UCL Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Science, University College London, London, UK.
Royal Free London NHS Foundation Trust Hospital, London, UK.
Mol Biol Rep. 2020 Mar;47(3):2005-2013. doi: 10.1007/s11033-020-05297-7. Epub 2020 Feb 18.
Current surgical reconstruction for soft tissue replacement involves lipotransfer to restore soft tissue replacements but is limited by survival and longevity of the fat tissue. Alternative approaches to overcome these limitations include using biodegradable scaffolds with stem cells with growth factors to generate soft tissue. Adipose derived stem cells (ADSCs) offer great potential to differentiate into adipose, and can be delivered using biodegradable scaffolds. However, the optimal scaffold to maximise this approach is unknown. This study investigates the biocompatibility of nanocomposite scaffolds (POSS-PCL) to deliver ADSCs with and without the addition of growth factors using platelet rich plasma (PRP) in vivo. Rat ADSCs were isolated and then seeded on biodegradable scaffolds (POSS-PCL). In addition, donor rats were used to isolate PRP to modify the scaffolds. The implants were then subcutaneously implanted for 3-months to assess the effect of PRP and ADSC on POSS-PCL scaffolds biocompatibility. Histology after explanation was examined to assess tissue integration (H&E) and collagen production (Massons Trichome). Immunohistochemistry was used to assess angiogenesis (CD3, α-SMA), immune response (CD45, CD68) and adipose formation (PPAR-γ). At 3-months PRP-ADSC-POSS-PCL scaffolds demonstrated significantly increased tissue integration and angiogenesis compared to PRP, ADSC and unmodified scaffolds (p < 0.05). In addition, PRP-ADSC-POSS-PCL scaffolds showed similar levels of CD45 and CD68 staining compared to unmodified scaffolds. Furthermore, there was increased PPAR-γ staining demonstrated at 3-months with PRP-ADSC-POSS-PCL scaffolds (p < 0.05). POSS-PCL nanocomposite scaffolds provide an effective delivery system for ADSCs. PRP and ADSC work synergistically to enhance the biocompatibility of POSS-PCL scaffolds and provide a platform technology for soft tissue regeneration.
目前用于软组织替代的外科重建涉及脂肪转移以恢复软组织替代物，但受到脂肪组织存活和寿命的限制。克服这些限制的替代方法包括使用具有生长因子的干细胞的可生物降解支架来生成软组织。脂肪来源的干细胞（ADSCs）具有分化为脂肪的巨大潜力，可以使用可生物降解的支架进行递送。然而，最大化这种方法的最佳支架尚不清楚。本研究通过体内使用富含血小板的血浆（PRP）来研究纳米复合支架（POSS-PCL）对 ADCS 的生物相容性，这些支架具有和不具有生长因子。从大鼠中分离 ADSC，然后将其接种在可生物降解的支架（POSS-PCL）上。此外，使用供体大鼠分离 PRP 来修饰支架。然后将植入物皮下植入 3 个月，以评估 PRP 和 ADSC 对 POSS-PCL 支架生物相容性的影响。解释后的组织学检查用于评估组织整合（H＆E）和胶原蛋白产生（Massons Trichome）。免疫组织化学用于评估血管生成（CD3、α-SMA）、免疫反应（CD45、CD68）和脂肪形成（PPAR-γ）。在 3 个月时，与 PRP、ADSC 和未修饰的支架相比，PRP-ADSC-POSS-PCL 支架显示出明显增加的组织整合和血管生成（p < 0.05）。此外，PRP-ADSC-POSS-PCL 支架的 CD45 和 CD68 染色水平与未修饰的支架相似。此外，与未修饰的支架相比，PRP-ADSC-POSS-PCL 支架在 3 个月时显示出增加的 PPAR-γ 染色（p < 0.05）。POSS-PCL 纳米复合支架为 ADSC 提供了有效的递送系统。PRP 和 ADSC 协同作用增强了 POSS-PCL 支架的生物相容性，并为软组织再生提供了平台技术。
