pHEMA水凝胶作为骨软骨缺损植入材料的动物实验研究

E. B. Makarova, M. Korch, F. Fadeyev, D. G. Bliznets, A. V. Bugayova, T. Shklyar, A. Safronov, K. A. Nokhrin, F. Blyakhman
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In the control series, four defects were not replaced with implants. Tissue regeneration was investigated by morphological and morphometric methods 30 days after operation. Results. The pHEMA implants were heterogeneous specimens with irregularly shaped pores – up to 30 × 10 μm at the surface and 300 × 120 μm inside. With >10% static compressive stress, the Young’s modulus was 54.7 kPa. For dynamic stress, increased frequency of compression-relaxation cycles from 0.01 Hz to 20.0 Hz led to increased storage modulus from 20 kPa to 38 kPa on average, and increased loss modulus from 2 kPa to 10 kPa. Indicators of semi-quantitative assessment of local inflammatory response to pHEMA implantation had the following values in points: pHEMA, 4.7 ± 0.3; pHEMA with allogeneic chondrocytes, 6.0 ± 1.0; control, 4.3 ± 0.3. 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摘要

目的:评价多孔聚甲基丙烯酸2-羟乙基(pHEMA)水凝胶植入骨软骨缺损的修复性软骨成骨特性。材料和方法。采用自由基聚合法制备直径为5mm的圆柱形pHEMA植入物。植入物经过光学显微镜和力学测试来表征材料的结构和粘弹性特性。实验1组将4个pHEMA标本植入兔股骨远端骨骺形成的缺损内。实验组2在植入前将同种异体软骨细胞涂于4个标本表面。在对照组中,有4个缺陷没有被植入物取代。术后30 d采用形态学和形态计量学方法观察组织再生情况。结果。pHEMA植入体为非均质样品,表面孔径达30 × 10 μm,内部孔径达300 × 120 μm。当静压应力>10%时,杨氏模量为54.7 kPa。对于动应力,压缩松弛周期频率从0.01 Hz增加到20.0 Hz,导致存储模量从平均20 kPa增加到38 kPa,损耗模量从平均2 kPa增加到10 kPa。半定量评价pHEMA植入局部炎症反应的指标分:pHEMA, 4.7±0.3;伴有异体软骨细胞的肺水肿,6.0±1.0;对照组,4.3±0.3。再生组织中结缔组织、骨组织和软骨组织的比例分别为:pHEMA, 79%, 20%, 1%;含软骨细胞的肺水肿,82%,16%,2%;对照组,9%,74%,17%。结论。在短期实验中,pHEMA植入物没有在周围组织中引发明显的炎症反应,可以归类为生物相容性材料。然而,所测试的植入物相对于骨和软骨细胞具有低导电性,在合成材料时可以通过稳定孔径和增加刚度来改善这一点。
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Testing of the pHEMA hydrogel as an implantation material for replacement of osteochondral defects in animals
Objective: to evaluate the features of reparative chondrogenesis and osteogenesis in animal experiments with the implantation of porous poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel into osteochondral defects. Materials and methods. Cylindrical pHEMA implants (5 mm in diameter) were synthesized by radical polymerization. The implants were subjected to light microscopy and mechanical tests to characterize the structure and viscoelastic properties of the material. In experimental group #1, four pHEMA specimens were implanted into formed defects in the distal femoral epiphysis of rabbits. In experimental group #2, allogeneic chondrocytes were applied to the surface of four specimens before implantation. In the control series, four defects were not replaced with implants. Tissue regeneration was investigated by morphological and morphometric methods 30 days after operation. Results. The pHEMA implants were heterogeneous specimens with irregularly shaped pores – up to 30 × 10 μm at the surface and 300 × 120 μm inside. With >10% static compressive stress, the Young’s modulus was 54.7 kPa. For dynamic stress, increased frequency of compression-relaxation cycles from 0.01 Hz to 20.0 Hz led to increased storage modulus from 20 kPa to 38 kPa on average, and increased loss modulus from 2 kPa to 10 kPa. Indicators of semi-quantitative assessment of local inflammatory response to pHEMA implantation had the following values in points: pHEMA, 4.7 ± 0.3; pHEMA with allogeneic chondrocytes, 6.0 ± 1.0; control, 4.3 ± 0.3. The ratio of connective, bone, and cartilage tissues proper in the regenerates had the following respective values: pHEMA, 79%, 20%, 1%; pHEMA with chondrocytes, 82%, 16%, 2%; control, 9%, 74%, 17%. Conclusion. In a short-term experiment, pHEMA implants did not trigger a pronounced inflammatory response in the surrounding tissues and can be classified as biocompatible materials. However, the tested implants had low conductivity with respect to bone and cartilage cells, which can be improved by stabilizing the pore size and increasing the rigidity when synthesizing the material.
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