Tissue Engineering Research Articles

Functionally graded hydrogels with opposing biochemical cues for osteochondral tissue engineering.

Osteochondral tissue (OC) repair remains a significant challenge in the field of musculoskeletal tissue engineering. OC tissue displays a gradient structure characterised by variations in both cell types and extracellular matrix components from cartilage to the subchondral bone. These functional gradients in the native tissue have been replicated to engineer osteochondral tissue in vitro. While diverse fabrication methods have been employed to create these microenvironments, emulating the natural gradients and effective regeneration of the tissue continues to present a significant challenge. In this study, we present the design and development of an interpenetrating (IPN) hydrogel with opposing dual biochemical gradients with the aim of regenerating the complete osteochondral unit. The gradients of biochemical cues were generated using an in-house built extrusion system in CMC-Silk IPN hydrogel having improved mechanical strength. Firstly, we fabricated a hydrogel that exhibits a smooth transition of sCMC and TGF-β1 (SCT gradient hydrogel) from the upper to the lower region of the IPN hydrogel, with the intent of regenerating the cartilage layer. Secondly, a hydrogel with a HAp gradient (HAp gradient hydrogel) from the lower to the upper region was fabricated to facilitate the regeneration of the subchondral bone layer. Subsequently, we developed a dual biochemical gradient hydrogel with the goal of regenerating the entire osteochondral unit. The fabricated hydrogel demonstrated a smooth transition of sCMC + TGF-β1 and HAp gradients in opposing directions, along with a blend of both the biochemical cues at the interface. The results showed that the hydrogels having biochemical cues corresponding to the three zones (i.e., cartilage, interface and bone) of dual biochemical gradient hydrogel led to differentiation of BMSCs towards their respective lineages, thereby demonstrating their efficacy in directing the fate of progenitor cells. The developed dual gradient hydrogel provided biochemical signals that have the potential to facilitate tissue growth and regeneration of the entire osteochondral tissue with a smooth transition from cartilage (soft) to bone (hard) tissues. In summary, our study provides a simple and innovative method for incorporating biochemical cues into hydrogels. This promising approach is translatable and has the potential to be extrapolated to other interface tissues.&#xD.

Computational Fluid Dynamics (CFD) Analysis of Bioprinting.

Regenerative medicine has evolved with the rise of tissue engineering due to advancements in healthcare and technology. In recent years, bioprinting has been an upcoming approach to traditional tissue engineering practices, through the fabrication of functional tissue by its layer-by-layer deposition process. This overcomes challenges such as irregular cell distribution and limited cell density, and it can potentially address organ shortages, increasing transplant options. Bioprinting fully functional organs is a long stretch but the advancement is rapidly growing due to its precision and compatibility with complex geometries. Computational Fluid Dynamics (CFD), a carestone of computer-aided engineering, has been instrumental in assisting bioprinting research and development by cutting costs and saving time. CFD optimizes bioprinting by testing parameters such as shear stress, diffusivity, and cell viability, reducing repetitive experiments and aiding in material selection and bioprinter nozzle design. This review discusses the current application of CFD in bioprinting and its potential to enhance the technology that can contribute to the evolution of regenerative medicine.

Organoid bioinks: construction and application.

Organoids have emerged as crucial platforms in tissue engineering and regenerative medicine but confront challenges in faithfully mimicking native tissue structures and functions. Bioprinting technologies offer a significant advancement, especially when combined with organoid bioinks-engineered formulations designed to encapsulate both the architectural and functional elements of specific tissues. This review provides a rigorous, focused examination of the evolution and impact of organoid bioprinting. It emphasizes the role of organoid bioinks that integrate key cellular components and microenvironmental cues to more accurately replicate native tissue complexity. Furthermore, this review anticipates a transformative landscape invigorated by the integration of artificial intelligence with bioprinting techniques. Such fusion promises to refine organoid bioink formulations and optimize bioprinting parameters, thus catalyzing unprecedented advancements in regenerative medicine. In summary, this review accentuates the pivotal role and transformative potential of organoid bioinks and bioprinting in advancing regenerative therapies, deepening our understanding of organ development, and clarifying disease mechanisms.&#xD.

Organ-on-a-Chip: Ubi sumus? Fundamentals and Design Aspects

This review outlines the evolutionary journey from traditional two-dimensional (2D) cell culture to the revolutionary field of organ-on-a-chip technology. Organ-on-a-chip technology integrates microfluidic systems to mimic the complex physiological environments of human organs, surpassing the limitations of conventional 2D cultures. This evolution has opened new possibilities for understanding cell–cell interactions, cellular responses, drug screening, and disease modeling. However, the design and manufacture of microchips significantly influence their functionality, reliability, and applicability to different biomedical applications. Therefore, it is important to carefully consider design parameters, including the number of channels (single, double, or multi-channels), the channel shape, and the biological context. Simultaneously, the selection of appropriate materials compatible with the cells and fabrication methods optimize the chips’ capabilities for specific applications, mitigating some disadvantages associated with these systems. Furthermore, the success of organ-on-a-chip platforms greatly depends on the careful selection and utilization of cell resources. Advances in stem cell technology and tissue engineering have contributed to the availability of diverse cell sources, facilitating the development of more accurate and reliable organ-on-a-chip models. In conclusion, a holistic perspective of in vitro cellular modeling is provided, highlighting the integration of microfluidic technology and meticulous chip design, which play a pivotal role in replicating organ-specific microenvironments. At the same time, the sensible use of cell resources ensures the fidelity and applicability of these innovative platforms in several biomedical applications.

Enhanced Electroactive Phases of Poly(vinylidene Fluoride) Fibers for Tissue Engineering Applications.

Nanofibrous materials generated through electrospinning have gained significant attention in tissue regeneration, particularly in the domain of bone reconstruction. There is high interest in designing a material resembling bone tissue, and many scientists are trying to create materials applicable to bone tissue engineering with piezoelectricity similar to bone. One of the prospective candidates is highly piezoelectric poly(vinylidene fluoride) (PVDF), which was used for fibrous scaffold formation by electrospinning. In this study, we focused on the effect of PVDF molecular weight (180,000 g/mol and 530,000 g/mol) and process parameters, such as the rotational speed of the collector, applied voltage, and solution flow rate on the properties of the final scaffold. Fourier Transform Infrared Spectroscopy allows for determining the effect of molecular weight and processing parameters on the content of the electroactive phases. It can be concluded that the higher molecular weight of the PVDF and higher collector rotational speed increase nanofibers' diameter, electroactive phase content, and piezoelectric coefficient. Various electrospinning parameters showed changes in electroactive phase content with the maximum at the applied voltage of 22 kV and flow rate of 0.8 mL/h. Moreover, the cytocompatibility of the scaffolds was confirmed in the culture of human adipose-derived stromal cells with known potential for osteogenic differentiation. Based on the results obtained, it can be concluded that PVDF scaffolds may be taken into account as a tool in bone tissue engineering and are worth further investigation.

Enhancement of Bone Tissue Regeneration with Multi-Functional Nanoparticles by Coordination of Immune, Osteogenic, and Angiogenic Responses.

Inorganic nanoparticles are promising materials for bone tissue engineering due to their chemical resemblance to the native bone structure. However, most studies were unable to capture the entirety of the defective environment, providing limited bone regenerative abilities. Hence, this study aims to develop a multifunctional nanoparticle to collectively control the defective bone niche, including immune, angiogenic, and osteogenic systems. The nanoparticles, self-assembled by biomimetic mineralization and tannic acid (TA)-mediated metal-polyphenol network (MPN), are released sustainably after the incorporation within a gelatin cryogel. The released nanoparticles display a reduction in M1 macrophages by means of ROS elimination. Consequently, osteoclast maturation is also reduced, which is observed by the minimal formation of multinucleated cells (0.4%). Furthermore, the proportion of M2 macrophages, osteogenic differentiation, and angiogenic potential are consistently increased by the effects of magnesium from the nanoparticles. This orchestrated control of multiple systems influences the in vivo vascularized bone regeneration in which 80% of the critical-sized bone defect was regenerated with new bones with mature lamellar structure and arteriole-scale micro-vessels. Altogether, this study emphasizes the importance of the coordinated modulation of immune, osteogenic, and angiogenic systems at the bone defect site for robust bone regeneration. This article is protected by copyright. All rights reserved.

USING FOETAL SKELETOGENESIS TO EVALUATE AND IMPROVE IN VITRO CHONDROGENESIS PROTOCOLS

The reliable production of _in vitro_ chondrocytes that faithfully recapitulate _in vivo_ development would be of great benefit for orthopaedic disease modelling and regenerative therapy(1,2). Current efforts are limited by off-target differentiation, resulting in a heterogeneous product, and by the lack of comparison to human tissue, which precludes detailed evaluation of _in vitro_ cells(3,4).We performed single-cell RNA-sequencing of long bones dissected from first-trimester fetal limbs to form a detailed ‘atlas’ of endochondral ossification. Through 100-gene in-situ sequencing, we placed each sequenced cell type into its anatomical context to spatially resolve the process of endochondral ossification. We then used this atlas to perform deconvolution on a series of previously published bulk transcriptomes generated from _in vitro_ chondrogenesis protocols to evaluate their ability to accurately produce chondrocytes.We then applied single-nuclear RNA-sequencing to cells from the best performing protocol collected at multiple time points to allow direct comparison between the differentiation of _in vitro_ and _in vivo_ cells.We captured 275,000 single fetal cells, profiling the development of chondrocytes from multipotent mesenchymal progenitors to hypertrophic cells at full transcriptomic breadth. Using this atlas as the ground truth for evaluating _in vitro_ cells, we found substantial variability in cell states produced by each protocol, with many showing little similarity to _in vivo_ cells, and all exhibiting off-target differentiation.Trajectory alignment between _in vivo_ and _in vitro_ single-cell data revealed key differences in gene expression dynamics between _in vitro_ and _in vivo cells,_ with several osteoblastic transcription factors erroneously unregulated _in vitro,_ including _FOXO1._Using this information, we inhibited _FOXO1_ in culture to successfully increase chondrocyte yield _in vitro._This study presents a new framework for evaluating tissue engineering protocols, using single-cell data to drive improvement and bring the prospect of true engineered cartilage closer to reality.

Chitosan-Chitosan derivative for cartilage associated disorders: Protein interaction and biodegradability

Chitosan is a well-known biomaterial in the field of cartilage tissue engineering because of its flexibility. The construction of chitosan-based scaffolds is reviewed in several production methods, including freeze-drying, gelation, salt leaching, and electrospinning. In this review, many benefits of chitosan are discussed, including the interaction of chitosan with other materials and their effects, its adaptability, high reproducibility, biocompatibility, role in cellular differentiation, interactions with TGF-β (transforming growth factor-β), protein interactions, biodegradability, influencing osteoblast expression, and potential for treating bone diseases. The study also provides information on how mathematical models are used to analyze how MSC (mesenchymal stem cells) and chondrocyte distribution in multilayer hydrogels change in response to TGF-β diffusion. Results showed that collagen has weak mechanical properties and easily disintegrates during bone tissue formation, it is difficult to use alone as a biomaterial, and new scaffolds made of whey protein isolate (WPI) and chitosan may help repair osteochondral tissue. However, the thorough analysis reveals chitosan's crucial contribution to the development of cartilage tissue engineering as well as its potential to address issues in the field.

Hydrogen Sulfide Delivery to Enhance Bone Tissue Engineering Cell Survival

Though crucial for natural bone healing, local calcium ion (Ca2+) and phosphate ion (Pi) concentrations can exceed the cytotoxic limit leading to mitochondrial overload, oxidative stress, and cell death. For bone tissue engineering applications, H2S can be employed as a cytoprotective molecule to enhance mesenchymal stem cell (MSC) tolerance to cytotoxic Ca2+/Pi concentrations. Varied concentrations of sodium hydrogen sulfide (NaSH), a fast-releasing H2S donor, were applied to assess the influence of H2S on MSC proliferation. The results suggested a toxicity limit of 4 mM for NaSH and that 1 mM of NaSH could improve cell proliferation and differentiation in the presence of cytotoxic levels of Ca2+ (32 mM) and/or Pi (16 mM). To controllably deliver H2S over time, a novel donor molecule (thioglutamic acid—GluSH) was synthesized and evaluated for its H2S release profile. Excitingly, GluSH successfully maintained cytoprotective level of H2S over 7 days. Furthermore, MSCs exposed to cytotoxic Ca2+/Pi concentrations in the presence of GluSH were able to thrive and differentiate into osteoblasts. These findings suggest that the incorporation of a sustained H2S donor such as GluSH into CaP-based bone graft substitutes can facilitate considerable cytoprotection, making it an attractive option for complex bone regenerative engineering applications.

3D Bioprinting of Sugar Beet Pectin through Horseradish Peroxidase-Catalyzed Cross-Linking.

Horseradish peroxidase (HRP)-mediated hydrogelation, caused by the cross-linking of phenolic groups in polymers in the presence of hydrogen peroxide (H2O2), is an effective route for bioink solidification in 3D bioprinting. Sugar beet pectin (SBP) naturally has cross-linkable phenols through the enzymatic reaction. Therefore, chemical modifications are not required, unlike the various polymers that have been used in the enzymatic cross-linking system. In this study, we report the application of SBP in extrusion-based bioprinting including HRP-mediated bioink solidification. In this system, H2O2 necessary for the solidification of inks is supplied in the gas phase. Cell-laden liver lobule-like constructs could be fabricated using bioinks consisting of 10 U/mL HRP, 4.0 and 6.0 w/v% SBP, and 6.0 × 106 cells/mL human hepatoblastoma (HepG2) cells exposed to air containing 16 ppm of H2O2 concurrently during printing and 10 min postprinting. The HepG2 cells enclosed in the printed constructs maintained their viability, metabolic activity, and hepatic functions from day 1 to day 7 of the culture, which indicates the cytocompatibility of this system. Taken together, this result demonstrates the potential of SBP and HRP cross-linking systems for 3D bioprinting, which can be applied in tissue engineering applications.

Calcium Alginate Core–Shell Liquid Beads Encapsulated with Microalgae for Wastewater Treatment

Liquid beads are core–shell particles with a liquid core and a solid shell. Calcium alginate liquid beads have been emerging as a promising platform for cell encapsulation. These beads have demonstrated their capability of encapsulating and culturing a wide range of human cells for tissue engineering. However, a significant research gap remains in the application of alginate liquid beads for encapsulating photosynthetic microorganisms. Herein, fast‐growing microalgae strain Chlorella vulgaris is encapsulated into calcium alginate liquid beads to facilitate the removal of nutrients from wastewater, minimizing the risk of eutrophication. Liquid bead‐microalgae systems are prepared, using different calcium ion concentrations as crosslinking ions. It has been thoroughly characterized for their morphologies, cell growth patterns, nutrient removal capabilities, and overall stability throughout the wastewater treatment process, with upflow anaerobic sludge blanket effluent as the wastewater model. The results indicate that the liquid bead‐microalgae system with the highest calcium ion concentration (5%) performs more efficiently, exhibiting a well‐formed crosslinking structure, leading to rapid cell growth with the highest cell density and the most effective removal of nutrients. The findings from this study provide valuable insights for future optimization and upscaling efforts in wastewater treatment systems based on calcium alginate liquid beads.

Engineering Cell Instructive Microenvironments for In Vitro Replication of Functional Barrier Organs.

Multicellular organisms exhibit synergistic effects among their components, giving rise to emergent properties crucial for their genesis and overall functionality and survival. Morphogenesis involves and relies upon intricate and biunivocal interactions among cells and their environment, that is, the extracellular matrix (ECM). Cells secrete their own ECM, which in turn, regulates their morphogenetic program by controlling time and space presentation of matricellular signals. The ECM, once considered passive, is now recognized as an informative space where both biochemical and biophysical signals are tightly orchestrated. Replicating this sophisticated and highly interconnected informative media in a synthetic scaffold for tissue engineering is unattainable with current technology and this limits the capability to engineer functional human organs in vitro and in vivo. This review explores current limitations to in vitro organ morphogenesis, emphasizing the interplay of gene regulatory networks, mechanical factors, and tissue microenvironment cues. In vitro efforts to replicate biological processes for barrier organs such as the lung and intestine, are examined. The importance of maintaining cells within their native microenvironmental context is highlighted to accurately replicate organ-specific properties. The review underscores the necessity for microphysiological systems that faithfully reproduce cell-native interactions, for advancing the understanding of developmental disorders and disease progression.

Thixotropic chitosan hydrogels for biomedical applications: Unravelling the effect of chitosan concentration on the mechanical behaviour

Chitosan hydrogels are highly sought after in biomedical applications due to their biocompatibility, non-toxicity, and tunable mechanical properties. Nevertheless, achieving stable hydrogels with the required mechanical strength remains a notable obstacle. In this study, we prepared chitosan hydrogels with enhanced stability using minimal concentrations of glutaraldehyde to mitigate toxicity risks. The resulting hydrogel system is characterized by strong covalent bonds formed through imine and hydrogen bonding, facilitated by the aldehyde groups of glutaraldehyde. Rheological analyses reveal the viscoelastic properties of the hydrogels, showcasing stable gel-like structures with shear-thinning behavior, which are further enhanced with increasing chitosan concentration. Our observation demonstrates that the complex shear moduli of 0.5 - 1.5 w/v % chitosan hydrogel ranged between 3.08 kPa and 8.5 kPa, closely matching the shear moduli of the brain and connective tissues. The shear moduli obtained for the 2w/v% (10.2 kPa) and 2.5w/v% hydrogels (11.34 kPa) conform to the shear moduli of liver, fat, relaxed muscle, and breast gland tissue. Thixotropic studies reveal good structural recovery behaviour in the hydrogels. The swellability of 2w/v% and 2.5w/v% hydrogels (50-70%) suggests their suitability for bone tissue engineering, with moderate porosity required for bone growth (60-75%). Moreover, the yield stress values of 0.5 - 1.5 w/v % hydrogels satisfy the requirements for soft tissue engineering, while those of 2 and 2.5 w/v% match the requirements for bone tissue engineering. Our findings suggest that chitosan hydrogels of varying concentrations (0.5–2.5% w/v) hold promise for a range of biomedical applications, including tissue engineering for brain, nerve, soft, and bone tissues, and wound dressing. This research addresses the pressing need for stable chitosan hydrogels with tailored mechanical properties, potentially offering solutions to challenges in biomedical materials design.

Comparison of skeletal muscle decellularization protocols and recellularization with adipose-derived stem cells for tissue engineering

Decellularization is a novel technique employed for scaffold manufacturing, as a strategy for skeletal muscle (SM) tissue engineering applications. However, poor decellularization efficacy is still a problem for the use of decellularized scaffolds as truly biocompatible biomaterials. For recellularization, adipose-derived stem cells (ASCs) are a good option, due to their immunomodulatory and pro-regenerative capacity, but few studies have described their combination with muscle-decellularized matrices (mDMs). This work aimed to evaluate the efficiency of four multi-step decellularization protocols to produce mDMs and to investigate in vitro biocompatibility with ASCs. Here, we described the different efficacies of muscle decellularization methods, suggesting the need for stricter standardization of the method, considering the large range of applications in SM tissue engineering, which is also a promising platform for preclinical studies with rat disease models using autologous cells.

Tissue engineered multifunctional chitosan-modified polypropylene hernia mesh loaded with bioactive phyto-extracts

Surface modified tissue engineered polypropylene / PP hernia meshes were fabricated by incorporating Bacterial cellulose / BC and chitosan / CS and phytochemical extracts. Under current practice, hernia and other traumatic injuries to the abdominal organs are clinically treated with surgical meshes. Often the foreign body reaction and infections result in relapse in patients which dictates additional reparative surgical procedures and pain. To improve the outcome of clinical restorative procedures new biomaterials with improved characteristics are required. The functionalized meshes were physically and chemically characterized using SEM, mechanical testing, FTIR and XRD. The antimicrobial activity was qualitatively and quantitatively tested using E. coli and S. aureus strains of bacteria. In vitro biocompatibility and wound healing effect of the modified meshes were performed using NIH3T3 fibroblast cell lines. Furthermore, tissue engineering potential of the meshes was evaluated using confocal fluorescent microscopy. In vivo implantation of the meshes was performed in male wistar rats for 21 days. Therefore, PP meshes with sustained drug delivery system augmented with anti-inflammatory and anti-microbial characteristics were developed. The coatings hereby not only increased the tensile strength of meshes but also prevented the modified meshes from causing infection. Current study resulted in CS-BC bioactive PP meshes loaded with phytochemicals which showed anti-inflammatory, antibacterial and wound healing potential. These meshes can be valuable to lessen the post-surgical complications of implanted PP mesh and thus reduce rejection and recurrence.

Sensory neurons increase keratinocyte proliferation through CGRP release in a tissue engineered in vitro model of innervation in psoriasis

Skin denervation has been shown to cause remission of psoriatic lesions in patients, which can reappear if reinnervation occurs. This effect can be induced by the activation of dendritic cells through sensory innervation. However, a direct effect of nerves on the proliferation of keratinocytes involved in the formation of psoriatic plaques has not been investigated. We developed, by tissue engineering, a model of psoriatic skin made of patient skin cells that showed increased keratinocyte proliferation and epidermal thickness compared to healthy controls. When this model was treated with CGRP, a neuropeptide released by sensory neurons, an increased keratinocyte proliferation was observed in the psoriatic skin model, but not in the control. When a sensory nerve network was incorporated in the psoriatic model and treated with capsaicin to induce neuropeptide release, an increase of keratinocyte proliferation was confirmed, which was blocked by a CGRP antagonist while no difference was noticed in the innervated healthy control. We showed that sensory neurons can participate directly to keratinocyte hyperproliferation in the formation of psoriatic lesions through the release of CGRP, independently of the immune system. Our unique tissue-engineered innervated psoriatic skin model could be a valuable tool to better understand the mechanism by which nerves may modulate psoriatic lesion formation in humans. Statement of significanceThis study shows that keratinocytes extracted from patients’ psoriatic skin retain, at least in part, the disease phenotype. Indeed, when combined in a 3D model of tissue-engineered psoriatic skin, keratinocytes exhibited a higher proliferation rate, and produced a thicker epidermis than a healthy skin control. In addition, their hyperproliferation was aggravated by a treatment with CGRP, a neuropeptide released by sensory nerves. In a innervated model of tissue-engineered psoriatic skin, an increase in keratinocyte hyperproliferation was also observed after inducing neurons to release neuropeptides. This effect was prevented by concomitant treatment with an antagonist to CGRP. Thus, this study shows that sensory nerves can directly participate to affect keratinocyte hyperproliferation in psoriasis through CGRP release.

Construction of dentin-on-a-chip based on microfluidic technology and tissue engineering

Construction of dentin-on-a-chip based on microfluidic technology and tissue engineering

Silk-Based 3D Porous Scaffolds for Tissue Engineering.

Silk fibroin, extracted from the silk of the Bombyx mori silkworm, stands out as a biomaterial due to its nontoxic nature, excellent biocompatibility, and adjustable biodegradability. Porous scaffolds, a type of biomaterial, are crucial for creating an optimal microenvironment that supports cell adhesion and proliferation, thereby playing an essential role in tissue remodeling and repair. Therefore, this review focuses on 3D porous silk fibroin-based scaffolds, first summarizing their preparation methods and then detailing their regenerative effects on bone, cartilage, tendon, vascular, neural, skin, hepatic, and tracheal epithelial tissue engineering in recent years.

3D-printed short nanofibers/hydrogel-based vaginal films as a novel system for the delivery of anti-HIV microbicide drugs.

Acquired immunodeficiency syndrome (AIDS) is a global epidemic that affects the lives of millions of young women, particularly those who live in poverty-stricken regions and engage in unsafe sexual behaviors, forcing the development of unique pre-exposure anti-HIV prophylaxis tools. Using a combination of antiretroviral medications with various antiviral mechanisms significantly improves the prognosis for HIV patients. The integration of 3D printing technology, short nanofiber technology, and hydrogel into a single system known as "3D-printed nanocomposites" is an emerging approach that is gaining traction in tissue engineering, regenerative medicine, and biomedical applications. Based on these foundations, the current study aims to develop, for the first time, a 3D-printed short nanofiber/film for the vaginal delivery of ritonavir and efavirenz in a fixed-dose combination. To identify an optimal 3D-printable short nanofibers/hydrogel formulation, multiple formulations, and fragmentation methods were investigated. Following that, the generated vaginal films were evaluated using several physicochemical characterizations, mechanical properties measurements, and in vitro release studies. The findings revealed that only cryocutting is effective for polycaprolactone nanofiber fragmentation. The 3D-printed short nanofibers-loaded films had an ultimate tensile strength of 6.75 ± 1.27 MPa and elongation at break of 262.67 ± 44.32 MPa, suggesting their reliability for handling and vaginal application. Furthermore, the in vitro release study demonstrated that rapid EFZ release occurred during the first 45 minutes, whereas RIT release lasted more than 72 hours, indicating that the complex drug release profile was met. In summary, the study emphasizes that 3D printing of short nanofiber-based films is likely to be an effective platform for localized vaginal drug delivery, particularly anti-HIV therapies.

GelMA-based hydrogel biomaterial scaffold: A versatile platform for regenerative endodontics.

Endodontic therapy, while generally successful, is primarily limited to mature teeth, hence the pressing need to explore regenerative approaches. Gelatin methacryloyl (GelMA) hydrogels have emerged as pivotal biomaterials, promising a bright future for dental pulp regeneration. Despite advancements in tissue engineering and biomaterials, achieving true pulp tissue regeneration remains a formidable task. GelMA stands out for its injectability, rapid gelation, and excellent biocompatibility, serving as the cornerstone of scaffold materials. In the pursuit of dental pulp regeneration, GelMA holds significant potential, facilitating the delivery of stem cells, growth factors, and other vital substances crucial for tissue repair. Presently, in the field of dental pulp regeneration, researchers have been diligently utilizing GelMA hydrogels as engineering scaffolds to transport various effective substances to promote pulp regeneration. However, existing research is relatively scattered and lacks comprehensive reviews and summaries. Therefore, the primary objective of this article is to elucidate the application of GelMA hydrogels as regenerative scaffolds in this field, thereby providing clear direction for future researchers. Additionally, this article provides a comprehensive discussion on the synthesis, characterization, and application of GelMA hydrogels in root canal therapy regeneration. Furthermore, it offers new application strategies and profound insights into future challenges, such as optimizing GelMA formulations to mimic the complex microenvironment of pulp tissue and enhancing its integration with host tissues.