We are pleased to present a joint special issue spanning Advanced Therapeutics and Macromolecular Bioscience to highlight progress in the use of hydrogel biomaterials for therapeutic applications. Hydrogels have been broadly explored as functional biomaterials; their three-dimensional highly hydrated porous architecture captures features of native extracellular matrix, offering surrogate substrates for the growth of cells and networks for the controlled release of therapeutic agents.^[1-11] In hydrogels used for biomedical application, relevant properties may include tunable control of matrix stiffness or its dynamics,^{[12, 13]} shear-thinning and self-healing transformations in conjunction with injection from a syringe or to interface with additive manufacturing and 3D printing,^[14-16] or mechanisms to respond to physiologically relevant features like temperature, pH, or enzymatic activity.^[17-19] The applications for this versatile class of materials are therefore broad, and many new directions are actively being explored.

This special issue spans the journals of Advanced Therapeutics and Macromolecular Biosciences, with more application-focused pieces appearing in the former and those focused more on fundamental design and evaluation of hydrogels appearing in the latter. The pieces enclosed within this joint special issue include informative reviews alongside original research from some World leaders using hydrogels for biomedical applications. The polymers used to construct these hydrogels are broad, ranging from one-dimensional assembly of small supramolecular gelators to covalently crosslinked (bio)polymer networks. The application of these materials is just as broad, with their uses explored for three-dimensional support of cells, controlled release of encapsulated therapeutic agents, bioadhesive constructs for tissue regeneration, and 3D printing of hierarchically organized scaffolds. The breadth encompassed in these articles is indicative of the many possible therapeutic uses of hydrogels to uncover new knowledge about biology, derive new functional technologies, or contribute to improving the practice of medicine.

The issue of Advanced Therapeutics begins with a number of informative reviews on the application and use of a broad array of hydrogels for biomedical applications. Azevedo and colleagues describe the use of engineered hydrogels prepared from hyaluronan, a natural component of the extracellular matrix that has been frequently explored for its use in engineered biomaterials (2300182). A review by Cho and colleagues next discusses the use of bioadhesive hydrogels for skin-related applications, describing uses ranging from cosmetics and UV protection to intervention in an assortment of skin diseases (2300125). A perspective by Huang, Li, and colleagues describes the use of bioadhesives for tissue repair and regeneration, with specific focus on engineering the mechanical properties of these materials to serve in load-bearing applications in the body (2300139). Kim and colleagues review the use of hydrogels for immunoengineering, specifically as it relates to enhancing the function of both endogenous and engineered T-cells for the treatment of solid tumors (2300094). The use of hydrogels for the delivery and therapeutics to control diabetes is discussed by Webber and colleagues, describing routes for controlled and glucose-responsive delivery to better meet the temporal therapeutic need presented by blood glucose control (2300127). Finally, the reviews featured in this special issue close with a piece by Ye and colleagues describing the use of hydrogels for integration with the practice of dental medicine, describing features of this class of materials that offer benefits to improving oral health and oral tissue regeneration (2300128).

The research articles in the issue of Advanced Therapeutics begin with work by Appel and colleagues describing the use of injectable hydrogels for the controlled release of vaccines, with utility in reducing the number of administrations for expanded vaccine access in the context of global health (2300108). Dankers and colleagues next describe the use of a hydrogel-based formulation for the controlled delivery of an antibody to inhibit specific microRNAs and promote cardiac regeneration after ischemic injury, taking advantage of a supramolecular hydrogel design to facilitate facile local administration (2300241). The work of De Laporte and colleagues describes the use of hydrogels for temporal and sequential control of growth factor release to promote network vascularization, noting the importance of staged presentation of active signaling molecules for optimal vascularization (2300091). Kim and colleagues then show the use of an adhesive composite hydrogel patch prepared from dynamic network bonds, and explore the use of this material for the localized delivery of an anti-inflammatory pharmaceutical agent to treat atopic dermatitis (2300096). Work by Kouwer and colleagues next explores the use of hydrogels with labile covalent attachment of a potent estrogen analogue, using these materials in conjunction with adipose-derived stem cells for tissue regeneration in conjunction with surgery to repair the pelvic floor (2300199). Finally, Shin and colleagues show the use of a fibrous covalently crosslinked gelatin scaffold applied to prepared 3D-printed tissue engineered skeletal muscle constructs (2300170).

The issue of Macromolecular Bioscience begins with a review by Matson and colleagues on hydrogels for the controlled and localized release of gasotransmitters, biologically active gas molecules with diverse roles in tissue regeneration (2300138). From here, research papers in this issue begin with work by Baker and colleagues to apply alginate-based hydrogels with dynamic properties including stress-relaxation in preparing models of cornea tissue that better match the dynamic mechanical properties of the native tissue (2300109). Work from Bouvy and colleagues describes the use of supramolecular hydrogels for intraperitoneal injections, finding that the hydrogels coat the tissue of the peritoneal cavity and are well-tolerated and biocompatible when applied using this mode of delivery (2300005). Caliari and colleagues next describe the importance of passage number on the in vitro mechanosensitivity of mesenchymal stem cells to hydrogels, showing that cell function is altered with successive in vitro passages and pointing to a key experimental variable in the use of hydrogels for preparation of tissue culture models (2300110). A report from Mano and colleagues describes the use of a chitosan-based supramolecular hydrogel with dual light-directed covalent crosslinking for use as injectable biomaterials and in 3D printing applications, showing that tunable viscoelasticity affords integration with a range of fabrication techniques (2300058). Mooney and colleagues engineer a conductive hydrogel scaffold prepared from alginate, graphene nanoflakes, and carbon nanotubes for the 3D culture and alignment of fibroblasts, with an eye toward developing platforms to recreate dermal tissue or screen therapeutics (2300044). The article from Tayalia and colleagues describes the use of gelatin-based cryogels for the suspension of therapeutic cells, showing these materials are able to support cells during the process of injection-based delivery and can biodegrade in situ (2200562). Webber and colleagues then report on dynamic-covalent crosslinking of a small molecule supramolecular gelator using a multiarm polymer, targeting dynamic and glucose-responsive networks for the encapsulation and controlled release of therapeutics in response to changes in blood glucose level (2300001). This special issue closes with work from Wu and colleagues describing a composite hydrogel prepared from a mixture of dextran, chitosan, and silica nanoparticles for the delivery of therapeutic agents into sites of surgical resection, targeting application to limit post-surgical infection or to localize drug delivery to the site of tumor resection (2200565).

These exemplary works presented across this joint special issue of Advanced Therapeutics and Macromolecular Biosciences illustrate the breadth and possible uses of hydrogels for therapeutic applications. From the design of material building blocks, to the control of their mechanical properties, to integration of active therapeutic agents, to facilitating cell-material interactions, there are many possibilities for hydrogels to interface and intervene in the context of biomedicine. In the coming decades, it is envisioned that continued development and advancement of these various technologies will lead to better in vitro tissue models to aid in understanding and recreating biology alongside functional technologies that support health and intervene in disease states.

我们很高兴推出涵盖先进治疗学和高分子生物科学的联合特刊，以强调水凝胶生物材料在治疗应用中的应用进展。水凝胶作为功能性生物材料已被广泛探索；它们的三维高度水合的多孔结构捕获了天然细胞外基质的特征，为细胞生长和治疗药物的受控释放网络提供了替代基质。^{[ 1-11 ]}在用于生物医学应用的水凝胶中，相关特性可能包括基质刚度或其动力学的可调控制，^{[ 12, 13 ]}与注射器注射或与添加剂界面相结合的剪切稀化和自修复转变制造和 3D 打印，^{[ 14-16 ]}或响应生理相关特征（如温度、pH 或酶活性）的机制。^{[ 17-19 ]}因此，这种多功能材料的应用非常广泛，并且许多新的方向正在积极探索中。

本期特刊涵盖《Advanced Therapeutics》和《Macromolecular Biosciences》期刊，前者出现更多以应用为中心的文章，而后者出现更多关注水凝胶的基础设计和评估的文章。本联合特刊中包含的文章包括信息丰富的评论以及一些世界领导人使用水凝胶进行生物医学应用的原创研究。用于构建这些水凝胶的聚合物范围很广，从小型超分子凝胶剂的一维组装到共价交联的（生物）聚合物网络。这些材料的应用同样广泛，其用途包括细胞的三维支撑、封装治疗剂的控制释放、组织再生的生物粘附结构以及分层组织支架的 3D 打印。这些文章涵盖的广度表明了水凝胶的许多可能的治疗用途，以揭示生物学的新知识、推导出新的功能技术或有助于改善医学实践。

《先进治疗学》一期首先对各种水凝胶在生物医学应用中的应用和使用进行了一些信息丰富的评论。Azevedo 及其同事描述了由透明质酸制备的工程水凝胶的用途，透明质酸是细胞外基质的天然成分，人们经常探索其在工程生物材料中的应用 (2300182)。Cho 及其同事接下来的一篇评论讨论了生物粘附水凝胶在皮肤相关应用中的使用，描述了从化妆品和紫外线防护到干预各种皮肤疾病的用途 (2300125)。Huang、Li 及其同事的观点描述了使用生物粘合剂进行组织修复和再生，特别关注这些材料的机械性能的设计，以用于体内的承重应用 (2300139)。Kim 及其同事回顾了水凝胶在免疫工程中的应用，特别是因为它涉及增强内源性和工程化 T 细胞的功能以治疗实体瘤 (2300094)。Webber 及其同事讨论了使用水凝胶进行递送和治疗以控制糖尿病，描述了受控和葡萄糖响应递送的路线，以更好地满足血糖控制带来的临时治疗需求（2300127）。最后，本期特刊中的评论以叶及其同事的一篇文章结尾，描述了水凝胶与牙科医学实践相结合的用途，描述了此类材料的特点，这些材料有助于改善口腔健康和口腔组织再生（ 2300128）。

《Advanced Therapeutics》杂志上的研究文章首先介绍了 Appel 及其同事的工作，描述了使用可注射水凝胶来控制疫苗的释放，可在全球健康的背景下减少给药次数，从而扩大疫苗的获取范围 (2300108) 。Dankers 及其同事接下来描述了使用基于水凝胶的制剂来控制抗体的递送，以抑制特定的 microRNA 并促进缺血性损伤后的心脏再生，利用超分子水凝胶设计来促进轻松的局部给药 (2300241)。De Laporte 及其同事的工作描述了使用水凝胶对生长因子释放进行时间和顺序控制以促进网络血管化，并指出了活性信号分子分阶段呈现对于最佳血管化的重要性 (2300091)。Kim 及其同事随后展示了由动态网络键制备的粘合复合水凝胶贴片的用途，并探索使用这种材料局部递送抗炎药剂来治疗特应性皮炎 (2300096)。Kouwer 及其同事接下来的工作探索了使用具有强效雌激素类似物不稳定共价附着的水凝胶，将这些材料与脂肪干细胞结合使用，以进行组织再生，并结合手术修复盆底 (2300199)。最后，Shin 及其同事展示了纤维共价交联明胶支架的用途，该支架应用于制备的 3D 打印组织工程骨骼肌结构 (2300170)。

《高分子生物科学》一期首先由 Matson 及其同事对水凝胶进行了综述，该水凝胶用于控制和局部释放气体递质，即在组织再生中具有多种作用的生物活性气体分子 (2300138)。从这里开始，本期的研究论文首先由贝克及其同事应用具有动态特性（包括应力松弛）的藻酸盐基水凝胶来制备更好地匹配天然组织动态机械特性的角膜组织模型（2300109）。Bouvy 及其同事的工作描述了超分子水凝胶用于腹腔注射的用途，发现水凝胶覆盖腹膜腔组织，并且在使用这种递送模式时具有良好的耐受性和生物相容性 (2300005)。Caliari 及其同事接下来描述了传代次数对间充质干细胞对水凝胶的体外机械敏感性的重要性，表明细胞功能随着连续的体外传代而改变，并指出了使用水凝胶制备组织培养物的一个关键实验变量型号 (2300110)。Mano 及其同事的一份报告描述了使用具有双光定向共价交联的基于壳聚糖的超分子水凝胶作为可注射生物材料和 3D 打印应用，表明可调粘弹性可以与一系列制造技术集成 (2300058)。Mooney 及其同事设计了一种由藻酸盐、石墨烯纳米片和碳纳米管制备的导电水凝胶支架，用于成纤维细胞的 3D 培养和排列，着眼于开发重建真皮组织或筛选治疗方法的平台 (2300044)。Tayalia 及其同事的文章描述了使用基于明胶的冷冻凝胶来悬浮治疗细胞，表明这些材料能够在注射递送过程中支持细胞，并且可以原位生物降解 (2200562)。然后，Webber 及其同事报告了使用多臂聚合物对小分子超分子凝胶剂进行动态共价交联，以动态和葡萄糖响应网络为目标，用于封装和控制释放治疗药物，以响应血糖水平的变化 (2300001)。本期特刊以 Wu 及其同事的工作为结尾，描述了一种由右旋糖酐、壳聚糖和二氧化硅纳米粒子的混合物制备的复合水凝胶，用于将治疗剂输送到手术切除部位，目标是限制术后感染或定位药物运送到肿瘤切除部位（2200565）。

这些在《高级治疗学》和《高分子生物科学》联合特刊上发表的典型作品说明了水凝胶在治疗应用中的广度和可能用途。从材料构建块的设计，到其机械性能的控制，到活性治疗剂的整合，再到促进细胞与材料的相互作用，水凝胶在生物医学领域有很多界面和干预的可能性。在未来几十年中，预计这些不同技术的持续发展和进步将带来更好的体外组织模型，以帮助理解和重建生物学以及支持健康和干预疾病状态的功能技术。