Procter Philip, Hulsart-Billström Gry, Alves Antoine, Pujari-Palmer Michael, Wenner David, Insley Gerard, Engqvist Håkan, Larsson Sune
Department of Engineering Sciences, Division of Applied Material Science, Uppsala University, Uppsala, Sweden.
Biomimetic Innovations Ltd, Shannon, Ireland.
Front Bioeng Biotechnol. 2021 Nov 8;9:728042. doi: 10.3389/fbioe.2021.728042. eCollection 2021.
Osteoporotic fractures are a growing issue due to the increasing incidence of osteoporosis worldwide. High reoperation rates in osteoporotic fractures call for investigation into new methods in improving fixation of osteoporotic bones. In the present study, the strength of a recently developed bone bioadhesive, OsStic, was evaluated using a novel bone core assay in a murine animal model at 0, 3, 7, 14, 28, and 42 days. Histology and micro-CT were obtained at all time points, and the mean peak pull-out force was assessed on days 0-28. The adhesive provided immediate fixation to the bone core. The mean peak bone core pull-out force gradually decreased from 6.09 N (σ 1.77 N) at day 0 to a minimum of 3.09 N (σ 1.08 N) at day 7, recovering to 6.37 N (σ 4.18 N) by day 28. The corresponding fibrin (Tisseel) control mean peak bone core pull-out characteristic was 0.27 N (σ 0.27 N) at day 0, with an abrupt increase from 0.37 N (σ 0.28) at day 3, 6.39 N (σ 5.09 N) at day 7, and continuing to increase to 11.34 N (σ 6.5 N) by day 28. The bone cores failed either through core pull-out or by the cancellous part of the core fracturing. Overall, the adhesive does not interrupt healing with pathological changes or rapid resorption. Initially, the adhesive bonded the bone core to the femur, and over time, the adhesive was replaced by a vascularised bone of equivalent quality and quantity to the original bone. At the 42 day time point, 70% of the adhesive in the cancellous compartment and 50% in the cortical compartment had been replaced. The adhesive outwith the bone shell was metabolized by cells that are only removing the material excess with no ectopic bone formation. It is concluded that the adhesive is not a physical and biochemical barrier as the bone heals through the adhesive and is replaced by a normal bone tissue. This adhesive composition meets many of the clinical unmet needs expressed in the literature, and may, after further preclinical assessments, have potential in the repair of bone and osteochondral fragments.
由于全球骨质疏松症发病率不断上升，骨质疏松性骨折已成为一个日益严重的问题。骨质疏松性骨折的高再手术率促使人们对改善骨质疏松性骨固定的新方法进行研究。在本研究中，使用一种新型骨芯试验，在小鼠动物模型中于0、3、7、14、28和42天评估了一种新开发的骨生物粘合剂OsStic的强度。在所有时间点获取组织学和微型计算机断层扫描（micro-CT）图像，并在0至28天评估平均峰值拔出力。该粘合剂能立即固定骨芯。平均峰值骨芯拔出力从第0天的6.09 N（标准差1.77 N）逐渐下降至第7天的最低值3.09 N（标准差1.08 N），到第28天恢复至6.37 N（标准差4.18 N）。相应的纤维蛋白（Tisseel）对照平均峰值骨芯拔出特性在第0天为0.27 N（标准差0.27 N），第3天从0.37 N（标准差0.28）突然增加至第7天的6.39 N（标准差5.09 N），并持续增加至第28天的11.34 N（标准差6.5 N）。骨芯失败要么是通过芯拔出，要么是通过芯的松质部分断裂。总体而言，该粘合剂不会因病理变化或快速吸收而中断愈合。最初，粘合剂将骨芯与股骨粘结，随着时间推移，粘合剂被质量和数量与原始骨相当的血管化骨所取代。在第42天时间点，松质骨腔中70%的粘合剂和皮质骨腔中50%的粘合剂已被取代。骨壳外的粘合剂被仅去除多余物质且无异位骨形成的细胞代谢。得出的结论是，该粘合剂不是物理和生化屏障，因为骨通过粘合剂愈合并被正常骨组织取代。这种粘合剂组合物满足了文献中表达的许多临床未满足需求，并且在经过进一步的临床前评估后，可能在骨和骨软骨碎片修复方面具有潜力。
