Osteoarthritis (OA) is the fourth leading cause of disability in adults. Yet, few viable pharmaceutical options exist for pain abatement and joint restoration, aside from joint replacement at late and irreversible stages of the disease. From the first onset of OA, as joint pain increases, individuals with arthritis increasingly reach for drug delivery solutions, from taking oral glycosaminoglycans (GAGs) bought over the counter from retail stores (e.g., Costco) to getting injections of viscous, GAG-containing synovial fluid supplement in the doctor’s office. Little is known regarding the efficacy of delivery mode and/or treatment by such disease-modulating agents. This Review addresses the interplay of mechanics and biology on drug delivery to affected joints, which has profound implications for molecular transport in joint health and (patho)physiology. Multiscale systems biology approaches lend themselves to understand the relationship between the cell and joint health in OA and other joint (patho)physiologies. This Review first describes OA-related structural and functional changes in the context of the multilength scale anatomy of articular joints. It then summarizes and categorizes, by size and charge, published molecular transport studies, considering changes in permeability induced through inflammatory pathways. Finally, pharmacological interventions for OA are outlined in the context of molecular weights and modes of drug delivery. Taken together, the current state-of-the-art points to a need for new drug delivery strategies that harness systems-based interactions underpinning molecular transport and maintenance of joint structure and function at multiple length scales from molecular agents to cells, tissues, and tissue compartments which together make up articular joints. Cutting edge and cross-length and -time scale imaging represents a key discovery enabling technology in this process.

中文翻译：

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骨关节炎：跨长度量表的运输和药物输送新策略

骨关节炎（OA）是成年人残疾的第四大主要原因。然而，除了在疾病的晚期和不可逆阶段进行关节置换以外，几乎没有可行的药物用于减轻疼痛和恢复关节。从OA的初发开始，随着关节疼痛的加剧，关节炎患者越来越多地寻求药物递送解决方案，从服用从零售商店（例如Costco）柜台购买的口服糖胺聚糖（GAG）到注射含GAG的粘性注射剂滑液补充剂在医生的办公室。对于这种疾病调节剂的递送方式和/或治疗的功效知之甚少。这篇评论探讨了力学和生物学在药物输送到受影响关节方面的相互作用，这对于关节健康和（病理）生理学中的分子运输具有深远的意义。多尺度系统生物学方法有助于了解OA和其他关节（病理）生理学中细胞与关节健康之间的关系。这篇综述首先描述了在关节长的多尺度解剖学背景下OA相关的结构和功能的变化。然后，它根据大小和电荷，对已发表的分子转运研究进行了总结和归类，并考虑了通过炎症途径引起的通透性变化。最后，在分子量和药物递送方式的背景下概述了OA的药理干预措施。在一起 当前的最新技术表明需要新的药物递送策略，这些策略需要利用基于系统的相互作用来支持分子运输以及从分子剂到细胞，组织和组织区隔的多个长度尺度的分子运输和关节结构和功能的维持。共同组成关节。尖端，跨长度和时标成像是该过程中一项关键的发现支持技术。