Millions of people around the globe are affected by full-thickness
skin injuries. A delay in the healing of such injuries can lead to
the formation of chronic wounds, posing several clinical and economic
challenges. Current strategies for wound care aim for skin regeneration
and not merely skin repair or faster wound closure. The present study
aimed to develop a bioactive wound-healing matrix comprising natural
biomaterial silk fibroin (SF), clinical-grade human fibrin (FIB),
and human hyaluronic acid (HA), resulting in SFFIBHA for regeneration
of full-thickness burn wounds. A porous, hemostatic, self-adhesive,
moisture-retentive, and biomimetic scaffold that promotes healing
was the expected outcome. The study validated a terminal sterilization
method, suggesting the stability and translational potential of the
novel scaffold. Also, the study demonstrated the regenerative abilities
of scaffolds using in vitro cell culture experiments
and in vivo full-thickness burn wounds of critical
size (4 cm × 4 cm) in a rabbit model. Under in vitro conditions, the scaffold enhanced primary dermal fibroblast adhesion
and cell proliferation with regulated extracellular matrix (ECM) synthesis. In vivo, the scaffolds promoted healing with mature epithelium
coverage involving intact basal cells, superficial keratinocytes,
multilayers of keratohyalin, dermal regeneration with angiogenesis,
and deposition of remodeled ECM in 28 days. The relative gene expression
of the IL6 marker indicated transitions from inflammation to proliferation
stage. In addition, we observed skin appendages and rete peg development
in the SFFIBHA-treated wound tissues. Although wound closure was observed,
neither negative (untreated/sham) nor positive (commercially available
product;
NeuSkin) control wounds developed skin appendages/rete pegs or native
skin architecture. After 56 days, healing with organized ECM production
enabled the recovery of mechanical properties of skin with higher
tissue maturity in SFFIBHA-treated wounds. Thus, in a single application,
the SFFIBHA scaffold proved to be an efficient biomimetic matrix that
can guide burn wound regeneration. The developed matrix is a suture-less,
hemostatic, off-the-shelf product for potential wound regenerative
applications.