Gao Xiang, Yang Jirong, Liu Lingna, Hu Zilong, Lin Rui, Tang Lan, Yu Mei, Chen Zhiping, Gao Chongjian, Zhang Min, Li Li, Ruan Changshun, Liu Yanzhi
Zhanjiang Key Laboratory of Orthopaedic Technology and Trauma Treatment, Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, School of Ocean and Tropical Medicine, The Affiliated Hospital, The Second Affiliated Hospital, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, 524037, China.
Research Center for Human Tissue and Organ Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Bioact Mater. 2024 Dec 7;46:1-20. doi: 10.1016/j.bioactmat.2024.12.007. eCollection 2025 Apr.
Repair of osteoporotic bone defects (OBD) remains a clinical challenge due to dysregulated bone homeostasis, characterized by impaired osteogenesis and excessive osteoclast activity. While drug-loaded 3D-printed scaffolds hold great potential in the restoration of bone homeostasis for enhanced OBD repair, achieving the controlled release and targeted delivery of drugs in a 3D-printed scaffold is still unmet. Herein, we developed an electrostatic encapsulation strategy to motivate 3D-printed polyelectrolyte scaffolds (APS@P) with bone-targeting liposome formulation of salvianolic acid B (SAB-BTL). Benefiting from this strategy, SAB, an unstable and untargetable plant-derived osteogenic compound, was effectively encapsulated in APS@P, demonstrating stable and precise delivery with improved therapeutic efficacy. Owing to SAB-mediated bone homeostasis, APS@P significantly promoted angiogenesis and new bone formation while suppressing bone resorption, resulting in a significant 146 % increase in bone mass and improved microstructure compared to the OBD group. It was confirmed that the encapsulation of SAB into APS@P could promote the osteogenic differentiation of MSCs by stimulating Tph2/Wnt/β-catenin signaling axis, coupled with the stimulation of type H angiogenesis and the suppression of RANKL-mediate bone resorption, thereby enhance OBD repair. This study provides a universal platform for enhancing the bioactivity of tissue-engineered scaffolds, offering an effective solution for the efficient regeneration of osteoporotic bone.
由于骨稳态失调，骨质疏松性骨缺损（OBD）的修复仍然是一项临床挑战，其特征是成骨受损和破骨细胞活性过高。虽然载药3D打印支架在恢复骨稳态以增强OBD修复方面具有巨大潜力，但在3D打印支架中实现药物的控释和靶向递送仍未得到满足。在此，我们开发了一种静电包封策略，以激发3D打印的聚电解质支架（APS@P）与丹酚酸B的骨靶向脂质体制剂（SAB-BTL）。受益于该策略，SAB这种不稳定且无靶向性的植物源成骨化合物被有效地包封在APS@P中，显示出稳定且精确的递送，并提高了治疗效果。由于SAB介导的骨稳态，APS@P显著促进血管生成和新骨形成，同时抑制骨吸收，与OBD组相比，骨量显著增加146%，微观结构得到改善。证实将SAB包封到APS@P中可通过刺激Tph2/Wnt/β-连环蛋白信号轴促进间充质干细胞（MSC）的成骨分化，同时刺激H型血管生成并抑制RANKL介导的骨吸收，从而增强OBD修复。本研究为增强组织工程支架的生物活性提供了一个通用平台，为骨质疏松性骨的有效再生提供了一种有效解决方案。
