Settable polymer/ceramic composite bone grafts stabilize weight-bearing tibial plateau slot defects and integrate with host bone in an ovine model

Abstract

Bone fractures at weight-bearing sites are challenging to treat due to the difficulty in maintaining articular congruency. An ideal biomaterial for fracture repair near articulating joints sets rapidly after implantation, stabilizes the fracture with minimal rigid implants, stimulates new bone formation, and remodels at a rate that maintains osseous integrity. Consequently, the design of biomaterials that mechanically stabilize fractures while remodeling to form new bone is an unmet challenge in bone tissue engineering. In this study, we investigated remodeling of resorbable bone cements in a stringent model of mechanically loaded tibial plateau defects in sheep. Nanocrystalline hydroxyapatite-poly(ester urethane) (nHA-PEUR) hybrid polymers were augmented with either ceramic granules (85% β-tricalcium phosphate/15% hydroxyapatite, CG) or a blend of CG and bioactive glass (BG) particles to form a settable bone cement. The initial compressive strength and fatigue properties of the cements were comparable to those of non-resorbable poly(methyl methacrylate) bone cement. In animals that tolerated the initial few weeks of early weight-bearing, CG/nHA-PEUR cements mechanically stabilized the tibial plateau defects and remodeled to form new bone at 16 weeks. In contrast, cements incorporating BG particles resorbed with fibrous tissue filling the defect. Furthermore, CG/nHA-PEUR cements remodeled significantly faster at the full weight-bearing tibial plateau site compared to the mechanically protected femoral condyle site in the same animal. These findings are the first to report a settable bone cement that remodels to form new bone while providing mechanical stability in a stringent large animal model of weight-bearing bone defects near an articulating joint.

In Vivo Behavior of Bioactive Glass-Based Hybrids in Animal Models For Bone Regeneration

“…Certain strategies appear more promising: For example, scaffolds seeded with MSCs that secrete B2BMP7, allowing for cells, the implanted scaffold, and secreted growth factors functioning synergistically in tissue regeneration [70]. Other promising strategies include those specifically targeted towards high-load bearing and rapid return to function [78]. Several innovative strategies have been used for achieving a well-defined pore structure, including NaCl particle leaching [57,58].…”

“…Additionally, the degradation behavior has been identified as an important factor contributing to the rate of osteogenesis or new bone volume [18,81]. In a comparison of degradation kinetics under different loading conditions, it has been observed that mechanical loading may enhance the rate of degradation [78]. Results from studies reporting either enhanced osteogenesis (or greater bone formation) [32] or lack of a significant difference [34], in comparison to untreated or unfilled defects should be interpreted cautiously, since this tends to present a partially biased view of the biological/osteogenic response.…”

“…At the tibial site, cements containing ceramic granules remodelled to form new bone by week 16, while incorporation of bioactive glass in addition to ceramic granules resulted in material degradation and fibrous tissue ingrowth into the surgical defect (Figure 5). Furthermore, cements containing ceramic granules remodelled at a considerably higher rate at the loaded site compared to the unloaded site [78].…”

Concurrent Local Delivery of Diflunisal Limits Bone Destruction but Fails To Improve Systemic Vancomycin Efficacy during Staphylococcus aureus Osteomyelitis

“…Diflunisal was purchased from Sigma-Aldrich (St. Louis, MO) and dissolved in 100% DMSO at a final concentration of 10 mg/ml. Lysine triisocyanate (LTI) was purchased from Jinan Haohua Industry Co., Ltd. (Jinan, China) and refluxed with a dispersion of activated carbon (Fisher Scientific) in t-butyl methyl ether (TBME; Acros Organics) at 60°C for 22 h to remove high-molecular-weight impurities (43). For polyester triol synthesis, -caprolactone and stannous octoate were purchased from Sigma-Aldrich, and D,L -lactide and glycolide were purchased from Polysciences (Warrington, PA).…”

Creep, recovery, and stress relaxation behavior of nanostructured bioactive calcium phosphate glass–POSS/polymer composites for bone implants studied under simulated physiological conditions

“…7 Stress shielding is characterized by an adaptation of the bone to the stress redistribution, 3,[8][9][10] resulting in the bone either becoming thinner or more porous. 11 In this context, biodegradable polymer composite materials containing bioactive glass have been proposed recently as an alternative to metal implants for clinical practice [12][13][14][15][16][17][18] where the glass filler improves the composite stiffness and bioactivity while the polymeric matrix provides toughness. In addition, these composite materials will prevent the patient from having a post-surgery to remove the prosthesis and will further allow a gradual load transfer from the prosthesis to the regenerating bone, thus eliminating the stress-shielding problem already mentioned.…”