Wound healing: the role of gap junctional communication in rat granulation tissue maturation

Granulation tissue maturation is dependent upon the orientation of collagen fibers and cell differentiation. Gap junctions are intercellular membrane gated channels that facilitate direct communication between cells known as gap junctional intercellular communication (GJIC). The hypothesis is that GJIC modulates the maturation of granulation tissue during wound repair. In vitro, GJIC optimizes fibroblast-populated collagen lattice contraction and influences cell morphology. It is reported that LiCl increases GJIC in cultured cardiac myocytes. Polyvinyl alcohol (PVA) sponge implants with central reservoirs were placed within separate subcutaneous pockets on the backs of adult male Sprague-Dawley rats. Each PVA implant received either 20 mM LiCl or saline injections on days 5, 7, and 10 after implantation. On day 11 implants were harvested and processed for light microscopy. By H&E staining LiCl-treated implants showed increased vascularization and decreased cell density compared to saline controls. Polarized light microscopy of Sirius red-stained specimens revealed more intense collagen fiber birefringence secondary to dense, parallel-organized collagen fiber bundles after LiCl treatment. This suggests that LiCl enhancement of GJIC between fibroblasts advances the maturation of granulation tissue. It is proposed that the degree of GJIC between granulation tissue fibroblasts influences both the quantity and the quality of granulation tissue deposited during the wound healing process.