Human fascia lata ECM scaffold augmented with immobilized hyaluronan: inflammatory response and remodeling in the canine body wall and shoulder implantation sites.

Human fascia lata ECM scaffold augmented with immobilized hyaluronan: inflammatory response and remodeling in the canine body wall and shoulder implantation sites.
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DOI:
10.1080/09205063.2014.975394
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发表时间:
2015
期刊:
Journal of biomaterials science. Polymer edition
影响因子:
--
通讯作者:
Derwin KA
Derwin KA
中科院分区:
其他
文献类型:
--
作者:
Leigh DR;Kim MS;Kovacevic D;Baker AR;Tan CD;Calabro A;Derwin KA

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我们推测,酪胺取代的透明质酸(THA)固定到细胞外基质(ECM)支架可能是一种策略,以促进对ECM的抗炎反应。此外,我们认为植入部位可以影响ECM支架的炎症反应和重塑。8只比格犬在肩部损伤和体壁部位植入筋膜ECM移植物,用固定化低分子量(57 kDa)THA或仅用水治疗。在12周时对犬实施安乐死,并整块采集筋膜移植物进行组织学检查。与肩关节移植物相比,植入体壁的移植物具有显著更高的炎性细胞浸润和血管分布,以及显著更低的延迟(胶原蛋白密度),这表明在犬模型中,与肩关节损伤部位相比,体壁处的炎症和重塑反应更强烈、持久,并且可能是降解性的。然而,与水处理的对照相比,固定的低分子量THA的存在对筋膜ECM的炎症反应或重塑没有影响。重要的是,这些结果表明,生物材料植入物的炎症反应和重塑取决于植入位置,因此我们的动物模型需要仔细选择。此外,透明质酸(HA)在伤口愈合中的潜在抗炎优势似乎在将其作为不可降解的水凝胶呈现给宿主时并未实现,即使其结合HA结合蛋白的能力得以维持。进一步研究用未交联(游离)HA或固定化低MW THA治疗ECM作为将游离HA或其他生物分子递送至手术修复部位的手段是必要的。
We postulate that immobilization of tyramine-substituted hyaluronan (THA) into an extracellular matrix (ECM) scaffold may be a strategy to promote an anti-inflammatory response to the ECM. Further, we posit that the implantation site could influence the inflammatory response and remodeling of an ECM scaffold. Eight beagles underwent implantation of fascia ECM grafts, treated with either immobilized low molecular weight (57 kDa) THA or water only, in both the shoulder injury and body wall sites. Dogs were euthanized at 12 weeks and fascia grafts harvested en bloc for histology. Grafts implanted at the body wall had significantly higher inflammatory cell infiltrate and vascularity, and significantly lower retardance (collagen density), than grafts at the shoulder, suggestive of a more intense, persistent, and perhaps degradative inflammatory and remodeling response at the body wall than shoulder injury site in the canine model. However, the presence of immobilized low MW THA had no effect on the inflammation response or remodeling of fascia ECM compared to water-treated controls. Importantly, these results suggest that the inflammatory response and remodeling of biomaterial implants depends on the location of implantation and therefore our animal models need to be carefully chosen. Further, the potential anti-inflammatory advantages of hyaluronan (HA) in wound healing do not appear to be realized when presenting it to the host as non-degradable hydrogel even if its capacity for binding HA binding protein is maintained. Further study treating ECM with uncross-linked (free) HA or immobilized low MW THA as a means to deliver free HA or other biomolecules to a surgical repair site is warranted.
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