Biomedical Engineering Reference
In-Depth Information
4.3
Proposed differentiation pathway of circulating fibrocytes (Abe
et
al.
, 2001,
28
reproduced with permission)
capable of generating new endothelial cells, especially in ischemic tissues.
94
EPCs
are thought to participate in both angiogenesis and neovascularization.
12,69,94-100
They are capable of attaching themselves to injured (mature) endothelial cells
101-
102
and ECM fibers.
49
They promote tubular spouting via secretion of angiogenic
growth factors (such as VEGF.)
101-103
EPC production of angiogenic growth
factors is thought to be induced by the mechanical strain exerted on them by
resident endothelial cells
102-104
and ECM fibers.
49,105,106
Although uncertain, it
appears that BM-derived endothelial cells are not incorporated into the long-term
architecture of the dermal vascular network.
12,107
Hence, dermal blood vessels in
scars are lined by resident endothelial cells.
4.8
Historic developments and future trends
Efforts towards achieving effective cutaneous regeneration had their inception in
the 1970s. In 1971, J.F. Burke (of Massachusetts General Hospital) collaborated
with I.V. Yannas (of Massachusetts Institute of Technology) to design a scaffold,
intended for use on patients with severe burn injuries, especially those without
sufficient skin surface (<50% viable skin) for autologous skin grafts. In 1975, they
succeeded in synthesizing a biodegradable scaffold composed of collagen-GAG
copolymers. These DRTs were grafted onto wounded guinea pig skin, where
diminished wound contraction, coupled with partial regeneration was observed.
108,109
The efficacy of the scaffold is related to fiber composition, fiber size, pore size and
the spatial orientation of individual fibers (facilitating cell attachments along
more-physiological axes.)
In 1980, clinical trials (with positive results) were conducted on burn patients.
109,110
In 1989, Yannas and Salzman developed a method of selectively 'melting' the
quaternary collagen structure, without affecting tertiary structure.
111
Known as
'collagen banding', this process improved DRTs by adding an anti-platelet clotting
property. In the 1990s, Yannas and Orgill (of Brigham and Women's Hospital)
developed composite grafts (DRT with a removable silicone membrane), thereby
reducing a two-step grafting process to one and, in addition, allowing for seeding
of cultured autologous keratinocytes.
112
After extensive clinical trials, the Food
