Material Composition and Implantation Site Affect in vivo Device Degradation Rate

Kendell Pawelec, Jeremy M. L. Hix, Arianna Troia, Matti Kiupel, Erik Shapiro
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Abstract

Successful tissue engineering requires biomedical devices that initially stabilize wounds, then degrade as tissue is regenerated. However, the material degradation rates reported in literature are often conflicting. Incorporation of in situ monitoring functionality into implanted devices would allow real time assessment of degradation and potential failure. This necessitates introduction of contrast agent as most biomedical devices are composed of polymeric materials with no inherent contrast in medical imaging modalities. In the present study, computed tomography (CT)-visible radiopaque composites were created by adding 5-20wt% tantalum oxide (TaOx) nanoparticles into polymers with distinct degradation profiles: polycaprolactone (PCL), poly(lactide-co-glycolide) (PLGA) 85:15 and PLGA 50:50, representing slow, medium and fast degrading materials respectively. Radiopaque phantoms, mimicking porous tissue engineering devices, were implanted into mice intramuscularly or intraperitoneally, and monitored via CT over 20 weeks. Changes in phantom volume, including collapse and swelling, were visualized over time. Phantom degradation profile was determined by polymer matrix, regardless of nanoparticle addition and foreign body response was dictated by the implant site. In addition, degradation kinetics were significantly affected in mid-degrading materials, transitioning from linear degradation intramuscularly to exponential degradation intraperitoneally, due to differences in inflammatory responses and fluid flow. Nanoparticle excretion from degraded phantoms lagged behind polymer, and future studies will modulate nanoparticle clearance. Utilizing in situ monitoring, this study seeks to unify literature and facilitate better tissue engineering devices, by highlighting the relative effect of composition and implant site on important materials properties.
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材料成分和植入部位影响体内设备降解率
成功的组织工程需要生物医学设备在初期稳定伤口,然后随着组织的再生而降解。然而,文献报道的材料降解率往往相互矛盾。在植入设备中加入原位监测功能可实时评估降解情况和潜在故障。这就需要引入造影剂,因为大多数生物医学设备都是由高分子材料组成的,在医学成像模式中没有固有的对比度。在本研究中,通过在具有不同降解特性的聚合物(聚己内酯(PCL)、聚乳酸-聚乙二醇(PLGA)85:15 和 PLGA 50:50,分别代表慢、中和快降解材料)中添加 5-20wt% 的氧化钽(TaOx)纳米粒子,制作了计算机断层扫描(CT)可视不透射线复合材料。模仿多孔组织工程装置的不透射线模型被植入小鼠肌肉或腹腔,并通过 CT 进行 20 周的监测。模型体积的变化,包括塌陷和肿胀,随着时间的推移而可视化。模型降解情况由聚合物基质决定,与纳米粒子的添加无关,异物反应由植入部位决定。此外,由于炎症反应和液体流动的差异,降解动力学在中度降解材料中受到显著影响,从肌肉内的线性降解过渡到腹膜内的指数降解。降解模型中纳米粒子的排泄落后于聚合物,未来的研究将对纳米粒子的清除进行调节。本研究利用原位监测,通过强调成分和植入部位对重要材料特性的相对影响,力求统一文献,促进组织工程设备的改进。
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