Cellular and sub-chronic toxicity of hydroxyapatite porous beads loaded with antibiotic in rabbits, indented for chronic osteomyelitis.

Bioceramics have emerged as a hopeful remedy for site-specific drug delivery in orthopaedic complications, especially in chronic osteomyelitis. The bioresorbable nature of bioceramic materials shaped them into a versatile class of local antibiotic delivery systems in the treatment of chronic osteomyelitis. Hydroxyapatite (HA) based bioceramics with natural bone mimicking chemical composition are of particular interest due to their excellent biocompatibility, better osteoconductive and osteointegrative properties. Although HA has been widely recognized as an efficient tool for local delivery of antibiotics, information regarding its subchronic systemic toxicity have not been explored yet. Moreover, a detailed investigation of in vivo subchronic systemic toxicity of HA is critical for understanding its biocompatibility and futuristic clinical applications of these materials as novel therapeutic system in its long haul. Evaluation of biocompatibility and sub-chronic systemic toxicity are significant determinants in ensuring biomedical device's long-term functionality and success. Sub-chronic systemic toxicity allows assessing the potential adverse effects caused by leachable and nanosized wear particles from the device materials under permissible human exposure to the distant organs that are not in direct contact with the devices. In this context, the present study evaluates the sub-chronic systemic toxicity of in-house developed Hydroxyapatite porous beads (HAPB), gentamicin-loaded HAPB (HAPB + G) and vancomycin- loaded HAPB (HAPB + V) through 4 and 26-week muscle implantation in New Zealand white rabbits, as per ISO 10993-6 and ISO 10993-11. Analysis of cellular responses of HAPB towards Human Osteosarcoma (HOS) cell line through MTT assay, direct contact cytotoxicity, live/dead assay based on Imaging Flow Cytometry (IFC) showed its non-cytotoxic behaviour. Histopathological analysis of muscle tissue, organs like heart, lungs, liver, kidney, spleen, adrenals, intestine, testes, ovaries, and uterus did not reveal any abnormal biological responses. Our study concludes that the HAPB, gentamicin-loaded HAPB (HAPB + G) and vancomycin-loaded HAPB (HAPB + V) are biocompatible and did not induce sub-chronic systemic toxicity and hence satisfies the criteria for regulatory approval of HAs as a plausible candidate for clinical applications.

Hydroxyapatite carriers as drug eluting agents-An In Vitro analysis.

INTRODUCTION: Hydroxyapatite based drug carriers offer a customized alternative to the delivery of pharmacologic agents in the osseous skeleton. They have an added advantage of being biocompatible and osteoconductive. This in vitro study aims to quantify the drug eluting properties of HA granules by spectrophotometry. MATERIALS AND METHODS: HA and HASi beads were loaded with gentamicin/ amoxycillin- clavulanate/ vancomycin and grouped into 5. Drug elution was evaluated by means of UV spectrophotometry. RESULTS: Drug eluent levels were well above bactericidal levels in all 5 groups. CONCLUSION: HA and HASi are viable options for clinicians for targeted drug delivery.

First Report of a Tissue-Engineered Graft for Proximal Humerus Gap Non-union After Chronic Pyogenic Osteomyelitis in a Child: A Case Report.

CASE: An 11-year-old child who presented with a postseptic gap nonunion of 4 cm in the proximal humerus was treated with a customized hydroxyapatite-tricalcium phosphate-tricalcium silicate composite (HASi) scaffold loaded with culture-expanded autologous bone marrow-derived mesenchymal stem cells (MSCs) primed into osteogenic lineage. Union occurred at 3 months, and at 3 years, the child had improved joint mobility, with radiographic and computed tomographic imaging evidence of incorporation of the graft. CONCLUSIONS: This case demonstrated the feasibility of MSC directed into osteogenic lineage on HASi to repair a long bone defect owing to postseptic osteomyelitis, a condition notorious for a high failure rate.