Application of an innovative isoniazid-loaded biomimetic mineralized bone collagen scaffold in bone defect treatment

Abstract

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 via 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 Mycobacterium tuberculosis 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.