Biopaper Based on Ultralong Hydroxyapatite Nanowires and Cellulose Fibers Promotes Skin Wound Healing by Inducing Angiogenesis

Abstract

Skin injury that is difficult to heal caused by various factors remains a major clinical challenge. Hydroxyapatite (HAP) has high potential for wound healing owing to its high biocompatibility and adequate angiogenic ability, while traditional HAP materials are not suitable for wound dressing due to their high brittleness and poor mechanical properties. To address this challenge, we developed a novel wound dressing made of flexible ultralong HAP nanowire-based biopaper. This biopaper is flexible and superhydrophilic, with suitable tensile strength (2.57 MPa), high porosity (77%), and adequate specific surface area (36.84 m2·g−1) and can continuously release Ca2+ ions to promote the healing of skin wounds. Experiments in vitro and in vivo show that the ultralong HAP nanowire-based biopaper can effectively induce human umbilical vein endothelial cells (HUVECs) treated with hypoxia and rat skin tissue to produce more angiogenic factors. The as-prepared biopaper can also enhance the proliferation, migration, and in vitro angiogenesis of HUVECs. In addition, the biopaper can promote the rat skin to achieve thicker skin re-epithelialization and the formation of new blood vessels, and thus promote the healing of the wound. Therefore, the ultralong HAP nanowire-based biopaper has the potential to be a safe and effective wound dressing and has significant clinical application prospects.