W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, United States.
W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, United States.
Colloids Surf B Biointerfaces. 2023 Nov;231:113563. doi: 10.1016/j.colsurfb.2023.113563. Epub 2023 Sep 20.
Limitations in the current clinical management of critical-sized osseous defects have driven the need for multifunctional bone constructs. The ideal bone scaffold should possess advanced microarchitecture, well-defined pore interconnectivity, and supply biological signals, which actively guide and control tissue regeneration while simultaneously preventing post-implantation complications. Here, a natural medicine-based localized drug delivery from 3D printed scaffold is presented, which offers controlled release of curcumin, piperine from nano-sized polymeric micelles, and burst release of antibacterial carvacrol from the coating endowing the scaffold with their distinct, individual biological properties. This functionalized scaffold exhibits improved osteoblast (hFOB) cell attachment, 4-folds higher hFOB proliferation, and 73% increased hFOB differentiation while simultaneously providing cytotoxicity towards osteosarcoma cells with 61% lesser viability compared to control. In vitro, early tube formation (p < 0.001) indicates that the scaffolds can modulate the endothelial cellular network, critical for faster wound healing. The scaffold also exhibits 94% enhanced antibacterial efficacy (p < 0.001) against gram-positive Staphylococcus aureus, the main causative bacteria for osteomyelitis. Together, the multifunctional scaffolds provide controlled delivery of natural biomolecules from the nano-sized micelle-loaded 3D printed matrix for significant improvement in osteoblast proliferation, endothelial formation, osteosarcoma, and bacterial inhibition, guiding better bone regeneration for post-traumatic defect repair.
目前对临界尺寸骨缺损的临床治疗存在局限性，这推动了对多功能骨构建体的需求。理想的骨支架应具有先进的微观结构、明确的孔连通性，并提供生物信号，积极引导和控制组织再生，同时防止植入后的并发症。在这里，提出了一种基于天然药物的局部药物递送 3D 打印支架，该支架从纳米级聚合物胶束中提供姜黄素和胡椒碱的控制释放，从涂层中提供抗菌香芹酚的爆发释放，从而使支架具有独特的个体生物学特性。这种功能化支架表现出更好的成骨细胞（hFOB）细胞附着、4 倍的 hFOB 增殖、73%的 hFOB 分化，同时对骨肉瘤细胞具有细胞毒性，其活力比对照降低了 61%。在体外，早期管形成（p<0.001）表明支架可以调节内皮细胞网络，这对更快的伤口愈合至关重要。支架还表现出 94%增强的抗菌功效（p<0.001）对抗革兰氏阳性金黄色葡萄球菌，这是骨髓炎的主要致病细菌。总之，多功能支架提供了从负载纳米级胶束的 3D 打印基质中控制释放天然生物分子，可显著提高成骨细胞增殖、内皮形成、骨肉瘤和细菌抑制，指导创伤后缺损修复的更好的骨再生。
