Towards retrievable vascularized bioartificial pancreas: induction and long-lasting stability of polymeric mesh implant vascularized with the help of acidic and basic fibroblast growth factors and hydrogel coating.
We seek to improve existing methodologies for allogenic grafting of pancreatic islets. The lack of success of encapsulated transplanted islets inside the peritoneal cavity is presently attributed to poor vascularization of the implant. A thick, fibrotic capsule often surrounds the graft, limiting survival. We have tested the hypothesis that neovascularization of the graft material can be induced by the addition of proper angiogenic factors embedded within a polymeric coat. Biocompatible and nonresorbable meshes coated with hydrophilic polymers were implanted in rats and harvested after 1-, 6-, and 12-week intervals. The implant response was assessed by histological observations on the degree of vascularity, fibrosis, and inflammation. Macrostructural geometry of meshes was conducive to tissue ingrowth into the interstitial space between the mesh filaments. Hydrogel coating with incorporated acidic or basic FGF in an electrostatic complex with polyelectrolytes and/or with heparin provided a sustained slow release of the angiogenic growth factor. Anti-factor VIII and anti-collagen type IV antibodies and a GSL I-B4 lectin were used to measure the extent of vascularization. Vigorous and persistent vascularization radiated several hundred microns from the implant. The level of vascularization should provide a sufficient diffusion of nutrients and oxygen to implanted islets. Based on our observations, stable vascularization may require a sustained angiogenic signal to allow for the development of a permanent implant structure.
Prokop
A
A
Department of Chemical Engineering, Vanderbilt University School of Engineering, Nashville, Tennessee 37235, USA. ales.prokop@mcmail.vanderbilt.edu
Kozlov
E
E
Nun Non
S
S
Dikov
M M
MM
Sephel
G C
GC
Whitsitt
J S
JS
Davidson
J M
JM
D000818:Animals; D021522:Bioartificial Organs; D020099:Coated Materials, Biocompatible; D016220:Fibroblast Growth Factor 1 / Q000627:therapeutic use*; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007515:Islets of Langerhans / Q000098:blood supply* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013526:Surgical Mesh
D020099:Coated Materials, Biocompatible; D011108:Polymers; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate