The effect of incorporation of SDF-1alpha into PLGA scaffolds on stem cell recruitment and the inflammatory response.

The effect of incorporation of SDF-1alpha into PLGA scaffolds on stem cell recruitment and the inflammatory response.
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DOI:
10.1016/j.biomaterials.2010.01.144
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发表时间:
2010-05
期刊:
影响因子:
14
通讯作者:
Tang, Liping
Tang, Liping
中科院分区:
工程技术1区
文献类型:
--
作者:
Thevenot, Paul T.;Nair, Ashwin M.;Shen, Jinhui;Lotfi, Parisa;Ko, Cheng-Yu;Tang, Liping

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尽管在了解组织对生物材料的反应方面取得了重大进展,但大多数植入物仍然受到炎症反应的困扰,这些炎症反应可能导致纤维包膜。这在组织工程中具有可怕的后果,因为种子细胞和生物活性成分从天然组织中分离出来,限制了设计的再生潜力。此外,这些相互作用阻止了所需的组织整合和血管生成,从而阻止了设计的功能性。最近的证据支持间充质干细胞(MSC)和造血干细胞(HSC)具有改变炎症反应和促进愈合的有益作用。本研究的目的是检测干细胞是否可以靶向生物材料植入部位,以及增加局部干细胞反应是否可以改善组织对PLGA支架植入的反应。通过因子吸附和微渗泵输送将SDF-1α掺入,宿主来源的干细胞反应可以得到改善,从而使界面上的干细胞数量增加3倍,最长可达2周。这些相互作用被发现显著改变了急性肥大细胞反应,减少了支架植入物附近的肥大细胞和脱颗粒肥大细胞的数量。这导致随后下游炎症细胞反应的减少,并通过改变肥大细胞激活和干细胞参与,增加血管生成,减少对支架植入的纤维化反应。这些结果支持,增强自体干细胞的募集可以通过改变/绕过炎性细胞反应和启动干细胞参与植入物界面的愈合来改善组织对生物材料植入物的反应。
Despite significant advances in the understanding of tissue responses to biomaterials, most implants are still plagued by inflammatory responses which can lead to fibrotic encapsulation. This is of dire consequence in tissue engineering, where seeded cells and bioactive components are separated from the native tissue, limiting the regenerative potential of the design. Additionally, these interactions prevent desired tissue integration and angiogenesis, preventing functionality of the design. Recent evidence supports that mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC) can have beneficial effects which alter the inflammatory responses and improve healing. The purpose of this study was to examine whether stem cells could be targeted to the site of biomaterial implantation and whether increasing local stem cell responses could improve the tissue response to PLGA scaffold implants. Through incorporation of SDF-1α through factor adsorption and mini-osmotic pump delivery, the host-derived stem cell response can be improved resulting in 3X increase in stem cell populations at the interface for up to 2 weeks. These interactions were found to significantly alter the acute mast cell responses, reducing the number of mast cells and degranulated mast cells near the scaffold implants. This led to subsequent downstream reduction in the inflammatory cell responses, and through altered mast cell activation and stem cell participation, increased angiogenesis and decreased fibrotic responses to the scaffold implants. These results support that enhanced recruitment of autologous stem cells can improve the tissue responses to biomaterial implants through modifying/bypassing inflammatory cell responses and jumpstarting stem cell participation in healing at the implant interface.
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