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Biomaterials for tissue

engineering of skin
Tissue-engineered skin has been in clinical use for 25 years and
has developed greatly during this time. This review looks at the role
biomaterials need to play in providing for epidermal cover, dermal
replacement, and epidermal/dermal replacement, and describes the
major problems that remain. The majority of biomaterials in clinical use
are based on natural or extracted collagen. The clinical challenges in
using these materials are highlighted throughout – specifically safety
issues, improving the take of cultured cells on wound beds, improving
the rate of neovascularization of tissue-engineered skin, and developing
scaffolds that resist contraction and fibrosis.
Sheila MacNeil
Department of Engineering Materials, Kroto Research Institute, University of Sheffield, Broad Lane, Sheffield S3 7HQ, UK
E-mail: s.macneil@sheffield.ac.uk

Tissue-engineered skin includes cells delivered on their own, Skin physiology has been reviewed in depth in a series of articles
cells delivered within two- or three-dimensional biomaterials, spanning skin development and stem cells1, skin pigmentation2, sensory
biomaterials for replacement of the skin’s dermal layer (both with transduction3, and progress in tissue engineering of skin4.
and without cells), and biomaterials to support the replacement This review gives a snapshot of the biomaterials currently in clinical
of both the epidermis and dermis. In discussing these scenarios, use in this field (summarized in Table 1), looking at how they are
it is useful to look first at the role of skin and determine what used and in particular, flagging up where there are still major clinical,
functions biomaterials need to provide. practical, and safety challenges. Innovative materials could theoretically
help overcome many of these problems.
What does skin do and what do biomaterials
need to do? Skin barrier function
Tissue-engineered skin needs to: (a) provide a barrier layer of Fig. 1 illustrates the structure of normal skin, which provides an
renewable keratinocytes (the cells that form the upper barrier layer essential water-, electrolyte-, and bacteria-proof barrier to the outside
of our skin), which is (b) securely attached to the underlying dermis, world. When this function is lost through burns or chronic nonhealing
(c) well vascularized, and (d) provides an elastic structural support for ulcers, then patients are susceptible to bacterial infection. In burns
skin. patients with extensive skin loss, bacterial sepsis can be fatal.

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Open access under CC BY-NC-ND license.
Biomaterials for tissue engineering of skin REVIEW

Table 1 Biomaterials in use for tissue engineering of skin

Objective Approach Examples


Epidermal cover Delivers cultured keratinocytes so that they • Cultured epidermal sheets – Epicell5,6
‘take’ on the wound bed and form a new • Cultured epidermal sheets from plucked hair follicles – Epidex7
epidermal layer • Subconfluent cells on a synthetic carrier – Myskin8–11
• Cells delivered in a fibrin spray12
Dermal replacement Provides a dermal alternative to promote • Donor skin13
wound healing or is used in a two-stage • Permacol14
skin replacement protocol • Dermagraft15
• Transyte16
• Integra17,18
Epidermal/dermal replacement Acts as an alternative to a split-skin graft • Apligraf19,20
• Permaderm21
• Orcel22
• Tissue-engineered skin23
• Tissue-engineered oral mucosa24

The skin barrier function is achieved by layers of differentiated of the epidermis, become progressively stratified, lose their nuclei, and
keratinocytes fusing together in a tightly integrated epidermal sheet. eventually fuse into the crucial barrier layers of keratin sheets that are
The lower, thicker dermal layer consists of collagen fibers that, at their routinely shed from the skin surface.
upper surface, form a specialized basement membrane (BM) zone
for secure attachment of keratinocytes to the dermis. The dermis is Secure attachment to the dermis
vascularized and contains receptors for touch, temperature, and pain, as The epidermis is securely attached to the collagen fibers of the
well as hair follicles and sweat ducts, the latter lined with keratinocytes dermis by complex three-dimensional BM anchoring structures called
that contribute to epidermal regeneration. hemidesmosomes. (These are a collection of adhesion receptors that
The epidermal layer is relatively thin, 0.1–0.2 mm in depth, and extend through the cell membrane and act as anchoring filaments to
consists of a self-renewing population of keratinocytes programmed to bind keratinocytes to the lower BM.) The proteins that form the BM,
be replaced continuously for a lifetime from basal cells located on the collagen IV, collagen VII, and laminin, are vital for this attachment
BM zone1. The majority of keratinocytes move into the upper layers and are synthesized by the dermal fibroblasts (the cells that form the

Fig. 1 Structure of human skin showing the upper epidermal barrier layer and the much thicker dermal layer with hair follicles and sweat glands lined with epithelial
cells. (Reprinted with permission from59. © 1999 McGraw-Hill.)

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REVIEW Biomaterials for tissue engineering of skin

lower spongy layer of skin) under instruction from the keratinocytes25. keratinocytes lining the dermal inclusions (the sweat glands and
Genetic problems with BM components result in a range of blistering hair follicles) will rapidly migrate out of the dermis and form a new
diseases (collectively known as Epidermylosis Bullosa26) that vary epithelium. However, if the epidermis and all of the dermis is lost,
in their severity, but some forms can be fatal. (If the epidermal then this represents a major problem. Any loss of full-thickness skin
barrier layer cannot be maintained, then patients are wide open to of more than 4 cm in diameter will not heal well without surgical
bacterial infection). The reconstitution of this BM zone on the patient intervention27,30. When this is the case, it is often necessary to
remains one of the major challenges for tissue engineering today (see reconstitute the skin in two stages taking two separate operations31
below). (Fig. 2).
Ideally if a burn injury is not too extensive, then surgeons will take
Vasculature a split-thickness skin graft (all of the upper epidermal layer of skin and
Skin is well vascularized and this is essential for skin repair, which is some of the underlying dermal layer) from elsewhere in the body and
normally excellent for individuals in good health. However, if there is use it to graft the damaged area (Figs. 2a and 2b). The site from which
extensive skin loss, such as occurs in burns injuries, then the patient the skin graft has been removed will then heal by keratinocytes within
cannot repair skin rapidly enough27. Additionally, if the normal wound the dermis migrating upwards and proliferating.
healing mechanisms are compromised because of poor vasculature However, if the extent of burn injury is extensive, then it is often
(usually age or diabetes associated), then skin repair can be slow or necessary to ‘build up’ the skin in two stages. One material is used to
fail to occur. This is a major problem in the western world with aging provide a dermal equivalent that must become vascularized before an
populations and increasing incidence of diabetes28. Achieving rapid epidermal material (most often a very thin split-thickness graft, but
neovasularization in tissue-engineered materials is another major occasionally cultured cells or tissue-engineered skin) can be placed on
challenge (see below). top (Figs. 2c and 2d)17,27,30.
In addition to burns injuries, tissue-engineered materials can benefit
Elasticity and support patients with chronic ulcers and those requiring reconstructive surgery4.
The dermis also provides support and elasticity through a complex The biomaterials in current use for tissue engineering are discussed in
architecture of enzymatically cross-linked collagen and elastin fibers29. the next three sections.
Failures of repair can result in skin contraction, fibrosis (where
fibroblasts produce scar-like material), and scarring. Contraction23 Epidermal cover
and fibrosis24 of tissue-engineered materials are emerging as other Culture of human adult skin cells from a small biopsy of the patient’s
problems (see below). skin was developed in the 1970s32,33 by expanding keratinocytes
on lethally irradiated mouse fibroblasts in the presence of mitogens
Why do we need tissue-engineered (small proteins that stimulate cells to divide) and bovine fetal calf
materials? serum. This works well and gives reliable expansion of keratinocytes
In partial thickness burns, in which the upper epidermal layer is even for the elderly. By the early 1980s, small sheets of keratinocytes
completely lost but part of the dermis remains, the epidermal (referred to as cultured epithelial autografts, CEAs) were being used to

(a) (b)

(c) (d)

Fig. 2 Reconstruction of full thickness burn injuries. In the majority of cases, (a) a full thickness skin defect is treated with (b) a split thickness skin graft taken from
elsewhere on the body. Where sufficient skin grafts are not available, then full thickness defects are repaired in two stages using (c) a dermal substitute, which is
then covered by (d) an epidermal material, usually a very thin split thickness skin graft. (Reprinted with permission from60. © 2008 Woodhead Publishing.)

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treat patients with extensive burns injuries5. These cells are grown on placed cell surface down onto the wound bed, and keratinocytes still
a feeder layer of lethally irradiated mouse fibroblasts (used to provide capable of leaving this integrated sheet of cells enter the wound bed
a good surface for the cells to attach to, and also to provide growth and form a new epithelium. The backing dressings with any residual
factors to encourage proliferation of the keratinocytes) until they are differentiated cells are removed some 7–10 days later31.
2–3 cell layers thick and the cells have joined to each other in a thin As handling cells in this way is quite difficult, alternative
sheet. To detach the cells, it is necessary to add an enzyme to loosen approaches for detaching and delivering cells have since been
the attachment of the cells to the underlying tissue culture plastic developed. For cell detachment, growing cells on temperature-sensitive
and then gently scrape the sheet from the plastic using mechanical poly(N-isopropylacrylamide) (PNIPAM) has been advocated34. Cells
force (a tricky job when one wants to avoid ripping these sheets grow into sheets on PNIPAM-coated tissue culture dishes, then the
into pieces). Sheets of cells are then wrapped around a piece of inert temperature is decreased to collapse the polymer chains and release
backing dressing for delivery to the patient. the cell sheet. Keratinocytes can also be expanded in culture, made
There are practical problems in delivering keratinocytes as small into suspensions, and sprayed onto wound beds in media35 or with
sheets. The sheets are fragile and many of the keratinocytes are already fibrin12. Alternatively, keratinocytes are expanded then seeded onto
differentiated beyond the point at which they can take any active part various carrier/transfer dressings, ranging from bovine collagen
in providing a new epithelium. Nevertheless, this was a breakthrough coated membranes36 to a chemically defined polymer carrier dressing
methodology and is available commercially as Epicel6. The cells are (Myskin37, Fig. 3).

(a) (b)

(c) (d)

Fig. 3 Plasma polymerization can be used to produce surfaces that are either nonadherent or keratinocyte adherent. (a) Plasma rig. The sample to be coated is
placed within the vacuum chamber and a high radiofrequency energy is used to break the material into fragments under vacuum. This introduces the material to be
coated as a gas, which becomes attached to the surface. (b) This technique is used to produce a background surface coated with octadiene, which is nonadhesive
for the majority of cells. Onto this is placed a template of the letters ‘TONY’ coated with acrylic acid. Skin cells from Tony Ryan of the University of Sheffield, UK,
were expanded in the laboratory and placed on this surface. They adhered to the acrylic acid-coated surface but failed to adhere to the octadiene-coated surface.
(c) The clean room conditions under which patients’ skin cells are expanded from a small skin biopsy. (d) An acrylic acid plasma polymerized silicone carrier
(Myskin™). Patients’ cells are placed on the acrylic acid-coated surface and kept in media for transport to the patient. The clinician or dressings nurse picks up the
Myskin carrier and places it with the cells facing downwards onto the wound bed.

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(a) (b)

Fig. 4 (a) A neuropathic diabetic ulcer that has failed to heal for 3 years, and (b) after eight applications of the patient’s own cells delivered on the Myskin carrier9.

Myskin is a synthetic polymer of acrylic acid coated onto medical Integra17,18 was developed for the treatment of full-thickness
grade silicone by plasma polymerization37,38. This avoids the use of burns injuries. It consists of a dermal replacement material, composed
bovine collagen. Cells attach readily to this surface (after conventional of bovine tendon collagen with a glycosaminoglycan (chondroitin-6-
expansion in the laboratory), but when cells on the transfer dressing sulphate) added to it, onto which a silicone membrane is sealed to
are placed on the wound bed, the surface has been designed so that the upper surface to act as a temporary epidermal substitute layer.
cells can leave it without the need for trypsinization (using an enzyme This artificial membrane is designed for temporary use only. (In the
to detach the cells from the substrate), change in temperature, or any absence of living cells, it is very difficult to see how one could create
outside intervention. Fig. 4 shows an example of a diabetic ulcer that a permanent artificial dermal barrier.) It controls moisture loss from
resisted healing for three years but did heal after eight applications of the wound and bacterial entry into the wound. The most important
the patient’s own cells delivered on the Myskin carrier in an outpatient function of Integra is that it serves as a template to generate a
clinic9. neodermis. Following vascularization of the material from the patient’s
Thus biomaterials can assist in the transport and delivery of wound bed, which normally takes about three weeks, the silicone layer
keratinocytes to a wound bed. Depending on the design of the is peeled off and an epidermal layer is provided, usually using a very
material, cells will leave the carrier dressing in a passive36,37 or active34 thin skin graft.
manner. However, a major issue that none of these materials directly The neodermis that forms under either Integra or donor skin gives a
addresses is how to improve the attachment of the keratinocytes to better wound bed for take of future skin grafts than if the wounds were
the underlying wound bed, given that clinical wound beds that require allowed to heal through the formation of disordered granulation tissue.
the use of cultured cells are often less than ideal. Integra has been evaluated in an economic study for its use in chronic
wounds compared with using split-thickness skin39. Donor skin has now
Dermal replacement been used for more than 20 years with good results40. The advantages
Currently, three types of biomaterials are in use for dermal of both donor skin and Integra are that they can give immediate barrier
replacement: natural dermal collagen obtained from human allodermis protection.
(dermis derived from skin donated to skin banks) or porcine dermis Dermagraft is a cryopreserved human fibroblast dermal substitute
(Permacol14), extracted bovine collagen, and nonwoven polygalactic for chronic wounds that has been shown to increase the rate of
acid scaffolds (Dermagraft15 and Transcyte16). healing15. In this product, donor fibroblasts are seeded onto a
Donor skin obtained from accredited skin banks can be used as a bioabsorbable polyglactin mesh scaffold. Transcyte16 is similar to
temporary wound dressing or to provide a permanent allodermis4. Dermagraft15 in design, in that it contains human donor fibroblasts
Permacol is cross-linked porcine collagen that is sometimes used as a that have been grown on a porcine collagen coated bioabsorbable
temporary skin dressing14. polyglactin scaffold. But this product also has a silicone membrane

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(a) (b)

(c) (d)

Fig. 5 (a) Split thickness skin is (b) sectioned and stained with haematoxylin. (c) Once denuded of all cells, the remaining de-epidermized acellular dermis is pliable
and (d) can be reconstituted with laboratory-expanded keratinocytes and fibroblasts for experimental or clinical use41.

attached to it to act as a temporary barrier (as in Integra17). Transcyte of reconstructed skin in which the de-epidermized acellular
is recommended for use in major burns to provide a dermal alternative dermis is reconstituted with keratinocytes and fibroblasts isolated
and a temporary epidermal barrier. from a patient’s skin biopsy. These cells are expanded up in the
laboratory and then added back to the acellular dermis. However,
Epidermal/dermal replacement when this reconstructed skin is taken to the clinic (as shown in
As is evident from the previous section, collagen is the favorite Fig. 6), then problems with delayed vascularization23 can lead to
biomaterial for tissue engineering, whether in the form of mature loss of relatively thick reconstituted tissue-engineered skin grafts
human cross-linked collagen (donor skin obtained from skin banks) or and for those grafts that survive, some may undergo significant
collagen extracted from bovine or porcine skin or tendon. However, contraction23,42,43.
there are three issues to be tackled: safety, neovascularization, and Neovascularization has been identified as a problem for tissue-
contraction. engineered constructs (not just skin). Constructs lacking any intrinsic
With respect to safety, currently bovine collagen is approved by the vasculature can be slow to vascularize and fail to integrate. This is one
US Food and Drug Administration (FDA) for clinical use as the risks are of the major problems in the field at present. Novel approaches to
viewed as low, if the collagen is sourced from herds known to be free improve the rate of neovascularization of tissue-engineered skin are
of bovine spongiform encephalitis (BSE). The other major source of badly needed.
collagen dermal substitute is natural dermis from cadaveric skin. Here The problem of contraction is also a challenge. It is possible to
screened donors from accredited tissue banks must be used to reduce alter the cross-linked structure of the dermal scaffold so that it resists
the risk of transmission of viral diseases. contraction (as is seen in the case of Permacol14) but this leads
Fig. 5 illustrates tissue-engineered skin based on natural dermis. to another interesting and important problem. Scaffold materials
Fig. 5a shows the appearance of normal skin before processing that are extensively cross-linked can initiate fibrosis, encapsulation
and Fig. 5b is a haematoxylin and eosin (H&E) stained section (formation of a thick layer of connective tissue around an implant),
through the skin visualized using light microscopy. Fig. 5c shows and a relatively extreme immune response44. A recent theory on
the gross appearance of the dermis that remains after epidermal this proposed by Badylak44 and others45 is that unless neutrophils
and dermal cells have been removed by a mixture of NaCl and and macrophages can degrade implanted collagenous structures,
phosphate-buffered saline washing41. Fig. 5d shows the appearance they will activate lymphocyte TH2 cells, which provoke an extreme

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(a) (b)

Fig. 6 (a) The use of tissue-engineered skin to treat extensive contraction following burns injury. (Reprinted with permission from23. © 2003 Blackwell Publishing.)
(b) Keratinocytes contract human allodermis in the laboratory.

inflammatory reaction, rather than the induction of TH1 helper enzyme, lysyl oxidase, to cross link the gathered-in collagen fibers. An
immune cells, which lead to constructive remodeling of natural inhibitor of lysyl oxidase found in sweet peas, beta-aminoproprionitrile
scaffolds45. (β-APN), can reduce this42.
Fig. 6b illustrates the ability of skin cells to contract natural dermis, Fig. 7 illustrates natural human dermis used to make tissue-
the subject of some investigation in our laboratory43,46,47. This suggests engineered oral mucosa. Fig 7a shows the morphology of normal
that skin cells, particularly keratinocytes, use a collagen cross-linking buccal mucosa (the lining of the mouth), and Fig. 7b is tissue-

(a) (b)

(c) (d)

Fig. 7 (a) Normal buccal mucosa stained with haematoxylin and eosin. (b) Tissue-engineered buccal mucosa. (c) A 10 cm x 2 cm piece of tissue-engineered buccal
mucosa used to treat scarring of the urethra. (d) Some 18 months post treatment with tissue-engineered buccal mucosa to replace scarred tissue, the patient’s
urethra remains open and unscarred. (Reprinted with permission from24. © 2008 Elsevier.)

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engineered buccal mucosa in which de-epidermized acellular dermis is How can the safety of biomaterials be ensured?
reconstituted with epithelial cells and fibroblasts from a small biopsy While natural collagen scaffolds can work well, the devil is in the
taken from the patient’s mouth. Fig 7c illustrates the gross morphology detail of how they are extracted, processed, and sterilized to be fit for
of a tissue-engineered oral mucosa produced in this way. Fig 7d is purpose with low risk for the patient. The risk of disease transmission
taken 18 months after this tissue-engineered construct has been used from human skin can be reduced with good skin banking practices,
to replace scar tissue in the urethra. The urethra is free of scarring. We especially if combined with skin sterilization41,48,49, but cannot be
have recently reported a pilot study getting tissue-engineered buccal completely eliminated. Bovine-derived collagen approved by the FDA
mucosa into clinical use24. The initial vascularization was excellent is currently perceived as low risk, but this depends on herds not being
because this is a very well vascularized wound bed, but we did find previously exposed to BSE. Accordingly, the development of alternative
fibrosis occurred in two out of the five patients studied, suggesting that synthetic scaffolds is to be welcomed. Frontrunner materials are poly-L-
further work needs to be undertaken to produce scaffolds that resist lactide (PLLA), polycaprolactone (PCL), and polyglycolic acid (PGA)50,51.
fibrosis. These have been approved by the FDA and used clinically for a number
of years in a range of applications, such as resorbable sutures, fracture
Biomaterials challenges in tissue engineering plates, and stents52. (Dermagraft15 and Transcyte16 are both based on
skin synthetic scaffolds and have been in clinical use for several years.)
The problems of existing materials have been flagged up throughout There is much interest in producing scaffolds by electrospinning
this review and can be summarized as follows: (Fig. 8a). This versatile method can produce three-dimensional open
• Safety issues – avoiding animal-derived materials; porous structures that approximate the structure of collagenous dermis.
• Improving the ‘take’ of cultured keratinocytes on wound beds – can Natural materials, such as collagen and chitosan, can be spun on their
we make a synthetic BM glue? own or together with synthetic polymers. One can spin parallel
• Improving the rate of neovascularization of tissue-engineered skin; (Fig. 8b), or random (Fig. 8c) fibers, depending on the speed of
and spinning. These fibers can be used in vitro to determine optimal fiber
• Developing scaffold materials that resist contraction and fibrosis. diameter and the spaces between fibers that cells can bridge.

(a) (b)

(c) (d)

Fig. 8 (a) Electrospinning of fibers. Production of (b) parallel and (c) random fibers. (c),(d) Polylactic fibers have had rhodamine added to help in visualization, and
cell nuclei have been stained blue with DAPI. (c) Fibroblasts are seen throughout the random scaffold. (d) Fibroblasts are able to bridge gaps between fibers61.

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(a) (b)

(c) (d)

Fig. 9 A random biodegradable 75% PLA, 25% PGA electrospun scaffold (a) before and (b) after culture with small vessel endothelial cells, here stained with Toto
red. (c),(d) Three months after implantation of cell-free scaffold fibers into the flank of rats. Scaffold fibers seen at (c) low and (d) high magnification show good
vascularization and penetration of granulation tissue.

It is possible to vary the ratio of PLA to PGA to produce scaffolds research to improve take of cells by attaching avidin (a naturally
with different rates of degradation in vivo. Fig. 9 shows the appearance occurring protein with an extremely high affinity for binding to
of a random spun scaffold of 75% PLA and 25% PGA. Fig. 9b shows the natural vitamin biotin) to the cells and biotin to a collagen
a culture of small vessel endothelial cells on this scaffold in vitro, and substrate shows that this approach can improve attachment54.
Figs. 9c and 9d show the appearance of the scaffold implanted into But a major challenge is that whatever is to be used on the wound
the flank of rats at three months. In Fig. 9c, taken at deliberately bed must be something that’s clinically acceptable. In recent years
low power, one can see that there is good tissue penetration and there has been considerable research into developing synthetic,
vascularization of the scaffold (introduced cell-free into these rats). often self-assembling, biomimetic matrices incorporating natural
Fig. 9d shows a higher power to illustrate the appearance of these cell adhesion sequences as microenvironments for directing tissue
fibers, which break down over a period of several months. morphogenesis55. The task of making a synthetic BM-equivalent
Alternative approaches are to get skin cells to generate their glue that one could ideally spray on the wound bed before delivering
own scaffold in vitro. This can be achieved either with some existing cultured cells (on their own or in scaffolds) is a major challenge, but
scaffold support (as in Dermagraft15 and Transcyte16) or as recently one which these new generations of three-dimensional synthetic
demonstrated53, seeding fibroblasts into human fibrin and encouraging scaffolds may achieve.
the cells over seven weeks to produce their own matrix, which is then
subsequently freeze dried and sterilized to be used as a scaffold for How can materials improve neovascularization of
repopulation with living cells for future clinical use. tissue-engineered skin?
The biomaterials commonly in use, such as donor skin or Integra
How can attachment of cultured skin cells to wound often take two–three weeks to become well vascularized. A number
beds be promoted? of biomaterials are being developed to enhance angiogenesis, ranging
Keratinocytes delivered on their own as sheets, as a spray, or from from the introduction of large pore sizes into scaffolds to promote
carrier dressings lack components of the BM, and have an uphill faster vascularization56, to the release of potent angiogenic factors
struggle in attaching well to challenging wound beds. Laboratory-based such as basic fibroblast growth factor (bFGF) from a three-dimensional

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peptide-amphiphile injectable scaffold57, and synthetic biomaterials Summary and future outlook
representing simplified components of the extracellular matrix Tissue engineering of skin is a maturing field and the biomaterials
(ECM)55. However, none of these are yet in clinical use to the best of (mostly collagen) used in tissue-engineered products have benefited
my knowledge and there is a real clinical need to improve the rate of patients since the 1990s. However, it would be wrong to conclude
vascularization for tissue-engineered skin products to prevent loss of that there is no room for improvement. In the future, it is hoped that
grafts. new biomaterials will be produced to overcome at least some of the
problems identified in this review.
How can scaffolds resist contraction and fibrosis? Eliminating or reducing the risk of disease transmission could be
Finally, if even standard skin grafts can contract when moved from achieved either by using synthetic collagen-mimetic materials or
one position on the body to another43, what chance do we have of recombinant-produced collagen. Next, can biomaterials be designed to
producing natural or synthetic scaffolds that resist contraction and improve the attachment of cultured cells to the underlying wound bed?
fibrosis? How skin cells affect the biophysical properties of the dermis Hopefully, our knowledge of angiogenesis and biomaterials design will
is poorly understood but the natural elasticity of skin is based on its lead to materials that become vascularized more rapidly than current
elastin content. There is a growing body of research investigating ones. Finally, we need to combine our understanding of wound healing
elastin as a biomaterial for tissue engineering that should offer new and immune responses with biomaterials to produce biodegradable
insights and approaches for producing scaffolds better able to resist scaffolds that lead to rapid healing without suffering significant
contraction58. contraction in the short term or fibrosis in the longer term.

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