Bioinspired Wound Dressing

“由于慢性伤口无法像急性伤口那样快速愈合，慢性伤口护理方面的创新一直不足，这被证明是成功治疗慢性伤口的重大挑战。一些慢性伤口无法恢复，导致败血症或截肢。患有慢性伤口的患者可能需要长期住院，这给卫生保健服务带来了更大的压力。慢性伤口还没有完全被理解，有重要的步骤是在体内按顺序进行愈合伤口，这些是：体内平衡，炎症，增殖和重塑，但慢性伤口不会超过炎症阶段。人们已经认识到，慢性伤口在潮湿的环境中愈合得更好。水凝胶是三维的亲水网络，可以被合成设计成吸收其重量约1000倍的水而不溶解。当肿胀时，它们能够模拟生物组织。它们具有敷料所需的大多数理想特性，特别是处理伤口床的水分，冷却效果被认为可以大大减少与伤口相关的疼痛，使气体交换，并且可以在不造成进一步创伤的情况下取出。由于这些原因，它们被用作干燥、光滑或坏死伤口的敷料。然而，一个缺点是，当肿胀时，它们会失去结构完整性。互穿网络（IPN）水凝胶是含有两个或多个交联聚合物单元的水凝胶，由于其在膨胀时强度和稳定性的增加，在结构上更有利。它们在生物医学用途上特别有趣，因为它们与细胞外基质有相似之处，由于细胞含有许多蛋白质，IPN可以由许多聚合物单元组成，这些相似之处使它们成为帮助组织再生的伤口敷料的绝佳候选者。项目目的在本项目中，我们提出设计一种刺激细胞外基质（ECM）合成的敷料，以促进增殖伤口愈合阶段的进展。ECM是异构的，并且在健康的环境中不断更新。它由两种主要成分组成：糖蛋白（纤维连接蛋白、蛋白聚糖、层粘连蛋白）和纤维蛋白（胶原蛋白、弹性蛋白）。体外基质影响结缔组织的分化、锚定和附着，促进愈合过程。因此，设计一种能够调节ECM活性的伤口敷料是一个理想的目标。因此，在这个项目中，建议进一步探索由聚合物网络组成的水凝胶基敷料的设计，这些敷料具有模仿ECM的潜力。合成材料的使用将提供调节水凝胶的能力，以产生更强的伤口敷料，使气体交换和吸收多余的伤口渗出液，而不会失去结构完整性，使伤口愈合并超越炎症阶段。一种具有成本效益的水凝胶将被开发出来，它由交联聚合物的渗透网络组成，在膨胀时提供足够的强度。适当的单体单位，从天然或合成材料，将选择适合慢性伤口愈合。聚合过程将被优化，水凝胶的性能将被评估为平衡含水量（EWC）、机械和剥离强度、粘弹性性能和水蒸气吸附性能。”

"The innovations in chronic wound care have been inadequate, proving to be a significant challenge to treat successfully chronic wounds, due to their inability to heal quickly like acute wounds. Some chronic wounds never recover leading to sepsis or amputations. Patients with chronic wounds can require hospitalisation for long periods of time, which puts an increased strain on health care services.Chronic wounds are not completely understood, there are important steps that are carried out in sequence within the body to heal wounds, these are: homeostasis, inflammation, proliferation and remodelling but chronic wounds do not progress beyond the inflammation stage. HydrogelsIt has become recognised that chronic wounds heal better when maintained in a moist environment. Hydrogels are three-dimensional hydrophilic networks that can be synthetically designed to absorb ca. 1000 times their weight of water without solubilising. When swollen they are able to simulate biological tissue. They possess the majority of the ideal characteristics required of dressings, in particular that of managing the wound bed moisture, a cooling effect believed to considerably reduced the pain associated with the wound, enable gaseous exchange and can be removed without causing further trauma. For these reasons they are used as dressings for dry, sloughy, or necrotic wounds. One disadvantage, however, is that when swollen they lose structural integrity.Interpenetrating network (IPN) hydrogels are hydrogels that contain two or more cross-linked polymeric units, which are structurally more favourable due to their increased strength and stability upon swelling. They are particularly interesting for biomedical use, as they share similarities with the extracellular matrix, due to cells containing many proteins, IPN can consist of many polymer units, these similarities make them an excellent candidate for wound dressings to aid in tissue regeneration. Project aimIn this project we propose to design a dressing to stimulate extracellular matrix (ECM) synthesis to promote progress through the proliferation wound healing stage. The ECM is heterogeneous and in a healthy environment is constantly renewed. It consists of two main components glycoproteins (fibronectin, proteoglycans, laminin) and fibrous proteins (collagen, elastin). The ECM influences the differentiation as well as anchorage and attachment of connective tissue to enhance the healing process. The design of a wound dressing capable of regulating ECM activity is therefore a desirable objective. In this project, it is thus proposed that the design of hydrogel-based dressings consisting of polymeric networks with the potential to mimic the ECM are explored further.The use of synthetic materials will provide the ability to tune the hydrogel, to produce a stronger wound dressing, that enables gaseous exchange and absorption of excess wound exudate, without losing structural integrity and enabling the wound to heal and progress beyond the inflammatory stage. A cost-effective hydrogel will be developed that consists of an interpenetration network of crosslinked polymers, that provides adequate strength upon swelling. Appropriate monomer units, from natural or synthetic materials, will be selected to suit the healing of chronic wounds. The polymerisation process will be optimised, the properties of the hydrogel that will be assessed are equilibrium water content (EWC), mechanical and peel strength, viscoelastic properties and water vapour sorption properties. "