Graduate School of Biomedical Engineering, University of New South Wales, Sydney, New South Wales 2052, Australia.
Inaugural Paul Trainor Chair of Biomedical Engineering, Graduate School of Biomedical Engineering, University of New South Wales, Sydney, New South Wales 2052, Australia.
ACS Biomater Sci Eng. 2020 Nov 9;6(11):6009-6020. doi: 10.1021/acsbiomaterials.0c01081. Epub 2020 Oct 21.
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.
骨关节炎（OA）是导致成年人残疾的第四大原因。然而，除了在疾病晚期和不可逆转阶段进行关节置换外，针对减轻疼痛和恢复关节，几乎没有可行的药物选择。从 OA 的最初发作开始，随着关节疼痛的加剧，关节炎患者越来越多地寻求药物输送解决方案，从在零售店（例如 Costco）购买口服糖胺聚糖（GAG）到在医生办公室接受粘性、含 GAG 的滑液补充剂注射。对于这些疾病调节药物的输送方式和/或治疗效果知之甚少。本综述探讨了力学和生物学在药物输送到受影响关节中的相互作用，这对关节健康和（病理）生理学中的分子运输有深远的影响。多尺度系统生物学方法有助于理解 OA 和其他关节（病理）生理学中细胞与关节健康之间的关系。本综述首先描述了 OA 相关的结构和功能变化，同时考虑了炎症途径引起的通透性变化，在关节解剖的多长度尺度背景下进行了解释。然后，按尺寸和电荷对已发表的分子运输研究进行了总结和分类，考虑了通过炎症途径诱导的渗透性变化。最后，根据分子量和药物输送方式概述了 OA 的药物干预措施。综上所述，当前的最新技术表明，需要新的药物输送策略，以利用系统相互作用为基础的分子运输，并从分子药物到细胞、组织和组织隔室等多个长度尺度维持关节结构和功能，这些结构和功能共同构成了关节。尖端和跨长度和时间尺度的成像代表了这一过程中的一项关键发现技术。
