Silk biomaterials in wound healing and skin regeneration therapeutics: From bench to bedside

Silk biomaterials are known for biomedical and tissue engineering applications including drug delivery and implantable devices owing to their biocompatible and a wide range of ideal physico-chemical properties. Herein, we present a critical overview of the progress of silk-based matrices in skin regeneration therapeutics with an emphasis on recent innovations and scientific findings. Beginning with a brief description of numerous varieties of silks, the review summarizes our current understanding of the biological properties of silk that help in the wound healing process. Various silk varieties such as silkworm silk fibroin, silk sericin, native spider silk and recombinant silk materials have been explored for cutaneous wound healing applications from the past few decades. With an aim to harness the regenerative properties of silk, numerous strategies have been applied to develop functional bioactive wound dressings and viable bio-artificial skin grafts in recent times. The review examines multiple inherent properties of silk that aid in the critical events of the healing process such as cell migration, cell proliferation, angiogenesis, and re-epithelialization. A detailed insight into the progress of silk-based cellular skin grafts is also provided that discusses various co-culture strategies and development of bilayer and tri-layer human skin equivalent under in vitro conditions. In addition, functionalized silk matrices loaded with bioactive molecules and antibacterial compounds are discussed, which have shown great potential in treating hard-to-heal wounds. Finally, clinical studies performed using silk-based translational products are reviewed that validate their regenerative properties and future applications in this area. STATEMENT OF SIGNIFICANCE: The review article discusses the recent advances in silk-based technologies for wound healing applications, covering various types of silk biomaterials and their properties suitable for wound repair and regeneration. The article demonstrates the progress of silk-based matrices with an update on the patented technologies and clinical advancements over the years. The rationale behind this review is to highlight numerous properties of silk biomaterials that aid in all the critical events of the wound healing process towards skin regeneration. Functionalization strategies to fabricate silk dressings containing bioactive molecules and antimicrobial compounds for drug delivery to the wound bed are discussed. In addition, a separate section describes the approaches taken to generate living human skin equivalent that have recently contributed in the field of skin tissue engineering.