Acellular / Smart Materials - 3D Architecture: UK RMP Hub

非细胞/智能材料 - 3D 建筑：英国 RMP 中心

• 批准号: MR/R015651/1
• 负责人: Molly Stevens
• 金额: $ 545.46万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR015651%2F1
• 关键词: Acellular; Smart; Materials; 3D; Architecture

We have identified a significant unmet need for improved therapies to treat tissue degenerative diseases and injuries in eye, liver and musculoskeletal tissue. These conditions represent a considerable obstacle to health and quality of life, as well as a staggering burden to the economy. We will combine the expertise of world-leading UK research groups to design and manufacture innovative biomaterials and drug delivery strategies to develop the needed therapies. Importantly, the focus will be on accelerating the process of translating our scientific discoveries and advances into real-world applications. Our strategy stems from research on smart materials for specific clinical applications in eye, liver and musculoskeletal repair. We will investigate a range of highly innovative materials that can be tailored according to the specific clinical needs. We will develop exciting smart technologies where implanted materials will react to internal or external stimuli to, for example, release drugs that improve wound healing and reduce inflammation, or growth factors to enhance the regeneration of damaged or lost tissue. We will design flexible material platforms that can be easily modified to achieve a wide range of complex functionalities. We will introduce advanced manufacturing routes to produce materials that mimic the complex structure and multi-functionality of biological tissues. For applications in eye repair, we will develop injectable polymer sheets embedded with cells that would simultaneously replace lost retinal pigment epithelium and photoreceptors which cause visual impairment. We will also build 3D tissue engineered constructs for corneal repair. For our work on musculoskeletal tissue, we will develop injectable materials and 3D printed scaffold materials to repair fractures and defects in long bones, for example the tibia. The structure of the scaffolds will be designed to support and increase bone formation while embedded nanoparticles will be used for controlled delivery of growth factors. Our second target in the musculoskeletal tissue is shoulder rotator cuff repair where we have already novel electrospun material technologies in clinical trials. Here, we will improve these materials by introducing bioresponsive cues to regulate the activity of cells, modulate inflammation, enhance the formation of blood vessels and promote tissue growth. For osteoarthritis treatment, we will develop 3D constructs with controlled gradients that promote physical organisation of cartilage resulting in a more native-like functional material. The third clinical application targeted in this project is liver repair. We will aim to improve transplantation therapies by focussing on three promising pathways: 1) extending graft life-time using microparticles for localised delivery of immunomodulatory compounds, 2) enhancing cell engraftment with localised release of growth factors, and 3) developing innovative anti-fibrosis materials, including gels, patches and sprays. Importantly, we will complement our development pipeline with research on materials safety and immune response.Through the UKRMP2 Acellular Hub we will steer our research towards applications with high success potential in alignment to identified clinical needs, manufacturing feasibility, regulatory compliance and product safety assurance.

我们已经确定了对治疗眼、肝和肌肉骨骼组织中的组织变性疾病和损伤的改进疗法的显著未满足的需求。这些条件对健康和生活质量构成了相当大的障碍，也给经济造成了惊人的负担。我们将联合收割机结合世界领先的英国研究小组的专业知识，设计和制造创新的生物材料和药物输送策略，以开发所需的治疗方法。重要的是，重点将是加快将我们的科学发现和进步转化为现实世界应用的进程。我们的战略源于对智能材料的研究，用于眼睛，肝脏和肌肉骨骼修复的特定临床应用。我们将研究一系列高度创新的材料，这些材料可以根据特定的临床需求量身定制。我们将开发令人兴奋的智能技术，植入材料将对内部或外部刺激做出反应，例如释放药物，改善伤口愈合和减少炎症，或生长因子，以增强受损或丢失组织的再生。我们将设计灵活的材料平台，可以很容易地修改，以实现广泛的复杂功能。我们将引入先进的制造路线，生产模仿生物组织复杂结构和多功能的材料。对于眼睛修复的应用，我们将开发嵌入细胞的可注射聚合物片，这些细胞将同时取代导致视力障碍的视网膜色素上皮细胞和感光细胞。我们还将构建用于角膜修复的3D组织工程结构。对于我们在肌肉骨骼组织方面的工作，我们将开发可注射材料和3D打印支架材料，以修复长骨（例如胫骨）的骨折和缺陷。支架的结构将被设计为支持和增加骨形成，而嵌入的纳米颗粒将用于生长因子的受控递送。我们在肌肉骨骼组织中的第二个目标是肩袖修复，我们已经在临床试验中使用了新型静电纺丝材料技术。在这里，我们将通过引入生物反应线索来调节细胞的活性，调节炎症，增强血管的形成和促进组织生长来改善这些材料。对于骨关节炎治疗，我们将开发具有受控梯度的3D结构，以促进软骨的物理组织，从而产生更天然的功能材料。该项目针对的第三个临床应用是肝脏修复。我们的目标是通过专注于三种有前途的途径来改善移植疗法：1）使用微粒局部递送免疫调节化合物来延长移植物寿命，2）通过局部释放生长因子来增强细胞植入，以及3）开发创新的抗纤维化材料，包括凝胶，贴剂和喷雾剂。重要的是，我们将通过对材料安全性和免疫反应的研究来补充我们的开发管道。通过UKRMP2脱细胞中心，我们将引导我们的研究走向具有高成功潜力的应用，以符合已确定的临床需求，制造可行性，法规合规性和产品安全性保证。

项目成果

Carboxylated-xyloglucan and peptide amphiphile co-assembly in wound healing.

• DOI: 10.1093/rb/rbab040
• 发表时间: 2021-10
• 期刊: Regenerative biomaterials
• 影响因子: 6.7
• 作者: Ajovalasit A;Redondo-Gómez C;Sabatino MA;Okesola BO;Braun K;Mata A;Dispenza C
• 通讯作者: Dispenza C

A blueprint for translational regenerative medicine.

• DOI: 10.1126/scitranslmed.aaz2253
• 发表时间: 2020-12-02
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Armstrong JPK;Keane TJ;Roques AC;Patrick PS;Mooney CM;Kuan WL;Pisupati V;Oreffo ROC;Stuckey DJ;Watt FM;Forbes SJ;Barker RA;Stevens MM
• 通讯作者: Stevens MM

Engineering Anisotropic Muscle Tissue using Acoustic Cell Patterning.

• DOI: 10.1002/adma.201802649
• 发表时间: 2018-10
• 期刊: Advanced materials (Deerfield Beach, Fla.)
• 作者: Armstrong JPK;Puetzer JL;Serio A;Guex AG;Kapnisi M;Breant A;Zong Y;Assal V;Skaalure SC;King O;Murty T;Meinert C;Franklin AC;Bassindale PG;Nichols MK;Terracciano CM;Hutmacher DW;Drinkwater BW;Klein TJ;Perriman AW;Stevens MM
• 通讯作者: Stevens MM