Biomedical Engineering Reference
In-Depth Information
derived from neonatal foreskins. Subsequently, Organogenesis Corporation (Can-
ton, Massachusetts) made these sheets for a successful clinical trail in diabetic foot
infections.
8
Today, the resulting product, 'Apligraf', is used mostly to treat chronic
wounds. Early thoughts were that some of this material actually 'took' into the
wounds. Most clinicians today believe Apligraf works as a very advanced dress-
ing, providing both a barrier and a rich source of growth factors to the wound.
Ioannis V. Yannas and John F. Burke worked together to develop a dermal
template composed of bovine collagen and chondroiten-6-sulfate derived from
shark cartilage. They believed that dermis was the most difficult part of skin to
regenerate and if they could solve the problems of scarring and contraction that the
epidermal problem would then be less of an issue over the long term. Using a
guinea pig wound contraction model, they defined optimal characteristics of the
matrix including average pore size, cross-link density and percentage of
glycosaminoglycan. This matrix was covered by a silicone elastomer which
mimicked the natural permeability of skin. One of the reasons for the success of
this technique was the way burns were treated at the Massachusetts General
Hospital and Shriners Burns Institute in Boston. Burke was an advocate of early
excision and grafting. As such, after excision of the burn, there was a clean sterile
bed to apply the matrix. The matrix was left in place for two to four weeks when
at a time of election, the patient was returned to the operating room to have the
silicone removed and replaced by a very thin epidermal autograft. The advantage
of this technique is that the epidermal autograft left very little scarring at the donor
site and could be re-harvested. Also, the patient was effectively physiologically
closed after the first procedure, could recover with the matrix in place and then,
when stable, have the thin epidermal autograft. The surprising outcome in humans
was the long-term results of a supple mobile skin, which patients preferred when
compared to the standard meshed autografting techniques.
9,10
This matrix was first
commercially made by Marion Laboratories (Kansas City, Missouri) and then
transferred to Integra LifeSciences Corporation (Plainsboro, New Jersey). Its
indications have subsequently been extended to reconstructive surgery.
1.3 Intellectual property and financial issues
Burn patients provide a relatively small market for skin substitutes. Without
intellectual property (IP) protection, it is unlikely that corporations would take on
the high costs of developing these products without the anticipation of several
years of sales without significant competition. Each of these inventions obtained
patents that were crucial in the development of the products. Even with patent
protection, the small market size for burns combined with limits on charges for
products has made it difficult for corporations to reap significant profits from skin
substitutes. As a result, companies have looked at other markets to expand the
potential use of the products, for example, acute wounds following trauma or
surgical excision and chronic wounds. The cost of current skin substitutes range
