Developing Multimodal Cu-TCP@PCL Periosteal Patch with Modulated Morphogenesis and Osteogenic Enhancement for Bone Tissue-Engineering Application

Abstract

Background Critical-sized bone defects present significant clinical challenges. The periosteum, a fibrous structure, plays a pivotal role in inspiring spontaneous healing. However, replicating its functions in an engineered substitute remains difficult due to fabrication limitations in stably controlling structural and biochemical cues. Methods Here, we developed a hierarchical scaffold serving as a tissue-engineered periosteum (TEPO) via modular layer-by-layer assembly for bone repair. The TEPO is composed of fibrous poly(ε-caprolactone) with three complementary layers: an inner layer for geometric guidance, a structure-supporting mid-layer, and an outer ion-delivery layer incorporated with copper-doped tricalcium phosphate (Cu-TCP). This substitute aims to overcome the inherent trade-off between fiber alignment and porosity observed in conventional electrospinning. Results The fabricated TEPO produced highly aligned fibers with improved interfibrillar spacing while resembling the mechanical properties of the native periosteum. MC3T3-E1 osteoblasts cultured on the TEPO exhibited good cytocompatibility with cross-scale morphological elongation and significantly upregulated osteogenic markers and calcium nodule formation. Conclusion This proof-of-concept study demonstrates the integrated performance of the TEPO in modulating cell alignment and promoting osteogenic differentiation in vitro. The scaffold effectively integrates structural guidance with sustained biochemical cues, eliminating the need for exogenous growth factors, and offers a promising biomaterial platform for bone tissue engineering.