Wang Qian, Fang Xu, Feng Aihua, Dong Jun-Feng
Department of Spine Surgery, Shanghai East Hospital, Tongji University School of Medicine Shanghai China.
Department of Spinal Surgery, The First Dongguan Affiliated Hospital, Guangdong Medical University Guangdong China
RSC Adv. 2025 Aug 13;15(35):28730-28738. doi: 10.1039/d5ra03800f. eCollection 2025 Aug 11.
Bone defects, arising from various causes such as trauma, infection, tumor, surgical debridement, and congenital diseases, pose challenges to the natural self-healing process of bone tissue. Large-scale bone defects may lead to non-healing of the bone, and they need to be repaired through surgery using transplant materials. While graft materials serve as scaffolds for cell attachment and growth, infectious bone defects, like tuberculosis of the bone and joint, require anti-infective therapy concurrent with defect repair. This study aimed to construct a nano-scale drug-loaded mineralized collagen scaffold and assess its physicochemical, anti-infective, and osteogenic properties. By using isoniazid, hydroxyapatite and type I collagen, we achieved assembly through biomimetic mineralization principle and prepared a drug-loaded mineralized collagen scaffold. The scaffolds' surface morphology and composition were analyzed field emission scanning electron microscopy (SEM) and X-ray diffraction (XRD). After sterilization, the scaffolds were co-cultured with tuberculosis bacteria to evaluate the inhibition of growth. Additionally, the scaffolds were implanted into mice to assess degradation and drug sustained release. In a critical bone defect model in SD rats, osteogenesis was detected by Micro-CT, and biocompatibility was evaluated using HE staining of vital organs. The drug loading rate and entrapment efficiency of drug-loaded scaffolds were (6.25 ± 0.48)% and (54 ± 2.34)%, respectively. In co-culture with tuberculosis bacteria, the drug-loaded group showed a negative result in the BACTEC MIGT 960 detection system after continuous observation for more than 8 weeks, contrasting with positive results in the blank and non-drug-loaded groups. At the 8th week, acid-fast staining (AFS), auramine o staining, Micro-CT, and HE staining confirmed the drug-loaded scaffold's antibacterial properties, sustained-release capabilities, biocompatibility, and osteogenesis. Our findings demonstrate that drug-loaded biomimetic mineralized collagen scaffolds exhibit sustained-release properties, biodegradability, antibacterial efficacy, biocompatibility, and osteogenic potential. This novel drug-loaded collagen scaffold holds significant promise for the effective repair of infected bone defects.
骨缺损由创伤、感染、肿瘤、手术清创和先天性疾病等多种原因引起，对骨组织的自然自愈过程构成挑战。大面积骨缺损可能导致骨不愈合，需要通过使用移植材料进行手术修复。虽然移植材料可作为细胞附着和生长的支架，但感染性骨缺损，如骨与关节结核，需要在修复缺损的同时进行抗感染治疗。本研究旨在构建一种纳米级载药矿化胶原支架，并评估其物理化学、抗感染和成骨特性。通过使用异烟肼、羟基磷灰石和I型胶原，我们依据仿生矿化原理实现组装，制备了载药矿化胶原支架。采用场发射扫描电子显微镜（SEM）和X射线衍射（XRD）分析支架的表面形态和组成。灭菌后，将支架与结核杆菌共培养以评估对其生长的抑制作用。此外，将支架植入小鼠体内以评估降解和药物缓释情况。在SD大鼠的临界骨缺损模型中，通过Micro-CT检测成骨情况，并使用重要器官的HE染色评估生物相容性。载药支架的载药率和包封率分别为（6.25±0.48）%和（54±2.34）%。在与结核杆菌共培养时，连续观察8周以上，载药组在BACTEC MIGT 960检测系统中呈阴性结果，而空白组和未载药组呈阳性结果。在第8周时，抗酸染色（AFS）、金胺O染色、Micro-CT和HE染色证实了载药支架的抗菌性能、缓释能力、生物相容性和成骨能力。我们的研究结果表明，载药仿生矿化胶原支架具有缓释特性、生物可降解性、抗菌功效、生物相容性和成骨潜力。这种新型载药胶原支架在有效修复感染性骨缺损方面具有重大前景。
