TGF-beta modulates events of normal wound healing through multiple pathways that influence cell infiltration, proliferation, angiogenesis, extracellular matrix synthesis and remodeling. The effects of topically applied
TGF-beta 1 on wound healing in two models of healing were evaluated when the healing response was impaired by the administration of
methylprednisolone to rats or rabbits.
TGF-beta 1 increased the healing of linear incision
wounds on rats, as measured by breaking strength, to that of normal rats. Full thickness open
wounds were also created on the inner ears of rabbits to simulate a non-contracting
wound with limited blood supply. Healing was further impaired by the administration of
methylprednisolone. The single application of
TGF-beta 1 improved the healing of open
wounds.
TGF-beta 1 stimulated increased granulation tissue formation, as well as reepithelialization. The amount of granulation tissue and epithelialization were similar to
wounds from normal-healing control rabbits. The delayed healing caused by
methylprednisolone permitted the evaluation of multiple applications of
TGF-beta 1 to
wounds. Two applications of
TGF-beta 1 spaced 7 days apart further improved the healing response when compared to a single application. Thus, single or multiple topical applications of
TGF-beta 1 reversed impaired healing conditions secondary to
methylprednisolone when used on incisional or open
wounds. These observations support the hypothesis that
growth factors, such as
TGF-beta 1, may be useful as accelerators of
wound repair in patients with impaired healing conditions.