In vitro evaluation of bioactive strontium-based ceramic with rabbit adipose-derived stem cells for bone tissue regeneration.

The development of bone replacement materials is an important objective in the field of orthopaedic surgery. Due to the drawbacks of treating bone defects with autografts, synthetic bone graft materials have become optional. So in this work, a bone tissue engineering approach with radiopaque bioactive strontium incorporated calcium phosphate was proposed for the preliminary cytocompatibility studies for bone substitutes. Accumulating evidence indicates that strontium containing biomaterials promote enhanced bone repair and radiopacity for easy imaging. Hence, strontium calcium phosphate (SrCaPO4) and hydroxyapatite scaffolds have been investigated for its ability to support and sustain the growth of rabbit adipose-derived mesenchymal stem cells (RADMSCs) in vitro. They were characterized via Micro-CT for pore size distribution. Cells used were isolated from New Zealand White rabbit adipose tissue, characterized by FACS and via differentiation into the osteogenic lineage by alkaline phosphatase, Masson's trichome, Alizarin Red and von Kossa staining on day 28. Material-cell interaction was observed by SEM imaging of cell morphology on contact with material. Live-Dead analysis was done by confocal laser scanning microscopy and cell cluster analysis via µCT. The in vitro biodegradation, elution and nucleation of apatite formation of the material was evaluated using simulated body fluid and phosphate buffered saline in static regime up to 28 days at 37 °C. These results demonstrated that SrCaPO4 is a good candidate for bone tissue engineering applications and with osteogenically-induced RADMSCs, they may serve as potential implants for the repair of critical-sized bone defects.

Can iliac crest reconstruction reduce donor site morbidity?: a study using degradable hydroxyapatite-bioactive glass ceramic composite.

STUDY DESIGN: Prospective study. OBJECTIVE: To prospectively validate the hypothesis that iliac crest donor site morbidity may be a structural issue and by reconstructing the crest its incidence might be reduced. The study also evaluates the efficacy of Chitra hydroxyapatite-bioactive glass ceramic composite (Chitra-HABG) as a material for reconstructing the iliac crest. SUMMARY OF BACKGROUND DATA: Tricortical iliac crest bone graft harvesting is associated with significant donor site morbidity, varying from 3% to 61%. Reconstruction of the defect has been shown to reduce this morbidity, but the only materials which have been shown to be useful and readily available are bioactive apatite-wollastonite glass ceramic and morcellized beta-tricalcium phosphate. METHODS: Twenty-six patients in whom tricortical graft was harvested from the iliac crest and defect reconstructed with an indigenously developed and tested graft substitute-Chitra HABG-were followed up to duration of 1 year. Outcome measures were donor site morbidity as assessed clinically and radiologic assessment for ceramic incorporation, dissolution, fragmentation, and migration. RESULTS: At the end of 1 year from surgery, 25 of the 26 patients (96.15%) had no pain at the donor site, which had been reconstructed. Radiologic evaluation showed that in 21 cases the ceramic incorporation was complete, partial in 3, and absent in 2. Partial dissolution of ceramic was noticed in 3 patients and migration in 1. CONCLUSIONS: This study validates our hypothesis that the donor site morbidity after tricortical iliac crest graft harvesting is probably a structural issue and it can be reduced by reconstruction of the defect. It also highlights the fact that the Chitra-HABG block is an excellent material for reconstruction of the iliac crest defect, as it gets incorporated into the surrounding bone without adverse effects.

Preclinical safety and efficacy evaluation of 'BioCaS' bioactive calcium sulfate bone cement.

A new bioactive calcium sulfate-based formulation (named 'BioCaS') has been developed for bone filler applications. This is a self-setting injectable cement where the preset form comprises bassanite obtained from the uniform submicron-sized precursor crystals of gypsum, modified with hydrogen orthophosphate ions. The results of the safety and efficacy evaluation of BioCaS cement, done as per the International Standards and guidelines, are presented in this paper. The study plan consisted of in vitro screening tests of cytotoxicity and haemolysis and in vivo biocompatibility evaluation, including an acute systemic toxicity test (in mice), an intracutaneous reactivity test (in rabbits), a pyrogen test (in rabbits) and a maximization sensitization test (in guinea pigs). The efficacy of the material in healing bone defects was investigated by implanting it in artificially created defects in rabbit femora, with clinically established hydroxyapatite porous ceramic as the control, followed by histological analysis at 12, 26 and 52 weeks. Set BioCaS cement consisted of hydrogen orthophosphate incorporating low-dimensional gypsum crystal lattices, the bioactivity of which has been identified by immersion in simulated body fluid. BioCaS was proved to be non-cytotoxic and non-haemolytic in the screening tests. In the live/dead assay, human osteoblast-like human osteosarcoma cells adhered well and spread on the surface of the material, attaining typical morphology and affirming the bone cell compatibility of the material. In the biocompatibility evaluation there were no acute systemic effects and the material proved non-pyrogenic. There was no intracutaneous erythemic or oedematous reactivity and no hypersensitivity observed in the Magnusson-Kligman method. The material satisfied the biocompatibility requirements. Bone implantation study revealed BioCaS to be osteoconductive and its efficacy of healing the experimental bone defects in rabbit femora is on a par with that of hydroxyapatite ceramic. The material resorbed at a pace matching that of new bone formation. This property of osteotransductivity will help the defect to heal and gain strength faster.

Hydroxyapatite-bioactive glass ceramic composite as stand-alone graft substitute for posterolateral fusion of lumbar spine: a prospective, matched, and controlled study.

STUDY DESIGN: Prospective, matched, and controlled study. OBJECTIVE: To evaluate the efficacy of hydroxyapatite-bioactive glass ceramic composite (Chitra-HABg) as a stand-alone graft substitute in promoting posterolateral fusion in the lumbar spine as compared with autologous bone. BACKGROUND: The use of ceramics as stand-alone graft substitutes in posterolateral fusion remains controversial. The Chitra-HABg is a new composite that has undergone clinical trials in various orthopedic applications with excellent clinical and radiologic outcomes. METHODS: Twenty-four patients underwent instrumented posterolateral fusion, with Chitra-HABg laid on the left intertransverse bed and autogenous graft on the right side. The primary outcome measure was radiologic consolidation of the graft, and secondary outcome measures were the work status and the Modified Oswestry Disability index. The McNamara and Student chi test were applied for statistical analysis. RESULTS: Although the study was prematurely terminated owing to the high incidence of resorption of Chitra-HABg, 22 of the 24 subjects were followed-up for a minimum of 1 year. At the end of 1-year, excellent radiologic outcome was seen on the right side (autogenous graft) in all the cases, whereas 95% (21/22) of the cases had poor consolidation on the left side (Chitra-HABg). The clinical outcome was rated as good in 16/22 (73%) patients, fair in 5, and poor in only 1 patient, but this had no statistically significant association with the consolidation of the fusion mass. CONCLUSIONS: This study clearly demonstrates that hydroxyapatite-bioactive glass ceramic composites (Chitra-HABg) has no role as stand-alone bone graft substitutes in posterolateral fusion of the lumbar spine, as the composite undergoes resorption without the formation of bridging callus. LEVEL OF EVIDENCE: Level 1.