Philadelphia, USA 2018; personal discussions with Dr. Pankaj Gupta, University Hospitals of Cleveland, USA

[0366]

[14] Busin M & AlbE Curr Opin Ophthalmol. 2014; 25: 312-318

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[15] Groeneveld-van Beek, et al. Acta Ophthalmol. 2013; 91 : 145-150

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[16] Baydoun L, et al. Am J Ophthalmol. 2012; 154: 762-763

[0369]

[17] Dapena I, et al. Arch Ophthalmol. 2011; 129: 88-94

[0370]

[18] Eye Bank Association of America, Eye Banking Statistical Report 2017

[19] Eye Bank Association of America, Medical Standards 2015

[0371]

[20] OR visit in Eye Clinic Chemnitz, Germany 2018; personal discussions

[0372] with MD Roy Schendel, Klinikum Chemnitz, Germany

[0373]

[21] Kobayashi A, et al. BMC Ophthalmol. 2016; 16: 135

[0374]

[22] Park C Y, et al. Ophthalmology. 2015; 122: 2432-2442

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[23] Deutsche Gesellschaft für Gewebetransplantation Hannover, Germany

[0376] 2015; “LaMEK” tissue (pre-prepared DMEK grafts)

[0377]

[24] Lions VisionGift Portland, USA 2018; “Patient Ready DMEK™”

[0378]

[25] Tran KD, et al. Cornea. 2017; 36: 484-490

[0379]

[26] Parekh M, et al. Am J Ophthalmol. 2016; 166: 120-125

[0380]

[27] Augenklinik Sulzbach, Germany and Geuder AG Heidelberg, Germany

[0381] 2016; “Preloaded DMEK” / “Vorgeladenes

[0382] Glaskartuschen-Mikroinjektorsystem”

[0383]

[28] 57 th annual Eye Bank Association of America meeting Philadelphia,

[0384] USA 2018; Technical Skills Workshop

[0385]

[29] Parekh M, et al. Acta Ophthalmol. 2017; 95: 194-198

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[30] XXXI st annual European Eye Bank Association meeting Rotterdam, The Netherlands 2019; Lamellar graft Session VI

[0387]

[31] Lee C H, et al. J. Micromech. Microeng. 2010; 20: 035018

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[32] Lee S M, et al. J. Micromech. Microeng. 2008; 18: 125007

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[33] Annabi N, et al. Tissue Eng. Part B. Rev. 2010; 16: 371-383

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[34] Hollister S J Nat. Mater. 2005; 4:518-524

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Claims

1. A device (10) for the reliable support, storage and / or transport of a tissue graft or implant (11) for ophthalmic interventions, wherein the tissue graft or implant is an endothelial comeal graft or implant, the device (10) comprising: • a first opening (1), • a main body (2), • a tapered region (3), and • a second opening (4) opposite the first opening for the discharge of the tissue graft or implant, the tapered region (3) connecting the main body (2) and the second opening (4), characterized in that the first opening (1) has a funnel-like design and a circular cross-sectional shape, which is configured to be able to connect a tube (5) or a syringe (8, 12), the main body (2) is transparent and has a rectangular shape, the tapered region (3) is transparent and has a circular, lenticular or rectangular cross-sectional shape, the outer wall of the tapered region (3) has the same or a different shape than its inner wall, wherein the main body (2) comprises at least two flat and parallel opposite sides and is used for the microscopic examination of the tissue graft or implant, wherein the main body (2) is a transport position that ensures a stable positioning of the implant during microscopic evaluation, storage and transport, the funnel-like design means that the diameter of the first opening slightly increases towards the edge to gently take up and release the tissue graft or implant.

2. The apparatus (10) of claim 1, wherein The second opening (4) has a circular, lenticular or rounded rectangular cross-sectional shape.

3. The apparatus (10) according to claim 1 or 2, wherein The outer wall of the second opening (4) has a different shape than its inner wall.

4. The apparatus (10) according to claim 1 or 2, wherein The outer wall of the tapered region (3) has a different shape than its inner wall.

5. The apparatus (10) according to claim 1 or 2, wherein The device (10) is composed of glass or of plastic, wherein the plastic is transparent and has a refractive index ri in the range of ri = 1.30 to ri = 1.

71.

6. The apparatus (10) of claim 5, wherein The inner surface of the device (10) comprises: • a hydrophobic coating selected from a coating comprising a polymer, molybdenum disulfide, tungsten disulfide or graphite; or • a hydrophilic coating selected from a coating comprising any hydrophilic polymer; and / or • a surface pattern which is a micro- or nano-structured surface pattern in the range of 100 nm to 20,000 nm or a combination thereof.

7. The apparatus (10) according to any one of claims 1 to 2 and 6, wherein, The device further comprises a lid (13, 14, 15) for the first opening (1) and / or a lid (13, 14, 15) for the second opening (4).

8. The apparatus (10) of claim 5, wherein, The glass is a borate glass, wherein the plastic has a refractive index ri in the range of ri = 1.30 to ri = 1.

65.

9. The apparatus (10) of claim 5, wherein, The glass is a borate glass, wherein the plastic has a refractive index ri in the range of ri = 1.30 to ri = 1.

60.

10. The apparatus (10) of claim 6, wherein, The hydrophobic coating is selected from a coating comprising a polymer; or The hydrophilic coating is selected from a coating comprising polyethylene glycol, polyacrylate, polymethacrylate or a UV light-sensitive polymer; and / or The surface pattern is a micro- or nano-structured surface pattern in the range of 300 nm to 5,000 nm or a combination thereof.

11. The apparatus (10) of claim 6, wherein, The hydrophobic coating is selected from a coating comprising a polymer; or The hydrophilic coating is selected from a coating comprising polyethylene glycol, polyacrylate, polymethacrylate or a UV light-sensitive polymer; and / or The surface pattern is a micro- or nano-structured surface pattern in the range of 500 nm to 2500 nm or a combination thereof.

12. The apparatus (10) of claim 6, wherein, The hydrophobic coating is selected from a coating comprising a polymer; or The hydrophilic coating is selected from a coating comprising a polyethylene glycol, a polyacrylate, a polymethacrylate or a UV light sensitive polymer. and / or The surface pattern is a nano-microstructure.

13. The apparatus (10) of claim 1, wherein, The conical region (3) has an elliptical cross-sectional shape.

14. The apparatus (10) of claim 2, wherein, The second opening (4) has an elliptical cross-sectional shape.

15. The apparatus (10) according to any one of claims 6 and 10-12, wherein, The hydrophobic coating is selected from a coating comprising an organosiloxane, a silane, an acrylate or an epoxy resin.

16. The apparatus (10) of claim 6, wherein, The hydrophilic coating is selected from a coating comprising a hydrogel.

17. An assembly for loading, storing and transporting a tissue graft or implant (11) comprising: • a device (10) according to any one of claims 1 to 16, • at least one syringe (8, 12), • a tube (5), and • at least one cap (13, 14, 15).

18. The assembly of claim 17, wherein, The assembly further comprises a transportation device.

19. The assembly of claim 18, wherein, The transportation device is a device holder (20) comprising: • a round neck (18) with a holding structure (19), • a finger-like structure attached to an elliptical platform with a cavity (16), and • a bent strip column (17), The device holder is adapted to be placed in a container.

20. The assembly of claim 19, wherein, The finger-like structure and the elliptical platform with a cavity (16) do not optically interfere with the body (2) and the conical region (3) of the device (10).

21. The assembly of claim 19, wherein, The container comprises a standard tissue culture flask or a tissue culture flask (40) with two openings.

22. A washing assembly for washing and staining a tissue graft or implant (11) comprising: • a macroporous material (21) with interconnected pores and a porosity between 10 pm and 600 pm, • a device (10) according to any one of claims 1 to 16, • at least one syringe (8, 12), and • a double-way extension tubing (31) or a three-way stopcock (32).

23. A method for preparing a tissue graft or implant using a device (10) according to any one of claims 1 to 16 comprising the following steps: a) providing a tissue graft or implant (11), b) loading the tissue graft or implant (11) into the device (10), c) sealing the device (10) with at least one cap (13, 14, 15), d) evaluating and quality controlling the tissue graft or implant (11) within the device (10), e) transporting the device (10) with the tissue graft or implant (11), f) washing and staining the tissue graft or implant (11) within the device (10).

24. The method of claim 23, wherein, The device (10) is transported within a device holder (20).

25. The method of claim 23 or 24, wherein, The evaluation and quality control of the tissue graft or implant (11) is performed with the device (10) containing the tissue graft or implant (11) located in a transportation device and a container.

26. The method of claim 25, wherein, The container comprises a standard tissue culture flask or a tissue culture flask (40) with two openings.

27. The method of claim 23, wherein, The method further comprises the step of evaluating and quality controlling a tissue graft or implant (11) within the device (10).

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