Functionalised Biopolymers for Regenerative and Therapeutic Soft Robotics

用于再生和治疗软体机器人的功能化生物聚合物退行性疾病随着细胞衰老的延长而不断恶化组织功能，并被分为三个主要组：心脏、肿瘤和神经退行性疾病，所有这些都在全球非传染性疾病死亡率中占据重要地位[1]。人口老龄化增加了此类疾病的流行，刺激了全球对改进治疗技术的需求[2]。组织工程学和再生医学方法试图通过包括支架、干细胞疗法和受控药物输送在内的主动和被动治疗来改进治疗方法。最近，在刺激下表现出生理行为变化的活性结构也被制造出来，以引起生化、机械、电或组合反应(也称为软机器人)[6，7]。通过体内和体外研究证明这些材料是可行的，但它们的可用材料受到限制，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衍生材料的操纵通过模拟细胞的外部环境来增强其生物、化学和物理特性。这暴露了几个研究空白，包括(1)来自天然ECM的电活性生物聚合物(EABPs)的可用性，(2)植入后可调和动态控制的设备，(3)诱导多能干细胞(IPSCs)向体外成熟细胞系(例如，心脏和神经元)的分化。2.目的和目标：这个项目最初的重点是ECM材料的制备和表征，以开发“概念验证”EABP。这些被假设为通过施加电场来操作，使得可移动的阳离子可以在负功能膜中扩散，从而导致渗透压梯度、不对称膨胀和从而致动。系统地评估这些“概念证明”新型2D生物聚合物膜中的电活性将包括与改变的材料组成相关的机电响应的特征，例如导电性、形貌、形态、机械性能和细胞存活率。应该为优化的电活性ECM衍生的生物聚合物定义基准值。在优化之后，将制造3D结构(显示出改善了细胞黏附和增殖)，用于心脏、神经元和IPSCs的体外实验。刺激的细胞增殖、机械相互作用、血管生成过程和电活动分别与生长、分化和成熟有关。总体目标是从ECM衍生的生物聚合物开发一种再生的、治疗性的、软机器人生物医学设备，通过受控的药物释放、电刺激和/或模型细胞系的机械驱动来引发受控的刺激驱动活动。研究方法的新颖性。通过ECM衍生材料产生离子EABPs，以提高周围ECM降解时的生物相容性和生化稳定性，这已被认为可以促进心肌细胞在体外和体内的成熟。其新奇之处在于，仅使用ECM衍生材料创建了EABP，以创建能够做出单一或多个刺激反应的软机器人。将众所周知的制造方法与新型ECM衍生EABP相结合，生产具有多模式功能的可再吸收软机器人。这些包括机械驱动、电刺激、产生、植入后受控给药或两者的组合的可能性。然而，与合成材料不同，功能在

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