The scope of biomaterials used in wound dressing is growing apace, drawing upon

research into myriad novel materials; in this section we will expound on some of the major
problems facing biomaterials for the application of wound care, recent developments in
designing new systems for wound care utilizing biomaterials, and possible new avenues of
investigation for the future of wound care biomaterials.
Challenges confronted in existing biomaterials used for wound treatment, generally
speaking, divide into one of two camps. Of primary concern is the manner in which the
biomaterial interacts with damaged tissue – in terms of its efficacy in bringing about its intended
outcome and avoiding undesirable outcomes or unintended side effects. Secondly, the manner
in which the biomaterial itself is procured must also be considered, for not only does it affect
how it addresses the aforementioned challenges, but it also must as with any medical
technology be viable outside of a controlled lab environment.
The first category of biomaterials we shall consider are those known as ‘traditional
dressings’, which are the first line of defense in isolating the wound from the environment; the
best representatives of this category are the gauze and gauze-cotton composites. The main
problem with these biomaterials is that they cause rapid dehydration or surface pain and trauma
when being removed from the tissue. This issue is partly ameliorated by the use of non-
adhesive inner surfaces. Additional problems include fluid leakage from the wound and
immunogenicity of the material itself (which is foreign). The main benefit of traditional dressings
is their low cost – they have the advantage in their consistency and sterility of production.
A second category of biomaterials are those utilizing natural biological tissues with
collagen-type structures (elastin and lipid), which include allografts and xenografts. Allografts
include skin fragments taken from patient relatives or cadavers either fresh or freeze-dried.
Major disadvantages of allografts include the necessitation of immunosuppressant use to
prevent tissue rejection, which makes infection easier. Other disadvantages include the inherent
difficulty in preparation of actual tissue or finding donors, the high cost and the limited shelf life –
making this often commercially unavailable. Xenografts are commercially available, as it
originates in pig skin. The main disadvantage of xenografts is its immunogenicity as the body
reacts to pig tissue – it holds the advantage in sterility, usability and availability.
A third category of biomaterials used for wound care include polymeric materials, which
includes both natural and artificial polymers. Generally, each type of material will have a specific
advantage or ‘specialty’ that it does best, while having its own set of drawbacks. A material that
does well in absorbing exudate will have drawbacks in a situation where tissue is dehydrated;
likewise a natural polymer might raise the chance of infection, but an artificial one might induce
immunogenicity if left for too long. Generally the specialized polymeric biomaterials will have a
higher cost and will need to be replaced less than traditional dressings, but more than the once
as in biological tissue grafts.
The shift in recent years has been away from single-material treatments, towards
combinations of polymers or materials in a variety of forms – gels, foams/sprays or particulate
systems that while having increased cost, have significantly improved outcomes for patient and
caretakers alike – more complete, hastened healing for the patient and decreased maintenance
for caretakers in a healthcare setting. In fact, combinatory systems can also include embedded
enzymes, hormones or drugs for specific purposes. Generally, biopolymers (natural or naturally-
derived materials) have the advantage over artificial polymers in terms of compatibility,
degradability and promotion of wound healing.
In recent years there has been a veritable outpouring of effort into engineering new
biomaterials for use in wound care, building on the recent shift towards biopolymers and other
composites that combine advantages of several individual materials. Recent studies of possible
biomaterials for use in wound care include a new semi-interpenetrating network (sIPN) that
incorporates polyethylene glycol and glycerin to make a wound-healing matrix, a tissue
equivalent based on cell-seeded biodegradable microfluidic constructs (on silk filaments), and
new wound dressing materials incorporating chitin and chitosan that has enhanced wound
healing in both humans and animals.
The sIPN is a hydrogel (water soluble materials which have absorbed water, forming a
gel) containing a synthetic polyethylene glycol (PEG) polymer as well as naturally derived
gelatin (which is the hydrolyzed product of collagen, an important protein in human skin
structure). Xu, Kleinbeck and Kao had a wide variety of considerations when designing and
testing the sIPN in wound care efficacy. The use of two main materials in the hydrogel drew
upon had its basis in each individual material’s strength – PEG, being synthetic, had stronger
mechanical strength and durability, especially in an aquatic environment; conversely, gelatin
had better elasticity and increased the biodegradability of the hydrogel as a whole. The study
also contained data about co-delivery efficacy of various drugs such as silver sulfadiazine,
bupivacaine, and keratinocyte growth factor, which showed that the drugs were able to retain
their function.
The strong points of the sIPN utilizing PEG and gelatin is that it is relatively low-cost,
easily used hydrogel which can absorb exudate and form a gel in situ (on site) when applied,
can have embedded drugs which maintain their pharmaceutical properties and which forms a
close but moist healing environment. Important considerations mentioned by Xu, Kleinbeck and
Kao include effectively commercialization of the technology from an academic lab so that it can
be produced on a large, sterile and nontoxic manner in an industrial setting. Additional
considerations include maintaining consistent quality and lowering costs, which must be met in
order for the sIPN to flourish in a clinical setting. While the clinical safety trial of sIPN alone was
expected to be completed in 2011, an additional, vital area of interest was to conduct clinical
safety testing when it was in use in combinatorial settings; that is, its efficacy could be enhanced
when it’s used in conjunction with other treatments currently on the market such as Acticoat,
Tissel/Talfa, Xeroform, or when it is conjugated with integrin binding proteins such as RGD or
PHRSN to promote skin regeneration.
Silk fibroin, another recent development, was tested by Borenstein et al. as a possibility
for forming a biodegradable microvascular scaffold; sufficient microvasculature is an important
requirement in promoting incorporation of cells into engineered scaffolding in replacing
damaged tissue in organs. The silk fibroin was derived from silk worm, had sericin (which
induces immunogenicity) removed, and which had benefits such as superior mechanical
strength elasticity compared with other biomaterials, chemical modifiable amino side chains
(useful for engineering specific functionality of the silk fibroin), and modifiable biodegradability
over a scale of days to years. All of these properties make silk fibroin undeniable as a candidate
microvascularizing scaffold biomaterial in implantation in damaged organ tissue.
Borenstein et al. demonstrated the usability of silk fibroin in constructing implantable
microvasculature for wound care, using microfabrication technology to ‘print’ leak-proof capillary
microchannels, and the silk surface of which supports the formation of a merged epithelial layer.
Assessment of the microvasculature suggested that the endothelium was viable for supporting
the establishment of an engineered microvasculature. Many possibilities exist for future work
building off of the silk fibroin microvasculature. Specifically, in terms of organ specificity, there
might be some benefit to seeding the exterior and interior of the microvasculature with location-
specific cells: keratinocytes on the exterior and vascular cells on the inside with a porous silk
membrane between. The entire construct would immediately ‘connect’ with host vasculature,
enabling the skin cells to be fed nutrients and oxygen. Another possible avenue of research
would be to ‘stack’ individual engineering microvasculature webs in 3D to create vertically or
linearly extended, large-scale vascular implantable tissues with appropriate lengths in all three
dimensions. The entire system would be a large scale culture which could fit the size of the
wound to be implanted in.
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Herman, I.M. Tissue Equivalents Based on Cell-Seeded Biodegradable Microfluidic
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