Next generation 3D-printed auricular implants involving degradable materials and cells for ultimate implant integration and tissue regeneration

下一代 3D 打印耳廓植入物涉及可降解材料和细胞，可实现最终植入物整合和组织再生

• 批准号: 2669482
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2669482
• 关键词: Next; generation; 3D; printed; auricular

Auricular reconstruction which is required to correct congenital birth defects remains a major challenge in plastic surgery1. Currently, casted non-degradable polymeric scaffolds, such as porous polyethylene (PE) are still widely used. Implant integration remains a problem with non-degradable scaffolds, with inflammation and infection still frequently occurring, and implant fracture and exposure (from skin) commonly observed. Inadequate biocompatibility and un-matching mechanics are likely reasons leading to those clinical complexities. This calls for re-consideration of materials and novel approaches for scaffold design and fabrication.A 2-fold approach is planned in this project: Firstly, we will improve 3D-printed HDPE scaffold developed at our collaborator's (Southern Medical School, China), and focus on two aspects of development: 1) modify the implant surface to add biocompatibility. With novel fibre spinning, a layer of biodegradable nanofibers (e.g. polycaprolactone (PCL)) will be deposited on the HDPE scaffold; 2) explore the feasibility to set up a drug delivery system in the scaffold, with the aim of delivering anti-bacterials or promoting angiogenesis and tissue ingrowth. Silver ions and VEGF (vascular endothelial growth factor) will be incorporated by pre-spinning blending or impregnation after fibre spinning. To assess the performance of the modified implant and its efficacy releasing the drugs, fibroblasts, endothelial cells, and chondrocytes will be cultured with the scaffolds and cell adhesion, proliferation, and differentiation assessed. Drug release profiles will be collected, and tissue deposition and ingrowth monitored particularly concerning vascularization and fibrous tissue growth and integration with the scaffold.Secondly, a tissue engineering approach will be adopted to assess whether native cartilage can be regenerated at the defect site. The bio-inert and non-degradable HDPE as the base scaffold material will be replaced by a natural polysaccharide printable material. Chondrocytes or mesenchymal stem cells will be mixed into the polysaccharide solution prior to printing, and printing parameters adjusted to fabricate following the auricular shape, maintain ultimate anatomical structure while retaining cell viability and phenotype. Formation of natural fibrous cartilage within the cell-containing scaffold will be assessed with the degradation of the initial scaffolding material measured.It is hoped that the newly developed auricular scaffolds can offer next generation auricular implants with improved clinical performances, with ultimate implant integration or native tissue regeneration.1. Ebrahimi A. et al, Reconstructive surgery of auricular defects: an overview, Trauma Mon. 20 (4), e28202 (2015).

矫正先天性先天性缺陷所需要的耳廓重建仍然是整形外科的主要挑战。目前，铸造的不可降解聚合物支架，如多孔聚乙烯（PE）仍被广泛使用。对于不可降解的支架，植入物的整合仍然是一个问题，炎症和感染仍然经常发生，植入物骨折和暴露（来自皮肤）也很常见。不充分的生物相容性和不匹配的机制可能是导致这些临床复杂性的原因。这就需要重新考虑材料和脚手架设计和制造的新方法。本项目计划采用两方面的方法：首先，我们将对合作伙伴（中国南方医学院）开发的3d打印HDPE支架进行改进，重点发展两个方面：1)修改植入物表面以增加生物相容性。通过新型纤维纺丝，一层可生物降解的纳米纤维（如聚己内酯（PCL））将沉积在HDPE支架上；2)探索在支架内建立药物输送系统的可行性，以输送抗菌药物或促进血管生成和组织长入。银离子与血管内皮生长因子（VEGF）通过纺丝前共混或纤维纺丝后浸渍的方式掺入。为了评估改良后的植入物的性能及其释放药物的功效，将在支架的基础上培养成纤维细胞、内皮细胞和软骨细胞，并评估细胞的粘附、增殖和分化。将收集药物释放概况，并监测组织沉积和长入，特别是关于血管化和纤维组织生长以及与支架的整合。其次，将采用组织工程方法来评估缺损部位的天然软骨能否再生。生物惰性和不可降解的HDPE作为基础支架材料将被天然多糖可打印材料所取代。在打印前将软骨细胞或间充质干细胞混合到多糖溶液中，并调整打印参数以按照耳廓形状制造，在保留细胞活力和表型的同时保持最终的解剖结构。在含有细胞的支架内形成的天然纤维软骨将通过测量初始支架材料的降解来评估。希望新开发的耳廓支架能够为下一代耳廓植入体提供更好的临床性能，最终实现植入体的整合或原生组织的再生。Ebrahimi A.等，耳廓缺损的再造术：综述，创伤医学杂志，20 (4),e28202（2015）。