Controlled Delivery of Keratinocyte Growth Factor Promotes Wound Healing In Vitro and In Vivo

摘要

Controlled delivery of growth factors using fibrin gels has been recently demonstrated by incorporating peptides that effectively link heparin-binding proteins into the fibrin matrix during polymerization. Using analogous peptides, we developed a novel method to conjugate keratinocyte growth factor (KGF) into the fibrin matrix during polymerization. The release profile was studied in vitro to determine the best gel formulations for sustained delivery. Approximately 60% of conjugated KGF was incorporated into the fibrin matrix as compared to only <2% using unmodified growth factor. To demonstrate the effectiveness of the KGF delivery system, we developed an in vivo model of wound healing using human skin equivalents transplanted onto athymic mice. The transplanted tissues were punch wounded and treated with fibrin supplemented with KGF. We found that fibrin- mediated delivery of KGF accelerated reepithelialization and increased vascularization of wounds in vivo. Our results suggest that fibrin may be a suitable biomaterial for controlled release of growth factors to increase cellular migration and growth, ultimately promoting faster healing.