A bioorthogonal click reaction-based platelet-rich plasma delivery system for accelerating wound healing.

Abstract

Platelet-rich plasma (PRP) demonstrates therapeutic potential for wound healing but is limited by its burst-release kinetics and short biological half-life. We developed snADM@PPRP, a composite biomaterial that integrates sulfonated hyaluronic acid into an acellular dermal matrix. This material employs bioorthogonal click chemistry to covalently immobilize PRP, while sulfonate groups (-SO₃⁻) electrostatically sequester cationic growth factors, thereby establishing a dual-mechanism sustained-release system. In vitro, snADM@PPRP exhibited high water absorption, enhanced mechanical properties, and prolonged growth factor release, significantly promoting fibroblast adhesion, proliferation, migration, and endothelial tube formation. In a murine full-thickness wound model, snADM@PPRP accelerated healing by alleviating inflammation, enhancing neovascularization, and increasing collagen deposition, achieving near-complete closure by day 21. This bioorthogonal click chemistry-based approach provides an effective strategy for tissue regeneration with broad therapeutic potential. STATEMENT OF SIGNIFICANCE: Platelet-rich plasma (PRP) therapy for wounds is limited due to the rapid leakage of growth factors. We developed a biomaterial scaffold that solves this problem using a unique click chemistry method to securely lock PRP in place. Furthermore, negative charges on the scaffold surface hold the positively charged growth factors, creating a dual mechanism for sustained release. In animal tests, this system significantly accelerated wound healing by promoting new blood vessel formation and tissue regeneration. Our work provides a more effective and reliable strategy for treating chronic wounds, offering a promising new tool for regenerative medicine.