Current Opinion in Biomedical Engineering

Regenerative Rehabilitation represents a multifaceted approach that merges mechanobiology with therapeutic intervention to harness the body's intrinsic tissue repair and regeneration capacity. This review delves into the intricate interplay between mechanical loading and cellular responses in the context of musculoskeletal tissue healing. It emphasizes the importance of understanding the phases involved in translating mechanical forces into biochemical responses at the cellular level. The review paper also covers the mechanosensitivity of macrophages, fibroblasts, and mesenchymal stem cells, which play a crucial role during regenerative rehabilitation since these cells exhibit unique mechanoresponsiveness during different stages of the tissue healing process...

CRISPR/Cas-based gene-editing technologies have emerged as one of the most transformative tools in genome science over the past decade, providing unprecedented possibilities for both fundamental and translational research. Following the initial wave of innovations for gene knock-out, epigenetic/RNA modulation, and nickase-mediated base-editing, recent efforts have pivoted towards long-sequence gene editing- specifically, the insertion of large fragments (>1 kb) into the endogenous genome. In this review, we survey the development of these CRISPR/Cas-based sequence insertion methodologies in conjunction with the emergence of novel families of editing enzymes, such as transposases, single-stranded DNA-annealing proteins, recombinases, and integrases...

Cancer continues to affect underserved populations disproportionately. Novel optical imaging technologies, which can provide rapid, non-invasive, and accurate cancer detection at the point of care, have great potential to improve global cancer care. This article reviews the recent technical innovations and clinical translation of low-cost optical imaging technologies, highlighting the advances in both hardware and software, especially the integration of artificial intelligence, to improve in vivo cancer detection in low-resource settings...

The nuclear lamina, a conserved structure in metazoans, provides mechanical rigidity to the nuclear envelope. A decrease in lamin levels and/or lamin mutations are associated with a host of human diseases. Despite being only about 15 nm thick, perturbation of components of the nuclear lamina dramatically impacts the deformation response of the entire nucleus through mechanisms that are not well understood. Here we discuss evidence for the recently proposed 'nuclear drop' model that explains the role of A-type lamins in nuclear deformation in migrating cells...

No abstract text is available yet for this article.

Pooled screening creates a pool of cells with genetic variants, allowing for the simultaneous examination for changes in behavior or function. By selectively inducing mutations or perturbing expression, it enables scientists to systematically investigate the function of genes or genetic elements. Emerging gene editing tools, such as CRISPR, coupled with advances in sequencing and computational capabilities, provide growing opportunities to understand biological processes in humans, animals, and plants as well as to identify potential targets for therapeutic interventions and agricultural research...

Base editors and prime editors have emerged as promising tools for the modeling and treatment of genetic diseases due to their ability to introduce targeted modifications in the genomic DNA of living cells. Several engineering approaches have been applied to improve their performance, ranging from simple protein design approaches to complex directed evolution schemes that can probe a vast landscape of mutational variants with minimal user intervention. These extensive efforts have led to new generations of editors with enhanced properties such as increased editing activity, tailored editing windows, increased targetability, smaller construct size for viral delivery, and decreased off-target effects...

With the advent of induced pluripotent stem cells and modern differentiation protocols, many advances in our understanding of disease have been made possible by in vitro disease modeling; in some cases, their use may have supplanted animal models. Yet in vitro models often rely on rigid cell culture substrates that could limit our ability to completely reproduce human disease in a dish. Nascent work, however, suggests that the combination of biomaterials and/or advanced microphysiological systems-which better recapitulate tissue properties-with stem cells expressing disease mimicking genetics, could substantially improve current disease modeling efforts where genetics alone is insufficient...

Somatosensory neuroprostheses are devices with the potential to restore the senses of touch and movement from prosthetic limbs for people with limb amputation or paralysis. By electrically stimulating the peripheral or central nervous system, these devices evoke sensations that appear to emanate from the missing or insensate limb, and when paired with sensors on the prosthesis, they can improve the functionality and embodiment of the prosthesis. There have been major advances in the design of these systems over the past decade, although several important steps remain before they can achieve widespread clinical adoption outside the lab setting...

Wearable sensors offer a unique opportunity to study movement in ecological contexts - that is, outside the laboratory where movement happens in ordinary life. This article discusses the purpose, means, and impact of using wearable sensors to assess movement context, kinematics, and kinetics during locomotion, and how this information can be used to better understand and influence movement. We outline the types of information wearable sensors can gather and highlight recent developments in sensor technology, data analysis, and applications...

Since the original report of repurposing the CRISPR/Cas9 system for genome engineering, the past decade has witnessed profound improvement in our ability to efficiently manipulate the mammalian genome. However, significant challenges lie ahead that hinder the translation of CRISPR-based gene editing technologies into safe and effective therapeutics. The CRISPR systems often have a limited target scope due to PAM restrictions, and the off-target activity also poses serious risks for therapeutic applications...

Therapeutic antibody engineering seeks to identify antibody sequences with specific binding to a target and optimized drug-like properties. When guided by deep learning, antibody generation methods can draw on prior knowledge and experimental efforts to improve this process. By leveraging the increasing quantity and quality of predicted structures of antibodies and target antigens, powerful structure-based generative models are emerging. In this review, we tie the advancements in deep learning-based protein structure prediction and design to the study of antibody therapeutics...

Trauma leading to severe hemorrhage and shock on average kills patients within 3 to 6 hours after injury. With average prehospital transport times reaching 1-6 hours in low- to middle-income countries, stopping the bleeding and reversing hemorrhagic shock is vital. First-generation intravenous hemostats rely on traditional drug delivery platforms, such as self-assembling systems, fabricated nanoparticles, and soluble polymers due to their active targeting, biodistribution, and safety. We discuss some challenges translating these therapies to patients, as very few have successfully made it through preclinical evaluation in large-animals, and none have translated to the clinic...

Bacterial and viral pathogens are devastating to human health and well-being. In many regions, dozens of pathogen species and variants co-circulate. Thus, it is important to detect many different species and variants of pathogens in a given sample through multiplexed detection methods. CRISPR-based nucleic acid detection has shown to be a promising step towards an easy-to-use sensitive, specific, and high-throughput method to detect nucleic acids from DNA and RNA viruses and bacteria. Here, we review the current state of multiplexed nucleic acid detection methods with a focus on CRISPR-based methods...

Abnormal cardiac development is intimately associated with congenital heart disease. During development, a sponge-like network of muscle fibers in the endocardium, known as trabeculation, becomes compacted. Biomechanical forces regulate myocardial differentiation and proliferation to form trabeculation, while the molecular mechanism is still enigmatic. Biomechanical forces, including intracardiac hemodynamic flow and myocardial contractile force, activate a host of molecular signaling pathways to mediate cardiac morphogenesis...

Human stem cells provide emerging methods for drug screening, disease modeling, and personalized patient therapies. To meet this growing demand for scale-up, stem cell manufacturing methods must be streamlined with continuous monitoring technologies and automated feedback to optimize growth conditions for high production and consistency. Label-free optical imaging and sensing, including multiphoton microscopy, Raman spectroscopy, and low-cost methods such as phase and transmitted light microscopy, can provide rapid, repeatable, and non-invasive monitoring of stem cells throughout cell differentiation and maturation...

The severe shortage of functional donor lungs that can be offered to recipients has been a major challenge in lung transplantation. Innovative ex vivo lung perfusion (EVLP) and tissue engineering methodologies are now being developed to repair damaged donor lungs that are deemed unsuitable for transplantation. To assess the efficacy of donor lung reconditioning methods intended to rehabilitate rejected donor lungs, monitoring of lung function with improved spatiotemporal resolution is needed. Recent developments in live imaging are enabling non-destructive, direct, and longitudinal modalities for assessing local tissue and whole lung functions...

Currently approved adoptive T cell therapy relies on autologous (obtained from the same patient) T cells, which often suffer from poor quality that diminishes treatment efficacy. Due to the heterogeneous nature of T cell quality between and within patients, significant efforts are aimed at optimizing cell manipulation and growth conditions for potent T cell products. We believe that touch-free imaging and sensing technologies are critical to monitor single-cell features during T cell manufacturing to ensure consistent and optimally timed methods for cell manipulation and growth...

Cell-based therapies harness functional cells or tissues to mediate healing and treat disease. Assessment of cellular therapeutics requires methods that are non-destructive to ensure therapies remain viable and uncontaminated for use in patients. Optical imaging of endogenous collagen, by second-harmonic generation, and the metabolic coenzymes NADH and FAD, by autofluorescence microscopy, provides tissue structure and cellular information. Here, we review applications of label-free nonlinear optical imaging of cellular metabolism and collagen second-harmonic generation for assessing cell-based therapies...

Musculoskeletal injuries including bone defects continue to present a significant challenge in orthopedic surgery due to suboptimal healing. Bone reconstruction strategies focused on the use of biological grafts and bone graft substitutes in the form of biomaterials-based 3D structures in fracture repair. Recent advances in biomaterials science and engineering have resulted in the creation of intricate 3D bone-mimicking structures that are mechanically stable, biodegradable, and bioactive to support bone regeneration...