Multi-Layered Electrospun Scaffold Design Strategies Targeting Osteosarcopenia

Abstract

Osteosarcopenia, the concurrent deterioration of bone density and skeletal muscle mass and function, represents a growing clinical challenge in ageing populations worldwide. Conventional single-tissue therapeutic approaches fail to address the intricate biochemical and mechanical crosstalk between bone and muscle at their shared interface. Electrospun nanofibrous scaffolds offer a versatile platform capable of recapitulating the hierarchical architecture of the musculoskeletal extracellular matrix (ECM). This review critically examines current strategies for designing multi-layered electrospun scaffolds that simultaneously target bone and muscle regeneration within the context of osteosarcopenia. We discuss the pathophysiological basis of bone–muscle crosstalk, highlighting the shared roles of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and chronic inflammation. To effectively mimic native tissues, we evaluate aligned compliant fibers (e.g., poly(ε-caprolactone) (PCL)-gelatin) for myogenic differentiation and random, stiffer mineralized fibers (e.g., poly(lactic-co-glycolic acid) (PLGA)/nano-hydroxyapatite (nHA)) for osteogenic differentiation. Furthermore, incorporating a gradient transition zone is strongly emphasized to minimize interfacial stress under physiological loading. Advanced electrospinning techniques—coaxial, emulsion, and melt electrowriting—are reviewed for spatially controlled and sequential delivery of vital growth factors like IGF-1 and bone morphogenetic protein-2 (BMP-2). Preclinical evaluation models are addressed, identifying a critical gap regarding the lack of aged and ovariectomised (OVX) composite defect animal models specific to osteosarcopenia. Finally, translational barriers, including manufacturing scalability and regulatory complexities, are evaluated. Thisreview proposes a unified design framework for osteosarcopenia-targeted scaffolds and identifies critical knowledge gaps requiring future investigation.