Functionalised Biopolymers for Regenerative and Therapeutic Soft Robotics

退行性疾病持续恶化组织功能，延长细胞衰老，主要分为三大类：心脏、肿瘤和神经退行性疾病，所有这些疾病都是全球非传染性疾病死亡率的重要组成部分。人口老龄化增加了这类疾病的患病率，刺激了全球对改进治疗技术的需求。组织工程和再生医学方法试图通过主动和被动治疗来改善治疗，包括支架、干细胞治疗和控制药物输送。最近，在刺激暴露后表现出生理行为变化的活性结构也被制造出来，以引发生化、机械、电或综合反应（也称为软机器人）[6,7]。这些方法已经通过体内和体外研究证明是可行的，但受到可用材料的限制，这些材料通常由合成或生物聚合物制成，不存在于天然细胞外基质（ECM）中。ECM衍生材料的操作通过模拟细胞外部环境来增强生物、化学和物理特性。这暴露了几个研究空白，包括：(1)从天然ECM中提取的电活性生物聚合物（EABPs）的可用性，(2)植入后可调谐和动态控制装置，(3)诱导多能干细胞（iPSCs）在体外分化为成熟细胞系（例如心脏和神经元）。2. 目的和目标。最初，该项目侧重于基于ecm的材料的制造和表征，以开发“概念验证”eabp。这些假设是通过施加电场来操作的，这样移动阳离子可以通过负功能化膜扩散，引起渗透压梯度，不对称膨胀，从而驱动。对这些“概念验证”的新型2D生物聚合物薄膜的电活性进行系统评估将包括机电响应的表征，例如，电导率、形貌、形态、机械性能和与改变的材料组成相关的细胞活力。应该为优化的电活性ECM衍生生物聚合物定义基准值。优化后，将制作3D结构（显示改善细胞粘附和增殖），用于心脏，神经元和ipsc的体外实验。受刺激的细胞增殖、机械相互作用、血管生成过程和电活动可以分别评估与生长、分化和成熟有关的情况。总体目标是利用ECM衍生的生物聚合物开发一种可再生的、治疗的、柔软的机器人生物医学设备，通过控制药物释放、电刺激和/或机械驱动模型细胞系来引发受控的刺激驱动活动。研究方法的新颖性通过ECM衍生材料生成离子EABPs，提高周围ECM降解后的生物相容性和生化稳定性，已被认为可以改善体外和体内心肌细胞的成熟。新颖之处在于仅使用ECM衍生材料创建eabp，以创建能够进行单次或多次刺激反应的软机器人。将熟知的制造方法与新型ECM衍生的EABPs相结合，生产具有多模式功能的可吸收软机器人。这些包括潜在的机械驱动、电刺激、发电、植入后的受控药物输送或两者的组合。然而，与合成材料不同的是，它的功能是在内部扩展的

Functionalised Biopolymers for Regenerative and Therapeutic Soft Robotics Degenerative diseases continuously deteriorate tissue functionality with prolonged cellular senescence and are classified into three main groups: cardiac, neoplastic, and neurodegenerative, all of which feature heavily in global mortality for noncommunicable diseases [1]. An aging population increases prevalence of such diseases stimulating global demand for improved therapeutic techniques [2]. Tissue engineering and regenerative medicine approaches have attempted to improve therapies through active and passive treatments involving scaffolds, stem cell therapies and controlled drug delivery. More recently, active structures exhibiting a change in physiological behaviour upon stimuli exposure have also been fabricated to elicit a biochemical, mechanical, electrical or combined response (also known as soft robots) [6,7]. These have proven feasible through in vivo and vitro studies but are limited by their available materials, often fabricated with synthetic or biological polymers, not present in the native extracellular matrix (ECM). Manipulation of ECM derived materials enhance the biological, chemical, and physical characteristics by mimicking cells external environment. This exposes several research gaps including (1) availability of electroactive biopolymers (EABPs) derived from the native ECM, (2) post implantation tuneable and dynamic controlled devices, (3) differentiation of induced pluripotent stem cells (iPSCs) into mature cell lines ex vivo (e.g., cardiac and neuronal). 2. Aims and objectives.Initially this project focuses on the fabrication and characterisation of ECM-based materials to develop 'proof of concept' EABPs. These are hypothesised to operate by applying an electric field such that mobile cations can diffuse through the negatively functionalised film inducing an osmotic pressure gradient, asymmetric swelling and therefore actuation.A systematic assessment of the electroactivity in these 'proof of concept' novel 2D biopolymeric films will include the characterisation of the electromechanical response, e.g., conductivity, topography, morphology, mechanical properties, and cell viability in relation to altered material composition. Benchmark values should be defined for an optimised electroactive ECM derived biopolymer.Following optimisation, 3D structures will be fabricated (shown to improved cell adhesion and proliferation) for in vitro experimentation on cardiac, neuronal, and iPSCs. Stimulated cell proliferation, mechanical interactions, angiogenic process and electroactivity can be assessed in relation to growth, differentiation, and maturation, respectively. The overarching objective is to develop a regenerative, therapeutic, soft robotic biomedical device from ECM derived biopolymers to elicit controlled stimulus driven activity through controlled drug release, electrical stimulation and/or mechanical actuation of model cell lines.3. Novelty of the research methodology.Generating ionic EABPs through ECM derived materials, for improved biocompatibility, biochemical stability of the surrounding ECM upon degradation which has been suggested to improve cardiomyocyte maturation in vitro and vivo. The novelty lies within the creation of EABPs solely using ECM derived materials to create a soft robot capable of single or multi stimulatory responses. Combining well understood fabrication methods with novel ECM derived EABPs to produce resorbable soft robotics with multiple mode functionality. These include the potential for mechanical actuation, electrical stimulation, generation, controlled drug delivery post implantation or a combination of each. However, unlike synthetic materials, functionality is extended within th