Preparation and Biocompatibility Evaluation of Nanoscale Isoniazide-Loaded Mineralized Collagen Implants for Tuberculous Bone and Joint Repair

Abstract

Bone and joint tuberculosis is an extremely severe infectious disease that commonly occurs due to the primary infection of a type of mycobacteria, called Mycobacterium tuberculosis. Under the current scenario, there are very limited supplies of bone grafts available for the treatment of deceased bone, including autogenous bone and synthetic biomaterials. The present study aimed to construct a nanoscale isoniazid-loaded mineralized collagen implant, and then to explore its physicochemical properties and to investigate its biocompatibility suitable for bone and joint repair. Using type I collagen as raw material and the principle of biomimetic mineralization for self-assembly of bone tissue, a new drug-loaded mineralized collagen implant was constructed by molecular coprecipitation with isoniazid. Its surface morphology, elemental composition, and porosity were characterized by field emission scanning electron microscope (SEM), X-ray diffraction (XRD), and pycnometer. The performance of the implant was gauged by sustained release and degradation, which were studied using an ultraviolet spectrophotometer and a simulated in vivo environment. The drug loading and encapsulation rates of the implants were (6.25 ± 0.48)% and (54 ± 2.34)%, respectively. The in vitro release time of the scaffold was more than 12 weeks and the degradation performance was excellent. The scaffold was then implanted into mice, and the inflammatory reaction of local tissue was observed by Haemotoxylin and Eosin (H&E) and Masson. The in vivo evaluation in mice showed that the scaffold was biocompatible. Overall, compared with traditional drug loading systems, the isoniazid biomimetic mineralized collagen implant constructed here has better drug release performance, biodegradability, and biocompatibility. This kind of collagen implant may find potential applications in tuberculous bone and joint repair.

Advances in biomimetic collagen mineralisation and future approaches to bone tissue engineering

“…Very few alternatives to autologous bone grafts are available for clinical use and, contrary to the marketing of some commercially available bone void fillers, a true bone substitute is yet to be developed. [ 163 ] Bone is a highly complex composite and mimicking its properties and structure necessitates the introduction of numerous components which adds variables to any engineered scaffold, this presents a barrier to development, especially considering the high cost of collagen. Achieving high mechanical properties in collagen based scaffolds, through physiological‐like ECM density and intrafibrillar mineralisation, is arguably essential to avoid collagenolytic digestion.…”

“…[ 161 ] In the past 5 years there has been increased focus on testing scaffolds in animal models, which utilise coprecipitated collagen–hydroxyapatite, typically in conjunction with a synthetic polymer for increased mechanical properties and structural control. [ 162 , 163 ] Zhang et al [ 164 ] mineralised collagen through coprecipitation which they dried and powdered before combining with a Chitosan solution to cast into a film, the film was then backed by electrospun PCL/PVP nanofibers loaded with berberine (a herbal monomer). The efficacy of this bilayer implant was like that of an un‐named, commercially available mineralised collagen membrane when implanted in rat femurs.…”

Diagnosis and Treatment of Skipped Multifocal Spinal Tuberculosis Lesions

“…Control analysis disclosed that the hydroxyapatite group had higher drug release concentration than the polylactic acid derivative group and also had a certain osteogenic effect, but the polylactic acid derivative group was superior in drug distribution 144 . Besides these, a novel collagen‐based slow‐release drug complex has likewise been demonstrated in animal studies 145 …”

“…144 Besides these, a novel collagen-based slow-release drug complex has likewise been demonstrated in animal studies. 145 Instead of titanium mesh implants, polyetheretherketone (PEEK) materials have a brilliant application prospect. 146 Xu et al 147 treated 18 pediatric patients with lumbar tuberculosis using the PEEK graft material together with posterior fixation.…”

Recent Advances in Nanotechnology-Based Strategies for Bone Tuberculosis Management

“…In one study [ 92 ], a nanoscale drug delivery system called isoniazid-loaded mineralized collagen scaffold was developed for bone tuberculosis treatment. This system, assessed through an in vivo mouse model, effectively delivered isoniazid directly to the affected bone areas, thereby demonstrating potential in targeting and treating bone tuberculosis.…”