Current Opinion in Biomedical Engineering最新文献

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.

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.

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.

Trauma, both psychological and physical, represents a complex and pervasive challenge to individual well-being. This paper explores the dynamic interplay between mental and physical health in the context of trauma, shedding light on the processes of regeneration that occur at their interface. Drawing from a comprehensive review of basic, clinical and interdisciplinary research, this paper elucidates the bidirectional relationships between mental and physical health outcomes following traumatic experiences. Especially the influence of inflammation, gut microbiome, stress hormones and the activation of the HPA axis are explored in more detail. In conclusion, stress-related disorders and mental diseases should be taken into account when patients display a disturbed healing after physical injury. Awareness for the significant impact of mental health on trauma outcome should be increased among physicians.

Due to the high incidence of cartilage-related pathologies such as focal defects and osteoarthritis, strategies are needed to restore the structure and function of osteochondral tissue. Articular cartilage and bone have distinctly different properties, rendering challenging the engineering of a robust interface that reduces stress concentrations and delamination. The osteochondral interface, which consists of a tidemark, calcified cartilage, cement line, and surrounding tissues, has a unique structure and function, but there is a dearth of quantitative data to describe it. Elucidating the structure–function relationships through characterization will be essential in defining design criteria for tissue engineering. Osteochondral engineering has used scaffold-based methods that, for example, use polymers in conjunction with ceramics. Excitingly, scaffold-free methods are emerging for engineering the articular cartilage layer, which can be interfaced with an underlying bone substrate. Critical must be the objective of designing an interface that displays mechanics robust enough to withstand the native environment.

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.