Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, People's Republic of China.
Int J Nanomedicine. 2024 Aug 14;19:8309-8336. doi: 10.2147/IJN.S467886. eCollection 2024.
The treatment of craniofacial bone defects caused by trauma, tumors, and infectious and degenerative diseases is a significant issue in current clinical practice. Following the rapid development of bone tissue engineering (BTE) in the last decade, bioactive scaffolds coupled with multifunctional properties are in high demand with regard to effective therapy for bone defects. Herein, an innovative bone scaffold consisting of GO/Cu nanoderivatives and GelMA-based organic-inorganic hybrids was reported for repairing full-thickness calvarial bone defect.
In this study, motivated by the versatile biological functions of nanomaterials and synthetic hydrogels, copper nanoparticle (CuNP)-decorated graphene oxide (GO) nanosheets (GO/Cu) were combined with methacrylated gelatin (GelMA)-based organic-inorganic hybrids to construct porous bone scaffolds that mimic the extracellular matrix (ECM) of bone tissues by photocrosslinking. The material characterizations, in vitro cytocompatibility, macrophage polarization and osteogenesis of the biohybrid hydrogel scaffolds were investigated, and two different animal models (BALB/c mice and SD rats) were established to further confirm the in vivo neovascularization, macrophage recruitment, biocompatibility, biosafety and bone regenerative potential.
We found that GO/Cu-functionalized GelMA/β-TCP hydrogel scaffolds exhibited evidently promoted osteogenic activities, M2 type macrophage polarization, increased secretion of anti-inflammatory factors and excellent cytocompatibility, with favorable surface characteristics and sustainable release of Cu. Additionally, improved neovascularization, macrophage recruitment and tissue integration were found in mice implanted with the bioactive hydrogels. More importantly, the observations of microCT reconstruction and histological analysis in a calvarial bone defect model in rats treated with GO/Cu-incorporated hydrogel scaffolds demonstrated significantly increased bone morphometric values and newly formed bone tissues, indicating accelerated bone healing.
Taken together, this BTE-based bone repair strategy provides a promising and feasible method for constructing multifunctional GO/Cu nanocomposite-incorporated biohybrid hydrogel scaffolds with facilitated osteogenesis, angiogenesis and immunoregulation in one system, with the optimization of material properties and biosafety, it thereby demonstrates great application potential for correcting craniofacial bone defects in future clinical scenarios.
创伤、肿瘤、感染和退行性疾病引起的颅面骨缺损的治疗是当前临床实践中的一个重大问题。在过去十年中，骨组织工程（BTE）的快速发展，对于骨缺损的有效治疗，人们对具有多功能特性的生物活性支架有很高的需求。在此，报道了一种由 GO/Cu 纳米衍生物和基于 GelMA 的有机-无机杂化材料组成的新型骨支架，用于修复全厚颅骨骨缺损。
在这项研究中，受纳米材料和合成水凝胶多功能生物学功能的启发，将铜纳米颗粒（CuNP）修饰的氧化石墨烯（GO）纳米片（GO/Cu）与甲基丙烯酰化明胶（GelMA）基有机-无机杂化材料结合，通过光交联构建了模拟骨组织细胞外基质（ECM）的多孔骨支架。研究了生物杂化水凝胶支架的材料特性、体外细胞相容性、巨噬细胞极化和成骨作用，并建立了两种不同的动物模型（BALB/c 小鼠和 SD 大鼠），进一步证实了体内新血管生成、巨噬细胞募集、生物相容性、生物安全性和骨再生潜力。
我们发现，GO/Cu 功能化的 GelMA/β-TCP 水凝胶支架表现出明显促进成骨活性、M2 型巨噬细胞极化、增加抗炎因子分泌和良好的细胞相容性，具有良好的表面特性和可持续释放 Cu。此外，在植入生物活性水凝胶的小鼠中发现了改善的新血管生成、巨噬细胞募集和组织整合。更重要的是，在大鼠颅骨骨缺损模型中，通过微 CT 重建和组织学分析观察到，GO/Cu 掺入水凝胶支架治疗后，骨形态计量学值和新形成的骨组织显著增加，表明骨愈合加速。
综上所述，基于 BTE 的骨修复策略为构建多功能 GO/Cu 纳米复合材料掺入的生物杂化水凝胶支架提供了一种有前途和可行的方法，该方法在一个系统中促进成骨、血管生成和免疫调节，通过优化材料性能和生物安全性，为未来临床场景中纠正颅面骨缺损提供了巨大的应用潜力。
