A robust adaptive immune response is essential for combatting pathogens. In the wrong context such as due to genetic and environmental factors, however, the same mechanisms crucial for self-preservation can lead to a loss of self-tolerance. Resulting autoimmunity manifests in the development of a host of organ-specific or systemic autoimmune diseases, hallmarked by aberrant immune responses and tissue damage. The prevalence of autoimmune diseases is on the rise, medical management of which focuses primarily on pharmacological immunosuppression that places patients at a risk of side effects, including opportunistic infections and tumorigenesis. Biomaterial-based drug delivery systems confer many opportunities to address challenges associated with conventional disease management. Hydrogels, in particular, can protect encapsulated cargo (drug or cell therapeutics) from the host environment, afford their presentation in a controlled manner, and can be tailored to respond to disease conditions or support treatment via multiplexed functionality. Moreover, localized delivery to affected sites by these approaches has the potential to concentrate drug action at the site, reduce off-target exposure, and enhance patient compliance by reducing the need for frequent administration. Despite their many benefits for the management of autoimmune disease, such biomaterial-based approaches focus largely on the downstream effects of hypersensitivity mechanisms and have a limited capacity to eradicate the disease. In contrast, direct targeting of mechanisms of hypersensitivity reactions uniquely enables prophylaxis or the arrest of disease progression by mitigating the basis of autoimmunity. One promising approach is to induce self-antigen-specific tolerance, which specifically subdues damaging autoreactivity while otherwise retaining the normal immune responses. In this review, we will discuss hydrogel-based systems for the treatment of autoimmune disease, with a focus on those that target hypersensitivity mechanisms head-on. As the field continues to advance, it will expand the range of therapeutic choices for people coping with autoimmune diseases, providing fresh prospects for better clinical outcomes and improved quality of life.

中文翻译：

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基于水凝胶的方法针对自身免疫性疾病的超敏机制


强大的适应性免疫反应对于对抗病原体至关重要。然而，在错误的环境下，例如由于遗传和环境因素，对自我保护至关重要的相同机制可能会导致自我宽容的丧失。由此产生的自身免疫表现为一系列器官特异性或系统性自身免疫疾病的发展，其特点是异常的免疫反应和组织损伤。自身免疫性疾病的患病率正在上升，其医疗管理主要集中于药物免疫抑制，这使患者面临副作用的风险，包括机会性感染和肿瘤发生。基于生物材料的药物输送系统为解决与传统疾病管理相关的挑战提供了许多机会。特别是，水凝胶可以保护封装的货物（药物或细胞治疗剂）免受宿主环境的影响，以受控的方式提供它们的呈现，并且可以定制以响应疾病状况或通过多重功能支持治疗。此外，通过这些方法对受影响部位进行局部递送有可能将药物作用集中在该部位，减少脱靶暴露，并通过减少频繁给药的需要来提高患者的依从性。尽管它们对治疗自身免疫性疾病有很多好处，但这种基于生物材料的方法主要关注超敏反应机制的下游影响，并且根除疾病的能力有限。相比之下，直接针对超敏反应机制独特地能够通过减轻自身免疫的基础来预防或阻止疾病进展。 一种有前途的方法是诱导自身抗原特异性耐受，它可以特异性地抑制破坏性的自身反应性，同时保留正常的免疫反应。在这篇综述中，我们将讨论基于水凝胶的治疗自身免疫性疾病的系统，重点关注那些直接针对超敏机制的系统。随着该领域的不断发展，它将扩大自身免疫性疾病患者的治疗选择范围，为更好的临床结果和改善生活质量提供新的前景。