RESUMEN
Many growth factors have been studied as additives accelerating lumbar fusion rates in different animal models. However, their low hydrolytic and thermal stability both in vitro and in vivo limits their workability and use. In the proposed work, a stabilized vasculogenic and prohealing fibroblast growth factor-2 (FGF2-STAB®) exhibiting a functional half-life in vitro at 37 °C more than 20 days was applied for lumbar fusion in combination with a bioresorbable scaffold on porcine models. An experimental animal study was designed to investigate the intervertebral fusion efficiency and safety of a bioresorbable ceramic/biopolymer hybrid implant enriched with FGF2-STAB® in comparison with a tricortical bone autograft used as a gold standard. Twenty-four experimental pigs underwent L2/3 discectomy with implantation of either the tricortical iliac crest bone autograft or the bioresorbable hybrid implant (BHI) followed by lateral intervertebral fixation. The quality of spinal fusion was assessed by micro-computed tomography (micro-CT), biomechanical testing, and histological examination at both 8 and 16 weeks after the surgery. While 8 weeks after implantation, micro-CT analysis demonstrated similar fusion quality in both groups, in contrast, spines with BHI involving inorganic hydroxyapatite and tricalcium phosphate along with organic collagen, oxidized cellulose, and FGF2- STAB® showed a significant increase in a fusion quality in comparison to the autograft group 16 weeks post-surgery (p = 0.023). Biomechanical testing revealed significantly higher stiffness of spines treated with the bioresorbable hybrid implant group compared to the autograft group (p < 0.05). Whilst histomorphological evaluation showed significant progression of new bone formation in the BHI group besides non-union and fibrocartilage tissue formed in the autograft group. Significant osteoinductive effects of BHI based on bioceramics, collagen, oxidized cellulose, and FGF2-STAB® could improve outcomes in spinal fusion surgery and bone tissue regeneration.
RESUMEN
AIMS: The aim of this study was to answer the question whether our newly developed injectable biodegradable "self-setting" polymer-composite as a bone adhesive is a good "bone-glue" candidate to efficiently fix comminuted fractures of pig femoral bones used as an ex-vivo experimental model. METHODS: Mechanical properties of adhesive prepared from α-tricalcium phosphate (TCP) powder and thermogelling copolymer were optimized by selecting the appropriate composition with adhesion enhancers based on dopamine and sodium iodinate. Setting time and injectability were controlled by rheology. Ex-vivo experiments of fixed pig bones were provided in terms of either the three-point bending test of bending wedge type fractured pig femurs (with LCP) or the axial compression test of 45° oblique fractured femurs (without LCP) in physiological saline solution at 37 °C. Fractured bones treated with optimized adhesive before and after bending tests were imaged by X-ray microtomography (µCT). RESULTS: Based on the rheological measurement, the adhesive modified with both dopamine and sodium iodinate exhibited optimal thixotropic properties required for injection via thin 22 G needle. This optimal adhesive composition showed an 8 min lag phase (processing time) followed by fast increase in storage modulus at 37 °C up to 1 GPa within 110 min. Self-setting of dopamine/iodinate modified adhesive was completed in 48 h exhibiting the maximum strength at compression of 7.98 MPa ± 1.39 MPa. Whereas unmodified adhesive failed in glue-to-bone adhesion, dopamine and dopamine/iodinate modified adhesive used for 45° oblique fracture fixation showed good and similar strength at compression (3.05 and 2.79 MPa, respectively). However, significantly higher elasticity of about 250% exhibited adhesive with iodinate enhancer. Moreover, mechanical properties of B2 fractures fixed with both LCP and dopamine/iodinate adhesive were approaching closely to the properties of original bone. Excellent adhesion between the adhesive and the bone fragments was proved by µCT. CONCLUSION: The polymer-composite bone adhesive modified with dopamine/iodinate exhibited very good fixation ability of femoral artificial comminuted fractures in an experimental model.