Search Results (475)

Recombinant protein hydrogels have emerged as transformative biomaterials that overcome the bioinertness and unpredictable degradation of traditional synthetic systems by leveraging genetically engineered backbones, such as elastin-like polypeptides, SF, and resilin-like polypeptides, to replicate extracellular matrix (ECM) dynamics and enable programmable functionality. Constructed through a hierarchical crosslinking strategy, these hydrogels integrate reversible physical interactions with covalent crosslinking approaches, collectively endowing the system with mechanical strength, environmental responsiveness, and controlled degradation behavior. Critically, molecular engineering strategies serve as the cornerstone for functional precision: domain-directed self-assembly exploits coiled-coil or β-sheet motifs to orchestrate hierarchical organization, while modular fusion of bioactive motifs through genetic encoding or site-specific conjugation enables dynamic control over cellular interactions and therapeutic release. Such engineered designs underpin advanced applications, including immunomodulatory scaffolds for diabetic wound regeneration, tumor-microenvironment-responsive drug depots, and shear-thinning bioinks for vascularized bioprinting, by synergizing material properties with biological cues. By uniting synthetic biology with materials science, recombinant hydrogels deliver unprecedented flexibility in tuning physical and biological properties. This review synthesizes emerging crosslinking paradigms and molecular strategies, offering a framework for engineering next-generation, adaptive biomaterials poised to address complex challenges in regenerative medicine and beyond. Full article

In the rapidly evolving field of biomedical engineering, hydrogels have emerged as highly versatile biomaterials that bridge biology and technology through their high water content, exceptional biocompatibility, and tunable mechanical properties. This review provides an integrated overview of both natural and synthetic hydrogels, examining their structural properties, fabrication methods, and broad biomedical applications, including drug delivery systems, tissue engineering, wound healing, and regenerative medicine. Natural hydrogels derived from sources such as alginate, gelatin, and chitosan are highlighted for their biodegradability and biocompatibility, though often limited by poor mechanical strength and batch variability. Conversely, synthetic hydrogels offer precise control over physical and chemical characteristics via advanced polymer chemistry, enabling customization for specific biomedical functions, yet may present challenges related to bioactivity and degradability. The review also explores intelligent hydrogel systems with stimuli-responsive and bioactive functionalities, emphasizing their role in next-generation healthcare solutions. In modern medicine, temperature-, pH-, enzyme-, light-, electric field-, magnetic field-, and glucose-responsive hydrogels are among the most promising “smart materials”. Their ability to respond to biological signals makes them uniquely suited for next-generation therapeutics, from responsive drug systems to adaptive tissue scaffolds. Key challenges such as scalability, clinical translation, and regulatory approval are discussed, underscoring the need for interdisciplinary collaboration and continued innovation. Overall, this review fosters a comprehensive understanding of hydrogel technologies and their transformative potential in enhancing patient care through advanced, adaptable, and responsive biomaterial systems. Full article

Stem cells, unspecialized cells with regenerative and differentiation capabilities, hold immense potential in regenerative medicine, exemplified by hematopoietic stem cell transplantation. However, their clinical application faces significant limitations, including their tumorigenic risk due to uncontrolled proliferation and cellular heterogeneity. This review explores how synthetic biology, an interdisciplinary approach combining engineering and biology, offers promising solutions to these challenges. It discusses the concepts, toolkit, and advantages of synthetic biology, focusing on the design and integration of genetic circuits to program stem cell differentiation and engineer safety mechanisms like inducible suicide switches. This review comprehensively examines recent advancements in synthetic biology applications for stem cell engineering, including programmable differentiation circuits, cell reprogramming strategies, and therapeutic cell engineering approaches. We highlight specific examples of genetic circuits that have been successfully implemented in various stem cell types, from embryonic stem cells to induced pluripotent stem cells, demonstrating their potential for clinical translation. Despite these advancements, the integration of synthetic biology with mammalian cells remains complex, necessitating further research, standardized datasets, open access repositories, and interdisciplinary collaborations to build a robust framework for predicting and managing this complexity. Full article

Spinal cord injury (SCI) remains one of the toughest obstacles in neuroscience and regenerative medicine due to both severe functional loss and limited healing ability. This article aims to provide a key integrative, mechanism-focused review of the molecular landscape of SCI and the new disruptive therapy technologies that are now evolving in the SCI arena. Our goal is to unify a fundamental pathophysiology of neuroinflammation, ferroptosis, glial scarring, and oxidative stress with the translation of precision treatment approaches driven by artificial intelligence (AI), CRISPR-mediated gene editing, and regenerative bioengineering. Drawing upon advances in single-cell omics, systems biology, and smart biomaterials, we will discuss the potential for reprogramming the spinal cord at multiple levels, from transcriptional programming to biomechanical scaffolds, to change the course from an irreversible degeneration toward a directed regenerative pathway. We will place special emphasis on using AI to improve diagnostic/prognostic and inferred responses, gene and cell therapies enabled by genomic editing, and bioelectronics capable of rehabilitating functional connectivity. Although many of the technologies described below are still in development, they are becoming increasingly disruptive capabilities of what it may mean to recover from an SCI. Instead of prescribing a particular therapeutic fix, we provide a future-looking synthesis of interrelated biological, computational, and bioengineering approaches that conjointly chart a course toward adaptive, personalized neuroregeneration. Our intent is to inspire a paradigm shift to resolve paralysis through precision recovery and to be grounded in a spirit of humility, rigor, and an interdisciplinary approach. Full article

Porcine rotavirus (PoRV), a primary etiological agent of viral diarrhea in piglets, frequently co-infects with other enteric pathogens, exacerbating disease severity and causing substantial economic losses. Its genetic recombination capability enables cross-species transmission potential, posing public health risks. Globally, twelve G genotypes and thirteen P genotypes have been identified, with G9, G5, G3, and G4 emerging as predominant circulating strains. The limited cross-protective immunity between genotypes compromises vaccine efficacy, necessitating genotype surveillance to guide vaccine development. While conventional molecular assays demonstrate sensitivity, they lack rapid genotyping capacity and face technical limitations. To address this, we developed a novel diagnostic platform integrating reverse transcription recombinase-aided amplification (RT-RAA) with CRISPR–Cas12a. This system employs universal primers for the simultaneous amplification of G4/G5/G9 genotypes in a single reaction, coupled with sequence-specific CRISPR recognition, achieving genotyping within 50 min at 37 °C with 10⁰ copies/μL sensitivity. Clinical validation showed a high concordance with reverse transcription quantitative polymerase chain reaction (RT-qPCR). This advancement provides an efficient tool for rapid viral genotyping, vaccine compatibility evaluation, and optimized epidemic control strategies. Full article

Tissue engineering is a growing field with multidisciplinary players in cell biology, engineering, and medicine, aiming to maintain, restore, or enhance functions of tissues and organs. The extracellular matrix (ECM) plays fundamental roles in tissue development, maintenance, and repair, providing not only structural support, but also critical biochemical and biomechanical cues that regulate cell behavior and signaling. Although its specific composition varies across different tissue types and developmental stages, matrix molecules influence various cell functional properties in every tissue. Given the importance of ECM in morphogenesis, tissue homeostasis, and regeneration, ECM-based bioscaffolds, developed through tissue engineering approaches, have emerged as pivotal tools for recreating the native cellular microenvironment. The aim of this study is to present the main categories of these scaffolds (i.e., natural, synthetic, and hybrid), major fabrication techniques (i.e., tissue decellularization and multidimensional bioprinting), while highlighting the advantages and disadvantages of each category, focusing on biological activity and mechanical performance. Scaffold properties, such as mechanical strength, elasticity, biocompatibility, and biodegradability are essential to their function and integration into host tissues. Applications of ECM-based bioscaffolds span a range of engineering and regenerative strategies, including cartilage, bone, cardiac tissue engineering, and skin wound healing. Despite promising advances, challenges remain in standardization, scalability, and immune response modulation, with future directions directed towards improving ECM-mimetic platforms. Full article

Human adipose stem cells (ASCs) are multipotent cells expressing mesenchymal stem cell (MSC) markers that are capable of multilineage differentiation and secretion of bioactive factors. Their “homing” to injured tissues is mediated by chemokines, cytokines, adhesion molecules, and signaling pathways. Enhancing ASC homing is critical for improving regenerative therapies. Strategies include boosting chemotactic signaling, modulating immune responses to create a supportive environment, preconditioning ASCs with hypoxia or mechanical stimuli, co-culturing with supportive cells, applying surface modifications or genetic engineering, and using biomaterials to promote ASC recruitment, retention, and integration at injury sites. Scaffolds provide structural support and a biomimetic environment for ASC-based tissue regeneration. Natural scaffolds promote adhesion and differentiation but have mechanical limitations, while synthetic scaffolds offer tunable properties and controlled degradation. Functionalization with bioactive molecules improves the regenerative outcomes of different tissue types. Ceramic-based scaffolds, due to their strength and bioactivity, are ideal for bone healing. Composite scaffolds, combining polymers, ceramics, or metals, further optimize mechanical and biological properties, supporting personalized regenerative therapies. This review integrates concepts from cell biology, biomaterials science, and regenerative medicine to offer a comprehensive understanding of ASC homing and its impact on tissue engineering and clinical applications. Full article

By stimulating living tissues with proper molecules, the angiogenesis and vasculogenesis processes can be observed. Prostaglandin E1 (PGE1), which is a molecule that widens blood vessels and which is used for several medical purposes, such as treating critical limb ischemia, is a typical leading molecule in angiogenesis studies. Nevertheless, its involvement in vasculogenesis and morphogenesis is a more specific subject in the field of developmental biology and therapeutic research. Vasculogenesis is the embryonic phenomenon in which endothelial progenitor cells generate new blood vessels. This phenomenon is distinct and divergent from angiogenesis, which entails the creation of novel blood vessels extending from pre-existing ones. Morphogenesis is the biological phenomenon responsible for the development of an organism or its components into a specific shape. Embryonic development and tissue regeneration are essential components. Current research is investigating the broader consequences of prostaglandins, such as PGE1, in the fields of developmental biology and regenerative medicine. Gaining knowledge about the impact of PGE1 on morphogenesis could provide valuable insights into congenital vascular abnormalities and innovative approaches for tissue repair and regeneration, especially in limb ischemia. In this study, a histologic and morphogenesis study was carried out on Artemia salina napi (first stage of development) by simulating the angiogenesis and morphogenesis processes using PGE1 as the top molecule with vasoactive properties and a series of benopyridyne (3-aminoquinolines, 5-amino quinolines, 8-aminoquinolines, 8-hydroxyquinolines and quinolines, respectively). A series of 30 Artemia salina napi were exposed to the compound listed before. Also, a lot of 30 unexposed Artemia salina napi was taken into account. In total, 210 Artemia salina napi were studied as a model for angionensis and morphogenesis. The study used wet experiments together with imaging reconstruction and graph-generating methodologies. The results show that PGE1 can initiate the shape of the vessel formation. Also, some quinoline series have a pro-mild morphogenetic and angiogenetic effect. Overall, PGE1 plays a significant role in mediating vasculogenesis and morphogenesis through its vasodilatory, anti-inflammatory, and pro-proliferative effects on endothelial cells. PGE1 is involved mainly in increasing the length of the vessel, while the number of vascular branching has an all-simulating general impact. However, the molecules with mild vasculogenic effects tend to develop more complex, limited vascular networks, having a more localized role in the angiogenetic process. Overall imaging and graph analysis showed significant and distinct properties of the vascular network-derived graph. Full article

Stem-cell behavior is governed not solely by intrinsic genetic programs but by highly specialized microenvironments—or niches—that integrate structural, biochemical, and mechanical cues to regulate quiescence, self-renewal, and differentiation. This review traces the evolution of stem-cell niche biology from foundational embryological discoveries to its current role as a central determinant in tissue regeneration and disease. We describe the cellular and extracellular matrix architectures that define adult stem-cell niches across diverse organs and dissect conserved signaling axes—including Wnt, BMP, and Notch—that orchestrate lineage commitment. Emphasis is placed on how aging, inflammation, fibrosis, and metabolic stress disrupt niche function, converting supportive environments into autonomous drivers of pathology. We then examine emerging therapeutic strategies that shift the regenerative paradigm from a stem-cell-centric to a niche-centric model. These include stromal targeting (e.g., FAP inhibition), which are engineered scaffolds that replicate native niche mechanics, extracellular vesicles that deliver paracrine cues, and composite constructs that preserve endogenous cell–matrix interactions. Particular attention is given to cardiac, hematopoietic, reproductive, and neurogenic niches, where clinical failures often reflect niche misalignment rather than intrinsic stem-cell deficits. We argue that successful regenerative interventions must treat stem cells and their microenvironment as an inseparable therapeutic unit. Future advances will depend on high-resolution niche mapping, mechanobiologically informed scaffold design, and niche-targeted clinical trials. Re-programming pathological niches may unlock regenerative outcomes that surpass classical cell therapies, marking a new era of microenvironmentally integrated medicine. Full article

Human-induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) have been shown to be useful for the development of cell-based regenerative strategies and for modelling drug discovery. However, stem cell-derived HLCs are not identical in nature to primary human hepatocytes (PHHs), which could affect the cell phenotype and, potentially, model reliability. Therefore, we employed the in-depth gene expression profiling of HLCs and other important and relevant cell types, which led to the identification of clear similarities and differences between them at the transcriptional level. Through gene set enrichment analysis, we identified that genes that are critical for immune signalling pathways become downregulated upon HLC differentiation. Our analysis also found that TAV.HLCs exhibit a mild gene signature characteristic of acute lymphoblastic leukaemia, but not other selected cancers. Importantly, HLCs present significant similarity to PHHs, making them genuinely valuable for modelling human liver biology in vitro and for the development of prototype cell-based therapies for pre-clinical testing. Full article

Background: The genus Dugesia (Platyhelminthes: Tricladida) includes a large diversity of free-living freshwater flatworms and is important for studies on regeneration and evolution. This study aims to describe a newly discovered asexual planarian species from southern China and explore its genetic characteristics and regenerative abilities. Methods: An integrative taxonomic analysis was conducted using morphology, karyology, histology, molecular phylogeny (18S, 28S, COI, mitogenome), and genome size estimation via flow cytometry. Regeneration was assessed by standardized amputations, and long-term asexual propagation was observed under laboratory conditions for three years. Results: Phylogenetic analyses using nuclear (18S, 28S rDNA) and mitochondrial (COI, mitogenome) markers confirmed that Dugesia cantonensis Guang Yang & Zhinan Yin, sp. nov. forms a distinct clade within Dugesia. Its 18,125 bp mitogenome contains 36 genes but lacks atp8. D. cantonensis displays a distinctive morphology, notably a pharynx located near the head. All body fragments regenerated into complete individuals within nine days. Remarkably, one individual produced ~10⁵ clonal descendants over three years via repeated amputation, maintaining stable regenerative ability and growth across generations. Karyological analysis revealed a diploid karyotype (2n = 16) consisting of eight chromosome pairs. The nuclear genome size was estimated at approximately 2.5 Gb using Danio rerio as an internal standard. Histological examination showed no detectable reproductive organs, confirming the species as an exclusively asexual lineage. Conclusions: D. cantonensis represents a new planarian strain with stable propagation and regeneration. These features make it a valuable resource for regenerative biology and comparative genomic studies. Full article

Achieving the appropriate primary stability for immediate or early loading in areas with low-density bone, such as the posterior maxilla, is challenging. A three-dimensional (3D) stabilization implant design featuring a tapered body with continuous cutting flutes along the length of the external thread form, with a combination of curved and linear geometric surfaces on the thread’s crest, has the capacity to enhance early biomechanical and osseointegration outcomes compared to implants with traditional buttressed thread profiles. Commercially available implants with a buttress thread design (TP), and an experimental implant that incorporated the 3D stabilization trimmed-thread design (TP 3DS) were used in this study. Six osteotomies were surgically created in the ilium of adult sheep (N = 14). Osteotomy sites were randomized to receive either the TP or TP 3DS implant to reduce site bias. Subjects were allowed to heal for either 3 or 12 weeks (N = 7 sheep/time point), after which samples were collected en bloc (including the implants and surrounding bone) and implants were either subjected to bench-top biomechanical testing (e.g., lateral loading), histological/histomorphometric analysis, or nanoindentation testing. Both implant designs yielded high insertion torque (ITV ≥ 30 N⋅cm) and implant stability quotient (ISQ ≥ 70) values, indicative of high primary stability. Qualitative histomorphological analysis revealed that the TP 3DS group exhibited a continuous bone–implant interface along the threaded region, in contrast to the TP group at the early, 3-week, healing time point. Furthermore, TP 3DS’s cutting flutes along the entire length of the implant permitted the distribution of autologous bone chips within the healing chambers. Histological evaluation at 12 weeks revealed an increase in woven bone containing a greater presence of lacunae within the healing chambers in both groups, consistent with an intramembranous-like healing pattern and absence of bone dieback. The TP 3DS macrogeometry yielded a ~66% increase in average lateral load during pushout testing at baseline (T = 0 weeks, p = 0.036) and significantly higher bone-to-implant contact (BIC) values at 3 weeks post-implantation (p = 0.006), relative to the traditional TP implant. In a low-density (Type IV) bone model, the TP 3DS implant demonstrated improved performance compared to the conventional TP, as evidenced by an increase in baseline lateral loading capacity and increased BIC during the early stages of osseointegration. These findings indicate that the modified implant configuration of the TP 3DS facilitates more favorable biomechanical integration and may promote more rapid and stable bone anchorage under compromised bone quality conditions. Therefore, such improvements could have important clinical implications for the success and longevity of dental implants placed in regions with low bone density. Full article

In recent years, the field of skeletal muscle tissue engineering has experienced significant advancements, evolving from traditional two-dimensional (2D) cell cultures to increasingly sophisticated three-dimensional (3D) engineered constructs. While 2D models have provided foundational insights into muscle cell biology, emerging 3D platforms aim to better recapitulate the complex native muscle environment, including mature muscle fibers, supportive vasculature, and native-like extracellular matrix (ECM) composition. Here, we provide a comprehensive review of current in vitro skeletal muscle models, detailing their design principles, structure, and functionalities as well as the advantages and limitations inherent to each approach. We put a special emphasis on 3D engineered muscle tissues (EMTs) developed through advanced bioengineering strategies and note that design criteria such as scaffold selection, perfusion system incorporation, and co-culture with supporting cell types have significantly enhanced tissue maturity and complexity. Lastly, we explore the application of these engineered models to disease studies, highlighting models of both mendelian muscle disorders and common polygenic diseases and the potential of these platforms for drug discovery and regenerative therapies. Although an ideal in vitro model that fully recapitulates native muscular architecture, vascularization, and ECM complexity is yet to be realized, we identify current challenges and propose future directions for advancing these bioengineered systems. By integrating fundamental design criteria with emerging technologies, this review provides a roadmap for next-generation skeletal muscle models poised to deepen our understanding of muscle biology and accelerate therapeutic innovation. Full article

Single-cell RNA sequencing (scRNA-seq) has revolutionized neuroscience by enabling the analysis of cellular heterogeneity and dynamic molecular processes at the single-cell resolution. In spinal cord research, scRNA-seq provides critical insights into cell type diversity, developmental trajectories, and pathological mechanisms. This review summarizes recent progress in the application of scRNA-seq to spinal cord development, injury, and neurodegenerative diseases and discusses the current challenges and future directions. Relevant studies focusing on the key applications of scRNA-seq, including advances in spatial transcriptomics and multi-omics integration, were retrieved from PubMed and the Web of Science. scRNA-seq has enabled the identification of distinct spinal cord cell populations and revealed the gene regulatory networks driving development. Injury models have revealed the temporal dynamics of immune and glial responses, alongside potential regenerative processes. In neurodegenerative conditions, scRNA-seq highlights cell-specific vulnerabilities and molecular changes. The integration of spatial transcriptomics and computational tools, such as machine learning, has further improved the resolution of spinal cord biology. However, challenges remain in terms of data complexity, sample acquisition, and clinical translation. Single-cell transcriptomics is a powerful approach for understanding spinal cord biology. Its integration with emerging technologies will advance both basic research and clinical applications, supporting personalized and regenerative therapy. Addressing these technical and analytical barriers is essential to fully realize the potential of scRNA-seq in spinal cord science. Full article

The crosstalk between autophagy and oxidative stress is a cornerstone of stem cell biology. These processes are tightly interwoven, forming a regulatory network that impacts stem cell survival, self-renewal, and differentiation. Autophagy, a cellular recycling mechanism, ensures the removal of damaged organelles and proteins, thereby maintaining cellular integrity and metabolic balance. Oxidative stress, driven by the accumulation of reactive oxygen species (ROS), can act as both a signalling molecule and a source of cellular damage, depending on its levels and context. The interplay between autophagy and oxidative stress shapes stem cell fate by either promoting survival under stress conditions or triggering senescence and apoptosis when dysregulated. Recent evidence underscores the bidirectional relationship between these processes, where autophagy mitigates oxidative damage by degrading ROS-generating organelles, and oxidative stress can induce autophagy as a protective response. This crosstalk is critical not only for preserving stem cell function but also for addressing age-related decline and enhancing regenerative potential. Understanding the molecular mechanisms that govern this interplay offers novel insights into stem cell biology and therapeutic strategies. This review delves into the intricate molecular dynamics of autophagy and oxidative stress in stem cells, emphasizing their synergistic roles in health, disease, and regenerative medicine applications. Full article