Preparation of a collagen/polymer hybrid gel for tissue membranes. Part II: In vitro and in vivo biological properties of the collagen gels

The aim of the present study was to evaluate the biological properties of a collagen–phospholipid polymer hybrid gel (MiC30 gel) designed for use as a tissue membrane. The following four types of collagen gels were synthesized and tested in vitro and in vivo: physically cross-linked collagen gel (Uc gel), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC)/N-hydroxysuccinimide-cross-linked collagen gel (EN gel), MiC30 gel and glutaraldehyde-cross-linked collagen gel (G gel). The cell adhesivity and proliferation rate were observed to be lowest for the MiC30 gel and highest for the Uc gel, indicating that the phospholipid–polymer-covered surface of the collagen gel interacted weakly with cells. The collagen gel was implanted into rats subcutaneously and was observed 1, 2 and 8 weeks after implantation. The Uc gel and G gel were degraded and induced an inflammatory response. Granulation was not observed for 8 weeks after implantation and the formation of foreign body giant cells was observed around both the Uc and G gels. On the other hand, cell infiltration and degradation were not observed in the case of the EN and MiC30 gels. The formation of foreign body giant cells was suppressed and the healing process was accelerated. The MiC30 gel is suitable for use as a biomaterial that is stable in vivo because it suppresses the foreign body response and accelerates the healing process.