Multifunctional Gel Scaffolds for Cell Delivery and Tissue Repair

用于组织重建的可注射生物材料支架仍未成为临床现实，因为许多支架的设计参数尚未得到充分优化和控制。目前迫切需要一种既能模拟自然组织的力学性能和结构，又能促进细胞粘附、增殖和分化的新型多功能支架。该项目的目的是开发新的基于超支聚（甘油三酯）/聚（己内酰胺）（HBPG/PCL）的可注射凝胶支架，该支架具有在体内促进骨生长和软骨再生的潜力，并以微创方式应用。因此，它们将使骨关节炎（OA）的有效治疗无需手术。骨性关节炎的病理特征是局部软骨丢失，邻近骨重塑和相关炎症。骨关节炎是全球范围内导致疼痛和残疾的主要原因之一。物理交联的HBPG/PCL颗粒将在无紫外线辐射的情况下，以安全有效的方式在体内形成机械强度逐渐增加的新型共价连接支架。它们将具有可调的弹性模量值，并将进行酶触发的拆卸。该提案将通过提高患者的生活质量、降低手术成本、缩短患者恢复时间、减少因残疾和/或疾病造成的生产力损失来促进英国国民保健服务体系的发展。该提案极大地扩展了Halacheva博士早期对生物材料支架的研究，并将由一名博士后研究助理（PDRA）和一名博尔顿大学资助的博士生进行为期15个月的研究。

Injectable biomaterial scaffolds for tissue reconstruction are still not a clinical reality because many of the scaffold design parameters have not been fully optimized and controlled. New multifunctional scaffolds that both mimic the mechanical properties and structure of natural tissues and are able to promote cell adhesion, proliferation and differentiation are now urgently needed. The aim of this project is to develop new hyper-branched poly(glycidol)/poly(caprolactam) (HBPG/PCL) based injectable gel scaffolds that have the potential to enable bone growth and the regeneration of cartilage in vivo, following application in a minimally invasive manner. They will thereby enable effective treatment of osteoarthritis (OA) without surgery. OA is characterized pathologically by localised loss of cartilage, remodeling of adjacent bone and associated inflammation. OA is one of the leading causes of pain and disability worldwide. New covalently-linked scaffolds that exhibit gradually increasing mechanical strength will be formed in vivo from physically cross-linked HBPG/PCL particles in a safe and effective way, in the absence of UV-radiation. They will feature tunable elastic modulus values and will undergo enzyme-triggered disassembly. The proposal will benefit the NHS by improving patients' quality of life, reducing surgical costs and boost the UK economy by shortening patient recovery times and reducing productivity losses due to disability and/or illness. The proposal greatly extends Dr. Halacheva's earlier studies on biomaterials scaffolds and will be conducted by a postdoctoral research associate (PDRA) and a University of Bolton funded Ph.D. student over a period of 15 months.