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Multiple adjacent gingival recessions (MAGRs) are commonly treated with autogenous grafts. However, several intra- and postsurgical complications have been described following autogenous grafts, leading clinicians to explore the use of different biomaterials to treat these conditions. The aim of the present study was to evaluate the root coverage outcomes of a novel porcine-derived acellular dermal matrix (PADM) in combination with the tunneled coronally advanced flap (TCAF) for the treatment of MAGRs. Ten patients with 33 type 1 recession defects (RT1s) were treated with PADM + TCAF. The outcomes of interest included the mean root coverage (mRC), the frequency of complete root coverage (CRC), changes in keratinized tissue width, volumetric gain at the treated sites (assessed with digital intraoral scanning), and patient-reported outcome measures. All treated sites healed uneventfully, and no complications were noted throughout the study. At 6 months, a statistically significant reduction in recession was noted at the treated sites, exhibiting an overall mRC of 89.14% ± 19.15% and a CRC of 72.7%. The average volume gain after 6 months was 26.28 ± 11.71 mm3, and the mean distance between the surface/mean thickness of the reconstructed volume (DD) was 0.63 ± 0.28 mm. The region-specific volumetric analysis revealed an overall higher linear dimensional gain at the midroot aspect (range: 0.72 to 0.78 mm, assessed 1 to 4 mm apical to the cementoenamel junction) compared to the other regions. The present study presents the clinical and volumetric outcomes of PADM + TCAF for the treatment of MAGRs. A significant amount of volumetric gain was also observed at 6 months as a result of the treatment, along with satisfactory esthetic and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

The demand for fish protein continues to increase and currently accounts for 17% of total animal protein consumption by humans. About 90% of marine fish stocks are fished at or above maximum sustainable levels, with aquaculture propagating as one of the fastest growing food sectors to address some of this demand. Cell-cultivated seafood production is an alternative approach to produce nutritionally-complete seafood products to meet the growing demand. This cellular aquaculture approach offers a sustainable, climate resilient and ethical biotechnological approach as an alternative to conventional fishing and fish farming. Additional benefits include reduced antibiotic use and the absence of mercury. Cell-cultivated seafood also provides options for the fortification of fish meat with healthier compositions, such as omega-3 fatty acids and other beneficial nutrients through scaffold, media or cell approaches. This review addresses the biomaterials, production processes, tissue engineering approaches, processing, quality, safety, regulatory, and social aspects of cell-cultivated seafood, encompassing where we are today, as well as the road ahead. The goal is to provide a roadmap for the science and technology required to bring cellular aquaculture forward as a mainstream food source.

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues.

Tissue engineering can provide in vitro models for drug testing, disease modeling, and perhaps someday, tissue/organ replacements. For building 3D heart tissue, the alignment of cardiac cells or cardiomyocytes (CMs) is important in generating a synchronously contracting tissue. To that end, researchers have generated several fabrication methods for building heart tissue, but direct comparisons of pros and cons using the same cell source is lacking. Here, we derived cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) and compare the assembly of these cells using three fabrication methods: cardiospheres, muscle rings, and muscle strips. All three protocols successfully generated compacted tissue comprised of hiPSC-derived CMs stable for at least 2 weeks. The percentage of aligned cells was greatest in the muscle strip (55%) and the muscle ring (50%) compared with the relatively unaligned cardiospheres (35%). The iPSC-derived CMs within the muscle strip also exhibited the greatest elongation, with elongation factor at 2.0 compared with 1.5 for the muscle ring and 1.2 for the cardiospheres. This is the first direct comparison of various fabrication techniques using the same cell source.

Osteoarthritis is characterized by enzymatic breakdown of the articular cartilage via the disruption of chondrocyte homeostasis, ultimately resulting in the destruction of the articular surface. Decades of research have highlighted the importance of inflammation in osteoarthritis progression, with inflammatory cytokines shifting resident chondrocytes into a pro-catabolic state. Inflammation can result in poor outcomes for cells implanted for cartilage regeneration. Therefore, a method to promote the growth of new cartilage and protect the implanted cells from the pro-inflammatory cytokines found in the joint space is required. In this study, we fabricate two gel types: polymer network hydrogels composed of chondroitin sulfate and hyaluronic acid, glycosaminoglycans (GAGs) known for their anti-inflammatory and prochondrogenic activity, and interpenetrating networks of GAGs and collagen I. Compared to a collagen-only hydrogel, which does not provide an anti-inflammatory stimulus, chondrocytes in GAG hydrogels result in reduced production of pro-inflammatory cytokines and enzymes as well as preservation of collagen II and aggrecan expression. Overall, GAG-based hydrogels have the potential to promote cartilage regeneration under pro-inflammatory conditions. Further, the data have implications for the use of GAGs to generally support tissue engineering in pro-inflammatory environments.

The current paradigm of medicine is mostly designed to block or prevent pathological events. Once the disease-led tissue damage occurs, the limited endogenous regeneration may lead to depletion or loss of function for cells in the tissues. Cell therapy is rapidly evolving and influencing the field of medicine, where in some instances attempts to address cell loss in the body. Due to their biological function, engineerability, and their responsiveness to stimuli, cells are ideal candidates for therapeutic applications in many cases. Such promise is yet to be fully obtained as delivery of cells that functionally integrate with the desired tissues upon transplantation is still a topic of scientific research and development. Main known impediments for cell therapy include mechanical insults, cell viability, host's immune response, and lack of required nutrients for the transplanted cells. These challenges could be divided into three different steps: 1) Prior to, 2) during the and 3) after the transplantation procedure. In this review, we attempt to briefly summarize published approaches employing biomaterials to mitigate the above technical challenges. Biomaterials are offering an engineerable platform that could be tuned for different classes of cell transplantation to potentially enhance and lengthen the pharmacodynamics of cell therapies.

Cardiovascular organ-on-a-chip (OoC) devices are composed of engineered or native functional tissues that are cultured under controlled microenvironments inside microchips. These systems employ microfabrication and tissue engineering techniques to recapitulate human physiology. This review focuses on human OoC systems to model cardiovascular diseases, to perform drug screening, and to advance personalized medicine. We also address the challenges in the generation of organ chips that can revolutionize the large-scale application of these systems for drug development and personalized therapy.

Over the past two decades, the Khoury plate technique has been widely utilized with much success to facilitate bone augmentation in critically deficient bone areas. Simply, the technique includes harvesting autogenous bone plates and utilizing them with external screw fixation. The rigidity of the bone plates enclosing the bony defect on both the buccal and lingual surfaces allows for tension-free bone remodeling to occur, favoring an ideal bone-forming environment. Following, a 4- to 6-month healing period, a flap is raised, screws may be removed, and implants are placed. With advancements made in tissue engineering, a novel mineral-organic resorbable bone adhesive (MORBA) formulated from underwater biomimetic marine proteins has recently been utilized for immediate bone-to-bone or bone-to-metal fixation. MORBA is a synthetic, injectable, self-setting, and resorbable load-bearing adhesive biomaterial that exhibits over 300 pounds of fixation strength. The unique adhesive properties of MORBA enable it to immediately stabilize dental implants into host bone. The present article describes a novel modification of the Khoury plate technique that utilizes MORBA as a substitute for screws during bone plate fixation. A step-by-step protocol is described that utilizes this novel biomaterial, favoring a more biologic approach to this conventional technique. This novel modification is surgically easier to conduct and is a more biocompatible option that avoids screw fixation and removal. [ABSTRACT FROM AUTHOR]

Tissue engineering strategies show great potential for repairing osteochondral defects in osteoarthritic joints; however, these approaches often rely on passaging cells multiple times to obtain enough cells to produce functional tissue. Unfortunately, monolayer expansion culture causes chondrocyte dedifferentiation, which is accompanied by a phenotypical and morphological shift in chondrocyte properties that leads to a reduction in the quality of de novo cartilage produced. Thus, the objective of this study was to evaluate transcriptional variations during in vitro expansion culture and determine how differences in cell phenotype from monolayer expansion alter development of functional engineered cartilage. We used an unbiased approach to explore genome-wide transcriptional differences in chondrocyte phenotype at passage 1 (P1), P3, and P5, and then seeded cells into hydrogel scaffolds at P3 and P5 to assess cells' abilities to produce cartilaginous extracellular matrix in three dimensional (3D). We identified distinct phenotypic differences, specifically for genes related to extracellular organization and cartilage development. Both P3 and P5 chondrocytes were able to produce chondrogenic tissue in 3D, with P3 cells producing matrix with greater compressive properties and P5 cells secreting matrix with higher glycosaminoglycan/DNA and collagen/DNA ratios. Furthermore, we identified 24 genes that were differentially expressed with passaging and enriched in human osteoarthritis (OA) genome-wide association studies, thereby prioritizing them as functionally relevant targets to improve protocols that recapitulate functional healthy cartilage with cells from adult donors. Specifically, we identified novel genes, such as TMEM190 and RAB11FIP4, which were enriched with human hip OA and may play a role in chondrocyte dedifferentiation. This work lays the foundation for several pathways and genes that could be modulated to enhance the efficacy for chondrocyte culture for tissue regeneration, which could have transformative impacts for cell-based cartilage repair strategies.

Spheroids exhibit enhanced cell-cell interactions that facilitate improved survival and mimic the physiological cellular environment in vivo. Cell spheroids have been successfully used as building blocks for engineered tissues, yet the viability of this approach with skeletal muscle spheroids is poorly understood, particularly when incorporated into three-dimensional (3D) constructs. Bioprinting is a promising strategy to recapitulate the hierarchical organization of native tissue that is fundamental to its function. However, the influence of bioprinting on skeletal muscle cell spheroids and their function are yet to be interrogated. Using C2C12 mouse myoblasts and primary bovine muscle stem cells (MuSCs), we characterized spheroid formation as a function of duration and cell seeding density. We then investigated the potential of skeletal muscle spheroids entrapped in alginate bioink as tissue building blocks for bioprinting myogenic tissue. Both C2C12 and primary bovine MuSCs formed spheroids of similar sizes and remained viable after bioprinting. Spheroids of both cell types fused into larger tissue clusters over time within alginate and exhibited tissue formation comparable to monodisperse cells. Compared to monodisperse cells in alginate gels, C2C12 spheroids exhibited greater MyHC expression after 2 weeks, while cells within bovine MuSC spheroids displayed increased cell spreading. Both monodisperse and MuSC spheroids exhibited increased expression of genes denoting mid- and late-stage myogenic differentiation. Together, these data suggest that skeletal muscle spheroids have the potential for generating myogenic tissue via 3D bioprinting and reveal areas of research that could enhance myogenesis and myogenic differentiation in future studies.

The tumor microenvironment (TME) is a diverse milieu of cells including cancerous and non-cancerous cells such as fibroblasts, pericytes, endothelial cells and immune cells. The intricate cellular interactions within the TME hold a central role in shaping the dynamics of cancer progression, influencing pivotal aspects such as tumor initiation, growth, invasion, response to therapeutic interventions, and the emergence of drug resistance. In immunologically 'cold' tumors, the TME is marked by a scarcity of infiltrating immune cells, limited antigen presentation in the absence of potent immune-stimulating signals, and an abundance of immunosuppressive factors. While strategies targeting the TME as a therapeutic avenue in 'cold' tumors have emerged, there is a pressing need for novel approaches that faithfully replicate the complex cellular and non-cellular interactions in order to develop targeted therapies that can effectively stimulate immune responses and improve therapeutic outcomes in patients. Microfluidic devices offer distinct advantages over traditional in vitro 3D co-culture models and in vivo animal models, as they better recapitulate key characteristics of the TME and allow for precise, controlled insights into the dynamic interplay between various immune, stromal and cancerous cell types at any timepoint. This review aims to underscore the pivotal role of microfluidic systems in advancing our understanding of the TME and presents current microfluidic model systems that aim to dissect tumor-stromal, tumor-immune and immune-stromal cellular interactions in various 'cold' tumors. Understanding the intricacies of the TME in 'cold' tumors is crucial for devising effective targeted therapies to reinvigorate immune responses and overcome the challenges of current immunotherapy approaches.

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating avatars (herein defined as an extension of digital twins) of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.

Dental-derived stem cells (DSCs) are attractive cell sources due to their easy access, superior growth capacity and low immunogenicity. They can respond to multiple extracellular matrix signals, which provide biophysical and biochemical cues to regulate the fate of residing cells. However, the direct transplantation of DSCs suffers from poor proliferation and differentiation toward functional cells and low survival rates due to local inflammation. Recently, elegant advances in the design of novel biomaterials have been made to give promise to the use of biomimetic biomaterials to regulate various cell behaviors, including proliferation, differentiation and migration. Biomaterials could be tailored with multiple functionalities, e.g., stimuli-responsiveness. There is an emerging need to summarize recent advances in engineered biomaterials-mediated delivery and therapy of DSCs and their potential applications. Herein, we outlined the design of biomaterials for supporting DSCs and the host response to the transplantation.

BACKGROUND: Due to the very limited ability of articular cartilage to repair itself, articular cartilage defects caused by natural degeneration or trauma often cannot be repaired on their own, which triggers or aggravates osteoarthritis and even leads to severe disability. Therefore, the repair treatment after articular cartilage injury has become an urgent clinical problem. OBJECTIVE: To summarize the hot research topics and development trends in the field of articular cartilage repair using bibliometric analysis. METHODS: Literature related to articular cartilage repair was searched from the Web of Science Core Collection from 2000 to 2023, and bibliometric and visualization analyses were carried out using VOSviewer, Citespeace and Bibliometrix R-package. RESULTS AND CONCLUSION: The annual publication volume in the field of articular cartilage repair shows an overall increasing trend, with the United States, China, and Germany being the top three countries in terms of publication volume, and the research institutions focus on universities and hospitals, with Harvard University, New York Hospital for Special Surgery, and Shanghai Jiao Tong University being the top three institutions in terms of publication volume. AMERICAN JOURNAL OF SPORTS MEDICINE is the journal that publishes the most research literature in the field, and BIOMATERIALS is the journal with the highest number of citations in the field. “Injectable hydrogels for cartilage and bone tissue engineering” is the most cited document published in the last decade, and the author with the most publications is Madry Henning, an active author in the field. The active authors in this field have formed a number of stable research teams with each other, and the cooperation between different teams needs to be further strengthened. Intra-articular injections, high tibial osteotomies, hydrogels, drug delivery, inflammation, cartilage regeneration, and scaffolds are the current hot topics of research in this field, and the application of 3D printing technology, bio-inks, silk proteins, injectable hydrogels, and exosomes in articular cartilage repair may be the frontier of research in this field. Integrating various innovative technologies and methods for more effective, durable and functional cartilage tissue regeneration and repair, and facilitating the clinical translation of the relevant technologies and methods by conducting more high-quality clinical studies may be the future research trend in this field. [ABSTRACT FROM AUTHOR]

The escalating threat of bacterial infections to human health necessitates innovative antibacterial strategies and materials. Despite this need, there is still a significant demand for materials that combine high mechanical and thermal properties with biocompatibility. To address these urgent issues, our study investigates the development of poly(vinyl alcohol) (PVA) composite with graphene flakes (GF) as fillers. The aim is to strengthen the unique properties of graphene to enhance antibacterial activity. Graphene oxide (GO) was used as a surfactant to achieve stable graphene dispersion in water, preserving its inherent properties while avoiding the drawbacks associated with common surfactants, such as property reduction and complex removal processes. In this study, the mechanical and thermal properties of PVA composites containing GO and GF are superior to those of pristine PVA. Especially, the PVA‐2 composite exhibited a notable enhancement in both tensile strength and elongation at break compared with the PVA composite, with increases of 7.8% and 15% respectively. Moreover, PVA‐2, 4, and 6 composites exhibit significant antibacterial efficacy, achieving 4.8 and 4.9 log CFU/cm2 for Staphylococcus aureus and Escherichia coli, respectively. These results indicate that the enhanced oxidative stress induced by GO as a surfactant, combined with the physical damage caused by the increased GF nanostructures. This study highlights the potential of PVA/GF/GO composites in biomedical and tissue engineering applications, providing a promising pathway for the development of new antibacterial materials. [ABSTRACT FROM AUTHOR]

This study focuses on the relationship between porosity, surface roughness, microstructure, strength, and thermal properties, as well as their effect on the bioactivity and biodegradability of fabricated akermanite (AK; Ca 2 MgSi 2 O 7) bioceramic scaffolds. Firstly, we prepared the AK nanopowders using the mechanical activation method, mixed them with varying proportions of space-holder agent (NaCl), specifically 15, 20, 30, 40, and 50 vol%, and sintered them at 1200 °C to create porous scaffolds. We investigated the physical properties and microstructure using the Archimedes method and field emission scanning electron microscopy (FE-SEM), respectively. The mechanical properties in terms of microhardness, compressive strength, longitudinal modulus, Young's modulus, bulk modulus, and shear modulus were measured. The bioactivity and biodegradability of prepared scaffolds were assessed after soaking in simulated body fluid (SBF) for 10 days by FE-SEM and inductively coupled plasma-atomic emission spectroscopy (ICP-AES), respectively. The results revealed that porous scaffolds with suitable mechanical properties, bioactivity, and biodegradability were prepared. The porosity had a significant impact on the mechanical and biodegradability of the investigated scaffolds. It reduced mechanical properties slightly while improving bioactivity and biodegradability. The microstructure study displayed that all scaffolds formed apatite layer on their surfaces. This is because of good bioactivity and the suitable porosity level of AK. The obtained findings provide promising prospects for the future use of AK in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Bioactive ceramic bone scaffolds are limited by their brittleness. To address this limitation, we developed a new method for preparing β-tricalcium phosphate (β-TCP)/polycaprolactone (PCL) porous composite scaffolds with a gradient structure using digital light processing technology and an impregnation process. The composite scaffolds exhibited compressive strength comparable to that of pure β-TCP scaffolds but with substantially higher toughness and reliability, especially during in vitro degradation. Owing to the gradient structure, the composite scaffolds could gradually shift from high strength and stiffness to moderate strength and low stiffness, which is beneficial for bone healing and remodeling. In femoral condyle defects without mechanical stimulation, the β-TCP/PCL composite scaffolds exhibited slightly lower cellular compatibility and osteoinductive ability than those of the pure β-TCP scaffolds. However, in radial defects, composite scaffolds demonstrated a better mechanical response and bone growth capacity. The composite scaffolds maintained their structural integrity after 2–4 months, whereas the β-TCP scaffolds fractured within 2 months. This study provides a novel methodology for the development of effective scaffold fabrication strategies for load-bearing or large segmental defects with complex stress applications for use in bone healing and remodeling. [ABSTRACT FROM AUTHOR]

Bioelectronics is a hot research topic, yet an important tool, as it facilitates the creation of advanced medical devices that interact with biological systems to effectively diagnose, monitor and treat a broad spectrum of health conditions. Electrical stimulation (ES) is a pivotal technique in bioelectronics, offering a precise, non-pharmacological means to modulate and control biological processes across molecular, cellular, tissue, and organ levels. This method holds the potential to restore or enhance physiological functions compromised by diseases or injuries by integrating sophisticated electrical signals, device interfaces, and designs tailored to specific biological mechanisms. This review explains the mechanisms by which ES influences cellular behaviors, introduces the essential stimulation principles, discusses the performance requirements for optimal ES systems, and highlights the representative applications. From this review, we can realize the potential of ES based bioelectronics in therapy, regenerative medicine and rehabilitation engineering technologies, ranging from tissue engineering to neurological technologies, and the modulation of cardiovascular and cognitive functions. This review underscores the versatility of ES in various biomedical contexts and emphasizes the need to adapt to complex biological and clinical landscapes it addresses. [ABSTRACT FROM AUTHOR]

Significant advances have been made in materials for biomedical applications, including tissue engineering, bioimaging, cancer treatment, etc. In the past few decades, nanostructure-mediated therapeutic strategies have been developed to improve drug delivery, targeted therapy, and diagnosis, maximizing therapeutic effectiveness while reducing systemic toxicity and side effects by exploiting the complicated interactions between the materials and the cell and tissue microenvironments. This review briefly introduces the differences between the cells and tissues of tumour or normal cells. We summarize recent advances in tumour microenvironment-mediated therapeutic strategies using nanostructured materials. We then comprehensively discuss strategies for fabricating nanostructures with cancer cell-specific cytotoxicity by precisely controlling their composition, particle size, shape, structure, surface functionalization, and external energy stimulation. Finally, we present perspectives on the challenges and future opportunities of nanotechnology-based toxicity strategies in tumour therapy. [ABSTRACT FROM AUTHOR]

Electroactive scaffolds are increasingly used to mimic the microenvironment of electroactive tissues such as the heart and nerves. Multi-network hydrogels have emerged as an important platform in the field of tissue engineering. In this study, alginate (Alg)-based conductive and multi-network nanocomposite hydrogels were prepared and characterized as promising scaffolds for electroactive tissues. Alg, which is derived from natural sources, was modified with methacrylate (AlgMA) to render it photosensitive (photoactive). Multiwall carbon nanotubes (MWCNTs) were chosen as potential nanomaterials for electrical conductivity. MWCNTs were modified with –COOH groups to produce MWCNT–COOH nanomaterials. Nanocomposite hydrogels were fabricated by incorporating 0.5%, 1.0%, and 3.0 wt% of MWCNT–COOH into the AlgMA network. The hydrogel scaffolds were assessed for their chemical, physical, mechanical, electrical, and biological characteristics. This study demonstrated that incorporating modified MWCNTs into an AlgMA network enhances its electrical activity. According to our results, good rheological properties, natural tissue-like mechanical properties, optimal electrical conductivity, and biological performance make AlgMA/MWCNT–COOH multi-network nanocomposite hydrogels crucial in the field of electroactive tissues. [ABSTRACT FROM AUTHOR]

BACKGROUND: Compared with traditional two-dimensional culture, three-dimensional microtissue culture can show greater advantages. However, more favorable cultivation methods in three-dimensional culture still need to be further explored. OBJECTIVE: To evaluate the cell behavior of microtissue and its ability to promote cartilage formation under two three-dimensional culture methods. METHODS: Cartilage-derived microcarriers were prepared by chemical decellularization and tissue crushing. DNA quantification and nuclear staining were used to verify the success of decellularization, and histological staining was used to observe the matrix retention before and after decellularization. The microcarriers were characterized by scanning electron microscopy and CCK-8 assay. Cartilage-derived microtissues were constructed by combining cartilage-derived microcarriers with human adipose mesenchymal stem cells through three-dimensional static culture and three-dimensional dynamic culture methods. The cell viability and chondrogenic ability of the two groups of microtissues were detected by scanning electron microscopy, live and dead staining, and RT-qPCR. RESULTS AND CONCLUSION: (1) Cartilage-derived microcarriers were successfully prepared. Compared with before decellularization, the DNA content significantly decreased after decellularization (P < 0.001). Scanning electron microscope observation showed that the surface of the microcarrier was surrounded by collagen, maintaining the characteristics of the natural extracellular matrix of cartilage cells. CCK-8 assay indicated that microcarriers had no cytotoxicity and could promote cell proliferation. (2) Scanning electron microscopy and live and dead staining results showed that compared with the threedimensional static group, the three-dimensional dynamic group had a more extended morphology of microtissue cells, and extensive connections between cells and cells, between cells and matrix, and between matrix. (3) The results of RT-qPCR showed that the expressions of SOX9, proteoglycan, and type II collagen in microtissues of both groups were increased at 7 or 14 days. The relative expression levels of each gene in the three-dimensional dynamic group were significantly higher than those in the three-dimensional static group at 14 days (P < 0.05). At 21 days, the three-dimensional static group had significantly higher gene expression compared with the three-diomensional dynamic group (P < 0.001). (4) The results showed that compared with three-dimensional static culture microtissue, three-dimensional dynamic culture microtissue could achieve higher expression of chondrogen-related genes in a shorter time, showing better cell viability and chondrogenic ability. [ABSTRACT FROM AUTHOR]

One of the challenges and limitations of bone tissue engineering includes fast degradation rates, reduced bioactivity, donor site morbidity, and unresolved risks of pathogen transmission. In the field of bone tissue engineering, gradient materials are promising for treating bone defects because they can create graded structures and compositions similar to natural bone. By controlling the amount of components in the structure, the degradation rate, bioactivity, and osteogenic capacity can be manipulated. In the current study, a gradient, multilayer, porous nanocomposite of calcium sulfate/glass (Gn CS/BG) with a gelatin coating (Gn CS/BG-Gel) was prepared using rotational casting technique. The SEM results showed an average pore size of approximately 400 μm within the Gn CS/BG-Gel nanocomposite. An elastic modulus (E) of around 240 MPa and an ultimate tensile strength (σ) of approximately 5.5 MPa were achieved for Gn CS/BG-Gel nanocomposite. The degradation analysis in a dynamic tris-buffer environment revealed a degradation rate of 68 % over a 63-day period, with a decrease in degradation rate as the bioactive glass (BG) content increased in each layer, indicating the influence of BG on the degradation process. The bioactivity results in a dynamic simulated body fluid suggested that increased BG content in each layer promoted hydroxyapatite formation, indicating improved bioactive behavior. The evaluation of ion release with ICP-OES, MTT and Acridine Orange assays using human bone marrow-derived mesenchymal stem cells (hBMSCs) confirmed the non-toxic nature of Gn CS/BG-Gel. Assessments of alkaline phosphatase (ALP) activity, calcium content, Alizarin Red staining and cell attachment behavior substantiated the osteogenic potential of Gn CS/BG-Gel. Collectively, the three-dimensional structure along with the Gn CS/BG-Gel composition contributed to the enhanced cellular responses. These findings hold significant promise for the development of biomaterials with potential applications in bone tissue engineering, and they contribute valuable insights to the field. [Display omitted] [ABSTRACT FROM AUTHOR]

Bioactive glass ceramics (BGC) play a pivotal role in bone tissue engineering, specifically addressing challenges associated with bone repair and regeneration. In this study, we developed silica-based 55S0P and 45S10P spherical BGC nanoparticles (NPs), without and with P 2 O 5 content, using a modified Stöber sol-gel process with base hydrolysis. The fabricated spherical NPs with pronounced textural features effectively contribute to enhanced surface roughness, a desirable parameter for improved biological activity in physiologically relevant solutions and tissue matrices. A comprehensive evaluation of the structural properties of these novel spherical BGC-NPs using diverse characterization techniques revealed distinct nano-textural features in the form of cracks and pores. The HR-TEM confirmed the nanoscale dimensions (170–190 nm) of particles with spherical surface morphology and also systematically analysed via DLS, FE-SEM studies. An augmented surface area with mesopores when phosphate added to the silica glass network was revealed by BET analysis. On the biological front, the study records the formation of an HCA layer on the surfaces of the BGC-NPs, the thickness of which increased with an increase in both phosphate content and immersion time (0, 3, 14 & 28 days) in the SBF solution. The zeta potential values attain a maximum from −22 mV to −23.6 mV for 55S0P and −21.5 mV to −26.4 mV for 45S10P BGC-NPs, and improved with increased immersion time, thereby favouring cellular adhesion for desired biological responses. In vitro, cell culture studies on MG-63 cells, after 24 and 72 h of incubation, demonstrated higher cell adhesion and proliferation, with pronounced biocompatibility. In addition, these BGC-NPs exhibited good hemocompatibility even at the highest test concentration (15 mg/ml) and demonstrated effective antibacterial activity against K. pneumoniae and E. coli. A combinatorial analysis of structural and biological properties revealed that the 45S10P BGC-NPs are more potent than 55S0P BGC-NPs for desired biological performances. In conclusion, the results suggest that the sol-gel fabricated BGC-NPs with enhanced nano-textural features are evidently suitable for applications in bone tissue engineering and regenerative medicine. [Display omitted] • Design and development of BGC-NPs (55S0P and 45S10P) via modified Stöber's method. • Confirmation of enhanced textural features by BET, FE-SEM and HR-TEM analyses. • Obtained high negative Zeta values supporting improved surface reactivity for bio-compatible applications. • Identification of HCA layer by Optical Absorption (OA), supported by XRD, FTIR & FE-SEM. • Enhanced cell viability, hemocompatibility and antibacterial activity with P 2 O 5 content for bone regenerative applications. [ABSTRACT FROM AUTHOR]

Introduction: The advances of self‐crossing hyaluronic acid (SC‐HA) fillers combination use with polydioxanone thread in minipigs were examined for compatibility, effectiveness, and immune response. Materials and Methods: A 12‐week experiment was conducted using 6 minipigs (3 male and 3 female each) to evaluate the effects of SC‐HA filler. The molecular weight of SC‐HA filler was fixed at 200 kDa and alternative storage modulus of G80, G250, and G500 were examined. The procedure involved injecting SC‐HA filler and polydioxanone threads into the skin tissue of anesthetized minipigs, and tissue sampling after 1 month (three minipigs), and 3 months (three minipigs) for histological staining and analysis. The immune reaction was observed during the experiment. Results: The practitioner reported it was easy to inject the SC‐HA filler in combination with polydioxanone threads. All four storage modulus of SC‐HA fillers were injectable within the polydioxanone thread containing cannula. Also, during the procedure, there were no immune responses at the treated sites. The results of the histological tissue examination confirmed that there was no chemical interaction between SC‐HA filler and the existing polydioxanone thread, and it was observed that SC‐HA filler was more uniformly distributed within the tissue with lower storage modulus, resulting in a higher production of collagen in the surrounding filler. When combined with scaffold polydioxanone thread, the scaffold polydioxanone thread helped spread the filler evenly, resulting in a more evenly distributed collagen around the filler. Conclusion: Today, the combination therapy of filler and polydioxanone thread in one procedure is challenging due to the high viscosity of conventional fillers. However, this study confirmed that combination therapy of filler and polydioxanone thread is possible with SC‐HA fillers. Additionally, it was found that polydioxanone thread does not seem to interfere with the crosslinking reaction of SC‐HA filler, and if used with a higher pH of polydioxanone, it may enhance the cross‐linking reaction and achieve a higher viscosity value. Finally, the study resulted in the idea of concrete as SC‐HA filler and reinforcing rod for polydioxanone thread. [ABSTRACT FROM AUTHOR]

Proarrhythmic cardiotoxicity remains a substantial barrier to drug development as well as a major global health challenge. In vitro human pluripotent stem cell-based new approach methodologies have been increasingly proposed and employed as alternatives to existing in vitro and in vivo models that do not accurately recapitulate human cardiac electrophysiology or cardiotoxicity risk. In this study, we expanded the capacity of our previously established 3D human cardiac microtissue model to perform quantitative risk assessment by combining it with a physiologically based pharmacokinetic model, allowing a direct comparison of potentially harmful concentrations predicted in vitro to in vivo therapeutic levels. This approach enabled the measurement of concentration responses and margins of exposure for 2 physiologically relevant metrics of proarrhythmic risk (i.e. action potential duration and triangulation assessed by optical mapping) across concentrations spanning 3 orders of magnitude. The combination of both metrics enabled accurate proarrhythmic risk assessment of 4 compounds with a range of known proarrhythmic risk profiles (i.e. quinidine, cisapride, ranolazine, and verapamil) and demonstrated close agreement with their known clinical effects. Action potential triangulation was found to be a more sensitive metric for predicting proarrhythmic risk associated with the primary mechanism of concern for pharmaceutical-induced fatal ventricular arrhythmias, delayed cardiac repolarization due to inhibition of the rapid delayed rectifier potassium channel, or hERG channel. This study advances human-induced pluripotent stem cell-based 3D cardiac tissue models as new approach methodologies that enable in vitro proarrhythmic risk assessment with high precision of quantitative metrics for understanding clinically relevant cardiotoxicity. [ABSTRACT FROM AUTHOR]

Arachis pintoi, commonly known as pinto or forage peanut, is used mainly in consortia with grass pastures and as cover plant. In addition to increasing the productivity of livestock and plantations, it contributes to the mitigation of environmental impacts (reduction of greenhouse gas emissions) and soil improvement (nitrogen fixation, reduction of fertilizers use), as well as to pests and disease management. Several cultivars that are tolerant to specific climates and soil conditions are suitable to be used as ground covers in agroforestry and silvopastoral systems, orchards, and plantations. Biotechnological and phytochemical investigations revealed the potential of pinto peanut as a sustainable source of resveratrol and other stilbenoids. Extracts from plants grown under natural conditions and from materials obtained in vitro displayed allelopathic, anthelmintic, or antioxidant activities. Other studies revealed the potential of pinto peanut for erosion control, phytoremediation, seed and essential oils production, materials for animal tissue engineering, synthesis of nanoparticles for drug delivery, and as green biorefineries to produce proteins, biochemicals, and biomaterials. [ABSTRACT FROM AUTHOR]

One of the goals of tissue engineering and regenerative medicine is restoring primary living tissue function by manufacturing a 3D microenvironment. One of the main challenges is protecting implanted non-autologous cells or tissues from the host immune system. Cell encapsulation has emerged as a promising technique for this purpose. It involves entrapping cells in biocompatible and semi-permeable microcarriers made from natural or synthetic polymers that regulate the release of cellular secretions. In recent years, droplet-based microfluidic systems have emerged as powerful tools for cell encapsulation in tissue engineering and regenerative medicine. These systems offer precise control over droplet size, composition, and functionality, allowing for creating of microenvironments that closely mimic native tissue. Droplet-based microfluidic systems have extensive applications in biotechnology, medical diagnosis, and drug discovery. This review summarises the recent developments in droplet-based microfluidic systems and cell encapsulation techniques, as well as their applications, advantages, and challenges in biology and medicine. The integration of these technologies has the potential to revolutionise tissue engineering and regenerative medicine by providing a precise and controlled microenvironment for cell growth and differentiation. By overcoming the immune system's challenges and enabling the release of cellular secretions, these technologies hold great promise for the future of regenerative medicine. [ABSTRACT FROM AUTHOR]

In this work, we studied the preparation of graphene dispersions by liquid-phase ultrasound exfoliation in aqueous solutions, using amphiphilic stabilizers, such as Pluronic F108 (Plu) and polyvinylpyrrolidone (PVP), as well as in N-MP. The resulting dispersions were characterized by TEM, dynamic light scattering, UV spectroscopy. Optimal conditions for ultrasonic treatment of few-layer graphene dispersions were established, which make it possible to obtain stable concentrated graphene dispersions (1–4 layers) with lateral dimensions of 50–2000 nm. Based on the developed graphene dispersions, composite films with various polymer matrices (polylactide, collagen, chitosan), using graphene as nano-filler, were obtained. The presence of the latter provided electrical conductivity up to 0.9 S cm−1, a change in electrical resistance during deformation with a strain sensitivity coefficient of 1.3–5.7, as well as an increase in breaking stress up to 97.1 ± 1.6 MPa and in elastic modulus up to 3.99 GPa. The designed films possess a wide variety of properties and are promising for use as flexible biosensors for biomechanical studies and electrically conductive matrices for tissue engineering. [ABSTRACT FROM AUTHOR]

Objective(s): The material used for bone tissue repair needs to be simultaneously osteoconductive, osteoinductive, and osteogenic. To overcome this problem, researchers combine hydroxyapatite (HA) with natural materials to improve properties. This paper compares the effects of angiogenesis and osteogenesis with different composites through in vivo experiments and characterization analysis. Materials and Methods: Chitosan/nHA (CS/nHA) and sodium alginate/nHA (SA/nHA) microspheres were synthesized via reverse-phase emulsification crosslinking and analyzed using scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), and X-ray diffraction (XRD). Implanted into mouse thigh muscles, their angiogenic and osteogenic potentials were assessed after 8 and 12 weeks through various staining methods and immunohistochemistry. Results: The mean vascular density (MVD) of CS/nHA, CaP/nHA, and SA/nHA groups was (134.92±35.30) n/mm², (159.09±22.14) n/mm², (160.31±42.23) n/mm² at 12 weeks, respectively. The MVD of the CaP/nHA and SA/nHA groups were significantly higher than that of the CS/nHA group. The collagen volume fractions (CVF) were 34.13%, 51.53%, and 54.96% in the CS/nHA, CaP/nHA, and SA/ nHA groups, respectively. In addition, the positive expression area ratios of OPN and CD31 in the CaP/ nHA and SA/nHA groups were also significantly higher than those in the CS/nHA group. Conclusion: The ability of SA/nHA composite microspheres in osteogenesis and angiogenesis is clearly superior to that of the CS/nHA group and is comparable to that of CaP/nHA, which has superior osteogenesis ability, indicating that SA/nHA composite microspheres have greater application prospects in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Doping Sr has the potential to enhance bioceramic properties. However, controlling purity, Sr concentration, and properties is crucial. Therefore, precise evaluation of synthesis variables is essential, achieved through experimental design techniques. This study synthesized Sr-doped calcium silicate wollastonite using a Plackett–Burman design with 11 variables to identify key factors affecting synthesis yield and physical, structural, and chemical attributes for tissue engineering. Results indicate that the strontium proportion significantly impacts material properties, affecting porosity, surface area, and pore volume. Moreover, observations reveal that calcination temperature contributes to heightened crystallinity and strontium doping. Adjusting calcium and strontium precursor concentrations while reducing the silicon to calcium and strontium ratio improves efficiency crystallinity, purity, and promotes the formation of the preferred β-CaSiO 3 phase. Overall, consistent and reproducible findings provide valuable insights into the variables influencing the process and facilitate optimization for future ceramic synthesis. [Display omitted] [ABSTRACT FROM AUTHOR]

Nerve repair and regeneration are still challenging issues in the world, mainly due to the complex anatomic structure and limited regeneration ability of natural nerves. Tissue engineering provides a structure and function similar to nerve tissue through scaffold materials, seed cells, and active factors, which is a promising method to treat nerve injury. Gelatin methacrylate (GelMA) hydrogel is a kind of gelatin modified by methacrylamide, which possesses adjustable mechanical properties, convenient processability, and excellent biocompatibility, has been widely used in nerve tissue engineering. In this paper, the research progress of GelMA-based hydrogel in nerve repair and regeneration in recent five years is reviewed, with emphasis on the advanced manufacturing technologies of three-dimensional (3D) GelMA scaffold and the application systems that can effectively promote nerve repair and regeneration. We also evaluated the challenges and prospects of GelMA-based hydrogels in the field of nerve repair and regeneration, which is of guiding significance to the research of nerve tissue engineering. [ABSTRACT FROM AUTHOR]

Despite the great progress in developing wound dressings, delayed wound closure still remains a global challenge. Thus, developing novel wound dressings and employing advanced strategies, including tissue engineering, are urgently desired. The carboxylated cellulose was developed through the in situ synthesis method and further reinforced by incorporating pal-KTTKS to stimulate collagen synthesis and improve wound healing. The developed composites supported cell adhesion and proliferation and showed good biocompatibility. To boost wound-healing performance, adipose-derived mesenchymal stem cells (MSC) were seeded on the pal-KTTKS-enriched composites to be implanted in a rat model of burn wound healing. Healthy male rats were randomly divided into four groups and wound-healing performance of Vaseline gauze (control), carboxylated cellulose (CBC), pal-KTTKS-enriched CBC (KTTKS-CBC), and MSCs seeded on the KTTKS-CBC composites (MSC-KTTKS-CBC) were evaluated on days 3, 7, and 14 post-implantation. In each group, the designed therapeutic dressings were renewed every 5 days to increase wound-healing performance. We found that KTTKS-CBC and MSC-KTTKS-CBC composites exhibited significantly better wound healing capability, as evidenced by significantly alleviated inflammation, increased collagen deposition, improved angiogenesis, and considerably accelerated wound closure. Nevertheless, the best wound-healing performance was observed in the MSC-KTTKS-CBC groups among all four groups. This research suggests that the MSC-KTTKS-CBC composite offers a great deal of promise as a wound dressing to enhance wound regeneration and expedite wound closure in the clinic. [ABSTRACT FROM AUTHOR]

Severe injuries to skeletal muscles, including cases of volumetric muscle loss (VML), are linked to substantial tissue damage, resulting in functional impairment and lasting disability. While skeletal muscle can regenerate following minor damage, extensive tissue loss in VML disrupts the natural regenerative capacity of the affected muscle tissue. Existing clinical approaches for VML, such as soft-tissue reconstruction and advanced bracing methods, need to be revised to restore tissue function and are associated with limitations in tissue availability and donor-site complications. Advancements in tissue engineering (TE), particularly in scaffold design and the delivery of cells and growth factors, show promising potential for regenerating damaged skeletal muscle tissue and restoring function. This article provides a brief overview of the pathophysiology of VML and critiques the shortcomings of current treatments. The subsequent section focuses on the criteria for designing TE scaffolds, offering insights into various natural and synthetic biomaterials and cell types for effectively regenerating skeletal muscle. We also review multiple TE strategies involving both acellular and cellular scaffolds to encourage the development and maturation of muscle tissue and facilitate integration, vascularization, and innervation. Finally, the article explores technical challenges hindering successful translation into clinical applications. [ABSTRACT FROM AUTHOR]

Objectives : This study aimed to analyze the efficacy of stem cell-based tissue engineering for the treatment of alveolar cleft (AC) and cleft palate (CP) defects in animal models. Design : Systematic review and meta-analysis. Setting : Preclinical studies on alveolar cleft repair in maxillofacial practice. Patients, Participants : Electronic search was performed using PubMed, Embase, and Cochrane databases. Pre-clinical studies, where stem cell-based tissue engineering was used in the reconstruction of AC and CP in animal models were included. Quality of the selected articles was evaluated using SYRCLE (SYstematic Review Centre for Laboratory animal Experimentation). Interventions : Review of alveolar cleft bone augmentation interventions in preclinical models. Main Outcome Measures : Outcome parameters registered were new bone formation (NBF) and/or bone mineral density (BMD). Results : Thirteen large and twelve small animal studies on AC (21) and CP (4) reconstructions were included. Studies had an unclear-to-high risk of bias. Bone marrow mesenchymal stem cells were the most widely used cell source. Meta-analyses for AC indicated non-significant benefits in favor of: (1) scaffold + cells over scaffold-only (NBF P =.13); and (2) scaffold + cells over empty control (NBF P =.66; BMD P =.31). Interestingly, dog studies using regenerative grafts showed similar to superior bone formation compared to autografts. Meta analysis for the CP group was not possible. Conclusions : AC and CP reconstructions are enhanced by addition of osteogenic cells to biomaterials. Directions and estimates of treatment effect are useful to predict therapeutic efficacy and guide future clinical trials of bone tissue engineering. [ABSTRACT FROM AUTHOR]

Additive manufacturing methods give the opportunity to produce interesting, new structures with a more complicated topology than would be possible using traditional methods. Using the selective laser sintering method, a disk with a high roughness and porous structure was produced. Studies of material surface were performed on microscopic devices. An in vitro experiment was performed on the manufactured disk using mice fibroblastic cells. The designed shape enabled the growth of the cell culture in the disc pores and ensured impermeability of the disc base. On the basis of the average viability of 79%, which is close to reference well (80%), preliminary results confirmed that the manufactured structures create sufficiently comfortable conditions for the cell cultures without the need to design their internal topography. Controlling the production parameters of SLS printing allows obtaining the structures characterized by spatial and surface porosity without designing inner geometry of the structure. Polyamide 2200 (PA2200) powder with a laser beam, offers new possibilities for producing surfaces used in the tissue engineering, bioreactors, and microfluidics devices. [ABSTRACT FROM AUTHOR]

The thermo-responsive materials are those temperature-sensitive materials that can change their properties when temperatures change. The thermo-responsive materials are categorised under the temperature stimulus-controlled materials of polymers, metals, oxides, alloys, ceramics, and composites. The three-dimensional (3D) printing process (also called an additive manufacturing (AM) process) is in which thermo-responsive materials are employed to form structures in required applications. The 3D printing of thermo-responsive materials is also known as four-dimensional (4D) printing since the application of the temperature leads to a change in the physical properties of the prepared components. In the recent past, many studies have been reported on the use of thermo-responsive materials in tissue engineering, drug delivery, bio-manufacturing, and bio-separation operations. The present study highlights the key applications of thermo-responsive materials by the 3D printing process. [ABSTRACT FROM AUTHOR]

Subcutaneous delivery of cell therapy is an appealing minimally-invasive strategy for the treatment of various diseases. However, the subdermal site is poorly vascularized making it inadequate for supporting engraftment, viability, and function of exogenous cells. In this study, we developed a 3D bioprinted scaffold composed of alginate/gelatin (Alg/Gel) embedded with mesenchymal stem cells (MSCs) to enhance vascularization and tissue ingrowth in a subcutaneous microenvironment. We identified bio-ink crosslinking conditions that optimally recapitulated the mechanical properties of subcutaneous tissue. We achieved controlled degradation of the Alg/Gel scaffold synchronous with host tissue ingrowth and remodeling. Further, in a rat model, the Alg/Gel scaffold was superior to MSC-embedded Pluronic hydrogel in supporting tissue development and vascularization of a subcutaneous site. While the scaffold alone promoted vascular tissue formation, the inclusion of MSCs in the bio-ink further enhanced angiogenesis. Our findings highlight the use of simple cell-laden degradable bioprinted structures to generate a supportive microenvironment for cell delivery. [ABSTRACT FROM AUTHOR]

Hydrogels are useful drug release systems and tissue engineering scaffolds. However, synthetic hydrogels often require harsh gelation conditions and can contain toxic by‐products while naturally derived hydrogels can transmit pathogens and in general have poor mechanical properties. Thus, there is a need for a hydrogel that forms under ambient conditions, is non‐toxic, xeno‐free, and has good mechanical properties. A recombinant spider silk protein‐derived hydrogel that rapidly forms at 37 °C is recently developed. The temperature and gelation times are well‐suited for an injectable in situ polymerising hydrogel, as well as a 3D cell culture scaffold. Here, it is shown that the diffusion rate and the mechanical properties can be tuned by changing the protein concentration and that human fetal mesenchymal stem cells encapsulated in the hydrogels show high survival and viability. Furthermore, mixtures of recombinant spider silk proteins and green fluorescent protein (GFP) form gels from which functional GFP is gradually released, indicating that bioactive molecules are easily included in the gels, maintain activity and can diffuse through the gel. Interestingly, encapsulated ARPE‐19 cells are viable and continuously produce the growth factor progranulin, which is detected in the cell culture medium over the study period of 31 days. [ABSTRACT FROM AUTHOR]

Tissue engineering has demonstrated its efficacy in promoting tissue regeneration, and extensive research has explored its application in rotator cuff (RC) tears. However, there remains a paucity of research translating from bench to clinic. A key challenge in RC repair is the healing of tendon–bone interface (TBI), for which bioactive materials suitable for interface repair are still lacking. The umbilical cord (UC), which serves as a vital repository of bioactive components in nature, is emerging as an important source of tissue engineering materials. A minimally manipulated approach is used to fabricate UC scaffolds that retain a wealth of bioactive components and cytokines. The scaffold demonstrates the ability to modulate the TBI healing microenvironment by facilitating cell proliferation, migration, suppressing inflammation, and inducing chondrogenic differentiation. This foundation sets the stage for in vivo validation and clinical translation. Following implantation of UC scaffolds in the canine model, comprehensive assessments, including MRI and histological analysis confirm their efficacy in inducing TBI reconstruction. Encouraging short‐term clinical results further suggest the ability of UC scaffolds to effectively enhance RC repair. This investigation explores the mechanisms underlying the promotion of TBI repair by UC scaffolds, providing key insights for clinical application and translational research. [ABSTRACT FROM AUTHOR]

Dysferlin is a multi‐functional protein that regulates membrane resealing, calcium homeostasis, and lipid metabolism in skeletal muscle. Genetic loss of dysferlin results in limb girdle muscular dystrophy 2B/2R (LGMD2B/2R) and other dysferlinopathies – rare untreatable muscle diseases that lead to permanent loss of ambulation in humans. The mild disease severity in dysferlin‐deficient mice and diverse genotype‐phenotype relationships in LGMD2B patients have prompted the development of new in vitro models for personalized studies of dysferlinopathy. Here the first 3‐D tissue‐engineered hiPSC‐derived skeletal muscle ("myobundle") model of LGMD2B is described that exhibits compromised contractile function, calcium‐handling, and membrane repair, and transcriptomic changes indicative of impaired oxidative metabolism and mitochondrial dysfunction. In response to the fatty acid (FA) challenge, LGMD2B myobundles display mitochondrial deficits and intracellular lipid droplet (LD) accumulation. Treatment with the ryanodine receptor (RyR) inhibitor dantrolene or the dissociative glucocorticoid vamorolone restores LGMD2B contractility, improves membrane repair, and reduces LD accumulation. Lastly, it is demonstrated that chemically induced chronic RyR leak in healthy myobundles phenocopies LGMD2B contractile and metabolic deficit, but not the loss of membrane repair capacity. Together, these results implicate intramyocellular Ca2+ leak as a critical driver of dysferlinopathic phenotype and validate the myobundle system as a platform to study LGMD2B pathogenesis. [ABSTRACT FROM AUTHOR]

Although epithelial folding is commonly studied using in vivo animal models, such models exhibit critical limitations in terms of real-time observation and independent control of experimental parameters. Here, we develop a tissue-scale in vitro epithelial bilayer folding model that incorporates an epithelium and extracellular matrix (ECM) hydrogel, thereby emulating various folding structures found in in vivo epithelial tissue. Beyond mere folding, our in vitro model realizes a hierarchical transition in the epithelial bilayer, shifting from periodic wrinkles to a single deep fold under compression. Experimental and theoretical investigations of the in vitro model imply that both the strain-stiffening of epithelium and the poroelasticity of ECM influence the folded structures of epithelial tissue. The proposed in vitro model will aid in investigating the underlying mechanism of tissue-scale in vivo epithelial folding relevant to developmental biology and tissue engineering. The study of epithelial folding is often hampered by limited real-time observation and limited control of experimental parameters. Here, the authors develop a tissue-scale in vitro epithelial folding model that incorporates an epithelium and extracellular matrix hydrogel, thus emulating folding behaviors found in in vivo contexts. [ABSTRACT FROM AUTHOR]

Beta-tricalcium phosphate (β-TCP) scaffolds manufactured through the foam replication method are widely employed in bone tissue regeneration. The mechanical strength of these scaffolds is a significant challenge, partly due to the rheological properties of the original suspension. Various strategies have been explored to enhance the mechanical properties. In this research, β-TCP scaffolds containing varying concentrations (0.25–1.00 wt%) of multi-walled carbon nanotubes (MWCNT) were developed. The findings indicate that the addition of MWCNTs led to a concentration-dependent improvement in the viscosity of β-TCP suspensions. All the prepared slurries exhibited viscoelastic behavior, with the storage modulus surpassing the loss modulus. The three time interval tests revealed that MWCNT-incorporated β-TCP suspensions exhibited faster structural recovery compared to pure β-TCP slurries. Introducing MWCNT modified compressive strength, and the optimal improvement was obtained using 0.75 wt% MWCNT. The in vitro degradation of β-TCP was also reduced by incorporating MWCNT. While the inclusion of carbon nanotubes had a marginal negative impact on the viability and attachment of MC3T3-E1 cells, the number of viable cells remained above 70% of the control group. Additionally, the results demonstrated that the scaffold increased the expression level of osteocalcin, osteoponthin, and alkaline phosphatase genes of adiposed-derived stem cells; however, higher levels of gene expersion were obtained by using MWCNT. The suitability of MWCNT-modified β-TCP suspensions for the foam replication method can be assessed by evaluating their rheological behavior, aiding in determining the critical additive concentration necessary for a successful coating process. [ABSTRACT FROM AUTHOR]

Recent advancements in tissue engineering have witnessed luffa-derived scaffolds, exhibiting their exceptional potential in cellular proliferation, biocompatibility, appropriate interconnectivity, and biomechanical strength. In vivo studies involved implanting fabricated scaffolds subcutaneously in Wistar rats to evaluate their impact on the heart, liver, and kidneys. This approach provided a safe and minimally invasive means to evaluate scaffold compatibility with surrounding tissues. Male Wistar rats were categorized into four distinct groups, Group A, B, C, and D are referred to as 3% LC implanted scaffolds, 5% LC implanted scaffolds, control (without luffa scaffolds), and Sham (without any scaffold implantation), respectively. Histological analysis in all the groups indicated that the animal models did not exhibit any signs of inflammation or toxicity, suggesting favorable tissue response to the implanted scaffolds. Initial observations revealed elevated levels of enzymes and biomarkers in the experimental groups after a 24 h interval, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, creatine kinase-MB (CK-MB), and serum creatinine. However, these parameters normalized 3 weeks post-implantation, with no significant increase compared to the control groups, suggesting that the implanted luffa-based scaffolds did not induce adverse effects on the heart, liver, and kidneys. Furthermore, the scaffold's significant pore size and porosity enable it to release drugs, including antibacterial medications. This study demonstrates promising results, indicating excellent scaffold porosity, sustained drug release, affirming the in vivo biocompatibility, absence of inflammatory responses, and overall tissue compatibility highlighting the immense potential of these luffa-based scaffolds in various tissue engineering and regenerative medicine applications. [ABSTRACT FROM AUTHOR]

The immune microenvironment is critical for the occurrence, progression, and treatment of diseases. Ultrasound tissue engineering technology utilizes ultrasound and the principles of tissue engineering to repair, regenerate, and functionally reconstruct biological tissues. Ultrasound therapy is a non‐invasive treatment modality that regulates the immune microenvironment and maintains homeostasis through various characteristic effects. Ultrasound‐responsive biomaterials utilize biological properties or drug/gene delivery to regulate the immune microenvironment under ultrasound stimulation for targeted and purposeful treatment. This article comprehensively and systematically reviews advancements in ultrasound tissue engineering technology for regulating the immune microenvironment. First, the changes in the immune microenvironment at different stages of the disease is briefly illustrated. It is then reviewed the regulation of the immune microenvironment by ultrasound and ultrasound‐responsive biomaterials in five types of diseases: tumor, cardiovascular system diseases, nervous system diseases, musculoskeletal diseases, and wound. Finally, the prospects of the ultrasound tissue engineering technology for regulating the immune microenvironment is summarized. [ABSTRACT FROM AUTHOR]

Piezocatalysts, because of their mechano‐electrical conversion properties, are exploited for various medical applications, such as sterilization, tissue engineering, biosensing, and disease theranostics. In particular, based on the unique advantage of the piezoelectric effect, piezocatalytic therapy (PCT) has been developed as a novel and promising candidate for tumor therapy. To optimize the utilization of piezocatalysts in tumor therapy, a comprehensive understanding of the antitumor mechanism associated with these materials is imperative. Here, the piezocatalytic action principle is elucidated by investigating piezocatalysts, reactants, energy inputs, and products. Subsequently, the antitumor mechanisms of PCT have been extensively discussed and are recapitulative as follows: restraining cell proliferation, inducing cell programmed death, hindering tumor metastasis, inhibiting tumor angiogenesis, and enhancing antitumor immunity. Additionally, the optimized therapeutic outcomes of PCT‐centric synergistic cancer therapy are systematically described. Finally, the main challenges and future research directions of piezocatalysis applied in cancer therapy are envisioned. It is believed that PCT will serve as a new‐generation ingenious tool for cancer treatment. [ABSTRACT FROM AUTHOR]

Electrospun nanofibers have gained prominence as a versatile material, with applications spanning tissue engineering, drug delivery, energy storage, filtration, sensors, and textiles. Their unique properties, including high surface area, permeability, tunable porosity, low basic weight, and mechanical flexibility, alongside adjustable fiber diameter distribution and modifiable wettability, make them highly desirable across diverse fields. However, optimizing the properties of electrospun nanofibers to meet specific requirements has proven to be a challenging endeavor. The electrospinning process is inherently complex and influenced by numerous variables, including applied voltage, polymer concentration, solution concentration, solution flow rate, molecular weight of the polymer, and needle-to-collector distance. This complexity often results in variations in the properties of electrospun nanofibers, making it difficult to achieve the desired characteristics consistently. Traditional trial-and-error approaches to parameter optimization have been time-consuming and costly, and they lack the precision necessary to address these challenges effectively. In recent years, the convergence of materials science and machine learning (ML) has offered a transformative approach to electrospinning. By harnessing the power of ML algorithms, scientists and researchers can navigate the intricate parameter space of electrospinning more efficiently, bypassing the need for extensive trial-and-error experimentation. This transformative approach holds the potential to significantly reduce the time and resources invested in producing electrospun nanofibers with specific properties for a wide range of applications. Herein, we provide an in-depth analysis of current work that leverages ML to obtain the target properties of electrospun nanofibers. By examining current work, we explore the intersection of electrospinning and ML, shedding light on advancements, challenges, and future directions. This comprehensive analysis not only highlights the potential of ML in optimizing electrospinning processes but also provides valuable insights into the evolving landscape, paving the way for innovative and precisely engineered electrospun nanofibers to meet the target properties for various applications. [ABSTRACT FROM AUTHOR]

Bioprinting approaches are of great promise for tissue engineering applications as they allow the fabrication of constructs able to mimic native tissues' mechanical and topographical features. Additional control over cells fate can be enhanced using stimuli-responsive materials, requiring the development of novel bioinks for this purpose. In this study, bioinks comprising κ-carrageenan, collagen, and magnetic nanoparticles were designed for 3D bioprinting applications. The characterization of this material was performed, where mechanical compressive tests yielded Young's moduli ranging from 8.25 to 18.4 kPa. Rheological assessments also revealed the shear-thinning behavior of the bioinks and a temperature-dependent gelation. The capability of these bioinks to produce 3D constructs by extrusion bioprinting was established through the printability evaluation and the development of complex structures, supporting the viability and proliferation of mesenchymal stromal cells (MSCs). Finally, as proof-of-concept, it was observed that the secretome of bioprinted MSCs stimulated with an external magnetic field of 80 mT was able to increase the number of tubes formed by human umbilical vein endothelial cells. [ABSTRACT FROM AUTHOR]

Soft tissue engineering has focused on green, solvent-free biopolymers with rubber-like characteristics. One of the well-known elastomeric polyesters is polyglycerol sebacate (PGS). The present investigation involves the synthesis of a novel biopolymer composed of PGS-co-poly(ε-caprolactone) (PCL) copolymer, alongside hydroxyapatite (HA) using bovine bone. These synthesized materials were utilized to build scaffolds using 18–22 kV electrospinning. By in situ polymerization, PGS-co-PCL/HA nanocomposites with 5% and 10% hydroxyapatite nanoparticles were developed. Various analysis such as FTIR, TGA, SEM, and DSC were utilized to examine the prepared samples. Introducing 10% HA to the PGS-co-PCL copolymer blends boosted nanocomposite mechanical strength by 300%. Meanwhile, PGS-co-PCL-based samples and their nanocomposites demonstrated promising biocompatibility and antibacterial characteristics. Biodegradability experiments revealed that at pH 7, PGS-co-PCL-HA10% was degraded by 45% within 30 days, whereas at pH 11, degradation accelerated to 65%. This study's findings provide a novel approach for soft tissue engineers to construct effective scaffolds with great biocompatibility and enhanced mechanical properties by combining PGS with co-PCL and adding HA nanoparticles. [ABSTRACT FROM AUTHOR]