The objective of this study was to design a light-responsive gelatin acrylate hydrogel for tunable cell-material interactions for tissue engineering applications. Hydrogels are widely used as cell scaffolds owing to their high water retention and cell encapsulation capabilities. Stereolithography techniques allow for the precise three-dimensional (3D) printing of hydrogels, creating complex tissue scaffold models. To enhance the limited tunabilities of 3D hydrogel cell scaffolds, photodegradable hydrogels that are responsive to light irradiation are known to enable controlled degradation and tunability, thereby promoting their application in tissue engineering. In this study, a photodegradable gelatin acrylate was synthesized by incorporating o-nitrobenzyl acrylate into the gelatin backbone, and the photodegradation behavior of the resulting gelatin acrylate hydrogel was evaluated using microsized patterned light irradiation to demonstrate the modulation of a limited area of the gelatin acrylate hydrogel surface. When human mesenchymal stem cells (hMSCs) were seeded on the light-irradiated hydrogel, cell spreading was enhanced by ca. 16-52%, whereas cell attachment decreased by ca. 25-40% compared with the unirradiated area of the hydrogel. These results suggested that the prepared gelatin acrylate hydrogel serves as a phototunable cell scaffold for fine-tuning biological microenvironments enabling postfabrication modulation that contributes to future regenerative medicine applications such as dynamic cell migration and vascular tissue modeling.

This study explored the proliferative and chondrogenic differentiation capacities of nanofiber containing silk fibroin hybrid Bombyx mori silkworm cocoons (Japan-China SP-01 variant from Indonesia) and PHA P(3HB-co-3HHx) on human adipose mesenchymal stem cells. First, the scaffolds were prepared for electrospinning by combining two distinct biomaterials, consisting of silk fibroin derived from hybrid Bombyx mori silkworm cocoons, with a combination of 3-hydroxybutyrate (3HB) and 3-hydroxyhexanoate (3HHx). The effects of various ratios of P(3HB-co-3HHx)/Silk Fibroin nanofiber mixture on proliferative and differentiation capacity were then investigated. Following that, the morphology, chemical compositions, contact angle, tensile strength, roughness, cell viability, and human adipose mesenchymal stem cell differentiation of the nanofiber were investigated by collagen type 2 gene expression. The results of scanning electron microscopy showed the mean diameter of the nanofiber ranged from 370-600 nm. Following that, 16,000 volts was prominent for nanofiber manufacture in all ratios. It was also demonstrated that the nanofiber has significant mechanical properties, acceptable hydrophilicity and smoothness, and appropriate cell viability (up to 99.1% compared to the control on silk fibroin nanofiber). Although PHA increased tensile strength, silk fibroin administration to the mixture predominantly enhanced chondrogenic differentiation, as evidenced by modulation of chondrogenic collagen type 2 (up to 8.718-fold) gene markers. Furthermore, the physicochemical characteristics of the nanofiber mixture significantly influenced the proliferation and differentiation of human adipose mesenchymal stem cells. The results of the tests showed that silk fibroin administration into a nanofiber mixture has improved chondrogenesis and showed great potential as a cartilage tissue scaffold.

Lignocellulosic jute-based nanofiber composite as biomimetic tissue scaffold.

Arthritis, encompassing degenerative disorders such as osteoarthritis (OA) and autoimmune diseases like rheumatoid arthritis (RA), remains a leading cause of chronic pain, disability, and socioeconomic burden worldwide. Conventional pharmacological and surgical therapies primarily offer symptomatic relief without addressing the underlying degeneration of cartilage and bone. Recent advances in regenerative medicine have introduced promising biological strategies, particularly mesenchymal stem cells, exosomes, and bioengineered tissue scaffolds, for functional joint restoration. MSCs exhibit remarkable differentiation potential, along with immunomodulatory and paracrine effects that support cartilage repair and immune homeostasis. MSC-derived exosomes replicate many of these therapeutic functions through their bioactive cargo of proteins, lipids, and microRNAs, offering a safer and more controllable cell-free alternative. Meanwhile, bioengineered scaffolds composed of natural or synthetic polymers provide essential structural and biochemical cues for tissue regeneration, especially when integrated with stem cells or exosomes. Despite encouraging preclinical and early clinical outcomes, challenges remain concerning safety, standardization, scalability, and regulatory approval. The integration of emerging technologies such as nanotechnology, artificial intelligence, and gene editing may further enhance regenerative outcomes and enable personalized arthritis therapies. Collectively, these convergent innovations represent a paradigm shift from symptomatic management toward true biological repair, positioning regenerative and stem cell-based therapies at the forefront of next-generation arthritis treatment.

Fabricating macroscopic tissue scaffolds that replicate native architecture, mechanics, and cellular density remains challenging. Here, we present a scalable, modular approach that combines agitation-driven assembly with fibrin-mediated fusion to produce centimeter-scale, cell-laden scaffolds with uniformly distributed, high-density cells and improved mechanical performance. The constructs are freestanding and mechanically more robust than monolithic hydrogels, while confocal imaging confirms deep, homogeneous cell penetration and high viability throughout centimeter-scale volumes. By overcoming tradeoffs among scaffold size, cell density, and mechanical integrity, this strategy provides a facile, versatile biofabrication platform for tissue engineering, regenerative medicine, and disease modeling.

Environmental context profoundly influences organismal biology, yet laboratory studies often rely on simplified conditions that may not fully capture natural phenotypic repertoire. This exploratory study investigated how rearing environment affects various aspects of Caenorhabditis elegans biology by comparing worms cultured in three-dimensional decellularized fruit tissue scaffolds with those raised on standard two-dimensional agar plates. While fat content and feeding rate remained stable across conditions, other life history traits demonstrated varying degrees of plasticity in response to environmental context. We observed that scaffold-grown worms exhibited reduced body size, altered reproductive strategies, and mild enhancements in stress resistance, burrowing ability, swimming kinematics and exploratory behavior. RNA sequencing revealed distinct transcriptional profiles between scaffold-grown and agar-grown worms, with most changes arising within one generation. Some traits showed evidence of intergenerational inheritance. Our findings highlight the sensitivity of C. elegans biology to rearing conditions and underscore the importance of considering environmental context in interpreting laboratory results. This work sets the foundation for future research into the mechanisms underlying environmental adaptation and phenotypic plasticity in model organisms.

3D bioprinting is a revolutionary technology that has recently emerged in the area of tissue regeneration owing to its ability to create complex tissue and organs for replacement. The requirement of various tissue types to offer patient-specific treatments is challenging; bioprinting uses a specialized material called 'bioink', which helps to address the issue. MXene, a well-known two-dimensional nanomaterial, has been gaining interest recently. It has been identified as a promising candidate in the field of tissue engineering because of its unique combination of different properties, such as biocompatibility, mechanical strength, and electrical conductivity. These are essential properties for the development of the next-generation bioinks. In this review, we report a comprehensive analysis of the latest advances in MXene-based bioinks in 3D bioprinting over conventional tissue scaffolding, focused on the materials' properties and their role in tissue regeneration. We highlight the ability of MXene in bioink, where MXene has the capacity to enhance cell growth by providing a conducive microenvironment for electrically active tissue, additionally supporting the 3D construct for stability. MXene in bioinks is advancing toward the field of tissue engineering for its application in therapeutic applications.

Abstract Pneumatic micro-extrusion (PME) presents challenges in achieving precise material deposition due to the small scale and high viscosity of the extruded material. Experimental methods alone often cannot capture the complex flow dynamics and interactions governing material transport in PME, underscoring the need for advanced computational modeling. This study establishes a 3D multiphase computational fluid dynamics (CFD) framework to simulate material deposition in PME, providing detailed insight into deposition behavior under varying process conditions. The CFD model, developed using ANSYS Fluent, is based on experimental boundary conditions defined to replicate pneumatic extrusion on a moving substrate. In this study, the effects of print speed and nozzle diameter are systematically investigated. Simulations revealed three deposition regimes: over-extrusion, normal extrusion, and under-extrusion. Lower print speeds produced over-extrusion with increased bead height and width, while normal extrusion maintained stable bead geometry. Higher speeds resulted in under-extrusion and discontinuities. Bead width decreased significantly between 10 and 15 mm/s, with discontinuities appearing at 20 mm/s. Besides, centerline velocity increased from 0.058 mm/s in the cartridge to 12.88 mm/s in the nozzle, closely matching experimental measurements (12.95 mm/s). Furthermore, pressure decreased slightly with increasing print speed, while nozzle velocity and wall shear stress remained unchanged. Additionally, nozzle diameter studies showed that smaller nozzles generated higher velocities and pressures, while larger nozzles produced broader but less cohesive deposition. Overall, these findings offer critical guidance for optimizing PME and improving scaffold fabrication for tissue engineering applications.

Recent advances in plant polyphenol-based adhesive hydrogels for biomedical applications.

Spinal cord injury (SCI), commonly resulting from sudden trauma such as traffic or sports accidents, leads to severe disruption of axonal connections and loss of sensory and motor function below the injury site. Despite numerous therapeutic efforts, effective strategies for neural repair remain limited. Tissue engineering has emerged as a promising approach for axonal regeneration, particularly through the design of three-dimensional (3D) polymeric scaffolds that can restore the structural and functional integrity of the injured spinal cord. This review focuses on recent advances in biomaterials and scaffold designs developed for SCI repair, emphasizing the role of nanocomposite systems that combine graphene oxide (GO), synthetic polymers such as PLGA-PEG, and bioactive ceramics like hydroxyapatite (HA). These hybrid materials offer improved biocompatibility, mechanical matching with spinal tissue, and enhanced cellular adhesion and guidance cues for axonal growth. The synergistic integration of these components enables the fabrication of multifunctional scaffolds capable of supporting stem cell differentiation and neurotrophic factor delivery. By critically summarizing the key parameters influencing scaffold performance, such as microarchitecture, surface modification, and mechanical compliance, this work outlines a framework for developing next-generation 3D nanocomposite scaffolds for SCI regeneration. The proposed approach highlights how GO/PLGA-PEG/HA systems can bridge the gap between experimental tissue engineering and clinically translatable neuroregenerative therapies.

The biological activity of polysaccharides from TCM is closely related to their structure. Through structural modifications, such as grafting modification and crosslinking reactions, their physicochemical properties can be significantly improved. Modified polysaccharides from TCM can form nanocarriers through self-assembly, constructing intelligent drug delivery systems and self-healing hydrogels. By esterification, etherification to graft hydrophobic small molecules, radical graft copolymerization, sulfonation reaction to graft ionic polymers, etc., the hydrophilic-hydrophobic balance of polysaccharides can be adjusted, improving their drug loading efficiency and targeted delivery ability. By synergizing crosslinking reactions such as Schiff base reaction, ionic crosslinking, and covalent crosslinking, hydrogels with excellent properties can be constructed. After structural modification, polysaccharides from TCM can achieve efficient encapsulation of hydrophobic active ingredients, construct intelligent drug delivery systems, develop self-healing hydrogels, and build tissue scaffolds. Although they have advantages such as high plasticity and good biocompatibility as delivery systems, there are also potential issues such as stability, immune response, and quality control that need further research and resolution.

Autografts, allografts or xenografts can be applied for treating damaged skin tissue, but these methods have certain disadvantages such as additional damage to donor regions, increased infection risk, and risk of disease transmission. On the other hand, tissue engineered skin substitutes provide more advantageous properties including large sources and good bioactivity. Tissue engineering is an interdisciplinary field of science that aims to develop tissue-engineered substitutes or tissue scaffolds in order to replace, repair, maintain, and regenerate the tissue functions. For producing functional tissue scaffolds for use in tissue engineering, different fabrication methods have been used by scientists. One such technique is electrospinning, which has been recognized as a promising method for creating microstructures that closely resemble the extracellular matrix of skin tissue. In this review article, the aim was first to provide information about skin tissue-related problems, current treatment methods, electrospinning method and its working principle, and to review the recent literature on the applications of electrospinning for use in skin tissue engineering.

The purpose of this study was to develop an optimized treatment for pathological myopia: a degradable cell-free suture-free tissue scaffold implant that reverses the excessive axial elongation and induces a therapeutic ridge. A form-deprivation (FD) myopia model was established in New Zealand White rabbits. Comprised of gelatin methacryloyl and a poly-L-lactide microfiber film, the tissue scaffold was implanted onto the posterior sclera of FD eyes (model + implant group; n =12), compared with model-only (n = 12) and controls eyes (n = 24). Ocular dimensions were monitored via ultrasound. Safety was assessed by electroretinogram, intraocular pressure, and apoptosis assays. The histology structure of regenerated tissue and sclera was shown. The axial length in model + implant eyes was significantly shorter than model-only eyes and the control eyes since 2 weeks after the implantation (13.79 ± 0.23mm, 15.15 ± 0.33mm, and 14.70 ± 0.18mm, P < 0.001) and maintained. The scaffold prompted the in situ regeneration of tissue mimicking the pseudo-lamellar arrangement of collagen fibers and major cell types found in native sclera, which formed an inward therapeutic ridge at the posterior sclera. The simulation indicated the ridge relieved outward macular traction significantly with minimum perturbation to stress distribution outside the central macula. Furthermore, collagen synthesis was prompted within the sclera itself. This innovative strategy, which avoids the long-term complications of foreign body compression, suturing, or tension fixation, effectively reversed myopic eye elongation and induced a therapeutic ridge. Demonstration of a degradable scaffold implantation as a treatment for pathological myopia with potential for minimally invasive clinical application was presented.

3D-printed self-healing hydrogels represent a significant advancement in regenerative medicine. Long-lasting, patient-tailored tissue scaffolds that evolve with native tissues may result. Preventing unwanted biomaterial growth is a major concern. The "Printability-Healing Paradox" is the central challenge, involving a trade-off between rheological properties for high-fidelity 3D printing and dynamic network features for self-healing. Resolving the paradox requires understanding hydrogel bioinks, chemical tools for self-healing (e.g., Schiff base, Diels-Alder, and hydrogen bonding), and rheological requirements for printability (e.g., shear-thinning and yield stress). Our review has explored advanced material design strategies, including multi-network architectures, nanocomposite reinforcement, and orthogonal crosslinking chemistries, to address this issue. Case studies in neuro, musculoskeletal, and cutaneous tissue engineering demonstrated how these methods might improve tissue-specific bio-functionality and alleviate problems. Designing smart materials is crucial for the profession to address the Printability-Healing Paradox. Developing multi-material printing platforms, AI-driven bioink design, and 4D characteristics will enable therapeutic structures that mimic biological organisms and adapt to the body.

Percutaneous puncture techniques have been widely adopted across various domains of modern clinical interventional therapy due to their high diagnostic specificity, minimal invasiveness, and rapid postoperative recovery. However, the nonholonomic kinematics arising from the interaction between flexible needles and soft tissues, combined with the complexity of human anatomical structures, pose significant challenges to robot-assisted flexible needle insertion. To address these challenges, this paper proposes an improved rapidly-exploring random tree (RRT) path planning algorithm incorporating soft actor critic (SAC)-guided sampling. By integrating SAC-guided sampling strategies, the algorithm offers effective sampling guidance for path planning, significantly reducing the randomness of the search process, minimizing the generation of invalid nodes, accelerating convergence, and improving both path quality and planning efficiency. A hybrid sampling strategy is employed to balance global exploration and local exploitation capabilities, thereby enhancing adaptability and planning performance in complex anatomical environments. Furthermore, a navigation and positioning robot is integrated to autonomously guide the needle toward the target, thereby improving the autonomy of the insertion procedure. Target insertion experiments demonstrate an error of 0.97 ± 0.41 mm in synthetic biomimetic tissue, demonstrating strong potential for clinical translation.

Abstract Conventional bone tissue scaffolds are constrained by the issues of limited mechanical adaptability and inadequate bioactivity. Here, inspired by the natural bone tissue structure and combined with architectural design concepts, a multifunctional biphasic bone scaffold with a ‘steel-cement’ structure was constructed. This biphasic system was composed of a 4D printed rigid lattice metamaterial scaffold (‘biosteel’) and a flexible hydrogel (‘biocement’) loaded with composite particles (Cu-PDA-ES@Dex). Eggshell (ES) was innovatively used as a carrier to design composite particles with sequential drug release capabilities, which were embedded in the hydrogel phase to achieve synergistic anti-infective and osteogenic functions. By precisely regulating the geometric parameters of the lattice metamaterials, the mechanical properties and porosity of the scaffolds were controllably adjusted, thereby meeting the regeneration requirements of bone defects in different parts. The combination of radiopaque intelligent materials and 4D printing technology endowed the scaffolds with dynamic shape memory and radiopaque characteristics, facilitating minimally invasive implantation, adaptive filling, and precise localization. The ‘steel-cement’ multifunctional biphasic scaffold established an innovative platform for intelligent bone regeneration with its antibacterial, osteogenic, and mechanical adaptability. This not only promoted the development of bone regeneration toward intelligence and precision, but also provided new insights into the high-value utilization of waste biological resources.

Cellular, acellular, and matrix-like products (CAMPs), also known as skin, dermal, or tissue substitutes, have been used to manage thermal injuries for over 20years with over 75 commercially available products today. Despite demonstrating long-term safety and efficacy, the use of CAMPs remains controversial in the burn community in terms of clinical benefit, economics, clinical algorithm, and lack of standardization in coding or categorization of specific products. Most clinical studies regarding CAMP use are product-specific prospective or retrospective studies comparing against split-thickness skin grafts alone, but very few have investigated the impact of product-agnostic CAMP use in burn care using the National Burn Repository (NBR). The goal of this study was to document CAMP use in burn management from 2016 to 2021 and provide a preliminary analysis of how CAMP use, including non-autologous and synthetic "tissue substitutes" categorization, may impact patient care compared to not using a CAMP at all. National Burn Repository data from 2008 to 2021 were analyzed (n = 388 775 patients). Surviving patients treated with complete procedure code data treated "tissue substitute" (synthetic or non-autologous) during their care were identified via ICD-10 procedure codes (n = 29 919 patients, 2016-2021 data). Aggregated metrics included patient demographic information (age, sex, race, and burn degree) and case measurements (length of stay [LOS], total body surface area [TBSA: second, third, and combined], complications, resource utilization, number of procedures, and number of excisional debridements). Additional analyses included determining the percentage of second- and third-degree burns (normalizing against total TBSA to obtain patient cohorts that are defined as "Predominantly second" and "Predominantly third") and normalizing patients' LOS per TBSA. An additional surviving patient cohort that was not treated with a CAMP (n = 46 589 patients) was identified to directly compare the case measurements listed above. The general frequency of patients treated with CAMPs has increased from 2016 to 2020. However, the number of patients treated with a CAMP, except patients aged 70years or older, decreased from 2020 to 2021. Patients with predominantly second-degree burns were treated with CAMPs more often than those with predominantly third-degree burns. CAMP use, regardless of burn depth or normalization against TBSA, was associated with higher LOS/TBSA and more procedures overall, but also associated with a significantly lower rate of skin, wound, or graft-loss-related complications and fewer resources utilized overall compared to patients not treated with a CAMP. Cellular, acellular, and matrix-like product/Skin substitutes separated into non-autologous and synthetic tissue substitutes categories demonstrated significant differences, but should be considered preliminary due to limitations in data collection. This study illustrates the first analysis of the ABA NBR to investigate specific care algorithms (CAMP use) in burns, including high TBSA burns. This begins to retrospectively elucidate outcomes associated with one care pathway or another, and ultimately highlights the general lack of standardization in burn care approach, documentation in the NBR, and coding. Future analysis will be required to add further specificity and validation of these results, and to understand the health economic implications of CAMP use for burns.

The creation of naturalbioinks suitable for three-dimensional(3D) bioprinting remains a significant challenge in developing functionaland biocompatible materials for tissue engineering. In this work,a novel bioink formulation was designed using food-grade polysaccharides,κ-carrageenan (KC), tragacanth gum (TG), and konjac glucomannan(KG), and thoroughly evaluated. Each component was tested at varyingconcentrations through rheological analysis, in vitro cytotoxicityassays (MTS test with HEK293T cells), and printability assessmentsusing a commercial bioprinter. Optimal concentration ranges were identifiedas ≥2% for KC, ≥1.5% for TG, and 1.5–2% for KG,which were then combined into two candidate hydrogel formulations(A and B). Both exhibited viscoelastic behavior and pseudoplasticflow characteristics. Formulation B (2% KG) demonstrated greater structuralrigidity (G′ ≈ 40 kPa) and excellentprint fidelity (>84%) under multiple extrusion conditions, whileformulationA (1.5% KG), though mechanically less robust, showed superior biocompatibility,achieving 86.5% cell viability after 24 h and 82.1% after 48 h. Overall,the study underscores the promise of food-derived polysaccharidesas sustainable and customizable bioink components, with potentialapplications in engineered tissue scaffolds, in vitro models, andbiocompatible 3D-printed systems.

Engineering shape-memory polymer microspheres as tunable curved surfaces for stem cell fate manipulation.

A comprehensive review on SEBS gel as a synthetic human tissue surrogate