Handheld device and methods for dispensing one or more wound healing agents

Abstract

Handheld devices and methods for the on site in vivo fabrication and deposition of support structures (e.g. scaffolds) and therapeutic agents (biological and or pharmaceuticals) for the healing of wounds (e.g., of chronic wounds). The scaffolds and therapeutic agents may be tailored to achieve a certain clinical outcome and can be embedded in multiple layers allowing for new therapeutic combinations.

Description

HANDHELD DEVICE AND METHODS FOR DISPENSING ONE OR MORE WOUND HEALING AGENTSCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 553,058, filed on February 13, 2024, the entire contents of which is hereby incorporated by reference in its entirety.TECHNICAL FIELD

[0002] The present disclosure relates to devices and methods for the on site in vivo fabrication and implantation of support structures (e.g., scaffolds) and biological and chemical therapeutic agents (e.g. cells, growth factors and drugs)) for healing of wounds or compromised tissue.BACKGROUND

[0003] Wounds that do not heal for at least six months are considered chronic wounds. Many chronic wounds last well over six months, even years, and can be a cause for high morbidity and mortality presented as infections, amputations, and death.BRIEF DESCRIPTION OF THE DRAWINGS

[0004] Features and advantages of the present disclosure will be apparent from the following description of various exemplary embodiments, as illustrated in the accompanying drawings, wherein like reference numbers generally indicate identical, functionally similar, and / or structurally similar elements.

[0005] FIG. 1 A is a perspective, first side, rear view of a handheld device for dispensing one or more wound healing agents, according to the present disclosure.

[0006] FIG. IB is an enlarged perspective, first side, front view of the handheld device of FIG. 1A, taken at detail IB in FIG. 1A, according to the present disclosure.

[0007] FIG. 1C is a vertical, cross-sectional view of the handheld device, taken along line 1C-1C in FIG. 1A, according to the present disclosure.

[0008] FIG. ID is a horizontal, cross-sectional view of the handheld device, taken along line ID-ID in FIG. 1A, according to the present disclosure.

[0009] FIG. IE is an enlarged perspective, first side, front view of the handheld device of FIG. 1A, taken at detail IE in FIG. 1A, according to the present disclosure.

[0010] FIG. IF is an enlarged, vertical, cross-sectional view of the handheld device, taken at detail IF in FIG. 1C, according to the present disclosure.

[0011] FIG. 2 shows a loading and unloading position of the handheld device of FIG. 1A, according to the present disclosure.

[0012] FIG. 3 shows the handheld device of FIG. 1A with a catheter mounted on a needle head of the handheld device, according to the present disclosure.

[0013] FIG. 4 shows a vial containing a wound healing agent for the handheld device of FIG. 1A, according to the present disclosure.

[0014] FIG. 5 A illustrates a first dispensing method for the handheld device of FIG.1A including electrospinning, according to the present disclosure.

[0015] FIG. 5B illustrates a second dispensing method for the handheld device of FIG. 1A including electro spraying, according to the present disclosure.

[0016] FIG. 5C illustrates a third dispensing method for the handheld device of FIG.1A including hydrogel dispensing, according to the present disclosure.

[0017] FIG. 5D illustrates a fourth dispensing method for the handheld device of FIG. 1A including gas blowing, according to the present disclosure.

[0018] FIG. 6A is a perspective, first side, rear view of a handheld device for dispensing one or more wound healing agents, according to another embodiment.

[0019] FIG. 6B is a first side view of the handheld device of FIG. 6A, according to the present disclosure.

[0020] FIG. 6C is a second side view of the handheld device of FIG. 6A, according to the present disclosure.

[0021] FIG. 6D is a plan view of the handheld device of FIG. 6A, according to the present disclosure.

[0022] FIG. 6E is a rear view of the handheld device of FIG. 6A, according to the present disclosure.

[0023] FIG. 6F is a front view of the handheld device of FIG. 6A, according to the present disclosure.

[0024] FIG. 6G is a vertical, cross-sectional view of the handheld device of FIG. 6A, taken along line 6G-6G in FIG. 6D, according to the present disclosure.

[0025] FIG. 6H is a horizontal, cross-sectional view of the handheld device of FIG.6A, taken along line 6H-6H in FIG. 6B, according to the present disclosure.

[0026] FIG. 7A is a perspective side view of the handheld device of FIG. 6A in a loading and unloading position, according to the present disclosure.

[0027] FIG. 7B is a perspective side view of the handheld device of FIG. 6A in a loaded position, according to the present disclosure.

[0028] FIG. 8A is a perspective, first side, rear view of a handheld device for dispensing one or more wound healing agents, according to another embodiment.

[0029] FIG. 8B is a first side view of the handheld device of FIG. 6A, according to the present disclosure.

[0030] FIG. 8C is a plan view of the handheld device of FIG. 6A, according to the present disclosure.

[0031] FIG. 8D is a vertical, cross-sectional view of the handheld device of FIG. 6A, taken along line 8D-8D in FIG. 6C, according to the present disclosure.

[0032] FIG. 9 is an enlarged, partial, vertical, cross-sectional view of the handheld device of FIG. 6G, according to the present disclosure.

[0033] FIG. 10 is a flow diagram of a method of dispensing a wound healing agent, according to the present disclosure.

[0034] FIG. 11 illustrates a computing device for controlling aspects of the handheld devices disclosed herein, according to the present disclosure.DETAILED DESCRIPTION

[0035] Features, advantages, and embodiments of the present disclosure are set forth or apparent from a consideration of the following detailed description, drawings, and claims. Moreover, the following detailed description is exemplary and intended to provide further explanation without limiting the scope of the disclosure as claimed.

[0036] Various embodiments are discussed in detail below. While specific embodiments are discussed, this is done for illustration purposes only. A person skilled in the relevant art will recognize that other components and configurations may be used without departing from the spirit and the scope of the present disclosure.

[0037] As used herein, the terms “first,” “second,”, “third,” “fourth,” etc., may be used interchangeably to distinguish one component from another and are not intended to signify location or importance of the individual components.

[0038] The terms “coupled,” “fixed,” “attached,” “connected,” and the like, refer to both direct coupling, fixing, attaching, or connecting as well as indirect coupling, fixing, attaching, or connecting through one or more intermediate components or features, unless otherwise specified herein.

[0039] The singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise.

[0040] Approximating language, as used herein throughout the specification and claims, is applied to modify any quantitative representation that could permissibly vary without resulting in a change in the basic function to which it is related. Accordingly, a value modified by a term or terms, such as “about,” “approximately,” “generally,” and “substantially” is not to be limited to the precise value specified. In at least some instances, the approximating language may correspond to the precision of an instrument for measuring the value, or the precision of the methods or the machines for constructing the components and / or the systems or manufacturing the components and / or the systems. For example, the approximating language may refer to being within a one, two, four, ten, fifteen, or twenty percent margin in either individual values, range(s) of values and / or endpoints defining range(s) of values.

[0041] Here and throughout the specification and claims, range limitations are combined, and interchanged. Such ranges are identified and include all the sub-ranges contained therein unless context or language indicates otherwise. For example, all ranges disclosed herein are inclusive of the endpoints, and the endpoints are independently combinable with each other.

[0042] Despite many efforts by scientists and healthcare professionals to find cures to chronic wounds there is still no satisfactory solution and chronic wounds represent an unmet clinical need. The prevalence of chronic wounds is staggering with about 3% of the elder population suffering from this condition. For example, there are about 6 million people in the US, 6 million in Europe, 6 million in South America, and 6 million in Asia who suffer from chronic wounds. The cost of treating the wounds and their complication amounts to about

[0043] Tissue engineering is a scientific field aimed to create or improve biological tissue function using bio-mimicking support structures for cells proliferation, migration and differentiation. Support structures may be synthetic or biological and can be seeded with cells, drugs, and / or other biochemical factors. Tissue engineering holds great promise as it offers the potential to repair or regenerate damaged tissues and organs where the body fails to do the same.

[0044] One line of tissue engineering products is aimed at providing skin tissue or skin tissue equivalents. An example is depicted in AU2010201787B, incorporated herein by reference in its entirety. The following provides a description of the manufacturing process of Apligraf ® one of the leading commercially available products:• Apligraf® is derived from human neonatal male foreskin tissue, which is used to establish fibroblast and keratinocyte cell banks.• The fibroblast and keratinocyte cell banks are tested for viruses, bacteria, fungi, mycoplasma, karyology, isoenzymes, and tumorigenicity before use.• The fibroblasts are cultured in a bovine type I collagen matrix, which forms the dermal layer of Apligraf®.• The keratinocytes are cultured on top of the dermal layer and allowed to stratify, forming the epidermal layer of Apligraf® with a well-differentiated stratum comeum.• The final product is tested for morphology, cell viability, epidermal coverage, sterility, mycoplasma, and physical container integrity.• Apligraf® is shipped in an agarose medium that contains animal-derived reagents, such as bovine pituitary extract.

[0045] The above description serves as a testimony to the convoluted methods used for the fabrication of such products. These methods necessitate the use of labs and sophisticated processes and machinery for the fabrication and delivery to the point of care ofthe final product, and a surgical procedure for its implantation on the wound. It should also be noted that the composition of the product is fixed, i.e., the scaffold material and the cells that are used are fixed and cannot be changed or tailored according to the needs of a specific wound. Another deficiency is that the product end shape is that of a thin layer and therefore cannot penetrate deep or tunneled wounds, resulting in its use only with superficial wounds.

[0046] Another line of products that is recently gaining popularity is the use of hydrogels, electrospinning, or electro sprayed nano particles that are used as biomedical scaffolds and or dressings. They can also serve as carriers and release agents for different biological and chemical therapeutic agents (e.g. cells, growth factors and drugs).

[0047] The choice between using hydrogels and formation by electrospinning, and electro-spraying, depends on the specific requirement of the intended application, as each technology brings its own set of advantages and disadvantages in the context of morphology, mechanical strength, porosity, degradation, fiber diameter, direction of fiber deposition, encapsulation of therapeutic agents, cell proliferation and migration, spatial control over the distribution of the therapeutic agents, and therapeutic agents delivery and release capabilities.

[0048] Furthermore, each of these technologies brings its own pros and cons in matching the above attributes to provide the optimal: scaffold, delivery, and release mechanism for a specific therapeutic agent and the host tissue.

[0049] Some hydrogels may have good bio compatibility, can be used in creating 3D volumes needed for deep wounds, have a mechanical strength that can be tuned to represent the strength needed in a certain tissue, and have a high water content that promotes nutrient and gas exchange and a conductive environment for cell survival. However, hydrogels can lack precise control over the potential release of therapeutic agents, have limited loading capacity and mediocre capability to adhere to the host tissue.

[0050] Electrospinning may provide for nano fibers with a high surface area and a structure that closely mimics the extra cellular matrix (ECM) thus providing for a good cell migration and proliferation substrate as well as good adhesion to the host tissue. The ability to control nanofiber diameter may allow for improved drug loading and controlled release capabilities. However, electrospun nanofibers may lack mechanical strength and therefore may not form 3D structures and fill up voids (especially voids with high aspect ratio).Another possible limitation of electrospinning technology is the high voltage used in creating the nano fibers. The high voltage may damage cells and other biological agents and may render this technology less effective as standalone for the administration of biological agents.

[0051] In some aspects, electro spraying may be an excellent technology for the burst delivery of biological and chemical agents as it allows for the control of particles size, their coating and encapsulation of bioactive agents. However, electro spraying may have limited penetration depth, low mechanical strength, may not create 3D structures and fill up voids, may have poor tissue adherence and lack the even distribution and controlled release of the scaffold material and its therapeutic agents.

[0052] Furthermore, each such technology may have a specific advantage or disadvantage relating to a specific therapeutic agents that is in use, being a certain cell, drug, molecule etc., and once a decision of the optimal delivery and release technology for a specific therapeutic agent is made, the specific technology may need to be furthered tuned so that it is better designed to carry, deliver and release the therapeutic agent of choice.

[0053] Combining hydrogels, electrospinning, electro spraying dispensing and gas blowing within a single device presents a formidable challenge in the field of biomaterials and tissue engineering. Integrating these methods in a seamless manner poses significant technical, engineering, and material science hurdles.

[0054] Following are a few examples of the hurdles that may need to be overcome in order to combine such technologies:

[0055] Process integration: Electrospinning and hydrogel formation may involve different processing conditions. Electrospinning may use high voltages to create fibers, while hydrogel formation may require mild conditions to avoid damaging bioactive components. Integrating these processes into a single, cohesive system without compromising the properties of either component is a complex task.

[0056] Material compatibility: Electrospinning may involve the use of polymer solutions, while hydrogels may be composed of cross-linked hydrophilic polymers. Ensuring compatibility between the materials used for electrospinning and hydrogel formation can be challenging. Achieving a balance between the structural properties offered by electrospinning and the water-retaining characteristics of hydrogels may help create a biomimetic scaffold.

[0057] Control of fiber orientation and pore size: Electrospinning may be able to create aligned fibers, which may help mimic the native extracellular matrix structure. Achieving control over fiber orientation while incorporating hydrogels adds an extra layer of complexity. Additionally, controlling the pore size, e.g., for cell infiltration and nutrient transport, may be challenging when combining these techniques.

[0058] Both electrospinning and hydrogel formation involve numerous parameters, such as solution viscosity, flow rates, and cross-linking times. Finding conditions that are suitable for both processes without compromising the final scaffold's integrity and functionality adds an additional layer of complexity.

[0059] Biological function: Tissue engineering scaffolds may not only provide structural support but may also promote cell adhesion, proliferation, and differentiation. Balancing the structural characteristics provided by electrospinning with the biological functionality of hydrogels may be challenging to afford the desired tissue-specific outcomes.

[0060] Some disclosures are described as follows.

[0061] US 10278685, incorporated herein by reference in its entirety, describes an on site in vivo, handheld electrospinning and gas blowing device but does not teach the inclusion of any therapeutic agent or the ability to use hydrogels. The gas blowing is used only for the deposition of the electrospinning nano fibers in a certain direction. Therefore, the disclosed device cannot be used to fill up voids and or use a combination of therapeutic agents and scaffold material, neither in parallel nor by creating confluent layers by depositing them is a serial manner.

[0062] US 10639203, incorporated herein by reference in its entirety, also describes a handheld electrospinning device for the fabrication of on site in vivo dressing with the inclusion of a pharmaceutical agent incorporated into the electrospinning solution. It fails to teach the inclusion of spraying / electro spraying or the use of hydrogels as other technologies for the fabrication and implantation of bio mimetic scaffold laden with therapeutic agents and does not teach the inclusion of other therapeutic agents such as cells, growth factors, blood and blood products. Therefore, this disclosed device, cannot be used to fdl up voids and or use a combination of therapeutic agents and scaffold material, neither in parallel nor by creating confluent layers by depositing them is a serial manner.

[0063] US 202230148084A1, incorporated herein by reference in its entirety, describes many variations for the ex- vivo fabrication of a meniscal implant with different layers, each layer with its own scaffold and cells, by using electrospinning technology. However, each layer is fabricated ex-vivo with laboratory scale equipment, and each layer of scaffold and cells are fabricated by their own designated devices and materials, once the ex- vivo, lab fabrication is completed the implant needs to be shipped to the user and it is intended to be implanted in the patient's body via a surgical procedure.

[0064] There is a need for a device and method that will allow the onsite administration of combinations of wound tailored scaffolds and therapeutic agents implanted in parallel and / or in a confluent layer by layer method to enable the use of new therapeutic combinations and provide a treatment for, e.g., chronic wounds. The present disclosure provides for incorporation of these different technologies for the implementation of each technology in a single handheld device capable of on site in vivo fabrication, i.e. formation directly on or in a patient in a clinical setting, and implantation of confluent layers of tailored scaffold materials (e.g., customized for a particular application or wound including the above-mentioned materials, or combinations thereof, fiber diameter, degradation rate, porosity / density, or fiber orientation) and therapeutic agents for the specific treatment situation.

[0065] Disclosed are devices and methods that enables the onsite, in vivo, fabrication and implantation of multiple biological stimulators manufactured by tissue engineering technologies, (here and after termed bioreactors) which may be tailored to treat a certain etiology / pathology and allow for the bioreactors’ implantation in multiple layers each with its own scaffold and therapeutic agent. The disclosed devices and methods may allow the use of new combinations of therapeutic agents and scaffolds never achievable before and may be poised to provide better clinical results compared with existing technologies.

[0066] The disclosed devices and methods may include electro spinning, electro spraying, gas blowing, and hydrogel dispensing technologies to allow for the fabrication of support structures, delivery vehicles, proliferation substrates and or migration substrates for the therapeutic agents of choice onto the host tissue. The device may deliver therapeutic agents including but not limited to iodine, silver, silver nitrate, PHMB (Polyhexamethylene biguanide), hypochloric solutions (e.g., K-SEPT), copper, antibiotics, M2 phenotype macrophages, platelet reach plasma, stem cells, whole blood, antibiotics, 02, 03, bonemarrow aspirates, fibroblasts, keratinocytes, adipose tissue, growth factors, enzymes, and / or proteases.

[0067] In some embodiments of using a device of the invention, a physician assesses a patient’s wound situation, e.g. the etiology and pathology that causes its healing to stall (infections, bio film, chronic inflammation, shortage of certain cells or growth factors, etc.) and applies a therapeutically relevant treatment, for example a tailored layer of the structural support, delivery and release mechanism or material (for example having desired morphology, mechanical strength, load capacity, and degradation properties) in combination with the therapeutic agents to improve the clinical efficacy of the treatment. The present disclosure allows the fabrication of a layer with combinations of structural support and therapeutic agents never before available. Each such layer may function as an independent bioreactor. The device may further allow the fabrication of different such layers / bio-reactors along the height axis of a wound. This may allow the use of never before available combinations of multiple bioreactors, each aimed at achieving a specific clinically significant outcome.

[0068] The device can be used to combine spraying / gas blowing, hydrogel dispensing, electro spraying and electrospinning technologies, and integrate them with multiple therapeutic agents in one device for use on site, i.e. withing the clinical setting, and in vivo, i.e., applied directly to the patient rather than requiring prefabrication. This multifunctional clinical platform may be used in methods of treating specific underlying etiologies and pathologies. The disclosed devices and methods can apply compositions with synergistic clinical effects to provide more effective wound treatment.

[0069] An electrospinning, electro spraying, hydrogel dispensing and gas blowing system, also referred to a handheld device, is presented. The system is comprised of a grip handle, which can include a USB port and an on / off trigger. The system includes a mainbody, with its rear part that includes an LCD display and a vial loading switch, and the main body front part which houses the vials. Connected to the main body front part is the co-axial needle head. The system can utilize two or more dispensing methods including the deposition of electrospun fibers by depositing an electrospun nanofiber forming composition by electrospinning, electro spraying droplets, hydrogel, and gas blowing. It is understood that the dispensing methods can be done in parallel as well. The system includes a battery and a high voltage converter, a printed circuit board (PCB), actuator inside the main body rear part, a vial inside the main body front part. The system can include a vial for electrospinning, a vial for electro spraying, a vial for hydrogel dispensing / gas blowing that can be loaded into the device. The needle head is connected to the main body front part.

[0070] The system can also include one or more actuators, electrodes, and identification connectors. The co axial needle head is connected to the main body front part. The system further includes a vial identification resistor, a vial identification PCB, and identification connectors. The lower part of the front part of the main body has a UV curing light and laser pointer. The vials include the vial identification resistors so that the PCB can identify the vials when the vials are inserted into the device. The device further includes a main electrical braid. A catheter can be used in conjunction with the needle head.

[0071] The present disclosure provides many possible advantages, for example as illustrated by the following. In the case of a chronic wound that has a persistent biofilm, the present disclosure can create on site in vivo a first layer comprising (e.g., consisting of) electrospun fibers to achieve a good adhesion to the host tissue. The electrospun nano fibers can include, for example, one or more of the following toxic therapeutic agents to eradicate the biofilm: iodine, Os, O2, silver, silver nitrate, PHMBs, hypochloric solutions, copper, enzymes, protease, or antibiotics. These therapeutic agents can be included in the electrospinning / electro spraying medium or they can be administrated by gas blowing them(spraying), from the spraying nozzle, in sequence or in parallel to the application of the nano fibers. Then the present disclosure can create a second layer comprising (e.g., consisting of) a hydrogel to create a barrier between the cytotoxic first layer and a third layer comprising (e.g., consisting of) electrospun nanofibers that serve as a transient epidermal tissue for wound closure. The third layer can further comprise (e.g., consist of) keratinocytes and fibroblasts, by, e.g., incorporating them into the electrospun medium or by, e.g., electro spraying / gas blowing them in sequence or in parallel to the application of the electrospun nano fibers. Without wishing to be bound by theory, it is believed that separation by the second layer reduces cell death associated with the toxic therapeutic agents that are contained in the first layer.

[0072] Referring now to the drawings, FIG. 1 A is a perspective, first side, rear view of an electrospinning, electro spraying, hydrogel dispensing and gas blowing system, also referred to as a handheld device 100 for dispensing one or more wound healing agents, according to the present disclosure. FIG. IB is an enlarged perspective, first side, front view of the handheld device 100, taken at detail IB in FIG. 1A, according to the present disclosure. FIG. 1C is a vertical, cross-sectional view of the handheld device 100, taken along line 1C- 1C in FIG. 1A, according to the present disclosure. FIG. ID is a horizontal, cross-sectional view of the handheld device 100, taken along line ID-ID in FIG. 1A, according to the present disclosure. FIG. IE is an enlarged perspective, first side, front view of the handheld device 100, taken at detail IE in FIG. 1A, according to the present disclosure. FIG. IF is an enlarged, vertical, cross-sectional view of the handheld device 100, taken at detail IF in FIG. 1C, according to the present disclosure.

[0073] The handheld device 100 includes a main body 102, a grip handle, also referred to as a handle 104, a co-axial needle head, also referred to as a needle head 106, and an on / off trigger, also referred to as a trigger 108. The main body 102 extends along alongitudinal centerline axis 101 from a proximal end 103 to a distal end 105. The handheld device 100 includes a first side 107 and a second side 109 opposite the first side 107. In the orientation of FIG. 1A, the proximal end 103 defines an end closest to a user when the user is holding the handheld device 100, the distal end 105 is an end farthest from the user, the first side 107 is a left side, and the second side 109 is a right side.

[0074] The main body 102 includes a main body rear part, also referred to as an actuator housing 110, and a main body front part, also referred to as a vial housing or a wound healing agent housing 112. The wound healing agent housing 112 is shown transparent but can be opaque. The wound healing agent housing 112 is configured to store one or more wound healing agents therein. Examples of the wound healing agents are provided below. In particular, the wound healing agent housing 112 includes one or more wound healing agent cavities 113 configured to receive the wound healing agents therein. In one embodiment, the wound healing agent cavities are reservoirs configured to receive the wound healing agents directly therein. In one embodiment, the wound healing agent cavities 113 are configured to receive one or more vials 200 that contain the wound healing agents therein, as detailed further below. In the embodiment shown, the handheld device 100 includes a plurality of wound healing agent cavities 113 for receiving a plurality of wound healing agents therein. In particular the plurality of wound healing agent cavities 113 include a first wound healing agent cavity 113a configured to receive a first wound healing agent therein, a second wound healing agent cavity 113b configured to receive a second wound healing agent therein, and a third wound healing agent cavity 113c configured to receive a third wound healing agent therein. While three wound healing agent cavities 113 are shown, the handheld device 100 can include any number of wound healing agent cavities 113 as desired.

[0075] The wound healing agent housing 112 can be opened to an open position for loading and unloading and closed to a closed position or a loaded position. In particular, the wound healing agent housing 112 is pivotable with respect to the actuator housing 110 such that that the wound healing agent housing 112 is pivoted, for example, about a hinge 115 to the loading and unloading position (shown in FIG. 2) and to the loaded position (shown in FIGS. 1A to IF). The wound healing agent housing 112 is detailed further below. The main body 102 includes a vial loading switch, also referred to as a loading switch 114, for actuating a lock to open the wound healing agent housing 112 (for example to load or unload the wound healing agents (e.g., by inserting the vials 200) in the wound healing agent cavity), and to close the wound healing agent housing 112 for use.

[0076] The one or more wound healing agents include any type of composition or material for facilitating healing of a wound of a patient. For example, the one or more wound healing agents are independently selected from cells, a drug, a synthetic polymer, a hydrogel a biological polymer, an antibacterial agent, or a combination thereof. In some embodiments, the one or more wound healing agents are independently selected from iodine, silver, silver nitrate, PHMBs, hypochloric solutions (K-SEPT), copper, antibiotics, M2 macrophages, platelet reach plasma, stem cells, adipose tissue, bone marrow aspirate, bone marrow aspirate derivatives, blood, blood products, antibiotics, O2, Os, fibroblast, keratinocytes, enzymes, protease, and growth factors, or combinations thereof. In some embodiments, at least one of the one or more wound healing agents is an antibacterial agent. In some embodiments, at least one of the one or more wound healing agents is a combination of fibroblast and keratinocyte. In some embodiments, at least one of the one or more wound healing agents comprises polylactic acid (PLA), poly (ethylene glycol) (PEG), poly e -caprolactone (PCL), collagen, methacrylated collagen, chitosan, gelatin, latex, dextran, fibroin, keratin, poly(lactic acid-co-glycolic acid) (PLGA), poly(vinylidene fluoride-co-hexafluoropropylene) (PVDFhfp), polyglycolic acid, polydiaxanone, poly (propylene carbonate), poly (ethylene oxide), poly (ester-urethane) urea, and poly (lactide -caprolactone). In some embodiments, the one or more wound healing agents independently form a scaffold material in vivo when dispensed onto a tissue or a wound in a patient. For example, the scaffold material includes at least one of a mat, a fiber, or a dressing.

[0077] The handle 104 extends generally perpendicularly from the main body 102. In particular, the handle 104 extends from the actuator housing 110 generally at the proximal end 103. The handle 104 allows the user to grab and to hold the handheld device 100 with one hand such that the handheld device 100 is handheld. The trigger 108 is positioned on the handle 104 such that the user can actuate the trigger 108 with one or more fingers. Actuation of the trigger 108 controls the handheld device 100 to dispense the one or more wound healing agents therefrom, as detailed further below. In this way, the handheld device 100 is configured to dispense one or more wound healing agents.

[0078] The main body 102 also includes a display 116 for displaying at least one of information indicative of a dispensing method or information indicative of dispensing parameters for the handheld device 100. Various examples of dispensing methods are shown and described further below with respect to FIGS. 5A to 5D. Examples of the dispensing parameters are detailed further below. The display 116 can include a liquid crystal display (LCD) display or any type of display for displaying the at least one of the information indicative of the dispensing method or the information indicative of dispensing parameters for the handheld device 100. In some embodiments, the display 116 includes a touchscreen such that the user can interact with the display 116 and send inputs to the handheld device 100. In some embodiments, the handheld device 100 includes one or more buttons, switches, or the like, for allowing the user to input parameters to the handheld device 100.

[0079] The handheld device 100 includes a charger port 118 for receiving a charger therein to supply power to the handheld device 100. In some embodiments, the handheld device 100 includes an electric power supply, such as, for example, a battery or the like. In such embodiments, the charger port 118 can receive the charger for charging the battery. In this way, the handheld device 100 can be powered by the electric power supply and can be wireless.

[0080] The handheld device 100 includes one or more actuators 120 disposed within the actuator housing 110 and configured to facilitate dispensing of the wound healing agents from the wound healing agent cavities 113. For example, the one or more actuators 120 include a first actuator 120a for facilitating dispensing the first wound healing agent from the first wound healing agent cavity 113a, a second actuator 120b for facilitating dispensing the second wound healing agent from the second wound healing agent cavity 113b, and a third actuator 120c for facilitating dispensing the third wound healing agent from the third wound healing agent cavity 113c. In the embodiment shown, the actuators 120 are linear actuators configured to move linearly. The actuators 120 can include any type of actuator for facilitating dispensing the wound healing agents from the wound healing agent cavities 113. Each of the one or more actuators 120 include a plunger 122 disposed in communication with the one or more wound healing agent cavities 113. The plunger 122 pushes, or otherwise forces, the wound healing agents out of the wound healing agent cavities 113 and towards the needle head 106. Each of the actuators 120 includes an encoder, also referred to as an actuator position sensor 124, associated therewith such that a controller (detailed further below) can determine a current position of the actuators 120.

[0081] The handheld device 100 includes a UV curing light and laser pointer, also referred to as a curing light 126. The curing light 126 is positioned in the wound healing agent housing 112 such that the curing light 126 is adjacent the distal end 105 of the handhelddevice 100. In this way, the curing light 126 can be used to measure a distance that the handheld device 100 is from a wound and can cure one or more of the wound healing agents (e.g., hydrogel), as detailed further below.

[0082] The handheld device 100 includes a main electrical braid 128, a printed circuit board (PCB), also referred to as a controller 130, an electrical power supply 132, and a high voltage converter 134. The main electrical braid 128 supplies power from the electrical power supply 132 to the various electrical components of the handheld device 100. The controller 130 receives controls the various electrical components of the handheld device 100, as detailed further below. The electrical power supply 132 supplies power to the controller 130 and the various electrical components. In the embodiment shown, the electrical power supply 132 includes one or more batteries (e.g., lithium-ion batteries, or the like). The electrical power supply 132, however, can include any type of electrical power supply (e.g., portable or non-portable) for supplying power for the handheld device 100. The high voltage converter 134 converts electrical power from high voltage alternating current (AC) to high-voltage direct current (HVDC) or vice versa. In particular, the high voltage converter 134 converts high voltage electrical power from the electrical power supply 132 to the controller 130 and to the other electrical components of the handheld device 100.

[0083] The handheld device 100 further includes one or more electrodes 140, one or more channels 142, and a needle tip 144. The one or more electrodes 140 are coupled to the wound healing agent cavities 113 to supply high voltage in the dispensing methods (e.g., electrospinning, electro spraying, or the like). In particular the one or more electrodes 140 include a first electrode 140a coupled to the first wound healing agent cavity 113a, a second electrode 140b coupled to the second wound healing agent cavity 113b, and a third electrode 140c coupled to the third wound healing agent cavity 113c. The channels 142 are disposed in the needle head 106 and are fluidly coupled with the wound healing agent cavities 113. Forexample, the channels 142 include a first channel 142a fluidly coupled with the first wound healing agent cavity 113a, a second channel 142b fluidly coupled with the second wound healing agent cavity 113b, and a third channel 142c fluidly coupled with the third wound healing agent cavity 113c. The electrodes 140 also define a channel and are fluidly coupled between the channels 142 and the wound healing agent cavities 113 to provide fluid communication from the wound healing agent cavities 113 to the channels 142.

[0084] The needle head 106 defines the needle tip 144. At the needle tip 144, the channels 142 are co-axial such that needle head 106 is a co-axial needle head. In this way, the needle head 106 includes two or more co-axial needles. In the embodiment shown, the first channel 142a is radially outward of the second channel 142b and the second channel 142b is radially outward of the third channel 142c at the needle tip 144.

[0085] According to the present disclosure, a fiber can be provided as a wound healing agent, which may be a nanofiber or a compound fiber. The method for making the nanofiber is affected by electrospinning a polymeric solution a channel in the needle as described above. The method for making the compound fiber is affected by coelectrospinning two polymeric solutions through co-axial channels in the needle to thereby produce the compound fiber, having a core and a shell surrounding the core. A first core forming polymeric solution is for forming a core of the fiber and a second shell forming polymeric solution is for forming the shell of the fiber. The first core forming polymeric solution can be dispensed through a central channel, for example, the third channel 142c, and the second shell forming polymeric solution can be dispensed through a surrounding channel, for example, the second channel 142b. Alternatively, the first core forming polymeric solution can be dispensed through the second channel 142b, and the second shell forming polymeric solution dispensed through the surrounding first channel 142a. The pores in the shell can be formed by, for example, using a second shell forming polymeric solution thatcomprises a water-soluble polymer such as polyethylene glycol (PEG). The polymer which forms the core of the fiber can include a therapeutic agent, for example, an antimicrobial agent such as Polyhexamethylene biguanide (PHMB) or a biological material such as collagen, and deliver the therapeutic agent to the wound.

[0086] The handheld device 100 can also include one or more identification connectors 146 for receiving an electrical signal from a wound healing agent identification resistor 202 on the vials 200 such that the controller 130 can identify the wound healing agents in the wound healing agent cavities 113 (e.g., in the vials 200). The handheld device 100 can include a vial identification PCB, also referred to as a wound healing agent identification controller 148, for receiving the electrical signal from the identification connectors 146, identifying the wound healing agents in the wound healing agent cavities 113, and sending a signal indicative of the wound healing agents to the controller 130.

[0087] In operation, the user actuates the loading switch 114 to open the wound healing agent housing 112 to the opened position (shown in FIG. 2). The user can load one or more wound healing agents into the wound healing agent cavities 113. In some embodiments, the wound healing agents are added directly into the wound healing agent cavities 113. In some embodiments, the user can load one or more vials 200 with the wound healing agents therein into the wound healing agent cavities 113, as shown in FIG. 2. Once the wound healing agents are loaded into the wound healing agent cavities 113, the user can close the wound healing agent housing 112 to the closed position, as shown in FIGS. 1A to IF, and power on the handheld device 100.

[0088] The controller 130 can automatically identify the type of wound healing agents that are in the wound healing agent cavities 113, as detailed above. The controller 130 can determine a dispensing method based on the wound healing agent in a particular wound healing agent cavity 113. For example, particular wound healing agents are dispensed withparticular dispensing methods. In this way, the controller 130 can select one dispensing method of a plurality of dispensing methods for each wound healing agent in the wound healing agent cavities 113. The dispensing methods can include, for example, electrospinning, electro spraying, hydrogel dispensing, or gas blowing, as detailed below with respect to FIGS. 5A to 5D. Based on the types of wound healing agents in the handheld device 100 and the selected dispensing method, the controller 130 is configured to set one or more dispensing parameters for dispensing the wound healing agents. The dispensing parameters can include for example, a voltage, a flow rate, control of the curing light 126, a dispensing time, or a dispensing order of the wound healing agents.

[0089] The user can then direct the handheld device 100 to the patient such that the needle tip 144 of the needle head 106 is directed at a wound. The user can then actuate (e.g., pull) the trigger 108. The controller 130 receives a trigger signal when the trigger 108 is actuated. When the controller 130 receives the trigger signal, the controller 130 controls the handheld device 100 to dispense the wound healing agents with the selected dispensing methods and the set dispensing parameters for each wound healing agent. In particular, the controller 130 controls the actuators 120 to force the wound healing agents towards the needle head 106. As the wound healing agents flow through the channels 142, the controller 130 controls the dispensing method. For example, the controller 130 can control the high voltage converter 134 to send high voltage to the electrodes 140 for electrospinning or electro spraying.

[0090] The controller 130 can control the handheld device 100 to dispense layers of the wound healing agents at, for example on or into, the wound. The controller 130 can dispense the wound healing agents sequentially based on a predetermined order for particular types of wound healing agents, or in parallel. In some embodiments, the controller 130 can dispense the wound healing agents as long as the user is actuating the trigger 108 (holding thetrigger 108 down). In some embodiments, the controller 130 can dispense the wound healing agents for a predetermined amount of time with a single actuation of the trigger 108. In some embodiments, the controller 130 can dispense the first wound healing agent with a first actuation of the trigger 108, dispense the second wound healing agent with a second actuation of the trigger 108, and dispense the third wound healing agent with a third actuation of the trigger 108.

[0091] Thus, the handheld device 100 allows the onsite administration of combinations of wound healing agents (e.g., tailored scaffolds) and therapeutic agents implanted in parallel and / or in a confluent layer by layer method to enable the use of new therapeutic combinations and provide a treatment for, e.g., chronic wounds. In particular, the handheld device 100 incorporates different technologies in a single handheld device for the onsite in vivo fabrication and implantation of layers of wound healing agents. In this way, the handheld device 100 is used to generate a wound healing composition at the wound. The wound healing composition can include one or more wound healing agents, as detailed further below.

[0092] FIG. 3 shows the handheld device 100 with a catheter 300 mounted on the needle head 106. In particular, the catheter 300 is mounted on the needle tip 144. The catheter 300 allows the handheld device 100 to dispense the wound healing agents internally.

[0093] FIG. 4 shows a vial 200 containing a wound healing agent for the handheld device 100, according to the present disclosure. The vial 200 defines a hollow interior to receive a respective wound healing agent therein. The vial 200 includes the wound healing agent identification resistor 202 and a vial channel 204. The vial channel 204 fits into the electrode 140 when the vial 200 is loaded into the handheld device 100 such that the vial channel 204 is fluidly coupled to the electrode 140. In this way, the vial channel 204 provides fluid communication between the vial 200 and a respective channel 142. The vial200 is substantially tubular but can include any shape having a hollow interior for receiving a wound healing agent, as desired.

[0094] FIG. 5 A illustrates a first dispensing method 400 for the handheld device 100. The first dispensing method 400 is electrospinning to generate continuous fibers.Electrospinning is a voltage-driven fabrication process for producing continuous polymeric fibers (e.g., nanofibers). In particular, the electrode 140 of the handheld device 100 generates an external electric field that produces the fibers from the wound healing agent.

[0095] FIG. 5B illustrates a second dispensing method 500 for the handheld device 100. The second dispensing method 500 is electro spraying to generate a spray of fibers (e.g., droplets). Electro spraying is an electrohydrodynamic process on the wound healing agent to elongate and solidify the wound healing agent to generate droplets of fibers of the wound healing agent. In particular, the electrode 140 generates electricity to create charged droplets of the wound healing agent.

[0096] FIG. 5C illustrates a third dispensing method 600 for the handheld device 100. The third dispensing method 600 includes hydrogel dispensing. The handheld device 100 can generate a hydrogel from the wound healing agent or dispense a preformed hydrogel. For example, the wound healing agent can include a mixture of polymers or pre-polymers (e.g., in a liquid state) that can form a hydrogel, i.e., a hydrogel forming composition. The handheld device 100 can dispense the hydrogel polymers or prepolymers from wound healing agent cavity 113, for example, by the actuators 120. After the hydrogel polymers or prepolymers are dispensed, the hydrogel polymers or prepolymers cure, or cross-link, and form the hydrogel in place. For photochemical curing, the curing light 126 can be illuminated to cure the hydrogel polymers or prepolymers. Alternatively, the wound healing agent can be formed as a hydrogel and stored in the wound healing agent cavity 113 as a hydrogel. Thehandheld device 100 can dispense the hydrogel from wound healing agent cavity 113, for example, by the actuators 120.

[0097] FIG. 5D illustrates a fourth dispensing method 700 for the handheld device 100. The fourth dispensing method 700 includes gas blowing, such as using an air pump to generate gas pressure to dispense the wound healing agent. For example, the handheld device 100 can include a small ventilator (e.g., air pump) or a small high-pressure gas container or canister from which the gas can be released for gas blowing the wound healing agents from the handheld device 100.

[0098] FIG. 6A is a perspective, first side, rear view of a handheld device 800 for dispensing one or more wound healing agents, according to another embodiment. FIG. 6B is a first side view of the handheld device 800. FIG. 6C is a second side view of the handheld device 800. FIG. 6D is a plan view of the handheld device 800. FIG. 6E is a rear view of the handheld device 800. FIG. 6F is a front view of the handheld device of FIG. 6A, according to the present disclosure. FIG. 6G is a vertical, cross-sectional view of the handheld device 800, taken along line 6G-6G in FIG. 6D, according to the present disclosure. FIG. 6H is a vertical, cross-sectional view of the handheld device 800, taken along line 6H-6H in FIG. 6B, according to the present disclosure.

[0099] The handheld device 800 may be the same as or similar to the handheld device 100. Accordingly, like numbers represent like components. The difference between the handheld device 800 and the handheld device 100 will be described in more detail to follow. The remaining structure and function are the same as described with respect to the handheld device 100 and will not be described herein. Additionally, any of the alternatives to the handheld device 100 apply equally to the handheld device 800 of FIGS. 6A to 6H.

[0100] The handheld device 800 includes a main body 802, a handle 804, a needle head 806, and a trigger 808. The main body 802 extends along a longitudinal centerline axis801 from a proximal end 803 to a distal end 805 and includes a first side 807 and a second side 809 opposite the first side 807. The main body 802 includes an actuator housing 810 and a wound healing agent housing 812. The handheld device 800 includes a loading switch 814, a hinge 815, a display 816, a charger port 818, one or more actuators 820 including a first actuator 820a and a second actuator 802b each having a plunger 822, an actuator position sensor 824 (e.g., a linear potentiometer), a curing light 826, a main electrical braid 828, a controller 830, an electrical power supply 832, a high voltage converter 834, an electrode 840, one or more channels 842, and a needle tip 844. The handheld device 800 also includes a ground port 819 for receiving a ground cable that the patient can hold to ground the patient.

[0101] The wound healing agent housing 812 contains the wound healing agents therein, and also contains the needle head 806. In particular, the wound healing agent housing 812 includes one or more wound healing agent cavities 813 including a first wound healing agent cavity 813a and a second wound healing agent cavity 813b. The wound healing agent cavities 813 are configured to receive one or more vials 900 (e.g., each including a vial channel 904), particularly, a first vial 900a in the first wound healing agent cavity 813a and a second vial 900b in the second wound healing agent cavity 813b. The wound healing agent housing 812 also includes a tip cone 850 that defines a generally conical shape that expands from the proximal end 803 of the tip cone 850 to the distal end 805 of the tip cone 850. In this way, the tip cone 850 helps to direct and to guide the wound healing agents as the handheld device 800 dispenses the wound healing agents.

[0102] The needle head 806 includes a first channel 842a and a second channel 842b that are co-axial at the needle tip 844. Because the first wound healing agent cavity 813a is located beneath the second wound healing agent cavity 813b, the first channel 842a includes a first horizontal channel, a vertical channel, and a second horizontal channel that define thefirst channel 842a such that the second horizontal channel is co-axial with the second channel 842b.

[0103] The electrode 840 is configured to hold the needle head 806. In this way, the electrode 840 acts as a base for the needle head 806. The electrode 840, with the needle head 806 thereon, is inserted and positioned in the wound healing agent housing 812. The electrode 840 receives electricity to generate an electric field, as detailed above.

[0104] In the embodiment shown, the handheld device 800 identifies the wound healing agents therein without the use of identification connectors and a wound healing agent identification controller. In this way, the vials 900 do not include wound healing agent identification resistors. Rather, the handheld device 800 identifies the wound healing agents mechanically. In particular, the vials 900 are inserted into one or more vial sleeves 906 that have grooves thereon. The groove pattern on each vial sleeve 906 is different. For example, the first vial sleeve 906a has a first groove pattern and the second vial sleeve 906b has a second groove pattern. The first vial 900a is inserted into a first vial sleeve 906a and the second vial 900b is inserted into a second vial sleeve 906b. The wound healing agent cavities 813 each have features (e.g., ridges, bumps, projections, or the like) that correspond to the groove patterns such that each respective wound healing agent cavity 813 only accepts a respective vial sleeve 906. For example, the first wound healing agent cavity 813a only accepts the first vial sleeve 906a and the second wound healing agent cavity 813b only accepts the second vial sleeve 906b. In this way, the handheld device 800 can identify the wound healing agents therein mechanically. It is understood that the handheld device 800 can be configured to identify the wound healing agents using connectors, a wound healing agent identification controller, and a wound healing agent identification resistors as descried above with respect to handheld device 100. Alternatively, the handheld device 100 can be configured to identify would healing agents mechanically as described above.

[0105] The handheld device 800 also includes a power buton 860, a high voltage buton 862, a curing light buton 864, and an actuator reset buton 866. The power buton 860 turns the handheld device 800 on or off. The high voltage buton 862 allows the user to send high voltage to the electrode 840 for dispensing the wound healing agents. The curing light buton 864 turns the curing light 826 on or off. The actuator reset buton 866 retracts the actuators 820 to an initial position after the wound healing agent has been dispensed. This allows the user to insert a new vial 900 into the wound healing agent housing 812. The handheld device 800 can also include one or more dispensing parameter butons 870 (shown schematically in dashed lines behind a cover in FIG. 6C). The dispensing parameter butons 870 allow the user to vary or to set the one or more dispensing parameters manually. The preferred embodiment, however, includes the controller 830 automatically seting the dispensing parameters, as detailed above. While physical butons are shown and described herein, the handheld device 800 can include virtual butons, switches, knobs, or any other actuation mechanism for activating the above functions.

[0106] FIG. 7A is a perspective side view of the handheld device 800 in a loading and unloading position. The needle head 806 is shown as being outside of the handheld device 800 in the loading and unloading position but can remain inside the wound healing agent housing 812 while the vials 900 are loaded or unloaded. FIG. 7B is a perspective side view of the handheld device 800 in a loaded position. The loaded position includes the vials 900 inserted into the wound healing agent cavities 813. Once the vials 900 are loaded, the user can close the wound healing agent housing 812 and operate the handheld device 800 to dispense the wound healing agents.

[0107] FIGS. 8A to 8D show various views of the handheld device 800 with a cover cone 880 thereon. The cover cone 880 provides an additional surface for dispensing the wound healing agents. The cover cone 880 also directs wound healing agents dispensed fromthe device to the wound and restricts wound healing agents, solvents, etc. from escaping or volatilizing into the environment. The cover cone 880 defines a generally conical shape that expands from the proximal end 803 of the cover cone 880 to the distal end 805 of the cover cone 880. The generally conical shape of the cover cone 880 begins at the distal end 805 of the tip cone 850. In this way, the cover cone 880 helps to direct and to guide the wound healing agents as the handheld device 800 dispenses the wound healing agents. In some embodiments, the handheld device 800 includes a replaceable cone sleeve that can be inserted in the cover cone 880 or the tip cone 850. The user can replace the replaceable cone sleeve after dispensing a wound healing agent from the handheld device 800. Such a configuration allows easier clean up after use.

[0108] The cover cone 880 can be attached to the handheld device 800 by snapping onto the wound healing agent housing 812. In this way, the cover cone 880 is coupled to the handheld device 800. The cover cone 880 includes a cover cone electrode 882 that produces an electric field. The cover cone electrode 882 can plug into the handheld device 800 when the cover cone 880 is attached to the handheld device 800 to receive electricity through the main electrical braid 828.

[0109] FIG. 9 is an enlarged, partial, vertical, cross-sectional view of the handheld device 800, according to the present disclosure. In FIG. 9, the handheld device 800 includes a camera 890 (shown schematically in FIG. 9) that can generate images or display a live feed, for example, on the display 816 or on an external display remote from the handheld device 800. The camera 890 is an optical wire camera (e.g., a camera at the end of a fiber optic cable). The camera 890 allows the user to view the wound or generate a timelapse of the wound overtime. In some embodiments, the controller 830 can include software (e.g., an artificial intelligence algorithm) that uses the images from the camera 890 to analyze a woundand advise the user on which formulation of the wound healing agents (e.g., or which vials 900) to use to treat the wound.

[0110] FIG. 10 is a flow diagram of a method 1000 of dispensing a wound healing agent, according to the present disclosure. While the method 1000 is described with respect to the handheld device 100, the method 1000 can be utilized with the handheld device 800. [oni] In step 1005, the method 1000 includes receiving an indication of a wound healing agent in the handheld device 100. In particular, the controller 130 receives the indication of the one or more wound healing agents in the wound healing agent cavities 113. The controller 130 can receive the indication via the wound healing agent identification controller 148 of FIGS. 1A to IF or via the mechanical means of FIGS. 6A to 6H.

[0112] In step 1010, the method 1000 includes determining a dispensing method of a plurality of dispensing methods for dispensing the one or more wound healing agents based on the indication of the one or more wound healing agents in the handheld device 100. In particular, the controller 130 can determine the dispensing method. For example, the controller 130 can be preprogramed to map the dispensing methods to particular wound healing agents. The dispensing method can include any of the dispensing methods detailed herein.

[0113] In step 1015, the method 1000 includes setting one or more dispensing parameters based on the indication of the wound healing agents. In particular, the controller 130 sets the one or more dispensing parameters based on the wound healing agents in the handheld device 100. For example, the controller 130 can be preprogramed to map the dispensing parameters to particular wound healing agents. The dispensing parameters can include any of the dispensing parameters detailed herein.

[0114] In step 1020, the method 1000 includes receiving a trigger signal. In particular, the controller 130 receives the trigger signal from the trigger 108. For example,when the user aims the handheld device 100 at a wound, the user can actuate the trigger 108, the trigger 108 generates the trigger signal and sends the trigger signal to the controller 130.

[0115] In step 1025, the method 1000 includes dispensing the one or more wound healing agents with the determined dispensing methods and based on the set dispensing parameters for each wound healing agent. In particular, the controller 130 can control the handheld device 100 (e.g., the actuators 120, the electrodes 140, etc.) to dispense the one or more wound healing agents towards the wound.

[0116] The method 1000 of dispensing the wound healing agents is exemplified in the following particular examples.EXAMPLES

[0117] Specific embodiments will be demonstrated by reference to the following examples. These examples are disclosed solely by way of illustrating the present disclosure and should not be taken in any way to limit the scope of the present disclosure. While the examples are described with respect to the handheld device 100, the examples are applicable for the handheld device 800 as well.

[0118] Example 1

[0119] Polybiguanide (PHMB) is mixed with polylactide (PLA) a known biocompatible polymer used for electrospining, and an homegenous solution with 2.5% PHMB concentration is achieved. The solution is stored in the first vial 200a. Autologous keratinocytes and fibroblasts in a ready to spray solution are obtained by using a system such as the Recell® system (A vita Medical, Valencia CA, USA) and stored in the second vial 200b. A hydrogel comprised of poly (ethylene glycol) (PEG) with high molecular weight and very limited porosity is loaded to the third vial 200c. The vials 200 are loaded to the wound healing agent housing 112 of the handheld device 100. The handheld device 100 recognizes each of the vials 200 and their content when the wound healing agentidentification resistor 202 is connected to the wound healing agent identification controller 148 via the identification connectors 146. Upon the recognition of the vials 200, a software embedded in the controller 130 will determine the sequence of the deposition (e.g., dispensing) of the materials by each vial 200, the method of dispensing or deposition (electrospinning, electro spraying, hydrogel dispensing, or gas blowing / spraying), the exact voltage, the flow rate, and the length of time of depositing (hence the amount of deposited substances) for each vial 200. The activation will start when the user squeezes the trigger 108.

[0120] In this example, the first layer will be the antibacterial solution in the first vial 200a. The antibacterial solution will be dispensed by electrospinning using a voltage of 20KV at the tip of the nozzle and a flow rate of 4.5ml / h at a distance of 20cm from the wound, measured by the curing light 126 (e.g., the laser pointer of the curing light), until a 1mm of coating is achieved, then the second layer of the hydrogel in the second vial 200b is dispensed via the catheter 300 and cured with the curing light 126 to form 1mm of a barrier and then the third layer consisting of the keratinocytes and fibroblasts in the third vial 200c is dispensed by spraying on top of the hydrogel layer. Together, the layers provide a transient epidermal layer that protects against infection and provide bio mimicking environment for native epidermal tissue growth.

[0121] Example 2

[0122] In the case of a deep wound that is stuck in the phase of chronic inflammation, the present disclosure can: create a first layer that reaches the depth of the wound by implanting hydrogels. The implanted hydrogels can contain bone marrow aspirates, blood or blood products (such as platelet rich plasma (PRP), M2 macrophages), stem cells, growth factors or steroids as the therapeutic agents. These therapeutic agents are all known catalysts for transforming chronic inflammation to acute inflammation and achieving woundangiogenesis which is the desired next stage in the healing of the wound. The therapeutic agents can be released in a controlled manner over a pre -determined period of time, for example by controlling the degradation and porosity of the hydrogel, enabling a continuous and consistent therapeutic environment inside the wound. Then the present disclosure can create a second layer consisting of electrospun nanofibers, as the support structure, together with keratinocytes and fibroblasts as the therapeutic agents, to create the dermis and epidermis layers of the skin, and help achieve wound closure. In this example, the present disclosure allows for the on site, in vivo implantation of two different bio-reactors, with different therapeutic agents, each is tailored mechanically and biologically to treat a different stage in the healing of the wound and each is placed in the specific location to optimally enhance the function of the host tissue according to its role in the process of the healing of the wound, e.g: a first layer in the dipper part of the wound for the generation of angiogenesis and the second layer in the external part of the wound for the generation of dermis and epidermis tissues.

[0123] Example 3

[0124] Autologous bone marrow aspirate (BMA) is derived from a patient by means known in the art. The BMA is mixed with 20 wt%, 8-arm, 20 kDa PEG hydrogel at a concentration of 2 mM to best match the modulus of bone marrow which is 4.4+ / - 1 Kpa as well as provide for a sustained release by degradation of the PEG and diffusion through its structure over 14 days. The mixed hydrogel is loaded into the third vial 200c. The first vial 200a will be loaded with a common biocompatible and biodegradable electrospinning polymer such as poly(lactic acid-co-gly colic acid) (PLGA). Autologous keratinocytes and fibroblasts in a ready to spray solution are obtained by using a system such as the Recell® system (A vita Medical, Valencia CA, USA) and stored in the second vial 200b. The vials 200 are loaded to the wound healing agent housing 112 of the handheld device 100. Thehandheld device 100 recognizes each of the vials 200 and their content when the wound healing agent identification resistor 202 connects to the wound healing agent identification controller 148 via the identification connectors 146. Upon the recognition of the vials 200, a software embedded in the controller 130 will determine the sequence of the deposition of the materials of each vial 200, the method of deposition (e.g., electrospinning, electro spraying, hydrogel, or gas blowing), the exact voltage, the flow rate, and the length of time of depositing (hence the amount of deposited substances) of each vial 200. The only action done by the operator after the loading of the vials 200 will be the aiming of the system and pushing the trigger 108.

[0125] In this example, the first layer will be the mixed hydrogel in the third vial 200c. It will be dispensed via the catheter 300 at a dispensing pressure of 0.2 MPa, a dispensing speed of 10 mm / s through a needle (e.g., the third channel 142c) with an inner diameter of 0.41mm. Once dispensed it will be cured with the curing light 126 to form 2 mm of a BMA active hydrogel layer. Then a second layer consisting of the keratinocytes and fibroblasts in the second vial 200b is dispensed by spraying in parallel to dispensing electrospun fibers from the first vial 200a. The dispensing parameters of the second vial 200b will be the same as for the third vial 200c, while the dispensing speed of the first vial 200a will be twice as fast (at 20 mm / s). The joint deposition of the first vials 200a and the second vial 200b provides a transient epidermal layer that protects against infection and provide bio mimicking environment for native epidermal tissue growth and wound closure. Each layer by itself and the combinations thereof was never before achievable.

[0126] Example 4

[0127] Another example for treating a wound that is stuck in the chronic inflammation stage with combinations of support structures and therapeutic agents that were never attainable before is the following application: 1- first layer of bone marrow aspirateencapsulated in electro sprayed droplets and a second layer of electro spun nano fibers with blood or blood products. In this example the first layer will be fabricated by obtaining autologous bone marrow by means common in the art and mixing it at a concentration of 2 mM concentration with a collagen-blended PLGA with 4.5% concentrations of HFP (hexafluoro-2 -propanol). This mixed solution when dispensed using a voltage of 20KV at the tip of the nozzle at a flow rate of 4ml / h at distance of 15cm from the wound, will produce droplets loaded with bone marrow aspirate and allow for the sustained release of the bone marrow over a period of 6-7 days by which time the droplets will degrade. The first layer will be 2 mm thick. 2- A second layer combined of electrospun nanofibers with autologous blood will be fabricated by obtaining autologous blood by means known in the art and loaded in the third vial 200c. The first vial 200a will be loaded with a common biocompatible and biodegradable electrospinning polymer such as PLGA. Both vials 200a, 200c will be dispensed simultaneously, the third vial 200c at a rate of 2 ml / h and the first vial 200a at 4.5 ml / h, the voltage at the tip of the needle of the first vial 200a will be 20Kv and the distance from the wound 20cm. In this way the nanofibers produced by first vial 200a and the sprayed autologous blood sprayed by third vial 200c will mix in the air on the way to the wound or when reaching the first layer (if not mixed by then) and form the second layer. The second layer should be 2 mm in thickness and provide the combination of a blood clot with a cell proliferation and migration support structure. The voltage, rate of dispensing for each nozzle, distance of application will be automatically decided by the handheld device 100 upon the detection of the vials 200 that are loaded as described above. The only action done by the operator after the loading of the vials 200 will be the aiming of the system and pushing the trigger 108.

[0128] Example 5

[0129] For the treatment of a partial thickness wound such as a second degree bum, the present disclosure, in any of the manners described above, can provide hydrogels as the support structure and delivery mechanism to therapeutic agents such as keratinocytes and fibroblasts or it can allow for the use of electrospinning of nano fibers as the support structure and use electro spraying or gas blowing as the delivery mechanism for the deposition of the keratinocytes and fibroblasts. The delivery of the keratinocytes and fibroblasts can happen just before, together, or just after the fabrication of the electrospun nano fibers in any of the manners described above. This combination was not achievable with a single device prior to the present disclosure.

[0130] Example 6

[0131] In an example of an electrospun fiber according to the present disclosure, the electrospun shell can be made of a polymer such as poly(8-caprolactone) (PCL, Mn= 80 kDa). Exemplary polymeric solutions include 10 % PCL in chloroform (CHCh) and 20 % PCL in acetic acid (AA). An antimicrobial agent PHMB was added to the polymer solution as a solution in AA and deionized water (DI) or as a solution in AA and formic acid (FA).

[0132] Electrospinnable solutions were developed using environmentally friendly solvents.

[0133] Solution compositions and electrospinning parameters are presented in the following table:

[0134] All three mats tested (formed from Samples B, C and D) had similar cumulative release curves. They displayed an immediate burst release of PHMB (65% considering the nominal weight of PHMB in the samples corresponding to 40 pg / mL). The release curves flatten off immediately after the initial burst release indicating that the burst release actually includes most of the PHMB in the mats. The mats continue to release a small amount of PHMB for a week or so, also considering PHMB degradation. The PCL- PHMB10-AA95 displayed marginally best results.

[0135] Example 7

[0136] Additional electrospinnable solutions were developed using polymers such as PCL (Mn= 80kDa) and or Polyethylene glycol (PEG, Mn= 6kDa) as the shell formic polymeric solution, and polyethylene oxide (PEO, Mn= 600kDa) as the core formic polymeric solution, along with PHMB.

[0137] Solution compositions and electrospinning parameters are presented in the following table:

[0138] The above are just a few non-limiting examples of the many combinations that can be achieved using the present disclosure.

[0139] FIG. 11 illustrates a computing device 1100 for controlling aspects of the handheld devices 100, 800, according to the present disclosure. The computing device 1100 can carry out instructions for controlling the components of the handheld devices 100, 1. While a single computing device 1100 is illustrated in FIG. 11, the handheld devices 100, 800 can include any number of computing devices 1100 for controlling the components thereof and performing the method of dispensing a wound healing agent.

[0140] The computing device 1100 includes a processing unit (CPU or processor) 1120 and a system bus 1110 that couples various system components including a memory 1130 such as read-only memory (ROM) 1140 and random -access memory (RAM) 1150 to the processor 1120. The computing device 1100 can include a cache of high-speed memory connected directly with, in close proximity to, or integrated as part of the processor 1120. The computing device 1100 copies data from the memory 1130 and / or the storage device 1160 to the cache for quick access by the processor 1120. In this way, the cache provides a performance boost that avoids processor 1120 delays while waiting for data. These and other modules can control or be configured to control the processor 1120 to perform various actions. Other memory 1130 may be available for use as well. The memory 1130 can include multiple different types of memory with different performance characteristics. It can be appreciated that the disclosure may operate on a computing device 1100 with more than one processor 1120 or on a group or cluster of computing devices networked together to provide greater processing capability. The processor 1120 can include any general-purpose processor and a hardware module or software module, such as module 1 1162, module 2 1164, and module 3 1166 stored in storage device 1160, configured to control the processor 1120 as well as a special-purpose processor where software instructions are incorporated into the actual processor design. The processor 1120 may essentially be a completely self-contained computing system, containing multiple cores or processors, a bus, memory controller, cache, etc. A multi-core processor may be symmetric or asymmetric.

[0141] The system bus 1110 may be any of several types of bus structures including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures. A basic input / output (BIOS) stored in ROM 1140 or the like, may provide the basic routine that helps to transfer information between elements within the computing device 1100, such as during start-up. The computing device 1100 further includes storage devices 1160 such as a hard disk drive, a magnetic disk drive, an optical disk drive, tape drive or the like. The storage device 1160 can include software modules 1162, 1164, 1166 for controlling the processor 1120. Other hardware or software modules are contemplated. The storage device 1160 is connected to the system bus 1110 by a drive interface. The drives and the associated computer-readable storage media provide nonvolatile storage of computer- readable instructions, data structures, program modules and other data for the computing device 1100. In one aspect, a hardware module that performs a particular function includes the software component stored in a tangible computer-readable storage medium in connection with the necessary hardware components, such as the processor 1120, system bus 1110, output device 1170, and so forth, to carry out the function. In another aspect, the system can use a processor and computer-readable storage medium to store instructions which, when executed by a processor (e.g., one or more processors), cause the processor to perform a method or other specific actions. The basic components and appropriate variations are contemplated depending on the type of device, such as whether the computing device 1100 is a small, handheld computing device, a desktop computer, or a computer server.

[0142] Although the exemplary embodiment described herein employs the storage device 1160, other types of computer-readable media which can store data that are accessible by a computer, such as magnetic cassettes, flash memory cards, digital versatile disks,cartridges, random -access memories (RAMs) 1150, and read-only memory (ROM) 1140, may also be used in the exemplary operating environment. Tangible computer-readable storage media, computer-readable storage devices, or computer-readable memory devices, expressly exclude media such as transitory waves, energy, carrier signals, electromagnetic waves, and signals per se.

[0143] To enable user interaction with the computing device 1100, an input device 1190 represents any number of input mechanisms, such as a microphone for speech, a touch- sensitive screen for gesture or graphical input, keyboard, mouse, motion input, speech and so forth. An output device 1170 can also be one or more of a number of output mechanisms known to those of skill in the art, such as, for example, a display. In some instances, multimodal systems enable a user to provide multiple types of input to communicate with the computing device 1100. The communications interface 1180 generally governs and manages the user input and system output. There is no restriction on operating on any particular hardware arrangement and therefore the basic features here may easily be substituted for improved hardware or firmware arrangements as they are developed.

[0144] Further aspects of the present disclosure are provided by the subject matter of the following clauses.

[0145] A handheld device for dispensing one or more wound healing agents, the handheld device comprising a main body, a trigger coupled to the main body, a needle head, a wound healing agent housing configured to receive the one or more wound healing agents therein, one or more actuators to facilitate dispensing the one or more wound healing agents from the wound healing agent housing, and a controller configured to determine a dispensing method of a plurality of dispensing methods for each of the one or more wound healing agents, and dispense, upon actuation of the trigger, the one or more wound healing agentsfrom the wound healing agent housing through the needle head by activating the one or more actuators.

[0146] The handheld device of the preceding clause, wherein the one or more wound healing agents are dispensed sequentially, or two or more of the wound healing agents are dispensed simultaneously.

[0147] The handheld device of any preceding clause, wherein the controller is configured to receive an indication of the one or more wound healing agents in the wound healing agent housing, and determine the dispensing method for each of the one or more wound healing agents based on the indication of the one or more wound healing agents.

[0148] The handheld device of any preceding clause, wherein the controller is configured to set one or more dispensing parameters for each of the one or more wound healing agents, and dispense the one or more wound healing agents based on the set one or more dispensing parameters for each of the one or more wound healing agents.

[0149] The handheld device of any preceding clause, wherein the needle head includes one or more channels that are co-axial at a needle tip of the needle head.

[0150] The handheld device of any preceding clause, wherein the controller is configured to dispense a first wound healing agent of the one or more wound healing agents by a first dispensing method and dispense a second wound healing agent of the one or more wound healing agents by a second dispensing method different than the first dispensing method.

[0151] The handheld device of any preceding clause, further comprising one or more vials in, or coupled to, the wound healing agent housing and in fluid communication with the needle head, the one or more vials containing the one or more wound healing agents therein.

[0152] The handheld device of any preceding clause, wherein the one or more dispensing methods are independently selected from electrospinning, electro spraying, hydrogel dispensing, or gas blowing.

[0153] The handheld device of any preceding clause, wherein one or more wound healing agents are deposited in a serial manner or a parallel manner.

[0154] The handheld device of any preceding clause, wherein the wound healing agent housing includes one or more wound healing agent cavities configured to receive the one or more wound healing agents therein.

[0155] The handheld device of any preceding clause, wherein the wound healing agent housing is movable from a closed position to an open position to receive the one or more wound healing agents.

[0156] The handheld device of any preceding clause, wherein the needle head includes one or more channels in fluid communication with the wound healing agent housing, the one or more channels configured to direct the one or more wound healing agents from the wound healing agent housing out of the handheld device.

[0157] The handheld device of any preceding clause, wherein the one or more channels include a first channel in fluid communication with a first wound healing agent cavity of the wound healing agent housing, and a second channel in fluid communication with a second wound healing agent cavity of the one or more wound healing agent cavities.

[0158] The handheld device of any preceding clause, further comprising a curing light configured to at least one of cure one or more of the wound healing agents or measure a distance.

[0159] The handheld device of any preceding clause, further comprising a catheter mounted on the needle head.

[0160] The handheld device of any preceding clause, further comprising a camera configured to generate images.

[0161] The handheld device of any preceding clause, wherein the one or more wound healing agents are independently selected from cells, a drug, a synthetic polymer, a hydrogel a biological polymer, an antibacterial agent, or a combination thereof.

[0162] The handheld device of any preceding clause, wherein the one or more wound healing agents are independently selected from iodine, silver, silver nitrate, PHMBs, hypochloric solutions (K-SEPT), copper, antibiotics, M2 macrophages, platelet reach plasma, stem cells, adipose tissue, bone marrow aspirate, bone marrow aspirate derivatives, blood, blood products, antibiotics, O2, Os, fibroblast, keratinocytes, enzymes, protease, and growth factors, or combinations thereof.

[0163] The handheld device of any preceding clause, wherein at least one of the one or more wound healing agents is an antibacterial agent.

[0164] The handheld device of any preceding clause, wherein at least one of the one or more wound healing agents is a combination of fibroblast and keratinocyte.

[0165] The handheld device of any preceding clause, wherein at least one of the one or more wound healing agents comprises polylactic acid (PLA), poly (ethylene glycol) (PEG), poly e -caprolactone (PCL), collagen, methacrylated collagen, chitosan, gelatin, latex, dextran, fibroin, keratin, poly(lactic acid-co-glycolic acid) (PLGA), poly(vinylidene fluoride- co-hexafluoropropylene) (PVDFhfp) , polyglycolic acid, polydiaxanone, poly (propylene carbonate), poly (ethylene oxide), poly (ester-urethane) urea, and poly (lactide -caprolactone).

[0166] The handheld device of any preceding clause, wherein the one or more wound healing agents independently form a scaffold material in vivo when dispensed onto a tissue or a wound in a patient.

[0167] The handheld device of any preceding clause, wherein the scaffold material comprises at least one of a mat, a fiber, or a dressing.

[0168] A handheld device for delivering one or more wound healing agents, the handheld device comprising a main body, a trigger coupled to the main body, a wound healing agent housing having a first wound healing agent cavity configured to receive a first wound healing agent of the one or more wound healing agents and a second wound healing agent cavity configured to receive a second wound healing agent of the one or more wound healing agents, and a needle head comprising a first channel in fluid communication with the first wound healing agent cavity and a second channel in fluid communication with the second wound healing agent, wherein the handheld device is configured to dispense, upon actuation of the trigger, the first wound healing agent from the first wound healing agent cavity through the first channel and to dispense the second wound healing agent from the second wound healing agent cavity through the second channel.

[0169] The handheld device of any preceding clause, further comprising one or more actuators to facilitate dispensing the one or more wound healing agents from the wound healing agent housing.

[0170] The handheld device of any preceding clause, further comprising a controller configured to: determine a dispensing method of a plurality of dispensing methods for each of the first wound healing agent and the second wound healing agent, and dispense, upon actuation of the trigger, the first wound healing agent and the second wound healing agent from the wound healing agent housing through the needle head.

[0171] The handheld device of any preceding clause, wherein the controller is configured to receive an indication of the first wound healing agent and the second wound healing agent in the wound healing agent housing, and determine the dispensing method foreach of the first wound healing agent and the second wound healing agent based on the indication of the first wound healing agent and the second wound healing agent.

[0172] The handheld device of any preceding clause, wherein the controller is configured to set one or more dispensing parameters for each of the first wound healing agent and the second wound healing agent, and dispense the first wound healing agent and the second wound healing agent based on the set one or more dispensing parameters for each of the first wound healing agent and the second wound healing agent.

[0173] The handheld device of any preceding clause, wherein the controller is configured to dispense the first wound healing agent by a first dispensing method and dispense the second wound healing agent by a second dispensing method different than the first dispensing method.

[0174] The handheld device of any preceding clause, wherein the first dispensing method and the second dispensing method are independently selected from electrospinning, electro spraying, hydrogel dispensing, or gas blowing.

[0175] The handheld device of any preceding clause, wherein the first wound healing agent and the second wound healing agent are dispensed sequentially or are dispensed simultaneously.

[0176] The handheld device of any preceding clause, wherein the needle head includes the first channel and the second channel are co-axial at a needle tip of the needle head.

[0177] The handheld device of any preceding clause, further comprising a first vial in the first wound healing agent cavity and a second vial in the second wound healing agent cavity, and in fluid communication with the needle head, the first vial containing the first wound healing agent therein and the second vial containing the second wound healing agent therein.

[0178] The handheld device of any preceding clause, wherein first wound healing agent and the second wound healing agent are deposited in a serial manner or a parallel manner.

[0179] The handheld device of any preceding clause, wherein the wound healing agent housing is movable from a closed position to an open position to receive the first wound healing agent and the second wound healing agent.

[0180] The handheld device of any preceding clause, further comprising a curing light configured to at least one of cure the first wound healing agent or the second wound healing agent or measure a distance.

[0181] The handheld device of any preceding clause, further comprising a camera configured to generate images.

[0182] The handheld device of any preceding clause, further comprising a catheter mounted on the needle head.

[0183] The handheld device of any preceding clause, wherein the first wound healing agent and the second wound healing agent are independently selected from cells, a drug, a synthetic polymer, a hydrogel a biological polymer, an antibacterial agent, or a combination thereof.

[0184] The handheld device of any preceding clause, wherein the first wound healing agent and the second wound healing agent are independently selected from iodine, silver, silver nitrate, PHMBs, hypochloric solutions (K-SEPT), copper, antibiotics, M2 macrophages, platelet reach plasma, stem cells, adipose tissue, bone marrow aspirate, bone marrow aspirate derivatives, blood, blood products, antibiotics, O2, Os, fibroblast, keratinocytes, enzymes, protease, and growth factors, or combinations thereof.

[0185] The handheld device of any preceding clause, wherein at least one of the first wound healing agent or the second wound healing agent is an antibacterial agent.

[0186] The handheld device of any preceding clause, wherein at least one of the first wound healing agent or the second wound healing agent is a combination of fibroblast and keratinocyte.

[0187] The handheld device of any preceding clause, wherein at least one of the first wound healing agent or the second wound healing agent comprises polylactic acid (PLA), poly (ethylene glycol) (PEG), poly e-caprolactone (PCL), collagen, methacrylated collagen, chitosan, gelatin, latex, dextran, fibroin, keratin, poly(lactic acid-co-glycolic acid) (PLGA), poly(vinylidene fluoride-co-hexafluoropropylene) (PVDFhfp) , polyglycolic acid, polydiaxanone, poly (propylene carbonate), poly (ethylene oxide), poly (ester-urethane) urea, and poly (lactide-caprolactone).

[0188] The handheld device of any preceding clause, wherein the first wound healing agent and the second wound healing agent are independently form a scaffold material in vivo when dispensed onto a tissue or a wound in a patient.

[0189] The handheld device of any preceding clause, wherein the scaffold material comprises at least one of a mat, a fiber, or a dressing.

[0190] A wound healing composition formed on a wound comprising a hydrogel layer, a wound healing agent, and an electrospun nanofiber layer, wherein the wound healing agent is dispersed within at least one of the hydrogel layer or electrospun nanofiber layer, and wherein the hydrogel layer, the electrospun nanofiber layer, or a combination thereof form a scaffold material.

[0191] The wound healing composition of any preceding clause, wherein the wound healing agent is selected from the group consisting of iodine, silver, silver nitrate, PHMBs, hypochloric solutions (K-SEPT), copper, antibiotics, M2 macrophages, platelet rich plasma (PRP), stem cells, adipose tissue, bone marrow aspirate, bone marrow aspirate derivatives,blood, blood products, antibiotics, O2, Os, fibroblast, keratinocytes, enzymes, protease, and growth factors, and combinations thereof.

[0192] The wound healing composition of any preceding clause, wherein the wound healing agent is an antibacterial agent.

[0193] The wound healing composition of any preceding clause, wherein the antibacterial agent is polyhexamethylene biguanide (PHMB).

[0194] The wound healing composition of any preceding clause, wherein the wound healing agent is selected from the group consisting of fibroblast, keratinocytes, blood, blood products, and bone marrow aspirate.

[0195] The wound healing composition of any preceding clause, wherein hydrogel layer and the electrospun nanofiber layer independently comprise one or more materials selected from the group consisting of polylactic acid (PLA), poly (ethylene glycol) (PEG), poly e -caprolactone (PCL), collagen, methacrylated collagen, chitosan, gelatin, latex, dextran, fibroin, keratin, poly(lactic acid-co-glycolic acid) (PLGA), poly(vinylidene fluoride-co- hexafluoropropylene) (PVDFhfp) , polyglycolic acid, polydiaxanone, poly (propylene carbonate), poly (ethylene oxide), poly (ester-urethane) urea, and poly (lactide -caprolactone).

[0196] The wound healing composition of any preceding clause, comprising a first layer of the electrospun nanofiber layer and a first therapeutic agent, a second layer comprising a hydrogel, and a third layer comprising a second therapeutic agent.

[0197] The wound healing composition of any preceding clause, wherein the first layer comprises PLA and PHMB, the second layer comprises a PEG hydrogel, and the third layer comprises keratinocytes and fibroblasts.

[0198] The wound healing composition of any preceding clause, wherein the hydrogel layer comprises and a first therapeutic agent, and the electrospun nanofiber layer comprises a second therapeutic agent.

[0199] The wound healing composition of any preceding clause, wherein the first therapeutic agent is selected from the group consisting of bone marrow aspirates, blood, blood products, PRP, M2 macrophages, stem cells, growth factors and steroids, and the second therapeutic agent comprises keratinocytes and fibroblasts.

[0200] The wound healing composition of any preceding clause, wherein the hydrogel layer comprises a PEG hydrogel and bone marrow aspirate and the electrospun nanofiber layer comprises PLGA and keratinocytes and fibroblasts.

[0201] The wound healing composition of any preceding clause, wherein the scaffold material comprises at least one of a mat, a fiber, or a dressing.

[0202] The wound healing composition of any preceding clause, wherein the electrospun nanofiber layer comprises a compound fiber having a core and a shell surrounding the core.

[0203] The wound healing composition of any preceding clause, wherein the core comprises a polyethylene oxide.

[0204] The wound healing composition of any preceding clause, wherein the core further comprises PHMB.

[0205] The wound healing composition of any preceding clause, wherein the shell comprises a poly e-caprolactone.

[0206] The wound healing composition of any preceding clause, wherein the core further comprises a polyethylene glycol.

[0207] A method of making a wound healing composition comprising loading a hydrogel forming composition, an electrospun nanofiber forming composition and a wound healing agent into a handheld device, actuating the handheld device, and dispensing the hydrogel forming composition, the electrospun nanofiber forming composition and the wound healing agent from the handheld device, wherein, upon dispensing, the hydrogelforming composition forms a hydrogel layer, and the handheld device electrospins the electospun nanofiber forming composition to form a electrospun nanofiber layer.

[0208] The method of any preceding clause, wherein the hydrogel forming composition is dispensed by a method selected from the group consisting of electrospinning, electro spraying, hydrogel dispensing, and gas blowing.

[0209] The method of any preceding clause, wherein the wound healing agent is mixed with the hydrogel forming composition or the electrospun nanofiber forming composition before loading the hydrogel forming composition or the electrospun nanofiber forming composition into the handheld device.

[0210] The method of any preceding clause, wherein the wound healing agent, the hydrogel forming composition and the electrospun nanofiber forming composition are separately loaded into the handheld device, and the wound healing agent is mixed with the hydrogel forming composition by simultaneously dispensing the wound healing agent and the hydrogel forming composition, or the wound healing agent is mixed with the electrospun nanofiber forming composition by simultaneously dispensing the wound healing agent and the electrospun nanofiber forming composition.

[0211] The method of any preceding clause, further comprising curing the hydrogel forming composition by illumination with a curing light on the handheld device.

[0212] A method of dispensing one or more wound healing agents from a handheld device that stores the one or more wound healing agents therein, the method comprising determining a dispensing method of a plurality of dispensing methods for each of the one or more wound healing agents, and dispensing the one or more wound healing agents from handheld device based on the dispensing method for each of the one or more wound healing agents.

[0213] The method of the preceding clause, further comprising receiving a trigger signal from a trigger of the handheld device, and dispensing the one or more wound healing agents in response to receiving the trigger signal.

[0214] The method of any preceding clause, further comprising activating one or more actuators to dispense the one or more wound healing agents.

[0215] The method of the preceding clause, further comprising dispensing the one or more wound healing agents sequentially, or dispensing two or more of the wound healing agents simultaneously.

[0216] The method of any preceding clause, further comprising receiving an indication of the one or more wound healing agents in the handheld device and determining the dispensing method for each of the one or more wound healing agents based on the indication of the one or more wound healing agents.

[0217] The method of any preceding clause, further comprising setting one or more dispensing parameters for each of the one or more wound healing agents, and dispensing the one or more wound healing agents based on the set one or more dispensing parameters for each of the one or more wound healing agents.

[0218] The method of any preceding clause, further comprising directing the one or more wound healing agents through one or more channels that are co-axial at a needle tip of a needle head of the handheld device.

[0219] The method of any preceding clause, further comprising dispensing a first wound healing agent of the one or more wound healing agents by a first dispensing method and dispensing a second wound healing agent of the one or more wound healing agents by a second dispensing method different than the first dispensing method.

[0220] The method of any preceding clause, further comprising dispensing the one or more wound healing agents from one or more vials containing the one or more wound healing agents therein.

[0221] The method of any preceding clause, wherein the one or more dispensing methods are independently selected from electrospinning, electro spraying, hydrogel dispensing, or gas blowing.

[0222] The method of any preceding clause, further comprising dispensing the one or more wound healing agents in a serial manner or a parallel manner.

[0223] The method of any preceding clause, further comprising storing the one or more wound healing agents in one or more wound healing agent cavities of the handheld device.

[0224] The method of any preceding clause, further comprising opening the handheld device from a closed position to an open position and receiving the one or more wound healing agents in the handheld device.

[0225] The method of any preceding clause, further comprising curing one or more of the wound healing agents.

[0226] The method of any preceding clause, further comprising measuring a distance to a wound with the handheld device.

[0227] The method of any preceding clause, further comprising dispensing one or more of the wound healing agents through a catheter mounted to the handheld device.

[0228] The method of any preceding clause, further comprising generating images with a camera of the handheld device.

[0229] The method of any preceding clause, wherein the one or more wound healing agents are independently selected from cells, a drug, a synthetic polymer, a hydrogel a biological polymer, an antibacterial agent, or a combination thereof.

[0230] The method of any preceding clause, wherein the one or more wound healing agents are independently selected from iodine, silver, silver nitrate, PHMBs, hypochloric solutions (K-SEPT), copper, antibiotics, M2 macrophages, platelet reach plasma, stem cells, adipose tissue, bone marrow aspirate, bone marrow aspirate derivatives, blood, blood products, antibiotics, O2, Os, fibroblast, keratinocytes, enzymes, protease, and growth factors, or combinations thereof.

[0231] The method of any preceding clause, wherein at least one of the one or more wound healing agents is an antibacterial agent.

[0232] The method of any preceding clause, wherein at least one of the one or more wound healing agents is a combination of fibroblast and keratinocyte.

[0233] The method of any preceding clause, wherein at least one of the one or more wound healing agents comprises polylactic acid (PLA), poly (ethylene glycol) (PEG), poly e- caprolactone (PCL), collagen, methacrylated collagen, chitosan, gelatin, latex, dextran, fibroin, keratin, poly(lactic acid-co-glycolic acid) (PLGA), poly(vinylidene fluoride-co- hexafluoropropylene) (PVDFhfp) , polyglycolic acid, polydiaxanone, poly (propylene carbonate), poly (ethylene oxide), poly (ester-urethane) urea, and poly (lactide -caprolactone).

[0234] The method of any preceding clause, wherein the one or more wound healing agents are independently form a scaffold material in vivo when dispensed onto a tissue or a wound in a patient.

[0235] The method of any preceding clause, wherein the scaffold material comprises at least one of a mat, a fiber, or a dressing.

[0236] Although the foregoing description is directed to the preferred embodiments, it is noted that other variations and modifications will be apparent to those skilled in the art and may be made without departing from the disclosure. Moreover, features described inconnection with one embodiment may be used in conjunction with other embodiments, even if not explicitly stated above.

Claims

CLAIMS1. A handheld device for dispensing one or more wound healing agents, the handheld device comprising: a main body; a trigger coupled to the main body; a needle head; a wound healing agent housing configured to receive the one or more wound healing agents therein; one or more actuators to facilitate dispensing the one or more wound healing agents from the wound healing agent housing; and a controller configured to: determine a dispensing method of a plurality of dispensing methods for each of the one or more wound healing agents; and dispense, upon actuation of the trigger, the one or more wound healing agents from the wound healing agent housing through the needle head by activating the one or more actuators.

2. The handheld device of claim 1, wherein the one or more wound healing agents are dispensed sequentially, or two or more of the wound healing agents are dispensed simultaneously.

3. The handheld device of claim 1, wherein the controller is configured to receive an indication of the one or more wound healing agents in the wound healing agent housing, and determine the dispensing method for each of the one or more wound healing agents based on the indication of the one or more wound healing agents.

4. The handheld device of claim 1, wherein the controller is configured to set one or more dispensing parameters for each of the one or more wound healing agents, and dispense the one or more wound healing agents based on the set one or more dispensing parameters for each of the one or more wound healing agents.

5. The handheld device of claim 1, wherein the needle head includes one or more channels that are co-axial at a needle tip of the needle head.

6. The handheld device of claim 1, wherein the controller is configured to dispense a first wound healing agent of the one or more wound healing agents by a first dispensing method and dispense a second wound healing agent of the one or more wound healing agents by a second dispensing method different than the first dispensing method.

7. The handheld device of claim 1, further comprising one or more vials in, or coupled to, the wound healing agent housing and in fluid communication with the needle head, the one or more vials containing the one or more wound healing agents therein.

8. The handheld device of claim 1, wherein the one or more dispensing methods are independently selected from electrospinning, electro spraying, hydrogel dispensing, or gas blowing.

9. The handheld device of claim 1, wherein one or more wound healing agents are deposited in a serial manner or a parallel manner.

10. The handheld device of claim 1, wherein the wound healing agent housing includes one or more wound healing agent cavities configured to receive the one or more wound healing agents therein.

11. The handheld device of claim 1, wherein the wound healing agent housing is movable from a closed position to an open position to receive the one or more wound healing agents.

12. The handheld device of claim 1, wherein the needle head includes one or more channels in fluid communication with the wound healing agent housing, the one or more channels configured to direct the one or more wound healing agents from the wound healing agent housing out of the handheld device.

13. The handheld device of claim 12, wherein the one or more channels include a first channel in fluid communication with a first wound healing agent cavity of the wound healing agent housing, and a second channel in fluid communication with a second wound healing agent cavity of the one or more wound healing agent cavities.

14. The handheld device of claim 1, further comprising a curing light configured to at least one of cure one or more of the wound healing agents or measure a distance.

15. The handheld device of claim 1, further comprising a catheter mounted on the needle head.

16. The handheld device of claim 1, further comprising a camera configured to generate images.

17. The handheld device of claim 1, wherein the one or more wound healing agents are independently selected from cells, a drug, a synthetic polymer, a hydrogel a biological polymer, an antibacterial agent, or a combination thereof.

18. The handheld device of claim 1, wherein the one or more wound healing agents are independently selected from iodine, silver, silver nitrate, PHMBs, hypochloric solutions (K- SEPT), copper, antibiotics, M2 macrophages, platelet reach plasma, stem cells, adipose tissue, bone marrow aspirate, bone marrow aspirate derivatives, blood, blood products, antibiotics, O2, Os, fibroblast, keratinocytes, enzymes, protease, and growth factors, or combinations thereof.

19. The handheld device of claim 1, wherein at least one of the one or more wound healing agents is an antibacterial agent.

20. The handheld device of claim 1, wherein at least one of the one or more wound healing agents is a combination of fibroblast and keratinocyte.

21. The handheld device of claim 1, wherein at least one of the one or more wound healing agents comprises polylactic acid (PLA), poly (ethylene glycol) (PEG), poly e- caprolactone (PCL), collagen, methacrylated collagen, chitosan, gelatin, latex, dextran, fibroin, keratin, poly(lactic acid-co-glycolic acid) (PLGA), poly(vinylidene fluoride-co- hexafluoropropylene) (PVDFhfp) , polyglycolic acid, polydiaxanone, poly (propylene carbonate), poly (ethylene oxide), poly (ester-urethane) urea, and poly (lactide -caprolactone).

22. The handheld device of claim 1, wherein the one or more wound healing agents independently form a scaffold material in vivo when dispensed onto a tissue or a wound in a patient.

23. The handheld device of claim 22, wherein the scaffold material comprises at least one of a mat, a fiber, or a dressing.

24. A handheld device for delivering one or more wound healing agents, the handheld device comprising: a main body; a trigger coupled to the main body; a wound healing agent housing having a first wound healing agent cavity configured to receive a first wound healing agent of the one or more wound healing agents and a second wound healing agent cavity configured to receive a second wound healing agent of the one or more wound healing agents; and a needle head comprising a first channel in fluid communication with the first wound healing agent cavity and a second channel in fluid communication with the second wound healing agent, wherein the handheld device is configured to dispense, upon actuation of the trigger, the first wound healing agent from the first wound healing agent cavity through the first channel and to dispense the second wound healing agent from the second wound healing agent cavity through the second channel.

25. The handheld device of claim 24, further comprising one or more actuators to facilitate dispensing the one or more wound healing agents from the wound healing agent housing.

26. The handheld device of claim 24, further comprising a controller configured to: determine a dispensing method of a plurality of dispensing methods for each of the first wound healing agent and the second wound healing agent; and dispense, upon actuation of the trigger, the first wound healing agent and the second wound healing agent from the wound healing agent housing through the needle head.

27. The handheld device of claim 26, wherein the controller is configured to receive an indication of the first wound healing agent and the second wound healing agent in the wound healing agent housing, and determine the dispensing method for each of the first wound healing agent and the second wound healing agent based on the indication of the first wound healing agent and the second wound healing agent.

28. The handheld device of claim 26, wherein the controller is configured to set one or more dispensing parameters for each of the first wound healing agent and the second wound healing agent, and dispense the first wound healing agent and the second wound healing agent based on the set one or more dispensing parameters for each of the first wound healing agent and the second wound healing agent.

29. The handheld device of claim 26, wherein the controller is configured to dispense the first wound healing agent by a first dispensing method and dispense the second wound healing agent by a second dispensing method different than the first dispensing method.

30. The handheld device of claim 29, wherein the first dispensing method and the second dispensing method are independently selected from electrospinning, electro spraying, hydrogel dispensing, or gas blowing.

31. The handheld device of claim 24, wherein the first wound healing agent and the second wound healing agent are dispensed sequentially or are dispensed simultaneously.

32. The handheld device of claim 24, wherein the needle head includes the first channel and the second channel are co-axial at a needle tip of the needle head.

33. The handheld device of claim 24, further comprising a first vial in the first wound healing agent cavity and a second vial in the second wound healing agent cavity, and in fluid communication with the needle head, the first vial containing the first wound healing agent therein and the second vial containing the second wound healing agent therein.

34. The handheld device of claim 24, wherein first wound healing agent and the second wound healing agent are deposited in a serial manner or a parallel manner.

35. The handheld device of claim 24, wherein the wound healing agent housing is movable from a closed position to an open position to receive the first wound healing agent and the second wound healing agent.

36. The handheld device of claim 24, further comprising a curing light configured to at least one of cure the first wound healing agent or the second wound healing agent or measure a distance.

37. The handheld device of claim 24, further comprising a camera configured to generate images.

38. The handheld device of claim 24, further comprising a catheter mounted on the needle head.

39. The handheld device of claim 24, wherein the first wound healing agent and the second wound healing agent are independently selected from cells, a drug, a synthetic polymer, a hydrogel a biological polymer, an antibacterial agent, or a combination thereof.

40. The handheld device of claim 24, wherein the first wound healing agent and the second wound healing agent are independently selected from iodine, silver, silver nitrate, PHMBs, hypochloric solutions (K-SEPT), copper, antibiotics, M2 macrophages, platelet reach plasma, stem cells, adipose tissue, bone marrow aspirate, bone marrow aspirate derivatives, blood, blood products, antibiotics, O2, Os, fibroblast, keratinocytes, enzymes, protease, and growth factors, or combinations thereof.

41. The handheld device of claim 24, wherein at least one of the first wound healing agent or the second wound healing agent is an antibacterial agent.

42. The handheld device of claim 24, wherein at least one of the first wound healing agent or the second wound healing agent is a combination of fibroblast and keratinocyte.

43. The handheld device of claim 24, wherein at least one of the first wound healing agent or the second wound healing agent comprises polylactic acid (PLA), poly (ethylene glycol) (PEG), poly e -caprolactone (PCL), collagen, methacrylated collagen, chitosan, gelatin, latex, dextran, fibroin, keratin, poly(lactic acid-co-glycolic acid) (PLGA), poly(vinylidene fluoride-co-hexafluoropropylene) (PVDFhfp) , polyglycolic acid, polydiaxanone, poly (propylene carbonate), poly (ethylene oxide), poly (ester-urethane) urea, and poly (lactide -caprolactone).

44. The handheld device of claim 24, wherein the first wound healing agent and the second wound healing agent are independently form a scaffold material in vivo when dispensed onto a tissue or a wound in a patient.

45. The handheld device of claim 44, wherein the scaffold material comprises at least one of a mat, a fiber, or a dressing.

46. A wound healing composition formed on a wound comprising: a hydrogel layer; a wound healing agent; and an electrospun nanofiber layer, wherein the wound healing agent is dispersed within at least one of the hydrogel layer or electrospun nanofiber layer, and wherein the hydrogel layer, the electrospun nanofiber layer, or a combination thereof form a scaffold material.

47. The wound healing composition of claim 46, wherein the wound healing agent is selected from the group consisting of iodine, silver, silver nitrate, PHMBs, hypochloric solutions (K-SEPT), copper, antibiotics, M2 macrophages, platelet rich plasma (PRP), stem cells, adipose tissue, bone marrow aspirate, bone marrow aspirate derivatives, blood, blood products, antibiotics, O2, Os, fibroblast, keratinocytes, enzymes, protease, and growth factors, and combinations thereof.

48. The wound healing composition of claim 47, wherein the wound healing agent is an antibacterial agent.

49. The wound healing composition of claim 48, wherein the antibacterial agent is polyhexamethylene biguanide (PHMB).

50. The wound healing composition of claim 47, wherein the wound healing agent is selected from the group consisting of fibroblast, keratinocytes, blood, blood products, and bone marrow aspirate.

51. The wound healing composition of claim 46, wherein hydrogel layer and the electrospun nanofiber layer independently comprise one or more materials selected from the group consisting of polylactic acid (PLA), poly (ethylene glycol) (PEG), poly e-caprolactone (PCL), collagen, methacrylated collagen, chitosan, gelatin, latex, dextran, fibroin, keratin, poly(lactic acid-co-glycolic acid) (PLGA), poly(vinylidene fluoride-co-hexafluoropropylene) (PVDFhfp) , polygly colic acid, polydiaxanone, poly (propylene carbonate), poly (ethylene oxide), poly (ester-urethane) urea, and poly (lactide-caprolactone).

52. The wound healing composition of claim 46, comprising a first layer of the electrospun nanofiber layer and a first therapeutic agent, a second layer comprising a hydrogel, and a third layer comprising a second therapeutic agent.

53. The wound healing composition of claim 52, wherein the first layer comprises PLA and PHMB, the second layer comprises a PEG hydrogel, and the third layer comprises keratinocytes and fibroblasts.

54. The wound healing composition of claim 46, wherein the hydrogel layer comprises and a first therapeutic agent, and the electrospun nanofiber layer comprises a second therapeutic agent.

55. The wound healing composition of claim 54, wherein the first therapeutic agent is selected from the group consisting of bone marrow aspirates, blood, blood products, PRP, M2 macrophages, stem cells, growth factors and steroids, and the second therapeutic agent comprises keratinocytes and fibroblasts.

56. The wound healing composition of claim 54, wherein the hydrogel layer comprises a PEG hydrogel and bone marrow aspirate and the electrospun nanofiber layer comprises PLGA and keratinocytes and fibroblasts.

57. The wound healing composition of claim 46, wherein the scaffold material comprises at least one of a mat, a fiber, or a dressing.

58. The wound healing composition of claim 46, wherein the electrospun nanofiber layer comprises a compound fiber having a core and a shell surrounding the core.

59. The wound healing composition of claim 58, wherein the core comprises a polyethylene oxide.

60. The wound healing composition of claim 59, wherein the core further comprisesPHMB.

61. The wound healing composition of claim 58, wherein the shell comprises a poly e- caprolactone.

62. The wound healing composition of claim 61, wherein the core further comprises a polyethylene glycol.

63. A method of making a wound healing composition comprising: loading a hydrogel forming composition, an electrospun nanofiber forming composition and a wound healing agent into a handheld device; actuating the handheld device; and dispensing the hydrogel forming composition, the electrospun nanofiber forming composition and the wound healing agent from the handheld device, wherein, upon dispensing, the hydrogel forming composition forms a hydrogel layer, and the handheld device electrospins the electospun nanofiber forming composition to form a electrospun nanofiber layer.

64. The method of claim 63, wherein the hydrogel forming composition is dispensed by a method selected from the group consisting of electrospinning, electro spraying, hydrogel dispensing, and gas blowing.

65. The method of claim 63, wherein the wound healing agent is mixed with the hydrogel forming composition or the electrospun nanofiber forming composition before loading the hydrogel forming composition or the electrospun nanofiber forming composition into the handheld device.

66. The method of claim 63, wherein the wound healing agent, the hydrogel forming composition and the electrospun nanofiber forming composition are separately loaded into the handheld device, and the wound healing agent is mixed with the hydrogel forming composition by simultaneously dispensing the wound healing agent and the hydrogel forming composition, or the wound healing agent is mixed with the electrospun nanofiber forming composition by simultaneously dispensing the wound healing agent and the electrospun nanofiber forming composition.

67. The method of claim 63, further comprising curing the hydrogel forming composition by illumination with a curing light on the handheld device.

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