Search Results (1,116)

Red blood cell (RBC) production from bone marrow hematopoietic stem cells (BMHSCs) in vitro overlooks the mechanical signals of the bone marrow niche and overly relies on growth factors. Considering that the fate of hematopoietic stem cells (HSCs) is determined by the natural bone marrow microenvironment, differences in mechanical microenvironments provide a reference for the regulation of HSC differentiation. This study seek to reveal the role of mechanobiology cues in erythropoiesis and provide a new perspective for the design of in vitro erythropoiesis platforms. The hydrogel platforms we designed simulate the stiffness gradient of the bone marrow niche to culture HSCs and induce their differentiation into the erythroid system. Cells on the low-stiffness scaffold have higher potential for erythrocyte differentiation and faster differentiation efficiency and promote erythrocyte differentiation after erythropoietin (EPO) restriction. In vivo transplantation experiments demonstrated that these cells have the ability for continuous proliferation and differentiation into mature erythrocytes. By combining mechanical cues with in vitro erythrocyte production, this method is expected to provide insights for in vitro hematopoietic design and offer a scalable cell manufacturing platform for transfusion medicine. Full article

Organoids and microphysiological systems (MPSs) have emerged as physiologically relevant platforms that recapitulate key structural and functional features of human organs, tissues, and microenvironments. As one of the essential components that define the success of these systems, hydrogels play the central role of providing a three-dimensional, biomimetic scaffold that supports cell viability, spatial organization, and dynamic signaling. Natural polymer-based hydrogels, derived from materials such as collagen, gelatin, hyaluronic acid, and alginate, offer favorable properties including biocompatibility, degradability, and an extracellular matrix-like architecture. This review presents recent advances in the design and application of such hydrogels, focusing on crosslinking strategies (physical, chemical, and hybrid), the viscoelastic characteristics, and stimuli-responsive behaviors. The influence of these materials on cellular processes, such as stemness maintenance, differentiation, and morphogenesis, is critically examined. Furthermore, the applications of organoid culture and dynamic MPS platforms are discussed, highlighting their roles in morphogen delivery, barrier formation, and vascularization. Current challenges and future perspectives toward achieving standardized, scalable, and translational hydrogel systems are also addressed. Full article

Gene therapy is a groundbreaking strategy in regenerative medicine, enabling precise cellular behavior modulation for tissue repair. In situ nucleic acid delivery systems aim to directly deliver nucleic acids to target cells or tissues to realize localized genetic reprogramming and avoid issues like donor cell dependency and immune rejection. The key to success relies on biomaterial-engineered delivery platforms that ensure tissue-specific targeting and efficient intracellular transport. Viral vectors and non-viral carriers are strategically modified to enhance nucleic acid stability and cellular uptake, and integrate them into injectable or 3D-printed scaffolds. These scaffolds not only control nucleic acid release but also mimic native extracellular microenvironments to support stem cell recruitment and tissue regeneration. This review explores three key aspects: the mechanisms of gene editing in tissue repair; advancements in viral and non-viral vector engineering; and innovations in biomaterial scaffolds, including stimuli-responsive hydrogels and 3D-printed matrices. We evaluate scaffold fabrication methodologies, nucleic acid loading–release kinetics, and their biological impacts. Despite progress in spatiotemporal gene delivery control, challenges remain in balancing vector biocompatibility, manufacturing scalability, and long-term safety. Future research should focus on multifunctional “smart” scaffolds with CRISPR-based editing tools, multi-stimuli responsiveness, and patient-specific designs. This work systematically integrates the latest methodological advances, outlines actionable strategies for future investigations and advances clinical translation perspectives beyond the existing literature. Full article

Hydrogel is widely used as a scaffolding material for tissue engineering due to its excellent cytocompatibility and potential for biofunctionalization. However, its poor mechanical property limits its further application. Fabrication of fiber-reinforced hydrogel composite scaffolds has emerged as a solution to overcome this problem. However, existing strategies usually produce nonporous composite scaffolds, where the interfiber pores are completely filled with hydrogel. This design can hinder oxygen and nutrient exchange between seeded cells and the culture medium, thereby limiting cell invasion and colonization within the scaffold. In this study, sodium alginate (SA) hydrogel was exclusively grafted onto the surface of the constituent fibers of the melt electrowritten scaffold while preserving the porous structure. The grafted hydrogel amount and pore size were precisely controlled by adjusting the SA concentration and the crosslinking ratio (SA: CaCl₂). Experimental results demonstrated that the porous composite scaffolds exhibited superior swelling capacity, degradation ratio, mechanical properties, and biocompatibility. Notably, at an SA concentration of 0.5% and a crosslinking ratio of 2:1, the porous composite scaffold achieved optimal cell adhesion and viability. This study highlights the critical importance of preserving porous structures in composite scaffolds for tissue-engineering applications. Full article

This review explores the emerging role of functionalized hydrogels in modulating the microbiome for therapeutic applications in tissue regeneration and infection control. The skin and gut microbiomes play crucial roles in maintaining tissue homeostasis, regulating immune responses, and influencing the healing process. Disruptions in microbial balance—such as those observed in chronic wounds, autoimmune conditions, or post-surgical environments—can impair regeneration and increase susceptibility to infection. Hydrogels, due to their tunable physical and chemical properties, serve as versatile platforms for delivering probiotics, prebiotics, antimicrobials, and immune-modulatory agents. The encapsulation of beneficial bacteria, such as Lactobacillus plantarum or Prevotella histicola, within hydrogels could enhance bacterial viability, targeted delivery, and immune tolerance. Additionally, hydrogels functionalized with silver nanoparticles, nitric oxide donors, and bacteriocins have demonstrated effective biofilm disruption and pathogen clearance. These systems also promote favorable immune responses, such as M2 macrophage polarization and the induction of regulatory T cells, which are essential for tissue repair. Innovative approaches, including 3D bioprinting, self-healing materials, and photothermal-responsive hydrogels, expand the clinical versatility of these systems. Full article

The application of cellular spheroids in bone tissue engineering research has gained significant interest in the last decade. Compared to monolayer cell cultures, the 3D architecture allows for more physiological cell–cell and cell–extracellular matrix (ECM) interactions that make cellular spheroids a suitable model system to investigate the bone ECM in vitro. The use of 3D model systems requires fine-tuning of the experimental methods used to study cell morphology, ECM deposition and mineralization, and cell–ECM interactions. In this study, we use a construct made of MC3T3-E1 cellular spheroids encapsulated in an alginate hydrogel to study and characterize the deposited ECM. Spheroid shape and structure were evaluated using confocal microscopy. The deposited collagenous ECM was characterized using Second Harmonic Imaging Microscopy (SHIM), quantitative hydroxyproline (HYP) assay, and Transmission Electron Microscopy (TEM). The use of hydrogel constructs enabled easy handling and imaging of the samples, while also helping to preserve the spheroid’s stability by preventing cells from adhering to the culture dish surface. We used a non-modified alginate hydrogel that did not facilitate cell attachment and therefore functioned as an inert encapsulating scaffold. Constructs were cultured for up to 4 weeks. SHIM, HYP assay, and TEM confirmed the deposition of a collagenous matrix. We demonstrated that alginate-encapsulated bone spheroids are a convenient and promising model for studying the bone ECM in vitro. Full article

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

Marine biomass represents a valuable yet underexploited resource for the development of high-value biomaterials. Recent advances have highlighted the significant potential of marine-derived polysaccharides, proteins, and peptides in biomedical applications, most notably in drug delivery and wound healing. This review provides a comprehensive synthesis of current research on the extraction, processing and pharmaceutical valorization of these biopolymers, with a focus on their structural and functional properties that allow these materials to be engineered into nanocarriers, hydrogels, scaffolds, and smart composites. Key fabrication strategies such as ionic gelation, desolvation, and 3D bioprinting are critically examined for their role in drug encapsulation, release modulation, and scaffold design for regenerative therapies. The review also covers preclinical validation, scale-up challenges, and relevant regulatory frameworks, offering a practical roadmap from sustainable sourcing to clinical application. Special attention is given to emerging technologies, including stimuli-responsive biomaterials and biosensor-integrated wound dressings, as well as to the ethical and environmental implications of marine biopolymer sourcing. By integrating materials science, pharmaceutical technology and regulatory insight, this review aims to provide a multidisciplinary perspective for researchers and industrial stakeholders seeking sustainable and multifunctional pharmaceutical platforms for precision medicine and regenerative therapeutics. Full article

New stable three-dimensional hydrogels were obtained in an inert gas atmosphere in light in an aqueous dispersion of the main components: cod collagen, methyl methacrylate, polyethylene glycol, RbTe_1.5W_0.5O₆ complex oxide, and modifying additives. The analysis of the new hydrogels’ cytotoxicity using the MTT assay showed that the cytotoxicity of the sample extracts was observed in a number of examples, but was decreased with increasing dilution of the extracts. The decrease in cell viability at high concentrations of the extract is likely caused by a decrease in the number of specific components of the complete culture medium used to produce extracts. It is related to the well-known adsorption of medium proteins by the gel component, high-molecular compounds included in the matrix. The stimulating effect of the substances included in its composition was observed with a significant dilution of the extract, i.e., the proliferative activity of the cells increased. The extract of the hydrogel hydrolysate sample and all its dilutions did not show cytotoxicity in the MTT assay examples. It determines the prospect of its use on the wound surface, since hydrogel destruction occurs under the action of body enzymes. The new hydrogel is a promising material for creating wound coverings or scaffolds. Full article

Hydrogels have emerged as multifunctional biomaterials in cardiac surgery, offering promising solutions for myocardial regeneration, adhesion prevention, valve engineering, and localized drug and gene delivery. Their high water content, biocompatibility, and mechanical tunability enable close emulation of the cardiac extracellular matrix, supporting cellular viability and integration under dynamic physiological conditions. In myocardial repair, injectable and patch-forming hydrogels have been shown to be effective in reducing infarct size, promoting angiogenesis, and preserving contractile function. Hydrogel coatings and films have been designed as adhesion barriers to minimize pericardial adhesions after cardiotomy and improve reoperative safety. In heart valve and patch engineering, hydrogels contribute to scaffold design by providing bio-instructive, mechanically resilient, and printable matrices that are compatible with 3D fabrication. Furthermore, hydrogels serve as localized delivery platforms for small molecules, proteins, and nucleic acids, enabling sustained or stimuli-responsive release while minimizing systemic toxicity. Despite these advances, challenges such as mechanical durability, immune compatibility, and translational scalability persist. Ongoing innovations in smart polymer chemistry, hybrid composite design, and patient-specific manufacturing are addressing these limitations. This review aims to provide an integrated perspective on the application of hydrogels in cardiac surgery. The relevant literature was identified through a narrative search of PubMed, Scopus, Web of Science, Embase, and Google Scholar. Taken together, hydrogels offer a uniquely versatile and clinically translatable platform for addressing the multifaceted challenges of cardiac surgery. Hydrogels are poised to redefine clinical strategies in cardiac surgery by enabling tailored, bioresponsive, and functionally integrated therapies. Full article

The One Health paradigm—recognizing the interconnected health of humans, animals, and the environment—promotes the development of sustainable technologies that enhance human health while minimizing ecological impact. In this context, bio-based hydrogels have emerged as a promising class of biomaterials for advanced medical applications. Produced through biotechnological methods such as genetic engineering and microbial fermentation, these hydrogels are composed of renewable and biocompatible materials, including recombinant collagen, elastin, silk fibroin, bacterial cellulose, xanthan gum, and hyaluronic acid. Their high water content, structural tunability, and biodegradability make them ideal candidates for various biomedical applications such as wound healing, tissue regeneration, and the design of extracellular matrix (ECM)-mimicking scaffolds. By offering controlled mechanical properties, biocompatibility, and the potential for minimally invasive administration, sustainable hydrogels represent a strategic innovation for regenerative medicine and therapeutic interventions. This review discusses the characteristics and medical applications of these hydrogels, highlighting their role in advancing sustainable healthcare solutions within the One Health framework. Full article

Innovative changes to our current food system are needed, and one solution is cultivated meat, which uses modern engineering, materials science, and biotechnology to produce animal protein. This article highlights the advantages of incorporating whey protein isolate (WPI) and β-lactoglobulin (β-LG) into hydrogel networks to aid cell growth on cultivated meat scaffolds. The protein and polysaccharide (i.e., alginate) components of the scaffolds are food-grade and generally regarded as safe ingredients, enabling the transition to more food-safe, edible, and nutritious scaffolds. The impact of WPI and varying properties on cell performance was evaluated; alginate concentration and the addition of proteins into the hydrogels significantly altered their stiffness and strength. The results of this study demonstrate the innocuous nature of novel scaffolds and reveal enhanced cell proliferation on WPI and β-LG-modified groups compared to standard biomaterial controls. This work serves as a stepping stone for more comprehensive analyses of WPI, β-LG, and alginate scaffolds for use in cultivated meat research and production. Full article

The cryopreservation of three-dimensional (3D) biofabricated constructs is a key enabler for their clinical application in regenerative medicine. Unlike two-dimensional (2D) cultures, 3D systems such as encapsulated cell spheroids, molded hydrogels, and bioprinted tissues present specific challenges related to cryoprotectant (CPA) diffusion, thermal gradients, and ice formation during freezing and thawing. This review examines the current strategies for preserving 3D constructs, focusing on the role of biomaterials as cryoprotective matrices. Natural polymers (e.g., hyaluronic acid, alginate, chitosan), protein-based scaffolds (e.g., silk fibroin, sericin), and synthetic polymers (e.g., polyethylene glycol (PEG), polyvinyl alcohol (PVA)) are evaluated for their ability to support cell viability, structural integrity, and CPA transport. Special attention is given to cryoprotectant systems that are free of dimethyl sulfoxide (DMSO), and to the influence of hydrogel architecture on freezing outcomes. We have compared the efficacy and limitations of slow freezing and vitrification protocols and review innovative approaches such as temperature-controlled cryoprinting, nano-warming, and hybrid scaffolds with improved cryocompatibility. Additionally, we address the regulatory and manufacturing challenges associated with developing Good Manufacturing Practice (GMP)-compliant cryopreservation workflows. Overall, this review provides an integrated perspective on material-based strategies for 3D cryopreservation and identifies future directions to enable the long-term storage and clinical translation of engineered tissues. Full article

Stem cell-derived liver cells, organoids, and lab-grown liver tissue are promising regenerative therapies for liver disease. However, current culture conditions are sub-optimal, producing end-target cells and tissue phenotypes that are immature or unstable when compared to primary liver cells and tissue. Biopolymers used in culture substrates and scaffolds for tissue engineering significantly impact the quality of the end-target cells and tissue, influencing the efficacy of regenerative treatments. In addition, the biochemical properties of some biopolymers may preclude the translation of downstream bioengineered products into clinical practice. Therefore, this systematic review aims to evaluate the recent advances in biopolymers within liver tissue engineering, providing an overview of the current usage in the field and highlighting novel substrates that have strong potential to be translated into clinical therapy. Full article