Bioengineering Department, University of Texas at Arlington, Arlington, TX 76019-0138, USA.
Biomaterials. 2010 May;31(14):3997-4008. doi: 10.1016/j.biomaterials.2010.01.144. Epub 2010 Feb 24.
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-1alpha 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.
尽管人们对生物材料引起的组织反应有了重大的认识进展，但大多数植入物仍然受到炎症反应的困扰，这可能导致纤维化包裹。在组织工程中，这是一个严重的问题，因为种子细胞和生物活性成分与天然组织分离，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。最近的证据表明，间充质干细胞（MSC）和造血干细胞（HSC）可以产生有益的影响，改变炎症反应并改善愈合。本研究的目的是检查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对 PLGA 支架植入物的组织反应。通过因子吸附和微型渗透泵输送 SDF-1alpha，可以改善宿主来源的干细胞反应，导致界面处的干细胞群体增加 3 倍，持续长达 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减少，通过改变肥大细胞激活和干细胞参与，增加了血管生成并减少了对支架植入物的纤维化反应。这些结果表明，增强自体干细胞的募集可以通过改变/绕过炎症细胞反应并启动植入界面处干细胞参与愈合来改善对生物材料植入物的组织反应。
