Abstract
Angiogenesis plays a pivotal role in the wound healing process by supplying essential nutrients and oxygen to regenerating tissues thereby supporting tissue remodeling. Promoting the formation of new blood vessels is, therefore, a critical therapeutic strategy, particularly for ischemic and chronic wounds, where impaired blood supply often leads to delayed or incomplete healing. However, the development of effective pro-angiogenic biomaterials remains a challenge. In this work, by incorporating natural spider silk proteins (SSP) with poly(L-lactic acid) (PLLA) nanofiber via electrospinning, we developed a pro-angiogenic wound dressing. The incorporation of SSP led to a reduction in fiber diameter and the formation of a hierarchical structure that mimics the native extracellular matrix. Moreover, the combined effects of these biophysical and SSP-derived biochemical cues synergistically enhanced vascular regeneration, resulting in significant improvements in three key angiogenic parameters compared to pure PLLA controls: a 16.3% increase in blood vessel count, a 118.6% increase in vascular branching and a 32.8% increase in total vessel length. In vivo wound healing experiments showed a 29% improvement in the wound healing rate compared to the control group. This dual-mechanism strategy, synergizing structural biomimicry with bioactive cues, establishes a multifunctional platform to address complex wound healing challenges, particularly in ischemic and chronic wounds.