Wu Dongyu, Gao Shangjun, He Shaohua, Liu Wanling, Liu Qingwei, Lan Siyao, Chen Jiaxin, Li Fenglu, Ruan Renjie, Zhang Jin, Liu Guoming
College of Chemical Engineering, Fuzhou University, 2 Xueyuan Road, Fuzhou 350108, PR China; Qingyuan Innovation Laboratory, 1 Xueyuan Road, Quanzhou 362801, PR China.
Department of Orthopedics, Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University, Fuzhou 350108, PR China; Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, PR China.
Biomater Adv. 2026 Jan;178:214467. doi: 10.1016/j.bioadv.2025.214467. Epub 2025 Aug 21.
Critical-sized bone defects caused by trauma, congenital malformation, or tumor resection remain a major challenge around the world. Current bone tissue-engineering scaffolds are partially confined by inadequate scaffold architecture design that mismatches with natural bone tissue, which affect normal biological functions like inflammation modulation and biomineralization, thus impairing bone regeneration process. Herein, a biomimetic 3D-printed BMGP scaffold composed of polydopamine (PDA)-polylactide (PLA) scaffold and black phosphorus (BP) nanosheets/manganese carbonyl (MnCO) nanosheets/gelatin methacryloyl hydrogel (named as BMG hydrogel) was developed for augmenting bone regeneration via strengthening anti-inflammatory effect and promoting in-situ biomineralization process. Through infilling the BMG hydrogel into the gradient-porous PDA-PLA scaffold, the obtained BMGP scaffold successfully mimicked cancellous and compact bone structure and extracellular matrix component in natural bone tissue. Upon being implanted into the critical-sized bone defect, a Fenton-like reaction between the MnCO nanosheet and endogenous hydrogen peroxide effectively induced carbon monoxide release, thereby improving anti-inflammatory response and facilitating macrophage reversed from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. Meanwhile, the BP nanosheet underwent degradation and in-situ biomineralization, which accelerated calcium phosphate formation and enhanced osteogenesis. Based on in-vitro and in-vivo data, the 3D-printed BMGP scaffold that integrated structural and functional biomimicry exhibited desirable inflammatory inhibition and in-situ biomineralization performances, as well as favorable osteogenic effect in rat critical-sized femoral bone defect. In all, such biomimetic scaffold obviously propelled bone regeneration process, and provided a promising strategy for treating critical-sized bone defects in clinic.
由创伤、先天性畸形或肿瘤切除引起的临界尺寸骨缺损仍然是全球面临的一项重大挑战。当前的骨组织工程支架部分受到支架结构设计不足的限制，这种设计与天然骨组织不匹配，影响了诸如炎症调节和生物矿化等正常生物学功能，从而损害了骨再生过程。在此，开发了一种由聚多巴胺（PDA）-聚乳酸（PLA）支架和黑磷（BP）纳米片/羰基锰（MnCO）纳米片/甲基丙烯酰化明胶水凝胶（命名为BMG水凝胶）组成的仿生3D打印BMGP支架，通过增强抗炎作用和促进原位生物矿化过程来促进骨再生。通过将BMG水凝胶填充到梯度多孔PDA-PLA支架中，所获得的BMGP支架成功地模拟了天然骨组织中的松质骨和密质骨结构以及细胞外基质成分。植入临界尺寸骨缺损后，MnCO纳米片与内源性过氧化氢之间的类芬顿反应有效地诱导了一氧化碳释放，从而改善抗炎反应并促进巨噬细胞从促炎M1表型转变为抗炎M2表型。同时，BP纳米片发生降解并原位生物矿化，加速了磷酸钙的形成并增强了成骨作用。基于体外和体内数据，集成了结构和功能仿生的3D打印BMGP支架表现出理想的炎症抑制和原位生物矿化性能，以及在大鼠临界尺寸股骨缺损中良好的成骨效果。总之，这种仿生支架明显推动了骨再生过程，并为临床治疗临界尺寸骨缺损提供了一种有前景的策略。
