COATED HAIR AND ITS USE

Description

[0001] The present invention relates to the field of hair transplantation using autologous, donor, or synthetic hair. The present invention describes implantable hair which is coated, at least on an implantable portion, with a composition that comes into direct contact with the hair and contains at least one silk protein. Furthermore, the present invention relates to methods for producing such implantable hair and its cosmetic use.

[0002] For millennia, women and men have faced the problem of hair loss. Hair weakens or falls out. There are numerous reasons for this, including genetic predisposition, hormonal changes, stress, environmental factors, illnesses, chemotherapy, hair pulling, chemical hair treatments, hair coloring, age-related changes, poor or insufficient nutrition, accidents, and many other causes.

[0003] Accidents such as abrasions, necrosis, and burns, often accompanied by scarring, frequently lead to a distressing reduction in hair growth on the head or body. Asymmetrical hair loss, in particular, can be disfiguring. Furthermore, more pronounced hair growth, for example in the beard or chest area, can be desirable for emphasizing masculine physical characteristics. This can be of particular interest during gender reassignment surgery, from a female to a male appearance.

[0004] Treatments for hair loss, including medical and non-medical methods such as cosmetic procedures, often lead to unsatisfactory results, are not suitable for everyone, and / or frequently have side effects. Existing treatments for hair loss often fail to meet the high standards and expectations of individuals.

[0005] Furthermore, they often have disadvantages that affect people's physical and mental health. Social factors can also exacerbate people's suffering. Hair loss can lead to physiological and emotional problems that people cannot cope with. These can collectively lead to emotional trauma and beyond, resulting in a downward spiral.

[0006] A treatment or solution for hair loss that better meets needs and expectations, particularly regarding greater naturalness, fewer risks and side effects, increased ease of care, and / or a good price-performance ratio, would significantly improve people's quality of life. People would feel healthier and less disadvantaged, potentially gain more social acceptance and be less defined by their hair loss, and experience less stress and negative emotions. This can have a positive impact on the lives of those affected, including socially, emotionally, and financially. The demand for such a hair product for humans and potentially animals appears to be high.

[0007] A classic way to visually achieve the appearance of a full head of hair is through the use of wigs and toupees. However, a natural look and a normal, flexible daily life are often unattainable even with wigs and toupees. While there have been improvements in their development and quality in recent years, the solutions often amount to more of a concealment of the hair problem than a genuine solution. The edge of the net to which the hair is attached is clearly noticeable to the fingers. This means that both the wearer of the wig or toupee, and anyone else who touches their hair, is constantly reminded that it is an unnatural solution. Furthermore, wigs and toupees must be removed and prepared for reuse. This involves removing adhesive residue, washing, styling, and preparing the hairpiece for reattachment.People who use these products must adjust their daily routines accordingly. Since the hair in wigs and toupees is usually attached to the net by knotting, it can break off at the stressed knot points after a certain period. This is exacerbated by maintenance routines such as washing and combing. The edge of the net also loses stability over time, as it is stressed when the adhesives are removed and during cleaning. This results in frayed areas where the hair no longer has a secure hold.

[0008] The regular changing of wigs and toupees creates periods when these individuals are unwell. Spontaneous get-togethers with friends or colleagues may not always be possible. Travel and sporting activities like swimming are also limited, as wigs only provide sufficient support for a limited time. Furthermore, perspiration cannot evaporate easily, leading to itching. Body heat is also restricted, which can frequently result in headaches.

[0009] Furthermore, bacteria and other germs can accumulate on wigs and toupees, which can lead to health problems and unpleasant odors. A possible reaction to the adhesive, such as skin irritation or allergy, can also cause people to remove wigs and not reattach them. From an economic perspective, the lifespan of wigs is limited despite proper care, which restricts one's lifestyle both technically and financially. Therefore, the use of wigs and toupees is not a satisfactory solution for many people.

[0010] Other methods have been developed to reduce or conceal hair loss. These include, in particular, hormonal treatments with medication, hair transplants, artificial hair implants, spot tattooing to simulate short hair, and other procedures. For many of these methods, scientific evidence of effectiveness is lacking, or significant side effects occur that can negatively impact the well-being of the treated individual. Hair implantation is therefore of particular interest. These implants are permanently and naturally anchored in the skin (for example, on the scalp or face).

[0011] While the implantation of one's own hair, including its roots, is fundamentally a technical solution with many advantages, such a procedure is complex and expensive. Furthermore, only as many hairs are available for implantation as were previously removed from another area of ​​the individual, such as the back of the head. Therefore, the available resource of the individual's own hair is significantly limited. Complete baldness cannot be adequately treated with a hair transplant. After transplantation, the hair follicles also experience a shock, causing the implanted hairs to initially fall out.

[0012] Hair only grows back after several months, and a certain percentage of the hair does not survive the procedure and is lost. The result is therefore unpredictable and cannot reliably meet people's expectations. Depending on the method used, a permanent, unwanted scar after the extraction of hair follicles from the back of the head is also possible.

[0013] Without a protective layer, however, hair without roots cannot be implanted, or only with significant undesirable side effects, as it can lead to an immune reaction and inflammation, similar to ingrown hairs (frequently occurring with curly hair).

[0014] Foreign or artificial hair, especially without hair roots, would be available as a (virtually) unlimited resource.

[0015] The implantation of synthetic hair often fails to achieve a natural appearance, as the hair is made of materials such as polyester, which does not closely resemble natural hair in its look and texture. Furthermore, the recipient's body frequently recognizes foreign or synthetic hair as a foreign object and reacts accordingly. This can lead to a significant, undesirable immune response. Due to the ongoing immune reaction in the skin, inflammation and, in some cases, even necrosis can occur. This can damage nerve endings in the skin, potentially resulting in a loss of sensation in the affected areas.

[0016] To suppress the immune response, implantable synthetic hair is coated with chemical agents, such as silver salts. However, this has negative effects on physical well-being, as the immune system can be actively inhibited, yet immune reactions against the synthetic hair implants can still occur. Once the protective, optionally immunosuppressive agent diffuses away from the implanted hair and is therefore no longer present in a sufficient concentration, the implanted synthetic or foreign hairs are usually rejected. Anchoring a rootless and therefore smooth synthetic or foreign hair also frequently leads to inadequate anchoring.

[0017] Attempts have therefore been made to mechanically improve hair fixation in the skin using various anchoring mechanisms. For example, GB 1,504,258 describes hook-shaped anchors, while GB 2,006,018 describes loop-shaped anchors. WO 2011 / 064772 describes different forms of anchoring structures and also states that multiple individual hairs can be anchored in the skin via a common anchoring structure. Beyond mechanical anchoring, structures that target the collagen system are described, as in US 10,561,490 and WO 2020 / 180682. However, anchoring is largely achieved mechanically via surface structures of the implanted component.

[0018] To reduce the risk of an immune response, inert coatings have been described for the portions of the hair to be implanted, such as coatings with gold (see US 4,517,997). However, with an inert coating, the hair is held in the skin (e.g., the scalp) purely mechanically and cannot be supplied with nutrients or grow. The exchange of substances with the surrounding skin tissue is prevented by the barrier layer of inert material. Removing the worn-out hair requires comparatively harsh mechanical methods, such as tearing the artificial root, usually made of hard inert material, out of the skin, which can be quite painful and undesirable.

[0019] In US patent 2003 / 195625, hair was coated with a relatively thin barrier layer of inert material, such as gold, and surrounded by a thickened structure of bioresorbable material for mechanical anchoring. This allows the hair to fall out naturally after a certain period, once the bioresorbable material has sufficiently broken down. While this eliminates the need for the harsh mechanical removal of the worn-out hair, it does not achieve permanent hair anchoring. Furthermore, the barrier layer of inert material, which lies on the implantable part of the hair, prevents direct interaction and exchange of substances between the hair and the surrounding skin tissue. Ingrown hair and nutrient absorption from the surrounding skin tissue are thus prevented. Moreover, the use of two layers, including an inert layer of gold, is expensive and technically only feasible with considerable additional effort.

[0020] FR-A 3025431 describes the use of spider silk fibers as an artificial hair-like structure that does not cause an inflammatory or immune response.

[0021] There is therefore a need to provide a hair implant that is well-tolerated by the skin tissue and easy to manufacture. The hair implant should be able to remain in the skin long-term and, after a certain period, allow for an exchange of substances with the surrounding skin tissue of the recipient.

[0022] Surprisingly, it was discovered that a coating with a composition containing one or more silk proteins can produce implantable hair with particularly good properties. Such implantable hair is technically simple to manufacture. It can be anchored in the skin with good biocompatibility. It can also remain in the skin long-term. Exchange of substances with the surrounding skin tissue is facilitated.

[0023] Overall, spider silk is particularly distinguished by its antibacterial and antifungal properties. It promotes wound healing, is water-resistant, highly heat-stable, and biodegradable. The present invention relates to implantable hair characterized in that it is coated, at least on one implantable part, with a composition containing at least one silk protein.

[0024] One aspect of the present invention relates to implantable hair which is coated at least on an implantable part with a composition that comes into direct contact with the hair and contains at least one silk protein.

[0025] As used herein, the implantable part is the portion of the hair that can be implanted. Typically, implantation takes place in the skin. According to one embodiment, implantation takes place in the scalp. According to another embodiment, implantation takes place in one or more other areas of the face or the human or animal body. For example, implantation can take place in the area of ​​one or both eyebrows, in the area of ​​one or both eyelashes, in the area of ​​the mustache, in the area of ​​the goatee, in the area of ​​the sideburns, in the area of ​​one or both sideburns, in the area of ​​the chest, or in the area of ​​one or both legs. The present invention is suitable for the re-establishment or restoration of hair growth (hair restoration).

[0026] As used herein, the term "in direct contact with the hair" is to be understood in the broadest sense. Thus, the coating is preferably not merely one that coats a macroscopic substance which in turn is in contact with the hair. It is understood that the hair may optionally also be coated and / or dyed and / or otherwise modified. Therefore, direct contact within the meaning of the present invention can also occur with coated hair. It is thus understood that optionally a thin layer (preferably not thicker than 0.5 mm, more preferably not thicker than 0.1 mm, and particularly not thicker than 0.05 mm) of another material may be present between the hair and the composition. In this case, the person skilled in the art will also understand this to mean direct contact with the (then coated) hair.Such an intermediate coating can optionally improve the adhesion of the composition and / or the silk protein to the hair. If such an optional intermediate coating is present, it is preferably bioresorbable (biodegradable). If such an optional intermediate coating is present, it is preferably not inert. Preferably, an optional intermediate coating does not interfere with or prevent permanent hair anchorage. Preferably, an optional intermediate coating does not interfere with or prevent the exchange of substances between the hair and surrounding skin tissue.

[0027] In certain embodiments, the composition can also come into direct contact with the hair without an intermediate layer.

[0028] Preferably, the term "in direct contact with the hair" is characterized by the fact that there is no layer between the hair and the composition that is thicker than 0.5 mm, more preferably not thicker than 0.1 mm, and in particular not thicker than 0.05 mm.

[0029] In a preferred embodiment, the term "in direct contact with the hair" is characterized by the fact that there is no biologically inert layer between the hair and the composition, in particular wherein the layer is not thicker than 0.5 mm, more preferably not thicker than 0.1 mm, and in particular not thicker than 0.05 mm.

[0030] In a particularly preferred embodiment, no intermediate layer is present. Therefore, the hair (and thus its keratin structure) is particularly preferably in direct contact with the composition as defined herein.

[0031] The coating, containing at least one silk protein, can also be understood as a protective layer. This results in particularly biocompatible implantation into the skin. Such a coating, especially when the implantable hair is implanted under (largely) sterile conditions, also provides protection against bacteria and other germs that may be present on or in the skin and / or hair, as well as reducing undesirable immune reactions such as inflammation.

[0032] To utilize the wound-healing properties of spider silk, the anchoring device, which contains at least one silk protein, can additionally have a readily absorbable and / or bioresorbable outer layer, also containing at least one silk protein. After implantation, the body rapidly breaks down this readily absorbable and / or bioresorbable layer, transports it to the epidermis, and thereby promotes faster and less infectious wound healing. "Easily absorbable and / or bioresorbable" here refers to the ability to remove this layer, specifically to be mechanically and / or biologically broken down within an individual's body. It can then be bioresorbed. This can optionally involve uptake into tissues and / or body cells and / or extracellular metabolism. Furthermore, breakdown products can optionally be further metabolized within the body and / or excreted.

[0033] Silk protein is generally not perceived as a foreign body. The protective layer formed by the composition can at least partially separate the implantable hair from the surrounding tissue, thus reducing or preventing an immune response. This protective layer can also reduce or prevent bacterial infections and inflammation at the point where the implanted hair emerges. It can prevent bacteria and other germs from penetrating the implantation site or adhering to the implanted hair.

[0034] Unlike wigs, sebum can naturally transfer from the skin (such as the scalp) to the hair (naturally occurring and / or implanted hair) and does not get trapped in the mesh of wigs or toupees. This can protect the hair (naturally occurring and / or implanted hair) from environmental influences, physical stress, and / or dehydration.

[0035] The hair structure can be stabilized. For additional protection, implantable hair can be coated not only at the implantation site but also completely with a composition containing at least one silk protein. This can also simplify and improve hair styling.

[0036] The coating of the implantable portion of the implantable hair with the composition containing at least one silk protein can cover the entire implantable portion or a part thereof. Preferably, the coating of the implantable portion of the implantable hair with the composition containing at least one silk protein covers at least 25%, at least 50%, at least 75%, at least 90%, or at least 95% of the surface of the implantable portion. Particularly preferably, the coating of the implantable portion of the implantable hair with the composition containing at least one silk protein covers the entire implantable portion.

[0037] Optionally, the coating of the implantable portion of the implantable hair with the composition containing at least one silk protein can also encompass the exit site of the implantable hair from the recipient's skin after implantation. This can protect the exit site from bacteria and other germs and / or reduce or prevent an immune response. According to one embodiment of the present invention, the coating comprises the implantable portion (e.g., a real or artificial hair root and / or a real or artificial hair follicle and / or a real or artificial hair bulb) and the exit site of the implantable hair from the skin after implantation.

[0038] According to one embodiment of the present invention, the composition comprises at least 10 wt%, at least 25 wt%, at least 50 wt%, at least 75 wt%, at least 80 wt%, at least 90 wt%, at least 95 wt% or at least 99 wt%, one or more silk proteins, based on the dry mass of the composition.

[0039] According to one embodiment of the present invention, the composition comprises at least 10 wt%, at least 25 wt%, at least 50 wt%, at least 75 wt%, at least 80 wt%, at least 90 wt%, at least 95 wt% or at least 99 wt%, one or more silk proteins, based on the total mass of the composition.

[0040] The composition used as a coating, which contains at least one silk protein, may optionally also consist of one or more silk proteins and optionally their (cosmetically compatible) salts.

[0041] As used herein, "cosmetically compatible" is to be understood as acceptable in the implantation of the implantable hair into the skin.

[0042] The composition used as a coating can be solid, pasty, or liquid. It can optionally contain a cosmetically compatible solvent in addition to the at least one silk protein. Such a cosmetically compatible solvent can be selected, for example, from the group consisting of water, a cosmetically compatible liquid buffer, a hydroalcoholic mixture containing water and up to 5 vol% ethanol, dimethyl sulfoxide (DMSO), and combinations of two or more thereof.

[0043] Optionally, the composition used as a coating may also contain one or more preservatives, one or more antibacterial (e.g., bactericidal and / or bacteriostatic) agents, one or more antifungal agents, one or more antiviral agents, hemostatic agents, one or more vitamins, one or more bioactive substances that promote hair growth or blood circulation, one or more local anesthetics, one or more thickening agents, one or more hormones, one or more acidity regulators, or a combination of two or more of the aforementioned components.

[0044] Optionally, the composition used as a coating, regardless of its ingredients, can also be dried on the surface of the implantable hair.

[0045] Optionally, the composition used as a coating can also partially diffuse into the implantable hair. Preferably, however, over 50 wt.% of the at least one silk protein, based on the total amount of the composition remaining on or attached to the hair, remains on the surface of the implantable hair, and less than 50 wt.% of the at least one silk protein, based on the total amount in the composition remaining on or attached to the hair, diffuses into the hair.

[0046] According to the invention, the hair is at least partially in direct contact with the coating. Therefore, the coating borders at least partially directly on the hair structure enclosed by this layer. Thus, an exchange of substances can take place.

[0047] The invention also relates in general to hair implants with silk (such as spider silk and / or caterpillar silk) with medical and aesthetic functionality.

[0048] The silk protein can be any known silk protein. According to one embodiment, the at least one silk protein used has at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology to, or sequence identity with, an insect silk protein or a spider silk protein.

[0049] According to one embodiment, the at least one silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein from the family of true spinners. (Bombycidae), of spiders (Aranae), such as tarantulas (Mygalomorphae), the true spiders ( Araneomorphae ) and / or the segmented spiders (Mesothelae) on.

[0050] According to one embodiment, the at least one silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein from one of the genera Bombyx (e.g. Bombyx mori, Bombyx mandarina), Araneus, Nephila, Antheraea (e.g. Antheraea pernyi, Antheraea yamamai, Antheraea mylitta, Antheraea roylei, Antheraea proyeli, Antheraea paphia, Antheraea frithi, Antheraea assama), Arachnura, Caerostris, Argiope, Cyrtophora, Celaenia, Gasteracantha, Ordgarius, Neoscona, Zygiella, Parawixia, Neoscona, Dolophones, Aculeperia, Eriophora, Anepsion, Tegenaria, Heurodes, Cyclosa, Astracantha, Eriovixia, Nephilengys, Herennia, Acusilas, Neoscona, Poltys, Arkys, Poecilopachys, Hyalophora (e.g. Hyalophora cecropia), Samia (e.g. Samia cynthia), Attacus (Attacus atlas), Circula (e.g. Circula trifenestrata), Gonometa (e.g. Gonometa postica, Gonometa rufobrunnea) and / or Anaphe (e.g. Anaphe panda, Anaphe moloneyi) on.

[0051] According to one embodiment, the at least one silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein from one of the genera Bombyx, Araneus, Nephila, Antheraea, Arachnura, Caerostris, Argiope, Cyrtophora, Celaenia, Gasteracantha, Ordgarius, Neoscona, Zygiella, Parawixia, Neoscona, Dolophones, Aculeperia, Eriophora, Anepsion, Tegen Caria, Hero, Astractha, Astractha Eriovixia, Nephilengys, Herennia, Acusilas, Neoscona, Poltys, Arkys, Poecilopachys on.

[0052] According to one embodiment, the silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein of a genus selected from the group consisting of Bombyx, Araneus Antheraea and Nephila on.

[0053] According to one embodiment, the at least one silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein of a species selected from the group consisting of Bombyx mori, Bombyx mandarina, Antheraea pernyi, Antheraea yamamai, Antheraea mylitta, Antheraea roylei, Antheraea proyeli, Antheraea paphia, Antheraea frithi, Antheraea assama Araneus didenatus, Nephila clavipes, Araneus bicentenarius, Arachnura higginsi, Araneus circulissparsus, Araneus diadematus, Caerostris darwini, Argiope picta, Argiope trifasciata Nephila antipodiana, Cyrtophora beccarii, Celaenia excavata, Gasteracantha kuhlii, Argiope aurantia, Ordgarius furcatus, Ordgarius magnificus, Neoscona nautica, Neoscona rufofemorata, Zygiella calyptrata, Parawixia dehaani, Neoscona oxancensis, Gasteracantha cancriformis, Gasteracantha arcuata, Cyrtophora moluccensis, Cyrtophora parnasia, Dolophones conifera, Dolophones turrigera, Gasteracantha doriae, Gasteracantha mammosa, Cyrtophora exanthematica, Aculeperia ceropegia, Eriophora pustulosa, Anepsion depressium, Gasteracantha quadrispinosa, Eriophora transmarina, Araneus bicentenarius, Nephila maculata, Gasteracantha hasseltii,Tegenaria atrica, Heurodes turrita, Cyclosa insulana, Astracantha minax, Araneus mitificus, Eriovixia laglaisei, Cyclosa bifida, Nephilengys malabarensis, Argiope versicolor, Herennia ornatissima, Argiope aemula, Cyrtophora unicolor, Cyrtophora hirta, Argiope keyserlingi, Acusilas coccineus, Argiope argentata, Gasteracantha cancriformis, Neoscona domiciliorum, Argiope aetheria, Argiope Keyserlingi, Poltys illepidus, Arkys clavatus, Arkys lancearius, Poecilopachys australasia, Nephila clavipes, Nephila senegalensis, Nephila madagascariensis, Hyalophora cecropia, Samia Samia cynthia, Attacus atlas, Circula trifenestrata, Gonometa postica, Gonometa rufobrunnea, Anaphe panda, and / or Anaphe molecules on.

[0054] According to one embodiment, the silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein of a species selected from the group consisting of Bombyx mori, Antheraea pernyi, Araneus diadematus, Nephila clavipes, Araneus bicentenarius and Caerostris darwini on.

[0055] According to one embodiment, the at least one silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein. Bombyx died on.

[0056] According to one embodiment, the at least one silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein. Bird Antheraea on.

[0057] According to one embodiment, the at least one silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein. Araneus diadematus on.

[0058] According to one embodiment, the at least one silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein. Nephila clavipes on.

[0059] According to one embodiment, the at least one silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein. Araneus bicentenarius on.

[0060] According to one embodiment, the at least one silk protein exhibits at least 90% sequence homology, or at least 95% sequence homology, or at least 98% sequence homology or sequence identity with a silk protein. Caerostris darwini on.

[0061] Further silk proteins that can be used according to the present invention and their biochemical properties are described in WO 2007 / 025719, WO 2006 / 008163, WO 2004 / 024176, DE-A 10333253, US 2007 / 196429, US 2007 / 214520, US 2009 / 123967 and WO 2011 / 069643.

[0062] According to one embodiment of the present invention, the at least one silk protein is characterized in that it is selected from the group consisting of fibroin, sericin, spidroin 1 and spidroin 2. Spidroin 2 can optionally also “Araneus diadematus Fibroin 3" (ADF-3) or Araneus diadematusFibroin 4" (ADF-4) as described, for example, in WO 2007 / 025719 and WO 2006 / 008163. ADF-3 may have a sequence that exhibits at least 90% homology, or at least 95% homology, or at least 98% homology, or at least 99% homology to SEQ ID NO: 1 from WO 2006 / 008163. ADF-4 may have a sequence that exhibits at least 90% homology, or at least 95% homology, or at least 98% homology, or at least 99% homology to SEQ ID NO: 2 from WO 2006 / 008163. ADF-3 may have a sequence as described in SEQ ID NO: 1 from WO 2006 / 008163. ADF-4 may have a sequence as described in SEQ ID NO: 2 from WO 2006 / 008163.

[0063] According to one embodiment of the present invention, the at least one silk protein comprises at least two, at least three, at least four or more than four sequence segments, each having one of the following sequences SEQ ID NO: 1 to 6: GPGXX (SEQ ID NO: 1), GVPGX (SEQ ID NO: 2), GSGXX (SEQ ID NO: 3), GGYXX (SEQ ID NO: 4), PQQXX (SEQ ID NO: 5), GYGXX (SEQ ID NO: 6), where each X can be any natural amino acid independently of each other, preferably selected from the group consisting of V, G, A, S, Y, P and Q.

[0064] According to one embodiment of the present invention, the at least one silk protein comprises at least two, at least three, at least four or more than four identical sequence segments of a sequence SEQ ID NO: 1 to 6.

[0065] Fibroin is a well-known fibrous protein, exemplified by the silk glands of the silkworm. (Bombyx mori), but is also secreted by other species. For example, fibroin can comprise a heavy chain of the following sequence SEQ ID NO: 7:

[0066] Optionally, Fibroin can also include a light chain of the following sequence SEQ ID NO: 8:

[0067] Sericin is a well-known protein that, in its natural environment, can hold fibroin strands together. Sericin can be found, for example, in the silk glands of silkworms. (Bombyx mori), but can also be secreted by other species. Sericin can, for example, exhibit one of the following sequences SEQ ID NO: 9 to 11: Sericin 1 can include SEQ ID NO: 9: Sericin 2 can include SEQ ID NO: 10: Sericin 3 can include SEQ ID NO: 11:

[0068] Spidroins are fibrous proteins found in the silk of some spiders, such as... Nephila clavipes. Spidroin 1 can, for example, comprise the following sequence SEQ ID NO: 12:

[0069] Spidroin 2 can, for example, include the following sequence SEQ ID NO: 13:

[0070] Silk protein and compositions containing such a protein or a mixture of silk proteins are optionally available commercially, for example from AMSilk GmbH (Am Klopferspitz 19 im IZB, 82152 Planegg / Munich, Germany).

[0071] Silk protein can be naturally derived or synthetically produced. It can be extracted from an organism of its original genetic origin, for example, from or directly from spiders or caterpillars. It can be taken from a golden orb-weaver spider, as mentioned above. However, obtaining natural spider silk is technically difficult and expensive. Therefore, silk protein can alternatively be heterologously expressed. To produce heterologously expressed silk protein, deoxyribonucleic acid (DNA) can be extracted from the organism of its original genetic origin (such as a spider or caterpillar) and transferred into a host organism (e.g., bacteria, insect cells, mammalian cells, plant cells, or fungal cells such as yeast). During this process, promoter sequences and, optionally, enhancer and / or stop sequences, recognizable to the host organism, can be added.At least one silk protein can be produced by cells in cell culture. Optionally, one silk protein can remain in the host cell, which is then harvested in a batch process, or it can be secreted by the host cell. Such biotechnological methods are well known to those skilled in the art. Heterologous expression can, for example, be achieved in a bacterium, such as... Escherichia coli as described in US-A 2007 / 196429, US-A 2007 / 214520, US-A 2009 / 123967 and WO 2011 / 069643.

[0072] The at least one implantable part of the hair can be located at any point along the hair shaft. According to one embodiment, the implantable part is an implantable terminal end of the hair. For example, the hair can be coated and / or implantable with the composition containing the at least one silk protein over a length of up to 1 µm, from 1 to 10 µm, from 5 to 50 µm, from 10 to 100 µm, from 50 to 500 µm, from 100 µm to 1 mm, from 0.5 to 5 mm, or from more than 5 mm. The hair can then be implanted into the skin, such as the scalp, with this terminal end.

[0073] It is also possible to implant both terminal ends of the hair.

[0074] Then, optionally, after implantation, a formed ring closure can be cut open by optionally dividing the hair by making a cut between the two implanted terminal ends.

[0075] According to another embodiment, the implantable part is an implantable bend in the middle of the hair or a bendable part in the middle of the hair.

[0076] As understood herein, the "middle" of the hair is to be understood in the broadest sense as a portion of the hair that is not located at a terminal end, and therefore not at the root or the tip. Preferably, the middle of the hair lies along its length in the region of the inner 8 / 10 of the hair's length, and therefore in the region that does not lie in the outer 10% of the hair's length. Optionally, the middle may also lie (approximately) in the region of the mathematical midpoint of the hair (from the root to the tip) (+ / - 20%, preferably + / - 10%, and particularly + / - 5%).

[0077] The hair can be folded and contain a cut in the fold or foldable part, which, for example, can be coated with the composition containing at least one silk protein over a length of up to 1 µm, from 1 to 10 µm, from 5 to 50 µm, from 10 to 100 µm, from 50 to 500 µm, from 100 µm to 1 mm, from 0.5 to 5 mm, or from more than 5 mm. This part can then be implanted. Preferably, a V-shaped fold is implanted with the apex of the V-shape into the skin.

[0078] The implantable hair can be any type of hair. As used herein, the term "hair" is to be understood in its broadest sense as a fibrous structure that has an optical appearance similar to human or animal hair, preferably human hair or mammalian hair, in particular human hair. Optionally, the implantable hair may have a hair follicle and / or a hair root and / or a hair bulb, or it may have neither a hair follicle, a hair root, nor a hair bulb.

[0079] The implantable hair can be the patient's own hair, donor hair, or synthetic hair. According to one embodiment of the present invention, the implantable hair is human hair. This can be the patient's own hair or donor hair from a human or animal donor.

[0080] According to one embodiment of the present invention, the implantable hair is a human head hair. Alternatively, other body hair, such as chest hair, axillary hair, pubic hair, leg hair, beard hair and / or arm hair, can also be used.

[0081] Optionally, the human implantable hair can have a hair follicle and / or a hair root and / or a hair bulb, or it can have no hair follicle, hair root, or hair bulb. According to one embodiment of the present invention, the implantable hair is a cut human hair without a hair follicle, hair root, or hair bulb. Hair from a hairdresser can be used as an example.

[0082] According to an alternative embodiment of the present invention, the implantable hair is a synthetic hair or an animal hair. Such hairs are described in the prior art. A synthetic hair can also be referred to as artificial hair. Artificial hair can also contain silk or consist of silk.

[0083] Implantable hair can have any desired thickness. According to one embodiment, the implantable hair has an average diameter of 0.02 to 0.15 mm along its entire length.

[0084] Thinner or thicker hair can also be used. For example, the hair can have a medium diameter of 0.01 to 0.3 mm, 0.03 to 0.1 mm, 0.02 to 0.15 mm, 0.03 to 0.1 mm, 0.04 to 0.09 mm, 0.04 to 0.08 mm, 0.05 to 0.07 mm, or 0.09 to 0.5 mm.

[0085] The coating of the implantable hair with the composition containing at least one silk protein can vary in thickness. It can have a (largely) homogeneous thickness over larger areas or vary in thickness. With a uniform coating, the thickness can be in the nanometer, micrometer, or millimeter range. For example, the coating could have an average thickness of 0.01 to 0.3 mm, 0.03 to 0.1 mm, 0.02 to 0.15 mm, 0.03 to 0.1 mm, 0.04 to 0.09 mm, 0.04 to 0.08 mm, 0.05 to 0.07 mm, 0.09 to 0.5 mm, 0.09 to 1 mm, or 0.5 to 2 mm.

[0086] The coating can also be a droplet (such as a droplet at at least one terminal end of the hair or a droplet at a bent or bendable point of the hair) or any other shape.

[0087] The hair can be anchored by any suitable means. According to one embodiment of the present invention, the implantable hair has no thickening at the implantable portion that corresponds to a maximum circumference of more than twice the average circumference of the hair. This allows the use of an unprepared, cut hair (for example, cut human hair) for implantation, which is coated at a suitable implantable portion with the composition containing at least one silk protein. This allows a hair implant to be obtained that is coated with the composition containing at least one silk protein, without an artificially created hair root and / or hair follicle and / or hair bulb, and thus without special anchoring.

[0088] As used herein, the mean circumference of the hair is to be understood as the average circumference viewed over the entire length of the hair. Usually, a hair, especially a cut hair, is largely cylindrical, so the mean circumference is present along almost its entire length.

[0089] According to one embodiment of the present invention, implantable hair has an artificial thickening on the implantable part, which is formed by the composition (containing at least one silk protein), wherein the thickening corresponds to a maximum circumference around the hair of at least twice the mean circumference of the hair.

[0090] The extent of the artificial thickening formed from the compound can be adjusted depending on the application area. For example, it can have a maximum extent of 2.1 to 50 times, 2.5 to 30 times, 3 to 20 times, or 4 to 10 times the average circumference of the hair. This structure allows for firm anchoring in the skin. Optionally, the compound can be broken down in the skin over time after implantation. To further improve implant anchoring, an artificial form of the hair root and / or hair follicle and / or hair bulb can optionally be created.

[0091] The artificial shape can optionally differ from the natural shape and may optionally include additional structures that improve anchoring. This allows for the creation of a hair implant coated with a composition containing at least one silk protein, with an artificially replicated hair root and / or hair follicle and / or hair bulb, and thus with a special anchoring mechanism.

[0092] To improve the anchoring of the implantable hair, the implantable hair can have an artificial anchoring structure on the implantable part.

[0093] Optionally, the composition, which contains at least one silk protein, can be used to form an anchor on the hair implant to enable or improve its fixation in the skin. The anchor can take various forms. It can resemble a hair root and / or hair follicle and / or hair bulb, although the anatomical interior of a hair root and / or hair follicle and / or hair bulb is not depicted. It can also be similar in shape to a hair root and / or hair follicle and / or hair bulb.

[0094] However, it can also differ significantly from the shape of a hair root and / or hair follicle and / or hair bulb. An anchoring structure may optionally be selected from the group consisting of the shape of a cone, a blunt cone, a thickened cylinder, a mushroom, a teardrop, an ellipsoid, a cuboid (therefore a cube or an elongated rectangle), a spiral shape, a helical shape, a ring shape, a sphere, a honeycomb structure, a partial wrapping of the hair with a fiber or band, and a combination of two or more of these, and may optionally have projections (including barbs) extending from the hair structure and / or the anchoring structure.

[0095] According to one embodiment, an anchoring structure is selected from the group consisting of the shape of a cone, a truncated cone, a thickened cylinder, a mushroom, a drop, an ellipsoid, a cuboid (therefore a cube or an elongated rectangle), a spiral shape, a helical shape, a ring shape, a sphere, and a combination of two or more thereof and optionally having projections (including barbs) extending from the hair structure (optionally and / or the anchoring structure).

[0096] Specific examples of anchoring structures are described here and illustrated in the following. Figures 2 to 27 The structure is depicted. It is understood here that the structures are perceived three-dimensionally by a person skilled in the art. A largely symmetrical three-dimensional form is preferred.

[0097] Those skilled in the art are familiar with the aforementioned basic shapes. It will also be understood that an anchoring structure is preferably somewhat wider overall than the thickness of the hair (or the sum of the hairs combined with an anchoring structure) on the coated part. In a preferred embodiment, the anchoring structure, without optional projecting extensions, has a maximum diameter (in the plane of the diameter of the coated hair or hair bundle) that is 1.1 to 20 times, in particular 1.2 to 10 times, and in particular 1.5 to 5 times, as thick as the mean diameter of the hair (or the sum of the hairs combined with an anchoring structure) on the coated part. This allows for a good balance between, on the one hand, efficient and gentle hair implantation and, on the other hand, good and comparatively firm anchoring in the skin.

[0098] Hair can be wrapped with a fiber or a band in any suitable manner. A fiber can have a (largely) round or (largely) oval cross-section or a (largely) square (also: cuboid) cross-section. A fiber can be made of (largely) homogeneous material or, optionally, be composed of thinner fibers (e.g., braided, twisted, or parallel-fibered). A band has a flat geometry. A band can be made of (largely) homogeneous material or, optionally, be composed of thinner fibers and / or bands. In this context, a fiber or a band can be broadly understood as comprising or consisting of a composition according to the present invention. The thickness of a fiber or a band can be freely chosen.A thick fiber or band with a diameter equal to or greater than the hair's thickness can be used optionally. This allows for quick wrapping. A thin fiber or band with a diameter smaller than the hair's can also be used optionally. This allows for (largely) complete wrapping and enables the creation of (particularly) well-defined shapes. The wrapping can be linear (therefore (largely) parallel, spiral), net-like, braid-like (cross-wound and / or transverse), or a combination of different wrappings. An example of a linear (therefore (largely) parallel, spiral) wrapping is shown in... Figure 27The sheath (11) is shown as a spiral winding, and in this example, an additional anchoring structure (9) is attached. The winding can optionally be applied directly to the hair or to another structure already in contact with the hair, in particular a structure made of a composition according to the present invention, which contains at least one silk protein. The winding can be carried out in any suitable manner. For example, the hair (or hair bundle) can be rotated (preferably about its (largely) rotationally symmetrical axis), thereby winding one or more fibers and / or one or more bands. Alternatively, the hair (or hair bundle) can remain stationary, and the winding can be achieved by means of a circulating material (e.g., a circulating spindle). Optionally, the wrapped material can be bonded to the hair (e.g., its keratin structure).Optionally, different sections of one or more fibers and / or one or more tapes can be joined together. This can prevent unwanted unwinding. For example, a spiral winding can have fibers joined at least at one end, thus preventing unwinding. Methods suitable for this purpose are described in more detail below.

[0099] The coating, which contains at least one silk protein, may interact with bodily fluids, such as water, at the implantation site. This interaction can cause the coating to increase in volume, thereby facilitating or strengthening anchorage. In some embodiments of the present invention, the coating can absorb tissue fluid after implantation and optionally swell. This can improve the anchoring of the hair in the skin.

[0100] The embodiments according to the invention, as described herein, provide a hair implant coated with a composition containing at least one silk protein, with an anchor whose shape differs from that of the natural hair root and / or follicle and / or bulb. The anchor can have various forms, as described above. The thickening can thus have different shapes, including incisions or protrusions. Barbs and spiral shapes are also possible, either additionally or alternatively. Optionally, such an artificial attachment form can be designed to expand after the implantation of the implantable hair, thereby securing or improving the attachment of the hair implant.At the same time, the composition, which contains at least one silk protein, can also serve to protect against bacteria and other germs and / or to reduce or prevent an immune response in the body. The anchoring of the implantable hair can also include one or more loops in the hair.

[0101] An artificial anchoring structure can also be constructed from a composition that contains at least one silk protein.

[0102] It can also be additionally or exclusively composed of one or more other materials and then coated with the composition containing at least one silk protein. Such other materials can be, for example, plastics, preferably biocompatible plastics such as silicone, (methyl) methacrylate, polyvinyl chloride (PVC), polylactic acid, or other compatible plastic materials or mixtures thereof. Inert metals such as gold, platinum, or titanium and their alloys can also be used. An artificial anchoring structure can optionally also be coated with graphene. An artificial anchoring structure is preferably coated with a composition containing a silk protein.

[0103] According to one embodiment of the present invention, the implantable hair is incised at the implantable part. This also enables anchoring. For example, it allows skin and / or connective tissue to grow into the incisions of the implantable hair's structure. Skin and / or connective tissue can also optionally grow into a loop-shaped structure of the implantable hair.

[0104] According to one embodiment of the present invention, the implantable hair has a hair follicle, hair root, or hair bulb on the implantable part, which is coated with the composition. This can enable complete and permanent hair growth (autologous or donor hair). Thus, the implanted hair can be nourished by the skin and may even exhibit length growth. The coating of the hair root and / or reconstructed hair follicle and / or reconstructed hair bulb with the composition, which contains at least one silk protein, can also protect the hair implant from bacteria and germs and / or reduce or prevent an immune response.

[0105] According to one embodiment of the present invention, the implantable hairs are designed to be implanted individually. Therefore, they have a coating structure that typically contains a single hair. According to an alternative embodiment of the present invention, two or more implantable hairs are grouped together at their implantable parts in a coating or anchoring structure. This allows a hair implant to be obtained that is coated with the composition containing at least one silk protein, with an artificially replicated hair root and / or hair follicle and / or hair bulb, and thus with special anchoring, and which can contain one or more hairs.

[0106] The coating, comprising a composition containing at least one silk protein, can be homogeneous. Alternatively, the coating can also be inhomogeneous, exhibiting different strength and / or biological stability in different areas. According to one embodiment of the present invention, the coating has zones with different strength and / or biological stability. According to one embodiment of the present invention, the coating exhibits higher strength and / or biological stability in the interior, near the hair, than on the exterior.

[0107] This allows the outer layer to be broken down more quickly after the implantable hair, thus facilitating the ingrowth of skin and / or connective tissue, while the inner layer protects the hair for a long time and ensures its long-lasting hold in the skin. This makes it possible to obtain a hair implant coated with a composition containing at least one silk protein, with a real hair root and / or hair follicle and / or hair bulb, which was taken from the scalp or body hair of a person and can be implanted in the same person or a different person.

[0108] The insertion of implantable hair into another person is therefore a transplantation of foreign hair. This is typically recognized and attacked by the immune system as a foreign body. However, the immune reaction can be reduced or prevented by coating the implant with a composition containing at least one silk protein. This can prevent a rejection reaction. The acceptance of the foreign hair by the recipient, their tissue, and their immune system can be improved.

[0109] According to one embodiment of the present invention, the coating of the implantable hair, comprising the at least one silk protein, is designed such that, after implantation, the silk protein or a degradation product is transported to the hair and / or scalp located outside the body and conditions the hair and / or skin (e.g., the scalp).

[0110] The composition, which contains at least one silk protein, can optionally also be used to coat other materials, especially silicone or plastics, to which the hair or several hairs can be attached for implantation (or transplantation).

[0111] According to a preferred embodiment, the implantable hair was coated with the composition using a method for three-dimensional (3D) shaping, in particular 3D printing.

[0112] 3D shaping in connection with the present invention can also be understood as 3D printing. 3D shaping processes (e.g., 3D printing) suitable for applying (also: adding) and / or removing (also: subtracting) compositions containing at least one silk protein are known to those skilled in the art. A 3D shaping process in connection with the present invention can therefore be a subtractive process (therefore, removing already coated material), an additive process (therefore, adding material), or a combination of both.

[0113] According to a preferred embodiment, a 3D shaping method in connection with the present invention comprises the use of a light pulse, preferably in the ultraviolet (UV) spectral range, and particularly preferably a femtosecond laser, especially in the UV range, as described by way of example in Sidhu et al. ("The processing and heterostructuring of silk with light", Nature Materials, 2017, DOI: 10.1038 / NMAT4942, also published as: Nature Materials, 16:938-945). Such a method enables very precise material removal (e.g., silk protein), very precise cuts in material (e.g., silk protein), and the adhesion of one material (e.g., silk protein) to another material, such as hair material (e.g., keratin), and of similar or identical materials to each other (e.g., of a silk protein to similar or different silk proteins). This makes subtractive and additive 3D shaping methods and combinations thereof possible.

[0114] In a femtosecond laser, light pulses are emitted with a duration of a few femtoseconds or less (femtosecond: 10⁻¹⁵ s). The laser light, propagating at the speed of light, travels a distance of only about 0.3 µm in a vacuum and in air and similar gases at atmospheric pressure within one femtosecond, which is roughly one-hundredth the diameter of a human hair. A technical advantage of a femtosecond laser is therefore the precise and residue-free ablation of minute amounts of material without significant heat transfer (hence the principle of the precision scalpel). The material can also be directly converted into plasma by a femtosecond laser, which interacts very little thermally with the substrate.

[0115] A further technical advantage of using a femtosecond laser in connection with the present invention is that a composition containing at least one silk protein can be exposed to a light pulse (optionally a weaker, and therefore lower-energy) – preferably ultraviolet (UV) light. This allows the composition to change its properties for a very brief moment. A solid or pasty composition can become liquid for a short time and then solid or pasty again. If the composition is brought into contact with another material (e.g., a hair or a part thereof) during such a light pulse with a femtosecond laser, it can adhere to this material. This allows for a preferably permanent adhesion of the composition to the hair or a part thereof.

[0116] The method according to the invention can also include a process step of forming an anchorage of the composition, which contains at least one silk protein, to the part of the hair to be implanted. In this step, the hair can first be brought into contact with the composition, which contains at least one silk protein. Then, the composition at the point of contact with the hair can be exposed to a weaker light pulse, for example, from a femtosecond laser. This causes the composition to adhere to the hair at the point of contact. A layer containing the composition, which contains at least one silk protein, can thus be formed.

[0117] This process can be adequately and analogously applied to bond further layers of the composition, which contains at least one silk protein, to the composition. The layers formed in this way can also have different strengths.

[0118] A hair, or a portion thereof, can be partially or completely exposed to the composition, which contains at least one silk protein. The composition can then be exposed to a (weaker, and therefore lower-energy) light pulse from a femtosecond laser. This causes the composition to adhere to the hair at the point of contact. This process allows the hair to be partially or completely bonded to the composition, thus partially or completely encapsulating it. This can help strengthen the hair, extend its lifespan, protect it from environmental factors, and / or improve hair styling.

[0119] According to one embodiment of the present invention, the portion of the hair to be implanted can be brought into contact with one or more fibers and / or one or more bands containing or consisting of the composition of the present invention. As described above, this can optionally also be done by wrapping, as further specified above. Optionally, the hair can also be wrapped while the hair is in direct or indirect contact with a liquid or paste-like composition.

[0120] Optionally, a wrapped material can be bonded to the hair (e.g., its keratin structure). This can be done in any desired way, for example, by a light pulse, particularly in the UV range, as described herein. Preferably, this can be achieved by a femtosecond laser, as described herein. A light pulse, particularly in the UV range, and especially a femtosecond laser, as described herein, also allows for post-processing of the wrapping. This can, for example, include stabilizing the wrapping by (partially) bonding different sections of the fibers / tapes.

[0121] According to one embodiment of the present invention, the portion of the hair to be implanted can be brought into contact with the liquid or paste-like composition containing at least one silk protein. Optionally, the portion to be implanted can be immersed, coated, or sprayed with such a composition. Further possibilities are described herein. A portion of the composition can remain on the portion of the hair to be implanted (for example, in droplet form). The liquid or paste-like composition can then dry and / or harden on the portion of the hair to be implanted. Here, hardening is understood in the broadest sense as an increase in strength. This preferably results in the composition forming an anchor that is strong enough to allow implantation. The degree of hardness is preferably sufficient to achieve a desired half-life in the surrounding tissue of the body, particularly the skin.The composition preferably remains elastic. Elasticity of the anchoring structure can be advantageous so that it is less or not at all noticeable after implantation and causes no or minimal pressure sores and / or no or less pain. To accelerate hardening, the part to be implanted can be left to dry in the air after contact with the liquid or paste-like composition, or alternatively, by changing the environment, for example, by providing ventilation or changing the temperature. The desired hair anchoring structure can then be cut and / or ablated from the hardened composition using a laser, such as a femtosecond laser.

[0122] According to a preferred embodiment, the production of the implantable hair in connection with the present invention comprises the at least partial removal of silk protein. According to a preferred embodiment, 3D shaping in connection with the present invention comprises the at least partial removal of silk protein by means of a light pulse, preferably in the ultraviolet (UV) spectral range. This takes advantage of the fact that silk proteins, and optionally other components of this composition, can absorb UV radiation. According to a preferred embodiment, 3D shaping in connection with the present invention comprises the at least partial removal of silk protein by means of plasma ablation.According to a preferred embodiment, 3D shaping in connection with the present invention comprises the at least partial removal of silk protein using a femtosecond laser, particularly in the ultraviolet (UV) spectral range. A method based on plasma ablation using a femtosecond laser, particularly in the ultraviolet (UV) spectral range, is generally known to those skilled in the art (Sidhu et al., Nature Materials, 2017, DOI: 10.1038 / NMAT4942, also published as: Nature Materials, 16:938-945). Preferably, the ablation is carried out using a short-duration light pulse with a duration of <100 ps (picoseconds), <10 ps, ​​<1 ps, <100 fs (femtoseconds), or <10 fs. With a femtosecond laser, therefore, even the smallest amounts of material from the liquid, pasty or solid composition containing at least one silk protein can be removed by stronger light pulses, especially in the UV light range.

[0123] The precise application capabilities of a femtosecond laser allow for the creation of various anchoring structures on the hair. For example, honeycomb structures can be formed, which may contain cavities. Further examples are illustrated in the figures. The resulting cavities and / or edges can be brought into contact with a liquid or paste-like composition containing at least one silk protein. This composition can then be exposed to a light pulse from the femtosecond laser to improve or enable adhesion of the composition to the honeycomb structure.

[0124] According to a preferred embodiment, the production of the implantable hair comprises the at least partial (e.g. thermal) melting of the composition and / or the at least one silk protein, in particular by means of a femtosecond laser, especially in the ultraviolet (UV) spectral range.

[0125] Melting, in the broadest sense, means that the composition is at least partially liquefied or at least its viscosity is reduced. Melting is a process that occurs through a usually short-term, usually localized, increase in temperature. Preferably, the temperature increase is caused by photon irradiation. Melting is preferably the melting of only a portion of the composition and / or a silk protein by means of a light pulse, in particular a UV light pulse.

[0126] As an alternative to a UV light pulse, a high radiation intensity of longer-wavelength light (with lower-energy photons) can also be used. Multiphoton effects (e.g., 2-photon and / or 3-photon effects) can be utilized here, as described in Sidhu et al. (Nature Materials, 2017, DOI: 10.1038 / NMAT4942, also published as: Nature Materials, 16:938-945).

[0127] After brief melting, the structure preferably re-hardens. Melting is preferably achieved using a short light pulse with a duration of <100 ps, ​​<10 ps, ​​<1 ps, <100 fs, or <10 fs. Preferably, the melting and hardening of a portion of the composition and / or the silk protein occurs very briefly, therefore in the range of <100 ns (nanoseconds), <10 ns, <1 ns, <100 ps, ​​<10 ps, ​​<1 ps, <100 fs, or <10 fs. This can result in the shaping of the 3D surface structure in the nanometer and / or micrometer range, by allowing minute droplets of the at least partially melted material to adhere in a defined manner to the hair or an already hardened structure.

[0128] According to a preferred embodiment, the 3D shaping process comprises the partial removal of silk protein that has been applied to the hair, in particular by means of plasma ablation, in particular by means of a femtosecond laser, in particular in the ultraviolet (UV) spectral range.

[0129] Methods that can be used in connection with the present invention can also be used to process several hairs (even hundreds or thousands) simultaneously and coat them with the composition containing at least one silk protein. Coating processes can be automated.

[0130] The described 3D shaping methods can also be used to process multiple hairs (even hundreds or thousands) simultaneously and coat them with the composition, which contains at least one silk protein. A light pulse (e.g., a UV light pulse), such as a femtosecond laser, can also be used for this purpose. Several hairs, with their parts to be implanted, can be brought into contact with the composition containing at least one silk protein (e.g., by immersion in a liquid or paste-like composition, such as a thin layer in a Petri dish). A firmer viscosity of the composition can then be achieved (e.g., through aeration, temperature changes, or changes in light, such as exposure to UV light). Once the composition is firm enough to retain its shape and adheres well to the hair, the hairs, along with their hair anchors, can be removed using a femtosecond laser.Short light pulses can be used to create the anchoring structure for each hair, and the hair, along with the formed anchor, can then be detached from the assembly. Alternatively or additionally, the hair anchor can be further shaped with the femtosecond laser into a specific anchoring form, for example, to achieve a cone shape, to form extensions, a ring shape, and many others. A femtosecond laser can be used to create a wide variety of anchoring shapes, and these shapes can also be combined, for example, a honeycomb shape, a ring shape with extensions, etc. Examples of structures are described here and also shown in the [references / documents]. Figures 2 to 27 shown.

[0131] According to a preferred embodiment, the implantable hair is at least partially coated with a solid or pasty composition having a 3D surface structure in the nano- or micrometer range that deviates from a largely cylindrical shape (therefore a hair-like shape, and preferably also a droplet shape). Possible shapes are shown here and by way of example in the Figures 2 to 27 described.

[0132] The implantable hair according to the present invention can be produced in any suitable manner. Methods as described herein represent preferred embodiments.

[0133] Another aspect of the present invention relates to a method for producing implantable hair according to the present invention, wherein the method comprises the following steps: (i) Providing: (A) hair that is not on the human or animal body, and (B) a composition containing at least one silk protein; and (ii) bringing into contact at least one implantable part of the hair with the composition.

[0134] Corresponding examples of procedures have already been given above; further examples are given below and in the example section.

[0135] It will be understood that all definitions and embodiments made in connection with the implantable hair according to the present invention also apply accordingly to the method for producing such implantable hair.

[0136] According to a preferred embodiment, the present invention relates to a method for producing implantable hair according to the present invention, wherein the method comprises the following steps: (i) Providing: (A) hair that is not on the human or animal body, and (B) a liquid, pasty, or solid (preferably liquid or pasty) composition containing at least one silk protein; (ii) contacting at least one implantable portion of the hair with the liquid, pasty, or solid composition; and (iii) optionally drying the implantable hair obtained from step (ii).

[0137] Steps (ii) and (iii) can optionally be repeated two or more times, which may allow for a greater layer thickness and / or the achievement of any desired coating shape.

[0138] The present invention also relates to implantable hair that is obtainable or obtained by a method as described herein.

[0139] The hair used in step (i) of providing the starting materials can be any type of hair. It can be, for example, human hair, animal hair, or synthetic hair. Corresponding embodiments are explained in more detail in connection with the implantable hair.

[0140] The liquid, pasty or solid composition used in step (i) of providing the starting materials, which contains at least one silk protein, may be any liquid, pasty or solid (preferably liquid or pasty) composition.

[0141] The liquid, pasty, or solid (preferably liquid or pasty) composition used for coating, which contains at least one silk protein, may contain a solvent or solvent mixture. Preferably, the at least one silk protein is soluble in a solvent or solvent mixture, or forms a colloid or hydrogel in a solvent.

[0142] A solvent can be a cosmetically compatible solvent. A cosmetically compatible solvent might be selected, for example, from the group consisting of water, a cosmetically compatible buffer, a hydroalcoholic mixture containing water and up to 5 vol% ethanol, dimethyl sulfoxide (DMSO), and combinations of two or more of these. A cosmetically compatible solvent may optionally remain wholly or partially on the implantable hair. Alternatively, it may evaporate, for example, through drying.

[0143] A solvent can also be an organic solvent. This preferably possesses at least a degree of polarity that allows for the solubility or colloidalization of the at least one silk protein. For example, an organic solvent can be selected from one or more alcohols (e.g., ethanol, methanol, propanol, and / or butanol), acetone, or acetonitrile. At least if the organic solvent is not cosmetically compatible at the concentration used, it is preferably evaporable, meaning it can be completely or partially removed by evaporation.

[0144] The liquid, pasty, or solid (preferably liquid or pasty) composition used for coating may optionally contain, in addition to a solvent, one or more preservatives, one or more antibacterial (e.g., bactericidal and / or bacteriostatic) agents, one or more antifungal agents, one or more antiviral agents, one or more detergents, one or more chelators, one or more hemostatic agents, one or more vitamins, one or more bioactive substances promoting hair growth or blood circulation, one or more local anesthetics, one or more thickening agents, one or more hormones, one or more acidity regulators, or a combination of two or more of these.

[0145] The terms "liquid" and "paste-like" are to be understood as they are commonly used. Preferably, a liquid composition at room temperature (20°C) under normal pressure (1013 mbar) has a viscosity of less than 5000 mPa·s (e.g., determined with a capillary viscometer). Preferably, a pasty composition at room temperature (20°C) under normal pressure (1013 mbar) has a viscosity of at least 5000 mPa·s (e.g., determined with a capillary viscometer).

[0146] The term "solid" is to be understood in the broadest sense as having a greater consistency than a pasty consistency, and therefore not flowing at room temperature (20°C) under normal pressure (1013 mbar). For example, soap can be liquid or pasty, or it can be a solid bar of soap (also known as hand soap). The term "solid" can also encompass waxy textures.

[0147] In one embodiment, the silk protein can have a firm or viscous pasty (wax-like) structure. This can result in good technical properties when forced through an injection needle and reduce or prevent damage (e.g., to the silk protein) during injection, thus improving the protective function of the silk protein.

[0148] Such a solid or viscous pasty (waxy) structure can optionally be achieved by subjecting a liquid or pasty composition to temperature and / or air drying until it becomes solid or viscous-pastry (waxy). This can optionally also be done with the aid of additional chemical substances.

[0149] Step (ii) of contacting can be carried out in any suitable manner. According to one embodiment of the present invention, step (ii) of contacting comprises immersing the hair or a part thereof in the liquid, pasty, or solid (preferably liquid or pasty) composition. According to another embodiment of the present invention, step (ii) of contacting comprises coating the hair or a part thereof with the liquid, pasty, or solid composition. According to a further embodiment of the present invention, step (ii) of contacting comprises spraying the hair or a part thereof with the liquid, pasty, or solid composition. It will be recognized that combinations of different contacting process steps can optionally be combined with one another.

[0150] According to one embodiment of the present invention, step (ii) of contacting comprises joining a hair (or hair bundle) with a (largely) solid composition containing one or more silk proteins. According to one embodiment of the present invention, step (ii) of contacting comprises inserting a hair (or hair bundle) into a prefabricated (largely) solid anchoring structure. According to one embodiment of the present invention, step (ii) of contacting comprises wrapping a hair (or hair bundle) with one or more fibers and / or one or more bands.

[0151] It will be understood that several contacting process steps can be combined. This can occur simultaneously and / or sequentially. For example, wrapping or inserting into a (largely) solid anchoring structure can also be done using a liquid or paste-like composition.

[0152] Step (ii) of contacting can be carried out at any temperature at which at least the primary structure of the at least one silk protein used is preserved and not denatured, so that no amino acid residues of the at least one silk protein decompose pyrolytically. According to one embodiment of the present invention, step (ii) is carried out at temperatures in the range of -40 to 250°C, -20 to 200°C, -10 to 180°C, -5 to 150°C, 0 to 150°C, 2 to 120°C, 3 to 100°C, 4 to 80°C, 4 to 60°C, 4 to 50°C, 4 to 40°C, 5 to 30°C, 10 to 25°C, or 15 to 25°C. According to one embodiment of the present invention, step (ii) is carried out at room temperature in the range of 15 to 25°C or from 18 to 22°C, in particular (about) 20°C.

[0153] If another method of bringing at least one implantable part of the hair into contact with the liquid, pasty, or solid composition according to step (ii) is successful, for example by vaporizing the hair or a part thereof (at elevated temperature and / or in a vacuum), such a procedure is also encompassed by the present invention. The silk protein coating can also optionally be vaporized.

[0154] Step (ii) of contacting can be carried out at any desired pressure. Preferably, the step is carried out at ambient pressure, for example in the range of 960 to 1100 mbar, 980 to 1050 mbar, or 990 to 1040 mbar.

[0155] Step (ii) of contacting at least an implantable portion of the hair with the liquid, paste, or solid composition may involve contacting a terminal end of the hair with the liquid, paste, or solid composition. This may involve, for example, dipping the terminal end of a single hair into such a composition, or dipping the terminal end of a bundle of several hairs into the composition. Alternatively, a terminal end of a single hair may be coated with the composition, or a terminal end of a bundle of several hairs may be coated with the composition. A terminal end of a single hair may also be sprayed with the composition, or a terminal end of a bundle of several hairs may be sprayed with the composition.

[0156] Step (ii) of bringing at least one implantable part of the hair into contact with the liquid, paste, or solid composition can also involve bringing both terminal ends of the hair into contact with the liquid, paste, or solid composition. The hair can then be drawn over a rod, for example, so that both ends are positioned to one side, hanging down, and both ends are immersed in, coated with, or sprayed with the composition. This can also be done analogously with a bundle of several hairs.

[0157] According to a preferred embodiment, the method of the present invention yields a 3D surface structure in the nano- or micrometer range that deviates from a largely cylindrical shape.

[0158] Deviating from a largely cylindrical shape is often technically advantageous because it improves the adhesion of the implanted hair to the scalp. The implanted hair can be anchored more firmly and permanently.

[0159] Optionally, step (ii) of bringing at least one implantable part of the hair into contact with the liquid, pasty or solid composition can also be carried out by means of 3D shaping (e.g. 3D printing).

[0160] According to a preferred embodiment, step (ii) of contacting comprises adhering the composition to the hair or a part thereof by means of a 3D shaping process, wherein a 3D surface structure in the nano- or micrometer range is obtained which deviates from the largely cylindrical shape of the hair (and preferably also a droplet shape).

[0161] According to a preferred embodiment, step (ii) of contacting comprises adhering the composition to the hair or part thereof by partially melting the composition and / or the at least one silk protein, in particular by means of a femtosecond laser, especially in the ultraviolet (UV) spectral range.

[0162] According to a preferred embodiment, the method includes the further step of partially removing silk protein that has been applied to the hair.

[0163] According to a preferred embodiment, this is achieved by means of plasma ablation. According to a preferred embodiment, this is achieved using a femtosecond laser, particularly in the ultraviolet (UV) spectral range.

[0164] These procedures are explained in more detail above.

[0165] According to a preferred embodiment, the method comprises the following steps: (i) Providing: (A) hair not located on the human or animal body, and (B) a largely solid or pasty composition containing at least one silk protein, which may optionally be one or more fibers or an at least partially dried composition according to the present invention; (ii) bringing into contact or keeping in contact at least one implantable part of the hair with the composition, wherein steps (i) and (ii) may optionally take place simultaneously; (iii) adhering the composition to the hair or a part thereof by partially melting the composition containing at least one silk protein, preferably by a pulse of light, in particular a femtosecond laser, particularly in the ultraviolet (UV) spectral range.

[0166] Step (ii) of bringing at least one implantable part of the hair into contact with the liquid, paste, or solid composition can also involve bringing a kink or bendable part of the hair into contact with the liquid, paste, or solid composition. The hair can then be drawn, for example, over a rod so that both ends are positioned to one side, hanging down, and the tip located at the bend of the rod is immersed in, coated with, or sprayed with the composition. This can also be done analogously with a bundle of several hairs.

[0167] Alternatively, in step (ii), the hair can also be completely immersed in the liquid, paste, or solid composition containing at least one silk protein, or completely coated or sprayed with it. This is also possible with several hairs at once.

[0168] Optionally, the hair obtained from step (ii) can be used for implantation. In this case, the coating of the hair can be applied at the implantation site or in its immediate vicinity.

[0169] Optionally, the hair obtained from step (ii) can also be subjected to an additional drying step (iii). This can extend the shelf life of the implantable hair. Drying can be carried out under any conditions. Preferably, the conditions are chosen such that neither the hair nor the at least one silk protein is pyrolytically decomposed. Drying can take place at room temperature (15 to 25°C, preferably about 20°C) or at elevated temperature (approximately in the range of above 20°C to 150°C, or from 30°C to 100°C, or from 40°C to 70°C). Drying can take place at normal pressure or at reduced pressure (e.g., in a vacuum). The drying process can also be spray drying, whereby the coated hair from step (ii) is deep-frozen or shock-frozen (preferably at temperatures <-10°C, <-20°C, <-60°C or about -196°C) and then the solvent is evaporated under vacuum.Drying can optionally take place in an airflow. Drying can also be accelerated with a hairdryer, if desired.

[0170] The harvested implantable hair can be stored under any suitable conditions, such as at ambient temperature or in a refrigerator. It can be packaged in various ways. For example, it can be sterilely packaged. It can be vacuum-packed or packaged under a protective gas atmosphere. It can be packaged transparently or in a light-protective manner. It can be packaged and / or stored in a liquid or paste-like composition containing at least one silk protein.

[0171] It will be understood that a silk protein, hair and / or the coated hair according to the present invention can optionally be stored at any suitable temperature, for example at temperatures in the range of -200 to 250°C, -100 to 250°C, -80 to 200°C, -50 to 180°C, -10 to 150°C, 0 to 150°C, 2 to 120°C, 3 to 100°C, 4 to 80°C, 4 to 60°C, 4 to 50°C, 4 to 40°C, 5 to 30°C, 10 to 25°C or 15 to 25°C. Preferably, if not stored at ambient temperature, it should be brought to a temperature close to ambient temperature before implantation, for example, 5 to 30°C, 10 to 25°C, or 15 to 25°C. Like many materials, spider silk fibers undergo a glass transition. The glass transition temperature can depend on the humidity. Water can act as a plasticizer in this process.

[0172] Optionally, a package may contain instructions for use, which teach, among other things, how the implantable hair can be implanted into the skin.

[0173] Therefore, the following is also described here: a kit (of parts) comprising: (A) implantable hair according to the present invention; and (B) instructions for use for implantation; as well as a kit including: (A) Hair; (B) at least one container containing a liquid, pasty, or solid (preferably liquid or pasty) composition containing at least one silk protein suitable for coating hair or an implantable part thereof; (C) optionally, instructions for use for coating the hair with the composition; and (D) optionally, instructions for use for implantation; and a kit including: (A) Hair; (B) at least one container containing a concentrate or powder for the preparation of a liquid, pasty, or solid (preferably liquid or pasty) composition containing at least one silk protein suitable for coating the hair or an implantable part thereof; (C) optionally, instructions for use for coating the hair with the composition; (D) optionally, instructions for use for implantation; and (E) optionally, at least one solvent for the preparation of the liquid or pasty composition from the concentrate or powder.

[0174] As described, the implantable hair can be used for implantation into human or animal skin.

[0175] Therefore, another aspect of the present invention relates to the cosmetic use of the implantable hair for implantation into human or animal skin, in particular human scalp.

[0176] Thus, another aspect of the present invention comprises a cosmetic method for implanting the implantable hair according to the present invention into human or animal skin, in particular human scalp, comprising the following steps: (i) Providing hair according to the present invention, (ii) introducing the hair into human or animal skin, in particular human scalp, preferably by means of one or more needles.

[0177] It will be understood that all definitions and embodiments made in connection with the implantable hair and its manufacturing process according to the present invention shall apply accordingly to the use of, or a method for using, such implantable hair.

[0178] According to one embodiment, the implantation takes place in the scalp. According to another embodiment, the implantation takes place in one or more other areas of the face or body. For example, implantation can take place in the area of ​​one or both eyebrows, in the area of ​​one or both eyelashes, in the area of ​​the mustache, in the area of ​​the goatee, in the area of ​​the sideburns, in the area of ​​one or both sideburns, in the area of ​​the armpits, in the area of ​​the pubic region, in the area of ​​one or both arms, in the area of ​​the chest, or in the area of ​​one or both legs. Depending on the area of ​​application, appropriate hair can be selected.

[0179] The implantation can be performed for any purpose. Typically, the aim is to increase hair growth in one or more areas of human or animal skin.

[0180] According to one embodiment, the implantation is preferably performed largely symmetrically on both sides of the body. However, in the case of an accident and / or scarring, it may also be advisable to subject one side of the body to more extensive or even exclusive implantation. The implantation can be performed to create or restore scalp hair. Hair implantation, including body hair, can also be of interest for emphasizing male physical characteristics, for example, in gender reassignment surgery. Longer eyelashes can also be implanted. A specific beard shape can also be achieved by implanting hair implantable according to the present invention.The implantation of the implantable hairs according to the invention can also be used for the reconstruction of eyebrows, eyelash transplantation after alopecia mechanica, alopecia areata, beard replacement, for example after a correction of a cleft lip and / or (optionally scarring traumatic) alopecia.

[0181] Optionally, in addition to hair implantation according to the invention, hair growth can also be simulated and / or the partial or complete absence of hair can be concealed in other ways. For example, eyebrows can be made up with makeup or drawn on with makeup. Tattooing to create the appearance of short hair and / or coloring the scalp are also possibilities.

[0182] The implanted, implantable hair according to the present invention can optionally grow permanently in the recipient's skin. It can also optionally migrate to the epidermis as part of skin renewal and eventually fall out. The duration of its residence in the skin can be defined by the anchoring method as described above. In this way, the natural hair life cycle can be simulated. The half-life can be selected in consultation with the recipient.

[0183] The half-life of the implanted hair can thus be chosen. Hair loss can be increased and accelerated by haptic and mechanical influences such as combing, washing the corresponding head or body area, wind, hair drying, rubbing from clothing, etc.

[0184] The implantation can, in principle, be performed using any known method. Numerous methods are fundamentally familiar to those skilled in the art. The following figures, claims, and examples describe further embodiments of the invention, which further illustrate the invention. Figure Description

[0185] Figure 1Figure 1 schematically depicts the implantation of one or more hairs (2) into the scalp (1) of a person. It also shows that hair transplantation can be performed in the area of ​​the eyebrow (3), eyelashes (4), mustache (5), or other facial hair (6) (e.g., chin beard, sideburns, or cheeks). Hair transplantation can also be performed on other parts of the body. For better illustration, the hair transplantation is shown viewed through a magnifying glass (7), highlighting the coating of the implantable part (here, by way of example, the implantable terminal end) of a hair (2). Figure 1 exemplified as a replica of a hair root or hair follicle or hair bulb (8) comprising silk protein (e.g. spider silk and / or caterpillar silk). Figures 2 to 27The figures show examples of structures that can serve to anchor the implantable hair (2) according to the invention. For example, a structure formed as a replica of a hair root, hair follicle, or hair bulb (8) comprising silk protein (e.g., spider silk and / or caterpillar silk) can be used, which optionally includes an additional anchoring structure (9). A structure that can serve to anchor the implantable hair (2) according to the invention can also have one or more incisions (10) and thereby achieve improved anchoring. As can be seen in the figures, an anchoring structure can optionally include an additional anchoring structure (9) made of or coated with a composition comprising silk protein (e.g., spider silk and / or caterpillar silk), which functions as barbs, a spiral shape like a screw, or protrusions (9) to enable or improve the attachment of the hair implant.The coating, the optional anchoring, and / or the optional structures on the anchoring can also have different degrees of hardness. Furthermore, the anchoring (9) can be ring-shaped, which can improve the ingrowth of the surrounding tissue. The anchoring (9) can also optionally have one or more appendages containing a composition comprising silk protein (e.g., spider silk and / or caterpillar silk), which are connected to the anchoring by a bridge or any other form of connection. The anchoring can also have a structure, e.g., honeycomb-shaped, which can have a higher degree of hardness than the surrounding anchoring. The implantable hair (2) can optionally contain a coating (11), either completely or partially, preferably on its implantable portion, consisting of a composition comprising silk protein (e.g., spider silk and / or caterpillar silk).An implantable hair (2) may also comprise a natural / real hair root (12) and / or hair follicle and / or hair bulb, which may be surrounded by a coating (13) containing a composition comprising silk protein (e.g., spider silk and / or caterpillar silk). Example

[0186] Spider silk can be obtained in various ways. For example, a silk protein as described in WO 2007 / 025719 and WO 2006 / 008163 is used, specifically fibroin-3 and / or -4 from the European garden spider. (Araneus diadematus). Such a thing is also called “Araneus diadematus Fibroin 3" (ADF-3) or Araneus diadematus Fibroin 4" (ADF-4) or also referred to as ("Major Ampullate Spidroin II" or "Spidroin 2"). The ADF-3 and / or ADF-4 spider silk protein described here as an example can be obtained commercially. It was produced as described in WO 2006 008163. Therefore, it was produced in a bacterial fermentation process by Escherichia coliBacteria (also E. coli or E. coli bacterium). Spider silk protein-coding DNA from the European garden spider was introduced into the E. coli bacteria via gene transfer. (Diademed Spider) Genetically modified E. coli bacteria were created that express spider silk proteins by fermenting, for example, beets or sugar cane.

[0187] The implantable hair used for transplantation comes primarily from India. Among Hindu pilgrims, it is customary to offer their hair as a sacrifice after taking a vow or at the beginning of a new phase of life. This takes place mainly in Indian temples, which is why the hair is also referred to as temple hair. To prepare the hair for the European market, for example, it is sorted according to its properties, such as length, bundled, bleached, and dyed.

[0188] For the implantation of the implantable hair, the patient's own hair can also be cut. To ensure good quality, it should ideally be unbleached and undyed. For coating the implantable hair, it is sorted and bundled into narrow strips. At the terminal end, the hairs are cut with a very sharp blade so that they all end at the same point. This ensures that each individual hair is coated with silk. The silk coating is then applied by dipping the implantable portion of the hair into the liquid or paste-like substance, or by rubbing it against the solid substance. To improve the distribution of the silk, the hair bundle is rotated while being dipped into the liquid or paste-like substance.

[0189] The hair is then left to dry. To accelerate the drying process, it is exposed to gentle air circulation. To form further silk coatings, the hair is dipped back into the liquid or paste-like mixture after the silk layer has dried, following the same principle.

[0190] These process steps are repeated until the desired thickness of the protective layer around the implantable hair and the anchoring point is achieved. To additionally create, for example, a mushroom-shaped anchoring point, the hair end to be implanted is, after a certain number of repetitions, only immersed in the liquid or paste-like composition up to the point where the mushroom-cap-shaped widening is desired.

[0191] Before implantation, the scalp is first locally anesthetized. This is done using a plunger filled with the local anesthetic, such as the "Comfort-in" injection device (Mika Medical Co. 93, Noksansaneopjung-ro, Gangseo-gu, Busan, Republic of Korea). The plunger has a nozzle at its lower end with an opening of approximately 0.15 mm. As soon as the trigger is pressed, the plunger is in contact with the skin for about 0.3 seconds, during which time it delivers the anesthetic under high pressure, thus preserving the skin's integrity. All layers of the skin are numbed.

[0192] To implant the implantable hair into the skin, particularly the scalp, a special device known in the prior art for this purpose is used, resembling a mechanical pencil. For this, classic CII hollow needles (punches) from Cole Instruments Inc. (1070 Powers Place, Alpharetta, GA 30009 USA) can be used with corresponding commercially available accessories. Such a device comprises an outer hollow needle with which the skin is pierced and an inner hollow needle into which the implantable hair is inserted and secured by a clamping mechanism. At the clamped point, there is an advance mechanism (also similar to a mechanical pencil) which pushes the terminal end of the implantable hair approximately 1 mm out of the tip of the inner hollow needle. The electrical release mechanism for advancing the inner hollow needle and releasing the clamp is controlled by foot pedal operation.

[0193] The inner diameter of the inner hollow needle can be approximately 0.05 to 0.6 mm wider than the hair implant anchor. The inner diameter of the outer hollow needle is only as wide as necessary to allow the inner hollow needle to slide through. The outer diameter of the outer hollow needle is approximately 0.2 to 0.9 mm.

[0194] The implantation device is held against the skin in the direction of hair growth at an angle corresponding to the natural emergence angle of the hair, approximately 45 degrees. The outer hollow needle is inserted into the skin. The trigger is then pressed using the pedal, which automatically advances the inner hollow needle through the outer hollow needle. Once the inner hollow needle reaches the tip of the outer hollow needle, the hair is advanced by the feed mechanism. As soon as the hair is advanced as described, the clamping mechanism is automatically released, freeing the hair. The implantation device is then withdrawn from the skin and prepared for the implantation of the next hair.

[0195] An alternative method is the implantation of the hair using a device similar to those already used in autologous hair transplantation. For this purpose, the "OKT Implanter" from Cole Instruments Inc. (1070 Powers Place, Alpharetta, GA 30009 USA) can be used, for example, whose needle can have a diameter of 0.6 to 1.14 mm. In autologous hair transplantation, the extracted hair, including the hair root, is placed into a needle that has a slit or a through-hole on one side. The hair is then pressed into the scalp and thereby implanted. Similarly, when implanting hair according to the invention that has a coating containing at least one silk protein and optionally an anchoring structure, the hair, including its anchoring structure, can be placed into the needle of the OKT Implanter, pressed into the skin, and thereby implanted.The hair can hang out of the opening of the needle, making it possible to implant even long hair.

[0196] Depending on the number of implantable hairs to be implanted, a treatment can take from a few hours to a few days.

Claims

1. Implantable hair, characterized in that it is coated at least in an implantable section with a composition that comes into direct contact with the hair and contains at least one silk protein.

2. Implantable hair according to Claim 1, wherein the at least one silk protein has at least 90% sequence homology to a spider silk protein or an insect silk protein, preferably wherein the at least one silk protein has at least 90% sequence homology to a silk protein from one of the genera Araneus, Bombyx, Nephila, Antheraea, Arachnura, Caerostris, Argiope, Cyrtophora, Celaenia, Gasteracantha, Ordgarius, Neoscona, Zygiella, Parawixia, Neoscona, Dolophones, Aculeperia, Eriophora, Anepsion, Tegenaria, Heurodes, Cyclosa, Astracantha, Eriovixia, Nephilengys, Herennia, Acusilas, Neoscona, Poltys, Arkys, Poecilopachys Hyalophora, Samia, Attacus, Circula, Gonometa and / or Anaphe, more preferably wherein the at least one silk protein has at least 90% sequence homology to a silk protein selected from a species from the group consisting of Bombyx mori, Bombyx mandarina, Antheraea pernyi, Antheraea yamamai, Antheraea mylitta, Antheraea roylei, Antheraea proyeli, Antheraea paphia, Antheraea frithi, Antheraea assama, Araneus didenatus, Nephila clavipes, Araneus bicentenarius, Arachnura higginsi, Araneus circulissparsus, Araneus diadematus, Caerostris darwini, Argiope picta, Argiope trifasciata, Nephila antipodiana, Cyrtophora beccarii, Celaenia excavata, Gasteracantha kuhlii, Argiope aurantia, Ordgarius furcatus, Ordgarius magnificus, Neoscona nautica, Neoscona rufofemorata, Zygiella calyptrata, Parawixia dehaani, Neoscona oxancensis, Gasteracantha cancriformis, Gasteracantha arcuata, Cyrtophora moluccensis, Cyrtophora parnasia, Dolophones conifera, Dolophones turrigera, Gasteracantha doriae, Gasteracantha mammosa, Cyrtophora exanthematica, Aculeperia ceropegia, Eriophora pustulosa, Anepsion depressium, Gasteracantha quadrispinosa, Eriophora transmarina, Araneus bicentenarius, Nephila maculata, Gasteracantha hasseltii, Tegenaria atrica, Heurodes turrita, Cyclosa insulana, Astracantha minax, Araneus mitificus, Eriovixia laglaisei, Cyclosa bifida, Nephilengys malabarensis, Argiope versicolor, Herennia ornatissima, Argiope aemula, Cyrtophora unicolor, Cyrtophora hirta, Argiope keyserlingi, Acusilas coccineus, Argiope argentata, Gasteracantha cancriformis, Neoscona domiciliorum, Argiope aetheria, Argiope Keyserlingi, Poltys illepidus, Arkys clavatus, Arkys lancearius, Poecilopachys australasia, Nephila clavipes, Nephila senegalensis, Nephila madagascariensis, Hyalophora cecropia, Samia Samia cynthia, Attacus atlas, Circula trifenestrata, Gonometa postica, Gonometa rufobrunnea, Anaphe panda and / or Anaphe moloneyi, especially wherein the at least one silk protein has at least 90% sequence homology to a silk protein from a species selected from the group consisting of Bombyx mori, Antheraea pernyi, Araneus diadematus, Nephila clavipes, Araneus bicentenarius and Caerostris darwini.

3. Implantable hair according to at least one of Claims 1 or 2, wherein the at least one silk protein is characterized in that: (a) it is selected from the group consisting of fibroin, sericin, spidroin 1 and spidroin 2; and / or (b) it comprises at least two sequence sections each having one of the following sequences SEQ ID NO: 1 to 6: GPGXX (SEQ ID NO: 1), GVPGX(SEQ ID NO: 2), GSGXX(SEQ ID NO: 3),GGYXX(SEQ ID NO: 4),PQQXX(SEQ ID NO: 5),GYGXX(SEQ ID NO: 6), where X may be any natural amino acid, and is preferably selected from the group consisting of V, G, A, S, Y, P and Q.

4. Implantable hair according to at least one of Claims 1 to 3, wherein the at least one implantable section is an implantable terminal end or an implantable kink in the middle of the hair or a kinkable portion in the middle of the hair.

5. Implantable hair according to at least one of Claims 1 to 4, wherein the implantable hair is characterized in that: (a) it is a human hair; (b) it is a human hair that has been cut off without the hair follicle and without the hair root and without the hair bulb; (c) it is a synthetic hair or an animal hair; and / or (d) over the entire length it has an average diameter of 0.02 to 0.15 mm.

6. Implantable hair according to at least one of Claims 1 to 5, wherein the implantable hair is characterized by at least one of the following features: (1) wherein the implantable hair, in the implantable section, has no thickening corresponding to a maximum circumference of more than twice the average circumference of the hair; (2) wherein the implantable hair, in the implantable section, has an artificial thickening which is formed by the composition, wherein the thickening corresponds to a maximum circumference around the hair of at least twice the average circumference of the hair; (3) wherein the implantable hair, in the implantable section, has an artificial anchoring structure that may optionally be selected from the group consisting of the form of a cone, a frustocone, a thickened cylinder, a mushroom, a droplet, an ellipsoid, a cuboid, a spiral form, a screw form, a ring form, a sphere, a honeycomb structure, a partial wrapping of the hair with a fibre or a tape, and a combination of two or more of these, and may optionally have appendages that project from the hair structure and / or the anchoring structure; (4) wherein the implantable hair is notched in the implantable section; (5) wherein the implantable hair, in the implantable section, has a hair follicle or a hair root or a hair bulb coated with the composition; (6) wherein two or more implantable hairs, in their implantable sections, are encompassed in a coating or anchoring structure; (7) wherein the coating has zones with different strength and / or biological stability, and especially has higher strength and / or biological stability in the interior close to the hair than on the outside, (8) wherein the coating of the implantable hair, comprising the at least one silk protein, is designed such that, after implantation, the silk protein or a degradation product is transported onto the hair outside the body and / or the scalp, where it cares the hair and / or the skin.

7. Implantable hair according to at least one of Claims 1 to 6, wherein the implantable hair has been coated with the composition by means of 3D shaping, especially 3D printing, in particular wherein the production thereof comprises the at least partial melting of the composition and / or of the at least one silk protein, especially by means of a femtosecond laser.

8. Implantable hair according to any of Claims 1 to 7, wherein the production thereof comprises the partial removal of silk protein that has been applied to the hair, especially by means of plasma ablation, especially by means of a femtosecond laser.

9. Implantable hair according to any of Claims 1 to 8, wherein the implantable hair has been at least partly coated with a solid or pasty composition having a 3D surface structure in the nano- or micrometre range that differs from a largely cylindrical form.

10. Method of producing implantable hair according to at least one of Claims 1 to 9, wherein the method comprises the following steps: (i) providing: (A) hair that is not on the human or animal body, and (B) a composition containing at least one silk protein; and (ii) contacting at least an implantable section of the hair with the composition.

11. Method according to Claim 10, wherein the contacting step (ii) comprises: (a) the dipping of the hair or a section thereof into the liquid or pasty composition; (b) the coating or spraying of the hair or a section thereof with the liquid or pasty or solid composition; (c) the sticking of the composition to the hair or a section thereof by means of a 3D shaping method, wherein a 3D surface structure in the nano- or micrometre range that differs from a largely cylindrical form is obtained; (d) the sticking of the composition to the hair or a section thereof by means of the partial melting of the composition and / or of the at least one silk protein, especially by means of a femtosecond laser; (e) the method comprises the further step of partly removing silk protein that has been applied to the hair, especially by means of plasma ablation, especially by means of a femtosecond laser,preferably affording a 3D surface structure in the nano- or micrometre range that differs from a largely cylindrical form.

12. Method according to either of Claims 10 or 11, wherein the method comprises the following steps: (i) providing: (A) hair that is not on the human or animal body, and (B) a liquid or pasty or solid composition containing at least one silk protein; (ii) contacting at least an implantable section of the hair with the liquid or pasty or solid composition; and (iii) optionally drying the implantable hair obtained from step (ii); and / or wherein the method comprises the following steps: (i) providing: (A) hair that is not on the human or animal body, and (B) a largely solid or pasty composition containing at least one silk protein that may optionally constitute one or more fibres or an at least partly dried composition according to Claim 11; (ii) contacting or maintaining contact of at least an implantable section of the hair with the composition, where steps (i) and (ii) may optionally also take place simultaneously, (iii) sticking the composition to the hair or a section thereof by means of partial melting of the composition containing at least one silk protein, preferably by means of a pulse of light, especially by means of a femtosecond laser, preferably affording a 3D surface structure in the nano- or micrometre range that differs from a largely cylindrical form.

13. Cosmetic use of implantable hair according to at least one of Claims 1 to 9 for implanting into human or animal skin, especially the human scalp.

14. Cosmetic method of implanting implantable hair according to at least one of Claims 1 to 9 into human or animal skin, especially the human scalp, comprising the following steps: (i) providing hair according to at least one of Claims 1 to 9; (ii) introducing the hair into the human or animal skin, especially the human scalp, by means of a needle.