Advancements in the Delivery of Growth Factors and Cytokines for the Treatment of Cutaneous Wound Indications.

Significance: Wound healing involves the phasic production of growth factors (GFs) and cytokines to progress an acute wound to a resolved scar. Dysregulation of these proteins contributes to both wound chronicity and excessive scarring. Direct supplementation of GFs and cytokines for treatment of healing and scarring complications has, however, been disappointing. Failings likely relate to an inability to deliver recombinant proteins at physiologically relevant levels to an environment conducive to healing. Recent Advances: Inspired by the extracellular matrix, natural biomaterials have been developed that resemble human skin, and are capable of delivering bioactives. Hybrid biomaterials made using multiple polymers, fabrication methods, and proteins are proving efficacious in animal models of acute and impaired wound healing. Critical Issues: For clinical translation, these delivery systems must be tailored for specific wound indications and the correct phase of healing. GFs and cytokines must be delivered in a controlled manner that will target specific healing or scarring impairments. Preclinical assessment in clinically relevant animal models of impaired or excessive healing is critical. Future Directions: Clinical success will likely depend on the GF or cytokine selected, their compatibility with the chosen biomaterial(s), degradation rate of the fabricated system, and the degree of control over release kinetics. Further testing is essential to assess which wound indications are most suited to specific delivery systems and to prove whether they provide superior efficacy over direct protein therapies.