Search

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.

Life is mechanobiological. Natural living materials exhibit remarkable, emergent and smart properties under mechanical loading. Such materials are classified as mechanoactive , in contrast to electroactive polymers and materials that exhibit advanced properties when subjected to electrical stimulation. Cutting edge, multiscale imaging technologies have proven enabling for the elucidation of molecular to meso-scale structure and function of natural mechanoactive materials. Using Microscopy-Aided Design And ManufacturE, (MADAME) this perspective article describes mechanoactive properties of natural materials including skin-on-bones ( periosteum ) and bone itself. In so doing, it demonstrates the principle to emulate natural smart properties using recursive logic, the basis of many computer algorithms, and to design and manufacture mechanoactive materials and products using advanced manufacturing methods that also incorporate principles of recursive logic. In sum, the MADAME approach translates physically the computer science paradigm of recursion by implementing Jacquard textile methods, which themselves form a historical basis for computing machines, together with additive manufacturing methods including multidimensional printing, stereolithography, laser sintering, etc. These integrated methods provide a foundation and translational pathway for scaled-up manufacture of disruptive mechanoactive materials that will find use in fields as varied as medicine, safety, transport and sports, for internal (implants) and external (wearables) applications., (Copyright © 2020 Knothe Tate.)

The role of molecular size selectivity in the onset and progression of osteoarthritis (OA), a degenerative disease of the musculoskeletal system and the most common cause of disability in aging adults, is unknown. Here we delivered a mixture of Texas-red (70 kDa), and Rhodamine-green (10 kDa) tagged, dextrans of neutral charge in a single bolus via heart injection to middle aged (8-10 months) and aged (17-19 months) Dunkin-Hartley Guinea pigs, a natural model for OA. We quantified tracer transport in serial-sectioned, cryofixed block specimens after five minutes' circulation. A remarkable separation of the molecules was observed in serial fluorescent images of whole joint sections. The larger, 70 kDa red tracer was abundant in the marrow cavity albeit less prevalent or absent in the bone, cartilage, meniscus and other tissues of the joint. Tissues of the meniscus, ligament, and tendon exhibited abundant 10 kDa tracer; volumes of tissue containing this molecular tracer were significantly lower in older than in younger animals. Surprisingly, muscle fiber bundles exhibited little fluorescence, while their bounding fasciae fluoresced either red or green. Small caliber channels through the articular cartilage appeared to show a degree of green fluorescence not observed in the surrounding cartilage matrix. This study opens up new avenues for study of musculoskeletal physiology in health and disease as well as new strategies for drug delivery.

Cell health and cell network patency dictate human physical and mental health throughout life. Cutting edge multiscale imaging and mapping of cell to organ structure and function is unravelling the remarkable plasticity of cellular networks, from bone to brain. Insights from these studies will enable the development of next generation implants to replace, repair and reprogram cellular networks, for promotion of mental and physical health., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)