Current Opinion in Biomedical Engineering最新文献

Surgical reattachment of tendon to bone is a clinical challenge, with unacceptably high retear rates in the early period after repair. A primary reason for these repeated tears is that the multiscale toughening mechanisms found at the healthy tendon enthesis are not regenerated during tendon-to-bone healing. The need for technologies to improve these outcomes is pressing, and the tissue engineering community has responded with many advances that hold promise for eventually regenerating the multiscale tissue interface that transfers loads between the two dissimilar materials, tendon, and bone. This review provides an assessment of the state of these approaches, with the aim of identifying a critical agenda for future progress.

Osteochondral tissue represents a complex biochemical and biophysical gradient between two distinctly different types of tissue. Its poor regeneration capabilities necessitate tissue engineering intervention; however, its complex structure and composition pose an immense engineering challenge. Though bone and cartilage engineering separately have seen success, fabricating the graded interface between these two dissimilar tissue types requires understanding and collaboration between multiple often-disunited disciplines. This review showcases innovative tissue engineering strategies utilised for fabrication of osteochondral interfaces in an attempt to bridge this gap, and highlights the potential of biofabrication techniques – namely 3D bioprinting – in providing a path towards future advancement in osteochondral and interfacial tissue engineering.

The need for organ transplants exceeds donor organ availability. In the quest to solve this shortage, the most remarkable area of advancement is organ production through the use of chimeric embryos, commonly known as blastocyst complementation. This technique involves the combination of different species to generate chimeras, where the extent of donor cell contribution to the desired tissue or organ can be regulated. However, ethical concerns arise with the use of brain tissue in such chimeras. Furthermore, the ratio of contributed cells to host animal cells in the chimeric system is low in the production of chimeras associated with cell apoptosis. This review discusses the latest innovations in blastocyst complementation and highlights the progress made in creating organs for transplant.

Age related macular degeneration and other retinal degenerative disorders are characterized by disruption of the outer blood retinal barrier (oBRB) with subsequent ischemia, neovascularization, and atrophy. Despite the treatment advances, there remains no curative therapy, and no treatment targeted at regenerating native-like tissue for patients with late stages of the disease. Here we present advances in tissue engineering, focusing on bioprinting methods of generating tissue allowing for safe and reliable production of oBRB as well as tissue reprogramming with induced pluripotent stem cells for transplantation. We compare these approaches to organ-on-a-chip models for studying the dynamic nature of physiologic conditions. Highlighted within this review are studies that employ good manufacturing practices and use clinical grade methods that minimize potential risk to patients. Lastly, we illustrate recent clinical applications demonstrating both safety and efficacy for direct patient use. These advances provide an avenue for drug discovery and ultimately transplantation.

Regenerative rehabilitation is a promising field aimed at harnessing the regenerative potential of stem-cell therapeutics to maximize functional recovery. Here, we outline recent advancements in the field of regenerative rehabilitation for treating knee osteoarthritis (KOA) and we highlight sex-specific considerations to promote knowledge translation to the clinic. A systematic review suggests that sexual dimorphism in the efficacy of regenerative rehabilitation approaches for the treatment of KOA may be partly attributed to the functional decline of female mesenchymal stem cells (MSCs) over the lifespan, particularly after menopause. These declines are likely to be accompanied by poor clinical outcomes. While evidence is far from adequate, physical therapeutics have emerged as a means to promote estrogen signaling in MSCs, potentially reversing menopause-related MSC dysfunction. This study calls for actions to dissect the effects of menopause, together with physical therapeutics, on stem-cell therapeutics toward the development of effective regenerative rehabilitation approaches.

The spatial distribution of the signaling molecules that mediate cell–cell communication and pattern formation is an important consideration for natural and engineered multicellular systems.

Signaling molecule concentration profiles directly impact cell response profiles, and various experimental techniques can be utilized to modulate these spatial distributions. Current strategies focused on physically or chemically modifying the extracellular space to affect signal distribution include performing experiments in microfluidic devices with dynamic user-controlled inputs and flow rates or adjusting the mesh sizes and protein binding affinities of extracellular matrix-mimicking hydrogels. Recent advances in synthetic biology have paved the way for new approaches that involve directly engineering the signaling molecules, their interactors, and their downstream effectors for fully orthogonal communication platforms.

Deriving from the mesoderm at mesenchymal condensation, in the nascent musculoskeletal system, interface tissues include periosteum, ligament, interosseous membrane, and joint capsules. They comprise common structural proteins, collagen, and elastin, woven into anisotropic composites with toughness and elasticity adapted to withstand prevailing dynamic loads. Together with their composite fibrous weave structure, the interface tissues' respective resident cells imbue unique properties to the tissues. For example, the progenitor cells of the periosteal cambium layer express claudin, a tight junction protein that confers anisotropic and smart functional barrier properties to the periosteal membrane; e.g. where permeability is higher in the muscle to bone direction than vice versa under high flow rates typical for trauma. This review compares properties of interface tissues, focusing on periosteum, the interosseous membrane (a specialized ligament structure), and the deep (investing) fascia. It highlights current gaps in understanding as well as opportunities to create and advance manufacture next generation medical textiles and devices that emulate interface tissue properties.

The ability to precisely control cellular function in response to external stimuli can enhance the function and safety of cell therapies. In this review, we will detail how the modularity of protein domains has been exploited for cellular control applications, specifically through design of multifunctional synthetic constructs and controllable split moieties. These advances, which build on techniques developed by biologists, protein chemists and drug developers, harness natural evolutionary tendencies of protein domain fusion and fission. In this light, we will highlight recent advances towards the development of novel immunoreceptors, base editors, and cytokines that have achieved intriguing therapeutic potential by taking advantage of well-known protein evolutionary phenomena and have helped cells learn new tricks via synthetic biology. In general, protein modularity, i.e., the relatively facile separation or (re)assembly of functional single protein domains or subdomains, is becoming an enabling phenomenon for cellular engineering by allowing enhanced control of phenotypic responses.