ArticleBioactive materials2026
Biomimetic injectable engineered hierarchical porous microspheres for enhanced synergistic cell therapy of critical limb ischemia.
Article in Bioactive materials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization
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