No abstract

Corneal epithelial tissue migration over the surface of a synthetic polymer can be inhibited by pores in the substrate. The effects of this substrate topography upon epithelial tissue migration were studied in vitro. Membranes of different porosities and structures were used to provide two series of surfaces having a graded increase in discontinuities: cellulose nitrate/acetate membranes with a tortuous network of pores, and track-etched polycarbonate membranes with columnar pores. Corneal epithelial tissue outgrowth was inhibited by increased pore size, and for both series of membranes, outgrowth was completely halted on membranes with mean diameter of the pores 0.9 microm at the pore densities measured. On the track-etched membranes with pores of <0.9 microm diameter, tissue outgrowth could be partially "rescued" by coating with fibronectin or collagen, but above this size, the inhibition predominated. The effect of porosity of the track-etched membranes upon the migration of dissociated epithelial cells was also examined. Although migration of these cells was reduced on membranes having pore sizes larger than 0.9 microm, it was not completely inhibited even on membranes of 2.3-microm pore diameter. Therefore, tissue movement of adult stratified epithelium may be inhibited by specific surface topographies, and in this assay system, epithelial tissue outgrowth was more affected than was the migration of dissociated epithelial cells.

Synthetic biodegradable polymeric matrices, with a dense top layer and porous under-layer, made of a (poly)ether/(poly)ester (PEO:PBT) copolymer called Polyactive, and also of poly-L-lactide (PLLA), are under investigation as part of a cell-seeded skin substitute for third-degree, large-scale skin defects. The biocompatibility of subcutaneously implanted matrices representing large body surface areas, were studied at 2, 4, 13, 26, and 52 weeks in rats. To investigate local or systemic effects, the weight development of the complete animal and of their hearts, kidneys, lungs, livers, and spleens, as well as the macroscopic and histologic appearance of the implants and organs, were monitored. Early inflammatory response was associated with surgical implantation trauma. All matrices showed neovascular and fibrous tissue ingrowth into the porous underlayer within 2-4 weeks after implantation. Copolymeric and PLLA matrices increasingly fragmented and liquified. After 1 year, small polymeric fragments embedded in fibrous, vascularized tissue could be retrieved at the implantation site. No systemic effects of the implants on the organs or on the animal as a whole were observed. These results and earlier studies on (skin) cell substrate properties and physicochemical characteristics of the matrices indicate the suitability of the matrices as part of a cell-seeded skin substitute.