Search Results (215)

Tissue engineering and regenerative medicine (TERM) rely on advanced biomaterials and scaffolds that require strict sterilization without sacrificing their structural and functional properties. Conventional sterilization methods, including steam, ethylene oxide, and gamma irradiation, often compromise scaffold integrity, alter surface chemistry and/or leave toxic residues. Ozone (O₃) has emerged as a promising alternative sterilant because of its strong oxidizing potential, broad-spectrum antimicrobial activity, and residue-free decomposition. Importantly, ozone sterilization can preserve—and in some cases enhance—scaffold bioactivity by maintaining cytocompatibility and favorable surface chemistries that support cell adhesion and differentiation. This review critically evaluates the role of ozone sterilization in the context of TERM applications, focusing on its physicochemical properties, disinfection kinetics, material compatibility and regulatory perspectives. Evidence from studies on polymethyl methacrylate (PMMA) scaffolds, bone implants, and hydrogel-based systems suggests that, under optimized conditions, ozone can achieve high sterilization efficacy without significant degradation of mechanical or chemical properties. However, challenges related to process validation, health and safety considerations, and scalability remain. The review highlights opportunities for integrating ozone into automated biomanufacturing workflows and identifies key research gaps to support the broader adoption of ozone sterilization in TERM applications. Full article

The advancement of modern regenerative medicine is closely associated with additive technologies that enable the creation of tissue-engineered constructs and personalized bioprostheses. Three-dimensional bioprinting allows precise modeling of tissue architecture and extracellular matrix microstructures. Recent studies demonstrate rapid growth in the use of 3D bioprinting for biomedical applications including regenerative medicine, pharmaceutical research, and biotechnology. Special attention is given to the development of bioinks that combine biological and structural functions and maintain cell viability during printing. Modern technologies allow the fabrication of skin, bone, vascular, and cartilage tissues with high structural accuracy. The technology is also actively used in reconstructive surgery for the production of personalized implants. However, challenges remain related to vascularization, standardization of materials, and ethical aspects of clinical use. This review summarizes the main principles of 3D bioprinting, technological approaches, biomedical applications, and future perspectives of additive technologies in regenerative medicine. Full article

Over the past 200 years (1820–2020), global life expectancy has nearly tripled, increasing from 26 to 72.91 years, due to factors such as poverty reduction and public health initiatives. Today, society faces different challenges than it did centuries ago. In patient care and healthcare system priorities, the goal is to develop smart, feasible, long-lasting, cost-effective, readily available, adverse-reaction-free, adaptable, and personalized solutions that minimize patient discomfort, reduce caregiver effort, and decrease hospitalization duration and costs. In this context, biomaterials serve as versatile tools capable of performing a wide range of diagnostic, therapeutic, and theragnostic functions. Thanks to their biocompatibility, biodegradability, surface chemistry, and responsiveness, biomaterials are currently addressing issues such as patient compliance (through controlled drug-delivery systems and smart wound dressings), long transplant waiting lists, transplant rejection, non-adaptable prosthetics (artificial organs), oncology treatment efficacy (nano-formulations for theragnostics and multiple tumor targeting), and inconsistent in vitro drug-testing models (organs-on-a-chip). In this review, we focus on biomaterials’ smartness, then explore databases for efficient product design, and finally highlight their applications in the biomedical field, especially in drug delivery, tissue engineering, and regenerative medicine. Full article

As natural nanoscale intercellular messengers, exosomes exhibit considerable potential in modulating inflammation, angiogenesis, immunoregulation, and tissue remodeling, making them attractive candidates for regenerative medicine. However, their clinical translation remains limited by rapid systemic clearance, nonspecific biodistribution, insufficient lesion retention, and functional attenuation in hostile pathological microenvironments. In this review, we propose that biomaterial engineering should evolve from providing passive exosome carriers to constructing active regulatory platforms capable of precise spatiotemporal control. We summarize engineering strategies along two complementary dimensions. In the temporal dimension, biomaterials can enable sustained, sequential, or microenvironment-responsive release to match the dynamic phases of tissue repair. In the spatial dimension, biomaterials can improve local retention, tissue anchoring, structural guidance, endogenous cell recruitment, and lesion-specific delivery. Using cutaneous wound healing, osteochondral regeneration, myocardial repair, and neural regeneration as representative examples, we further analyze these strategies through a “clinical challenge–engineering strategy–biological mechanism” framework, with particular attention to how engineered systems influence key signaling pathways such as PI3K/Akt, Wnt/β-catenin, NF-κB, and PTEN/PI3K/Akt/mTOR. We also discuss translational barriers, including exosome heterogeneity, safety concerns inherited from parental cells, large-scale GMP-compliant manufacturing, product standardization, storage stability, and regulatory classification of exosome–biomaterial hybrids. Finally, we highlight emerging directions, including multi-mechanism combinational systems, closed-loop responsive platforms, and artificial intelligence-assisted design for personalized exosome therapeutics. This review provides a design-oriented framework to accelerate the bench-to-bedside development of biomaterial-enabled precision exosome therapy. Full article

Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) are emerging as potent acellular therapeutics; however, their rapid clearance hinders their clinical translation. To address this issue, 3D-bioprinted genipin-crosslinked gelatin (GECL) was engineered for human health. GECL hydrogels were functionalised with human umbilical cord MSC-derived sEVs (hUCMSC-sEVs) to create a bioactive wound-healing platform. These hydrogels demonstrated favourable physicochemical, mechanical, and biodegradable properties while providing an extracellular matrix (ECM)-mimetic environment conducive to tissue regeneration. MSCs were isolated from the umbilical cords, and their small extracellular vesicles (sEVs) were extracted and incorporated into gelatin-based hydrogels via 3D bioprinting. These sEV-loaded scaffolds were embedded in full-thickness wounds in mice, and healing was evaluated through macroscopic observation, histological analysis, collagen deposition, and angiogenesis assessment. Compared with the untreated controls, both the hydrogel-only (B) and sEV-loaded hydrogel (BE) groups significantly accelerated in vivo wound healing. Notably, the BE group achieved complete wound closure within 14 days, restoring the skin architecture, which closely resembled the native tissue with well-organised epidermal and dermal layers, optimal thickness, and skin appendages. Histological and ultrastructural assessments revealed an increased collagen type I deposition, a reduced α-smooth muscle actin (α-SMA) expression, and a robust neovascularisation. The TEM revealed tight junctions and active cellular infiltration, indicating scaffold integration and functional remodelling. Immunohistochemistry further revealed an upregulated CD31 expression with a balanced α-smooth muscle actin (α-SMA) expression, reflecting coordinated angiogenesis and myofibroblast regulation. These results highlight sEV-functionalised GECL hydrogels as robust and clinically translatable acellular therapeutic green products for accelerated wound closure and functional skin regeneration, advancing the fields of regenerative medicine and life expectancy. Full article

In regenerative medicine, three-dimensional (3D) printing provides precise spatial control over the fabrication of complex, biomimetic tissue constructs, enabling the production of architecturally defined and functionally tailored scaffolds. By enabling precise layer-by-layer deposition of cells, biomaterials, and bioactive compounds, 3D printing overcomes many limitations associated with conventional scaffold fabrication methods. This approach facilitates the development of tailored structures that mimic the mechanical, biological, and structural characteristics of native tissues, thereby enhancing cellular organization, proliferation, and differentiation. Extensive research in tissue engineering has led to the development of 3D-printed scaffolds for the regeneration of vascular, skin, bone, cartilage, and soft tissues. Advances in bioink formulations—including growth factor-loaded systems, decellularized extracellular matrix components, and natural and synthetic polymers—have further improved tissue-specific functionality. Moreover, multimaterial and multiscale printing strategies enable the fabrication of heterogeneous constructs with controlled porosity, mechanical gradients, and spatially regulated biological cues. Although vascularized tissue constructs remain a major challenge for clinical translation, recent bioprinting advancements have significantly accelerated progress in this area. Integration of computer-aided design with patient-specific imaging data has further strengthened the potential of 3D printing for personalized regenerative therapies. Despite these advances, challenges related to scalability, regulatory approval, and long-term functionality persist. Nevertheless, continued progress in printing technologies, biomaterials, and regulatory and standards frameworks is expected to drive the clinical adoption of 3D printing. Ultimately, 3D printing represents a transformative approach in tissue engineering, redefining strategies for functional tissue regeneration and translational regenerative medicine. Full article

Marine algae, microalgae, and Cyanophyceae emerge as sustainable and versatile sources of biomacromolecules for the fabrication of hydrogels with broad biomedical potential. Their phycocolloids, such as alginate, agar, carrageenan, ulvan, and extracellular polysaccharides (EPS), exhibit intrinsic biocompatibility, tunable gelation behavior, and bioactive sulfated structures that support cell viability, tissue regeneration, and therapeutic delivery. This review provides a comprehensive overview of hydrogel fabrication strategies, including physical, chemical, and hybrid crosslinking approaches, and highlights recent advances in composite systems incorporating proteins, glycosaminoglycans, and functional nanomaterials. Applications in skin repair, cartilage and bone regeneration, neural and cardiovascular engineering, and controlled drug delivery are examined, alongside the expanding role of marine-derived hydrogels as bioinks for 3D and 4D bioprinting. Despite their promise, challenges remain related to extract variability, purification complexity, mechanical limitations, and the need for standardized characterization. Future perspectives emphasize genetic engineering of algae and cyanobacteria, development of multifunctional hybrid hydrogels, sustainable large-scale production, and pathways toward clinical translation. Together, these insights position marine-derived hydrogels as next-generation biomaterials with significant potential for regenerative medicine and therapeutic innovation. Full article

Transforming growth factor beta 3 (TGF-β3) is a homodimeric cytokine with potential therapeutic applications in wound healing, tissue engineering and regenerative medicine. Production of recombinant TGF-β3 in Escherichia coli faces significant challenges due to TGF-β3’s propensity for misfolding and aggregation, driven by a high disulfide bond content and low aqueous solubility. To address these limitations, the impacts of substituting non-conserved cysteine residues C7, C16 and C77 with serine on TGF-β3 folding, dimerization and activity were investigated. Whilst C7 and C16 form an intra-chain disulfide bond, C77 forms an inter-chain disulfide bond stabilizing dimer formation. Our results showed that the C7S, C16S double cysteine mutant protein exhibited reduced aggregation, increased dimer formation, and maintained wild-type biological activity in nano-luciferase reporter gene assay. In contrast, both C77S single and C7S, C16S, C77S triple mutants were purified predominantly in monomeric forms and displayed about 2.5-fold reduced activities. Our findings highlight the roles of the non-conserved C7, C16 and C77 cysteine residues in TGF-β3 folding and aggregation. The identification of the C7S, C16S mutant as a more soluble protein with wild-type TGF-β3 activity offers a promising strategy for improving recombinant TGF-β3 production to facilitate therapeutic applications. This study underscores the importance of targeted cysteine engineering to overcome the inherent challenges associated with the production of TGF-β3 and related complex disulfide-rich proteins. Full article

Advances in regenerative medicine have positioned platelets and their derivatives—including platelet-rich plasma, platelet-rich fibrin, platelet lysate, extracellular vesicles, and purified growth factors—as promising interventions specifically for skin and bone aging, two clinically accessible tissues with robust preclinical and clinical evidence for platelet-derived component-based rejuvenation and regeneration. Because much of the available evidence comes from injury models or age-associated inflammatory/degenerative diseases, we explicitly distinguish pathology-targeted inflammation resolution/repair from rejuvenation under physiological aging. This review summarizes the composition and core bioactivities of platelet-derived products and delineates their putative anti-aging mechanisms, encompassing proangiogenic signaling, immunomodulation, attenuation of oxidative stress, regulation of extracellular matrix turnover, and stimulation of osteogenesis. We further evaluate emerging applications that expand therapeutic performance, such as platelet-mimetic delivery vehicles, engineered and sustained-release formulations, and targeted use of subcellular structures. Evidence from recent preclinical and clinical studies indicates favorable safety profiles and signals of efficacy across cutaneous rejuvenation and skeletal regeneration, while underscoring persistent challenges related to product standardization, dosing, and outcome measures. Collectively, platelet-based therapeutics represent a versatile platform with broad applicability to anti-aging interventions in skin and bone and strong potential for translation through continued bioengineering and clinical validation. However, because most available evidence comes from injury models or age-associated diseases (e.g., photoaging, chronic wounds, osteoarthritis, osteoporosis), direct extrapolation to physiological aging is limited; throughout, we explicitly contrast these contexts, specify their indication-specific endpoints, and summarize the main translational limitations. Full article

Polydopamine (PDA) is a bioinspired polymer known for its strong adhesiveness, biocompatibility, and functional properties, making it highly useful in biomedical applications. This review highlights recent progress in PDA-based biomaterials, with a focus on their morphology, synthesis techniques, and various biomedical uses. It examines how PDA composites, which are formed at the nanoscale and macroscale levels, contribute to drug delivery, tissue engineering, wound healing, and cancer treatment. The ability of PDA to create stable, functional coatings and composites that bond well with different biomaterials enhances its therapeutic potential. This review also discusses challenges such as structural stability, toxicity, and production scale. Additionally, it covers different polymerization mechanisms and their implications for future clinical use. With ongoing advancements, PDA-based materials hold great promise for personalized medicine, including targeted drug delivery, photothermal therapy, and tissue regeneration. Overall, this overview emphasizes the vital role of PDA in the progression of biomedical technology and its potential for future applications. Full article

Centella asiatica has emerged as a strategic biomass for the sustainable production of high-value biochemicals at the interface of traditional medicine and modern biotechnology. This review consolidates the current knowledge on its phytochemical diversity, emphasizing triterpenoid saponins—asiaticoside, madecassoside, asiatic acid, and madecassic acid—as core bioactive molecules relevant to pharmaceutical, dermatological, nutraceutical, and functional-ingredient applications. Advances in green extraction technologies, including ultrasound-assisted, microwave-assisted, ohmic-heating, and supercritical CO₂ systems, have demonstrated superior efficiency in recovering high-purity biochemicals while significantly reducing solvent use, energy demand, and environmental impact compared with conventional methods. Complementary analytical and standardization platforms, such as HPLC, UPLC, and GC–MS, enable rigorous quality control across the entire value chain, supporting the development of reproducible and regulatory-compliant biochemical extracts. From a biomass valorization and biorefinery perspective, C. asiatica offers multiple metabolite streams that align with circular economy and field-to-market sustainability principles. Key challenges remain, including agronomic variability, scaling up green extraction, and supply chain resilience. However, emerging solutions, such as Good Agricultural and Collection Practices (GACP) guided cultivation, plant tissue culture, metabolic engineering, and integrated biorefinery frameworks, show strong potential for establishing a reliable and environmentally responsible production system. Collectively, C. asiatica represents a model species for sustainable biochemical production, combining scientific efficacy with industrial, economic, and ecological relevance. Full article

The Dof (DNA binding with one finger) transcription factor family is a plant-specific group of transcription factors that play critical roles in plant growth and development, stress response, and the regulation of secondary metabolism. Prunella vulgaris (P. vulgaris) has attracted considerable attention due to its medicinal value, with rosmarinic acid being one of its key bioactive components. However, the systematic identification of the Dof transcription factor family in P. vulgaris and its regulatory role in rosmarinic acid biosynthesis remains poorly understood. In this study, based on the whole-genome data of P. vulgaris, we identified 48 Dof transcription factor genes distributed across 14 chromosomes using bioinformatics approaches. Physicochemical analysis revealed that the encoded proteins have molecular weights ranging from 15,482.44 to 55,875.53 Da, amino acid lengths between 142 and 509, and theoretical isoelectric points from 4.84 to 10.2. All proteins were predicted to be hydrophilic and localized in the nucleus. Phylogenetic analysis classified them into four subfamilies, and multiple sequence alignment confirmed that all members contain a conserved C2-C2-type zinc finger domain. Analysis of cis-regulatory elements in the promoter regions identified numerous elements related to light responsiveness, hormone response, and development. Transcriptomic expression profiling demonstrated distinct tissue-specific expression patterns of Dof genes, with some showing high expression in spikes and seeds. Correlation analysis between gene expression and rosmarinic acid content identified three candidate genes potentially involved in the regulation of rosmarinic acid biosynthesis, which were further validated by RT-qPCR. Moreover, protein–protein interaction network predictions indicated 242 interactions among 23 Dof proteins. This study provides the first systematic identification of the Dof transcription factor family in P. vulgaris, offering important insights into the transcriptional regulation of rosmarinic acid biosynthesis and presenting potential genetic targets for enhancing rosmarinic acid production through genetic engineering. Full article

Biomaterials made with extracellular matrix obtained from allogeneic or xenogeneic tissues/organs or cultured cells have excellent biochemical and physical properties in supporting cell growth and tissue regeneration. These decellularized extracellular matrix-based biomaterials have been applied in clinical trials and have bright prospects in tissue engineering and regenerative medicine. Here, we systematically compare organ-derived and cell-derived decellularized extracellular matrix, summarize commonly used decellularization methods, including physical, chemical, and biological/enzymatic treatments, as well as combinations of these treatments, and characterize methods for decellularization, including histological staining, immunohistochemical techniques, biochemical analysis, scanning electron microscopy, and mechanical stress testing. Besides the production of decellularized extracellular matrix, the evolving intellectual property landscape and commercial products are also introduced. A significant focus is placed on summarizing clinical trial outcomes, demonstrating the efficacy of decellularized extracellular matrix scaffolds in diverse applications, including wound healing, cardiovascular repair, nerve regeneration, and breast reconstruction. Finally, we discuss persistent challenges and future directions, underscoring the translational potential of decellularized extracellular-matrix-based strategies for restoring tissue structure and function. Full article

Extracellular vesicles (EVs) derived from stem cells have emerged as promising mediators of osteogenesis, suggesting cell-free alternatives for bone tissue engineering and regenerative medicine. This review provides a comprehensive analysis of the main stem cell sources used for EV production, including bone marrow mesenchymal stem cells (BM-MSCs), adipose-derived stem cells (ADSCs), umbilical cord MSCs (UC-MSCs), induced pluripotent stem cells (iPSCs), and alternative stromal populations. Particular attention is given to the ways in which different conditioning and differentiation strategies, such as osteogenic induction, hypoxia, and mechanical stimulation, modulate EV cargo composition and enhance their therapeutic potential. We further discuss the in vitro models employed to evaluate EV-mediated bone regeneration, ranging from 2D cultures to complex 3D spheroids, scaffold-based systems, and bone organoids. Overall, this review emphasizes the current challenges related to standardization, scalable production, and clinical translation. It also outlines future directions, including bioengineering approaches, advanced preclinical models, and the integration of multi-omics approaches and artificial intelligence to optimize EV-based therapies. By integrating current knowledge, this work aims to guide researchers toward more consistent and physiologically relevant strategies to harness EVs for effective bone regeneration. Finally, this work uniquely integrates a comparative analysis of EVs from multiple stem cell sources with engineering strategies and emerging clinical perspectives, thereby providing an updated and translational framework for their application in bone regeneration. Full article

Wound repair preserves tissue integrity through four overlapping phases—hemostasis, inflammation, proliferation, and remodeling—coordinated by platelets, neutrophils, macrophages, fibroblasts, keratinocytes, endothelial cells, and stem/progenitor cells acting with growth factors, chemokines, extracellular matrix, and intracellular signaling. Disruption of these programs results in chronic non-healing wounds or fibrotic scarring. Recent work delineates microbial influences, epigenetic and transcriptomic regulation, and cellular heterogeneity resolved by single-cell and spatial omics. Concurrent advances in biomaterials, engineered scaffolds, stem cell-derived products, and genome-targeted approaches are enabling mechanism-based therapies. Persistent challenges include wound heterogeneity, systemic modifiers such as diabetes and aging, and safe, effective delivery of biologics. This review summarizes cellular and molecular mechanisms of cutaneous repair, outlines deviations that underlie pathological healing, and evaluates emerging concepts and translational strategies. Integrating classical models with contemporary insights supports the development of precision wound medicine and personalized interventions to improve outcomes and quality of life. Full article