Ogueri Kenneth S, Ogueri Kennedy S, McClinton Aneesah, Kan Ho-Man, Ude Chinedu C, Barajaa Mohammed A, Allcock Harry R, Laurencin Cato T
Department of Materials Science and Engineering, University of Connecticut, Storrs, Connecticut 06269, United States.
Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut 06030, United States.
ACS Biomater Sci Eng. 2021 Apr 12;7(4):1564-1572. doi: 10.1021/acsbiomaterials.0c01650. Epub 2021 Apr 1.
In an effort to understand the biological capability of polyphosphazene-based polymers, three-dimensional biomimetic bone scaffolds were fabricated using the blends of poly[(glycine ethylglycinato)(phenylphenoxy)]phosphazene (PNGEGPhPh) and poly(lactic--glycolic acid) (PLGA), and an in vivo evaluation was performed in a rabbit critical-sized bone defect model. The matrices constructed from PNGEGPhPh-PLGA blends were surgically implanted into 15 mm critical-sized radial defects of the rabbits as structural templates for bone tissue regeneration. PLGA, which is the most commonly used synthetic bone graft substitute, was used as a control in this study. Radiological and histological analyses demonstrated that PNGEGPhPh-PLGA blends exhibited favorable in vivo biocompatibility and osteoconductivity, as the newly designed matrices allowed new bone formation to occur without adverse immunoreactions. The X-ray images of the blends showed higher levels of radiodensity than that of the pristine PLGA, indicating higher rates of new bone formation and regeneration. Micro-computed tomography quantification revealed that new bone volume fractions were significantly higher for the PNGEGPhPh-PLGA blends than for the PLGA controls after 4 weeks. The new bone volume increased linearly with increasing time points, with the new tissues observed throughout the defect area for the blend and only at the implant site's extremes for the PLGA control. Histologically, the polyphosphazene system appeared to show tissue responses and bone ingrowths superior to PLGA. By the end of the study, the defects with PNGEGPhPh-PLGA scaffolds exhibited evidence of effective bone tissue ingrowth and minimal inflammatory responses. Thus, polyphosphazene-containing biomaterials have excellent translational potential for use in bone regenerative engineering applications.
为了了解聚磷腈基聚合物的生物学性能，使用聚[（甘氨酸乙基甘氨酸）（苯基苯氧基）]磷腈（PNGEGPhPh）与聚乳酸-乙醇酸共聚物（PLGA）的共混物制备了三维仿生骨支架，并在兔临界尺寸骨缺损模型中进行了体内评估。由PNGEGPhPh-PLGA共混物构建的基质通过手术植入兔的15 mm临界尺寸桡骨缺损处，作为骨组织再生的结构模板。本研究中，最常用的合成骨移植替代物PLGA用作对照。放射学和组织学分析表明，PNGEGPhPh-PLGA共混物在体内表现出良好的生物相容性和骨传导性，因为新设计的基质能够促进新骨形成，且无不良免疫反应。共混物的X射线图像显示其放射密度水平高于原始PLGA，表明新骨形成和再生率更高。微计算机断层扫描定量分析显示，4周后，PNGEGPhPh-PLGA共混物的新骨体积分数显著高于PLGA对照组。新骨体积随时间点的增加呈线性增加，共混物在整个缺损区域均观察到新组织，而PLGA对照组仅在植入部位的边缘观察到新组织。组织学上，聚磷腈体系似乎显示出比PLGA更好的组织反应和骨长入。在研究结束时，使用PNGEGPhPh-PLGA支架的缺损部位显示出有效的骨组织长入和最小的炎症反应迹象。因此，含聚磷腈的生物材料在骨再生工程应用中具有优异的转化潜力。
