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Collagen is the most abundant protein found in humans and is fundamental to tissue structure and function. Collagen products used in biomedical research are primarily derived from mammals, and despite being mainly responsible for providing strength to native connective tissue, collagen hydrogels have comparatively low mechanical properties without the use of additional cross‐linking strategies. Alternative sources of collagen, like fish collagen, are emerging as key biomaterials in tissue engineering and regenerative medicine (TERM). By addressing cultural/religious concerns, ease of extraction, absence of mammalian‐derived allergens, and retention of functional motifs, fish collagen has many promising characteristics that make it a suitable alternative to mammalian collagen. Several physical and chemical cross‐linking strategies of fish collagen are explored to create more stable and resilient scaffolds for a variety of TERM applications. This comprehensive review explores how these modifications are optimized in fish collagen hydrogel systems. Herein, the use of fish collagen and their reported sources for TERM research, as well as the types of treatments (including sterilization) used to alter collagen structures and functions, are presented to date. [ABSTRACT FROM AUTHOR]

This review explores core‐shell scaffolds in bone tissue engineering, highlighting their osteoconductive and osteoinductive properties critical for bone growth and regeneration. Key design factors include material selection, porosity, mechanical strength, biodegradation kinetics, and bioactivity. Electrospun core‐shell nanofibrous scaffolds demonstrate potential in delivering therapeutic agents and enhancing bone regeneration. Critical characterization techniques include structural, surface, chemical composition, mechanical, and degradation analyses. Scaling up production poses challenges, addressed by innovative electrospinning techniques. Future research focuses on regulatory and commercial considerations, while exploring advanced materials and fabrication methods to optimize scaffold performance for improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Cell therapy has emerged as a revolutionary tool to repair damaged tissues by restoration of an adequate vasculature. Dental Pulp stem cells (DPSC), due to their easy biological access, ex vivo properties, and ability to support angiogenesis have been largely explored in regenerative medicine. Methods: Here, we tested the capability of Dental Pulp Stem Cell-Conditioned medium (DPSC-CM), produced in normoxic (DPSC-CM Normox) or hypoxic (DPSC-CM Hypox) conditions, to support angiogenesis via their soluble factors. CMs were characterized by a secretome protein array, then used for in vivo and in vitro experiments. In in vivo experiments, DPSC-CMs were associated to an Ultimatrix sponge and injected in nude mice. After excision, Ultimatrix were assayed by immunohistochemistry, electron microscopy and flow cytometry, to evaluate the presence of endothelial, stromal, and immune cells. For in vitro procedures, DPSC-CMs were used on human umbilical-vein endothelial cells (HUVECs), to test their effects on cell adhesion, migration, tube formation, and on their capability to recruit human CD14+ monocytes. Results: We found that DPSC-CM Hypox exert stronger pro-angiogenic activities, compared with DPSC-CM Normox, by increasing the frequency of CD31+ endothelial cells, the number of vessels and hemoglobin content in the Ultimatrix sponges. We observed that Utimatrix sponges associated with DPSC-CM Hypox or DPSC-CM Normox shared similar capability to recruit CD45− stromal cells, CD45+ leukocytes, F4/80+ macrophages, CD80+ M1-macrophages and CD206+ M2-macropages. We also observed that DPSC-CM Hypox and DPSC-CM Normox have similar capabilities to support HUVEC adhesion, migration, induction of a pro-angiogenic gene signature and the generation of capillary-like structures, together with the ability to recruit human CD14+ monocytes. Conclusions: Our results provide evidence that DPSCs-CM, produced under hypoxic conditions, can be proposed as a tool able to support angiogenesis via macrophage polarization, suggesting its use to overcome the issues and restrictions associated with the use of staminal cells. [ABSTRACT FROM AUTHOR]

Spatiotemporally controlled two‐photon photodegradation of hydrogels has gained increasing attention for high‐precision subtractive tissue engineering. However, conventional photolabile hydrogels often have poor efficiency upon two‐photon excitation in the near‐infrared (NIR) region and thus require high laser dosage that may compromise cell activity. As a result, high‐speed two‐photon hydrogel erosion in the presence of cells remains challenging. Here we introduce the design and synthesis of efficient coumarin‐based photodegradable hydrogels to overcome these limitations. A set of photolabile coumarin‐functionalized polyethylene glycol linkers are synthesized through a Passerini multicomponent reaction. After mixing these linkers with thiolated hyaluronic acid, semi‐synthetic photodegradable hydrogels are formed in situ via Michael addition crosslinking. The efficiency of photodegradation in these hydrogels is significantly higher than that in nitrobenzyl counterparts upon two‐photon irradiation at 780 nm. A complex microfluidic network mimicking the bone microarchitecture is successfully fabricated in preformed coumarin hydrogels at high speeds of up to 300 mm s−1 and low laser dosage down to 10 mW. Further, we demonstrate fast two‐photon printing of hollow microchannels inside a hydrogel to spatiotemporally direct cell migration in 3D. Collectively, these hydrogels may open new avenues for fast laser‐guided tissue fabrication at high spatial resolution. [ABSTRACT FROM AUTHOR]

In this study, zinc silicate hybrid scaffolds with hierarchical meso/macroporous structures were synthesized using evaporation-induced self-assembly and sacrificial foamy templates. F127 triblock copolymer and polyurethane (PU) foam served as templates for mesoporosity and macroporosity, respectively. The scaffolds were calcined at 550, 650, and 750 °C for 2 h to remove the templates and form the crystalline phase. Analytical techniques, including BET, XRD, SEM, FTIR, and STA, were used to study the impact of calcination temperature on the scaffolds' meso-texture and crystalline phase. Results showed that increasing the calcination temperature to 750 °C significantly enhanced the overall crystallinity. The crystallized ZnO content increased from 10.3 wt% to 32 wt%, and the willemite (Zn 2 SiO 4) crystalline phase formed. Willemite content was approximately 3 wt% at 650 °C and 67 wt% at 750 °C, as determined by quantitative XRD analyses via Rietveld refinement. The emergence of the willemite phase adversely impacted the specific surface area, leading to a reduction from 123.18 m2/g to 2.18 m2/g, and compromised meso-texture-related characteristics, indicating a substantial disruption in mesoporosity. The pure willemite sample was also obtained by increasing the calcination temperature up to 1000 °C. Although the sample contained no secondary phase, the specific surface area and total mesopore volume were drastically reduced, indicating the negative effect of high calcination temperature on mesoporosity. In contrast to the mesostructure, the macrostructure of the scaffolds exhibited negligible sensitivity to calcination temperature, maintaining a mean macropore diameter of around 200 μm. Furthermore, the in vitro performance of the scaffolds was evaluated by assessing apatite formation ability, degradability, and cytocompatibility. It was demonstrated that the scaffolds calcined at 750 °C exhibited superior performance in terms of apatite formation and cytocompatibility when cultivated with MG-63 human osteosarcoma cells. [ABSTRACT FROM AUTHOR]

Corneal transplantation is the primary treatment for irreversible corneal diseases, but due to limited donor availability, bioengineered corneal equivalents are being developed as a solution, with biocompatibility, structural integrity, and physical function considered key factors. Since conventional evaluation methods may not fully capture the complex properties of the cornea, there is a need for advanced imaging and assessment techniques. In this study, we proposed a deep learning-based automatic segmentation method for transplanted bioengineered corneal equivalents using optical coherence tomography to achieve a highly accurate evaluation of graft integrity and biocompatibility. Our method provides quantitative individual thickness values, detailed maps, and volume measurements of the bioengineered corneal equivalents, and has been validated through 14 days of monitoring. Based on the results, it is expected to have high clinical utility as a quantitative assessment method for human keratoplasties, including automatic opacity area segmentation and implanted graft part extraction, beyond animal studies. [ABSTRACT FROM AUTHOR]

Spatiotemporally controlled two‐photon photodegradation of hydrogels has gained increasing attention for high‐precision subtractive tissue engineering. However, conventional photolabile hydrogels often have poor efficiency upon two‐photon excitation in the near‐infrared (NIR) region and thus require high laser dosage that may compromise cell activity. As a result, high‐speed two‐photon hydrogel erosion in the presence of cells remains challenging. Here we introduce the design and synthesis of efficient coumarin‐based photodegradable hydrogels to overcome these limitations. A set of photolabile coumarin‐functionalized polyethylene glycol linkers are synthesized through a Passerini multicomponent reaction. After mixing these linkers with thiolated hyaluronic acid, semi‐synthetic photodegradable hydrogels are formed in situ via Michael addition crosslinking. The efficiency of photodegradation in these hydrogels is significantly higher than that in nitrobenzyl counterparts upon two‐photon irradiation at 780 nm. A complex microfluidic network mimicking the bone microarchitecture is successfully fabricated in preformed coumarin hydrogels at high speeds of up to 300 mm s−1 and low laser dosage down to 10 mW. Further, we demonstrate fast two‐photon printing of hollow microchannels inside a hydrogel to spatiotemporally direct cell migration in 3D. Collectively, these hydrogels may open new avenues for fast laser‐guided tissue fabrication at high spatial resolution. [ABSTRACT FROM AUTHOR]

Advanced manufacturing of 3D‐structured materials enables the production of biomimetic muscle tissues. While models of muscle tissue exist, current approaches possess a limited ability to capture essential elements of the muscle tissue microarchitecture. Therefore, this paper aims to engineer the intrinsically complex muscle spindle‐like ellipsoid geometry using a polymer melt‐based electrohydrodynamic (EHD) printing system. EHD systems have conventionally reported fiber deposition in a layerwise fashion. However, without mitigation, the observed fiber sagging and residual charge phenomena for the melt electrowriting (MEW) process limit the ability to produce layered fibrous 3D constructs with in‐plane fiber alignment. However, in this work, fiber sagging and residual charge phenomena are leveraged as part of the design intent to deposit nonoverlapping suspended fibers between two stationary walls toward spindle‐like construct fabrication. Specifically, herein the structural and mechanical properties of the MEW‐enabled spindle‐like constructs are analyzed as a function of the process and design parameters that govern control over fiber sagging and residual charge. The results indicate that the collector speed and wall‐to‐wall distance are the key parameters for tuning the spindle morphology. Moreover, cycle number and fiber diameter are identified as effective parameters for tuning the spindle mechanical properties. [ABSTRACT FROM AUTHOR]

Nature-inspired microfluidic networks are revolutionizing microphysiological systems, allowing for the precise emulation of human physiology. This article delves into the fabrication techniques of leaf-venation-inspired (LVI) microfluidic networks and explores their transformative applications in organ-on-a-chip and tissue engineering, showcasing their pivotal role in advancing biomedical research. [ABSTRACT FROM AUTHOR]

Tissue engineering has emerged as a promising avenue for reconstructive urology, though only a limited number of tissue‐engineered urethral constructs have advanced to clinical testing. Presently, there exists a dearth of agreement regarding the most promising constructs deserving of implementation in clinical practice. The objective of this review was to provide a comprehensive analysis of preclinical trials findings of a tissue‐engineered urethra and to identify the most promising constructs for future translation into clinical practice. A systematic search of the Pubmed, Scopus, and PMC databases was conducted in accordance with the PRISMA statement. Manuscripts published in English between 2015 and 2022, reporting on the methodology for creating a tissue‐engineered urethra, assessing the regenerative potential of the scaffold in a male animal model, and evaluating the clinical and histological outcomes of treatment, were included. A total of 48 manuscripts met the inclusion criteria, with 12 being eligible for meta‐analysis. Meta‐analysis revealed no significant benefit of any matrix type in terms of complication rates. However, acellular matrices demonstrated significant advantage over cellular matrices in case of no postoperative stricture formation (odds ratio = 0.06 [95% CI 0.01; 0.23], p < 0.01). Among all subgroups (animal models and scaffold types), the usage of acellular matrices resulted in advantageous effects. The meta‐regression analysis did not show a significant impact of defect length (β1 = −0.02 [−0.28; 0.23], p = 0.86). We found that decellularized materials may carry less relevance for urethral reconstruction due to unfavorable preclinical outcomes. Natural polymers, used independently or with synthetic materials, resulted in better postoperative outcomes in animals compared to purely synthetic constructs. Acellular scaffolds showed promising outcomes, matching or exceeding cellular constructs. However, more studies are needed to confirm their clinical effectiveness. [ABSTRACT FROM AUTHOR]

Heart valve replacement surgeries are performed on patients suffering from abnormal heart valve function. In these operations, the problematic tissue is replaced with mechanical valves or with bioprosthetics that are being developed. The thrombotic effect of mechanical valves, reflecting the need for lifelong use of anticoagulation drugs, and the short‐lived nature of biological valves make these two types of valves problematic. In addition, they cannot adapt to the somatic growth of young patients. Although decellularized scaffolds have shown some promise, a successful translation has so far evaded. Although decellularized porcine xenografts have been extensively studied in the literature, they have several disadvantages, such as a propensity for calcification in the implant model, a risk of porcine endogenous retrovirus (PERV) infection, and a high xenoantigen density. As seen in clinical data, it is clear that there are biocompatibility problems in almost all studies. However, since decellularized sheep heart valves have not been tried in the clinic, a large data pool could not be established. This review compares and contrasts decellularized porcine and sheep xenografts for heart valve tissue engineering. It reveals that decellularized sheep heart valves can be an alternative to pigs in terms of biocompatibility. In addition, it highlights the potential advantages of bioinks derived from the decellularized extracellular matrix in 3D bioprinting technology, emphasizing that they can be a new alternative for the application. We also outline the future prospects of using sheep xenografts for heart valve tissue engineering. [ABSTRACT FROM AUTHOR]

Hydrogels have been used in the clinic since the late 1980s with broad applications in drug delivery, cosmetics, tissue regeneration, among many other areas. The past three decades have witnessed rapid advances in the fields of polymer chemistry, crosslinking approaches, and hydrogel fabrication methods, which have collectively brought many new hydrogel products, either injectable or non‐injectable, to clinical studies. In an article published in 2020 entitled "Hydrogels in the clinic", we reviewed the clinical landscape and translational challenges of injectable hydrogels. Here, we provide an update on the advances in the field and also extend the scope to include non‐injectable hydrogels. We highlight recently approved hydrogel products, provide an update on the clinical trials of injectable hydrogels, and discuss active clinical trials of topically applied and implantable hydrogels. [ABSTRACT FROM AUTHOR]

Assessing the biocompatibility of materials is crucial for ensuring the safety and well-being of patients by preventing undesirable, toxic, immune, or allergic reactions, and ensuring that materials remain functional over time without triggering adverse reactions. To ensure a comprehensive assessment, planning tests that carefully consider the intended application and potential exposure scenarios for selecting relevant assays, cell types, and testing parameters is essential. Moreover, characterizing the composition and properties of biomaterials allows for a more accurate understanding of test outcomes and the identification of factors contributing to cytotoxicity. Precise reporting of methodology and results facilitates research reproducibility and understanding of the findings by the scientific community, regulatory agencies, healthcare providers, and the general public. This article aims to provide an overview of the key concepts associated with evaluating the biocompatibility of biomaterials while also offering practical guidance on cellular principles, testing methodologies, and biological assays that can support in the planning, execution, and reporting of biocompatibility testing. [ABSTRACT FROM AUTHOR]

Approximately half of the adult population is suffering from periodontal disease, and conventional periodontal treatment strategies can only slow the progression of the disease. As a kind of tissue engineering, periodontal regeneration brings hope for the treatment of periodontal disease. Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound with a frequency of 1–3 MHz and a much lower intensity (< 1W/cm2) than traditional ultrasound energy and output. LIPUS has been adopted for a variety of therapeutic purposes due to its bioeffects such as thermal, mechanical, and cavitation effects, which induce intracellular biochemical effects and lead to tissue repair and regeneration ultimately. In this systematic review, we summarize the basic research of LIPUS in the treatment of periodontal disease in periodontal disease animal models and the influence of LIPUS on the biological behavior (including promoting osteogenic differentiation of stem cells and inhibiting inflammatory response) and potential mechanism of periodontal ligament stem cells (PDLSCs), hoping to provide new ideas for the treatment of periodontal disease. We believe that LIPUS can be used as an auxiliary strategy in the treatment of periodontal disease and play an exciting and positive role in periodontal regeneration. [ABSTRACT FROM AUTHOR]

Degenerative joint diseases, as a global public health issue, impose significant burdens on patients' lives and substantial economic costs on society. Currently, the primary modalities include physical therapy, pharmaceutical intervention, and surgical procedures. None of these approaches can alter the course of this degenerative process. Due to their commendable biocompatibility, biodegradability, and heightened efficacy in drug delivery, hydrogels present themselves as a novel noninvasive remedy for degenerative joint ailments. However, the clinical application of hydrogels still faces some challenges, including the uncontrolled discharge of encapsulated medications, the absence of adequate mechanical reinforcement for destabilized joints, and adaptability to fluctuating microenvironments. Recently, nanocomposite hydrogels, formed by introducing nanomaterials into hydrogels by physical or chemical means, can improve the limitations of hydrogels and extend their potential for biological applications in degenerative joint diseases. In this study, the pathologic features of degenerative joint diseases and the multiple applications of different types of nanocomposite hydrogels in targeting these different pathologic features are briefly described. It also concludes with an outlook on the use of nanocomposite hydrogels in clinical settings and discusses their challenges and limitations. [ABSTRACT FROM AUTHOR]

Placental‐derived stromal‐like cells (PLX‐PAD) have been shown to facilitate muscle tissue recovery after injury and stimulate angiogenesis. This work assesses the impact of PLX‐PAD cells on the vascularization and maturation of engineered skeletal muscle tissue. Specifically, their effects in direct co‐culture with endothelial cells, pericytes, and myoblasts seeded within microporous 3D scaffolds are characterized. Additionally, the impact of hypoxic PLX‐PAD cell‐conditioned medium (CM) on vascularization and muscle differentiation of engineered tissue is monitored. Co‐culture of PLX‐PAD with myocytes stimulated myocyte differentiation while PLX‐PAD CM promoted the formation of vascular networks. Implantation of a multi‐culture system of vascularized human skeletal muscle tissue and PLX‐PAD into a rectus abdominal defect in nude mice promoted myocyte differentiation, host vessel penetration, and tissue integration. These findings indicate the ability of placenta‐derived cells to induce the formation of vascularized engineered muscle constructs with potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Various studies have been carried out on renewable materials obtained from different natural resources and explored their applicability for multiple fields including biomedical. Among them, polysaccharides and polypeptides as alternatives to petroleum-based raw materials have attracted considerable attention because of their cost-effective, biocompatible, biodegradable, and eco-friendly, as well as their antimicrobial properties. Furthermore, the incorporation of these biobased materials in the formulation of polymeric materials could be advantageous. Recently, research on utilization of these biobased materials for the creation of nanocomposites of hydrogels (NCHs) has become a hotspot in the biomedical field. They have also paved the way for their uses in research for both in vivo and in vitro applications. Initially, in this review, we have briefly summarized the employment of biobased materials as well as different reinforcing materials in the formulation of biobased NCHs. We have also discussed their utilization as scaffolds for tissue engineering, carriers for drug delivery, material for wound dressing as well as biosensing and so on. Finally, we demonstrated the prospects and challenges associated with these materials, in order to deliver important information to produce biobased NCHs with desired properties for biomedical applications. [ABSTRACT FROM AUTHOR]

In recent years, natural polymers have attracted great interest for the development of release systems for vaccine formulations and drug delivery. Zein, a hydrophobic proline-rich protein mixture obtained from maize, is one of the most widely used polymers, very promising for applications in tissue engineering and the parenteral delivery of bioactive agents. Still, we have a limited understanding of the interaction between zein particles and the human immune system, in particular innate immunity/inflammation, which is the first line of defense of our body. Assessing the immune safety of nanoparticles is of central importance for ensuring that nano-formulations for medical use do not cause adverse effects on human health. Here, we evaluated the capacity of zein nanoparticles to induce/modulate the innate/inflammatory response, the development of innate memory, and the macrophage polarization by using reliable in vitro systems based on human primary monocytes and monocyte-derived macrophages. We observed that zein nanoparticles do not influence any of these aspects of the innate immune/inflammatory response, suggesting its safety and its potential efficiency as a nanocarrier for drug or antigen delivery. [ABSTRACT FROM AUTHOR]

In this study, the optimal engraving parameters were determined through the analysis of scanning electron microscopy (SEM) data, as follows: a laser power density of 5.5 × 105 W/cm2, an irradiation rate of 0.1 mm/s, a well radius of 60 μm, a distance between well centers of 200 μm, and a number of passes for each well of 20. After 1 week of in vitro cultivation, chondrocytes were located on the surface of the scaffolds, in the sockets and lacunae of decellularized cartilage. When implanted into animals, both cellular and acellular scaffolds were able to support cartilage in-growth and complete regeneration of the defect without clear boundaries with normal tissue. Nevertheless, the scaffolds populated with cells exhibited superior biocompatibility and were not subject to rejection, in contrast to cell-free constructs. [ABSTRACT FROM AUTHOR]

The document "Fundamental and Practical Perspectives in Regenerative Medicine" published in the International Journal of Molecular Sciences discusses the advancements and challenges in regenerative medicine. It highlights the shift towards a biomimetic approach, focusing on the human body's ability for renewal and regeneration. The use of biomaterials, tissue engineering, and cell-free methods are also explored as potential avenues for translational study. The document emphasizes the importance of fundamental research in shaping new technologies and treatments in regenerative medicine, while also acknowledging the need for clinical trials and regulatory frameworks to ensure safety and efficacy. [Extracted from the article]

Bioengineered materials represent an innovative option to support the regenerative processes of damaged tissues, with the final objective of creating a functional environment closely mimicking the native tissue. Among the different available biomaterials, hydrogels represent the solution of choice for tissue regeneration, thanks to the easy synthesis process and the highly tunable physical and mechanical properties. Moreover, hydrogels are biocompatible and biodegradable, able to integrate in biological environments and to support cellular interactions in order to restore damaged tissues' functionality. This review offers an overview of the current knowledge concerning hydrogel synthesis and characterization and of the recent achievements in their experimental use in supporting skin, bone, cartilage, and muscle regeneration. The currently available in vitro and in vivo results are of great interest, highlighting the need for carefully designed and controlled preclinical studies and clinical trials to support the transition of these innovative biomaterials from the bench to the bedside. [ABSTRACT FROM AUTHOR]

Nanofiber hydrogel composites integrate the high water content and biocompatibility of hydrogels with the high surface area-to-volume ratio nano-scale dimensions and ability to mimic the extracellular matrix ECM . This convergence presents promising applications in biomedicine. Advances in biomedical engineering have spurred high expectations for the performance and functionality of composite hydrogels notably in biomimetic materials drug delivery and tissue engineering. Nonetheless traditional nanofiber membranes struggle to replicate complex three-dimensional micro-nano environments. Their small pore sizes and high densities restrict nutrient transport. Furthermore the inadequate dispersion of continuous nanofibers hampers the materials' minimally invasive use. To address these limitations researchers have progressively introduced controllable-length short nanofibers into hydrogel networks. These nanofibers offer superior dispersibility enhancing their integration with hydrogels and the emulation of complex physiological conditions. To comprehensively understand the research status and performance advantages of short nanofiber composite hydrogels and to promote their development and application this paper reviews recent progress. It focuses on the functionalization and composite methods of short nanofibers summarizing their applications in the biomedical field and proposing current challenges and future directions. Functionalized short nanofibers serve crucial roles in composite hydrogels. Firstly by encapsulating cytokines or nanoparticles these fibers create a microenvironment within the hydrogel enhancing cell growth. Secondly surface modifications that immobilize therapeutic or monitoring agents on the fiber surface can prevent drug loss thereby enhancing therapeutic efficacy. Additionally these modifications increase the contact area between the drug and its environment improving detection sensitivity. Furthermore by modifying precursor materials prior to electrospinning short fibers can be functionally customized imparting specific properties and improving compatibility with the hydrogel matrix. The application of biotechnology such as the self-assembly of large molecules like DNA and peptides into short nanofibers not only endows them with specific biological functionality but also enables interaction with hydrogels enhancing their effects and further expanding the potential applications of short fibers in hydrogels. The binding mechanisms between short fibers and hydrogels are crucial. Besides simple physical blending the interfacial interaction between the two can be strengthened through a series of interactions including covalent bonding hydrogen bonding biotin interaction etc. Furthermore methods such as heat treatment mechanical stretching solvent diffusion and magnetic field control can orderly arrange short fibers in gels forming oriented structures which aid in mimicking the microstructure of natural oriented tissues such as muscles and nerves promoting tissue regeneration. The enhancement and functionalization of hydrogels become a significant research focus in biomedical materials science with the innovative incorporation of short fibers offering new pathways for improving hydrogel performance. This approach not only enhances the mechanical properties of hydrogels but also introduces new functionalities in a simple and effective manner. Short fiber-reinforced hydrogels demonstrate extensive potential applications in regulating cellular behavior optimizing drug delivery mechanisms and enhancing biosensing capabilities. These advancements provide a new material foundation and therapeutic strategy for regenerative medicine and precision medicine. However current research on composite hydrogels faces several significant challenges. Firstly the primary fabrication techniques for short nanofibers suffer from scalability issues and inconsistent fiber morphology. Innovative fabrication methods that enhance production efficiency and achieve uniform fiber dimensions are urgently needed. Secondly the precise control of the three-dimensional distribution and orientation of short fibers within the gel matrix is critical for optimizing the performance of composite hydrogels. This necessitates a deeper understanding of interfacial interactions and the development of advanced fiber assembly strategies. Lastly while the incorporation of short nanofibers improves the mechanical properties of composite materials they still fall short of the high-strength requirements for applications such as bone and joint repair. Thus advanced composite strategies that can match or exceed the mechanical properties of natural tissues are essential to ensure long-term stability and functionality in complex biomechanical environments. [ABSTRACT FROM AUTHOR]

This study evaluated the biocompatibility of dense and porous forms of Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV), Poly(ε-caprolactone) (PCL), and their 75/25 blend for bone tissue engineering applications. The biomaterials were characterized morphologically using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), and the thickness and porosity of the scaffolds were determined. Functional assessments of mesenchymal stem cells (MSCs) included the MTT assay, alkaline phosphatase (ALP) production, and morphological and cytochemical analyses. Moreover, these polymers were implanted into rats to evaluate their in vivo performance. The morphology and FTIR spectra of the scaffolds were consistent with the expected results. Porous polymers were thicker than dense polymers, and porosity was higher than 92% in all samples. The cells exhibited good viability, activity, and growth on the scaffolds. A higher number of cells was observed on dense polymers, likely due to their smaller surface area. ALP production occurred in all samples, but enzyme activity was more intense in PCL samples. The scaffolds did not interfere with the osteogenic capacity of MSCs, and mineralized nodules were present in all samples. Histological analysis revealed new bone formation in all samples, although pure PHBV exhibited lower results compared to the other blends. In vivo results indicated that dense PCL and the dense 75/25 blend were the best materials tested, with PCL tending to improve the performance of PHBV in vivo. [ABSTRACT FROM AUTHOR]

Solution blow spinning (SBS) is a versatile and cost-effective technique for producing nanofibrous materials. It is based on the principles of other spinning methods as electrospinning (ES), which creates very thin and fine fibers with controlled morphologies. Polylactic acid (PLA), a biodegradable and biocompatible polymer derived from renewable resources, is widely used in biomedical fields, environmental protection, and packaging. This review provides a theoretical background for PLA, focusing on its properties that are associated with structural characteristics, such as crystallinity and thermal behavior. It also discusses various methods for producing fibrous materials, with particular emphasis on ES and SBS and on describing in more detail the main properties of the SBS method, along with its processing conditions and potential applications. Additionally, this review examines the properties of nanofibrous materials, particularly PLA-based nanofibers, and the new applications for which it is thought that they may be more useful, such as drug delivery systems, wound healing, tissue engineering, and food packaging. Ultimately, this review highlights the potential of the SBS method and PLA-based nanofibers in various new applications and suggests future research directions to address existing challenges and further enhance the SBS method and the quality of fibrous materials. [ABSTRACT FROM AUTHOR]

This work presents the successful production of highly porous 3D nanofibrous hybrid scaffolds of polylactic acid (PLA)/polyethylene glycol (PEG) blends with the incorporation of calcium phosphate (CaP) bioceramics by a facile two-step process using the solution blow spinning (SBS) technique. CaP nanofibers were obtained at two calcium/phosphorus (Ca/P) ratios, 1.67 and 1.1, by SBS and calcination at 1000 °C. They were incorporated in PLA/PEG blends by SBS at 10 and 20 wt% to form 3D hybrid cotton-wool-like scaffolds. Morphological analysis showed that the fibrous scaffolds obtained had a randomly interconnected and highly porous structure. Also, the mean fiber diameter ranged from 408 ± 141 nm to 893 ± 496 nm. Apatite deposited considerably within 14 days in a simulated body fluid (SBF) test for hybrid scaffolds containing a mix of hydroxyapatite (HAp) and tri-calcium phosphate-β (β-TCP) phases. The scaffolds with 20 wt% CaP and a Ca/P ration of 1.1 showed better in vitro bioactivity to induce calcium mineralization for bone regeneration. Cellular tests evidenced that the developed scaffolds can support the osteogenic differentiation and proliferation of pre-osteoblastic MC3T3-E1 cells into mature osteoblasts. The results showed that the developed 3D scaffolds have potential applications for bone tissue engineering. [ABSTRACT FROM AUTHOR]

To date, severe bone defects remain a significant challenge to the quality of life. All clinically used bone grafts have their limitations. Bone tissue engineering offers the promise of novel bone graft substitutes. Various biomaterial scaffolds are fabricated by mimicking the natural bone structure, mechanical properties, and biological properties. Among them, gelatin methacryloyl (GelMA), as a modified natural biomaterial, possesses a controllable chemical network, high cellular stability and viability, good biocompatibility and degradability, and holds the prospect of a wide range of applications. However, because they are hindered by their mechanical properties, degradation rate, and lack of osteogenic activity, GelMA hydrogels need to be combined with other materials to improve the properties of the composites and endow them with the ability for osteogenesis, vascularization, and neurogenesis. In this paper, we systematically review and summarize the research progress of GelMA composite hydrogel scaffolds in the field of bone defect repair, and discuss ways to improve the properties, which will provide ideas for the design and application of bionic bone substitutes. [ABSTRACT FROM AUTHOR]

Simple Summary: STING agonists face challenges in breast cancer treatment due to their lower accumulation in tumors and rapid clearance from the body, resulting in a short duration of therapeutic effect. Novel phase-transitional liposomes loaded with STING agonists have been developed to overcome these limitations and are specifically designed for low-intensity focused ultrasound (LIFU)-assisted molecular imaging and precise treatment of breast cancer. With the assistance of LIFU, iRGD-modified liposomes (a targeting peptide) undergo a phase transition into microbubbles, leading to enhanced ultrasound molecular imaging of tumors and facilitating breast cancer immunotherapy by releasing STING agonists from the ultrasound-targeted liposomes. Background: Pharmacologically targeting the STING pathway offers a novel approach to cancer immunotherapy. However, small-molecule STING agonists face challenges such as poor tumor accumulation, rapid clearance, and short-lived effects within the tumor microenvironment, thus limiting their therapeutic potential. To address the challenges of poor specificity and inadequate targeting of STING in breast cancer treatment, herein, we report the design and development of a targeted liposomal delivery system modified with the tumor-targeting peptide iRGD (iRGD-STING-PFP@liposomes). With LIFU irradiation, the liposomal system exploits acoustic cavitation, where gas nuclei form and collapse within the hydrophobic region of the liposome lipid bilayer (transient pore formation), which leads to significantly enhanced drug release. Methods: Transmission electron microscopy (TEM) was used to investigate the physicochemical properties of the targeted liposomes. Encapsulation efficiency and in vitro release were assessed using the dialysis bag method, while the effects of iRGD on liposome targeting were evaluated through laser confocal microscopy. The CCK-8 assay was used to investigate the toxicity and cell growth effects of this system on 4T1 breast cancer cells and HUVEC vascular endothelial cells. A subcutaneous breast cancer tumor model was established to evaluate the tumor-killing effects and therapeutic mechanism of the newly developed liposomes. Results: The liposome carrier exhibited a regular morphology, with a particle size of 232.16 ± 19.82 nm, as indicated by dynamic light scattering (DLS), and demonstrated low toxicity to both HUVEC and 4T1 cells. With an encapsulation efficiency of 41.82 ± 5.67%, the carrier exhibited a slow release pattern in vitro after STING loading. Targeting results indicated that iRGD modification enhanced the system's ability to target 4T1 cells. The iRGD-STING-PFP@liposomes group demonstrated significant tumor growth inhibition in the subcutaneous breast cancer mouse model with effective activation of the immune system, resulting in the highest populations of matured dendritic cells (71.2 ± 5.4%), increased presentation of tumor-related antigens, promoted CD8+ T cell infiltration at the tumor site, and enhanced NK cell activity. Conclusions: The iRGD-STING-PFP@liposomes targeted drug delivery system effectively targets breast cancer cells, providing a new strategy for breast cancer immunotherapy. These findings indicate that iRGD-STING-PFP@liposomes could successfully deliver STING agonists to tumor tissue, trigger the innate immune response, and may serve as a potential platform for targeted immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Rotator cuff repair augmentation using biological materials has become popular in clinical practice to reduce the high retear rates associated with traditional repair techniques. Tissue engineering approaches, such as engineered tendon-fibrocartilage-bone composite (TFBC), have shown promise in enhancing the biological healing of rotator cuff tears in animals. However, previous studies have provided limited long-term data on TFBC repair outcomes. The effect of mechanical stimulation on TFBC has not been explored extensively. Purpose: To evaluate functional outcomes after rotator cuff repair with engineered TFBC subjected to mechanical stimulation in a 6-month follow-up using a canine in vivo model. Study Design: Controlled laboratory study. Methods: A total of 40 canines with an acute infraspinatus (ISP) tendon transection model were randomly allocated to 4 groups (n =10): (1) unilateral ISP tendon undergoing suture repair only (control surgery); (2) augmentation with engineered TFBC alone (TFBC); (3) augmentation with engineered TFBC and bone marrow-derived stem cells (BMSCs) (TFBC+C); and (4) augmentation with engineered TFBC and BMSCs, as well as mechanical stimulation (TFBC+C+M). Outcome measures—including biomechanical evaluations such as failure strength, stiffness, failure mode, gross appearance, ISP tendon and muscle morphological assessment, and histological analysis—were performed 6 months after surgery. Results: As shown in the mechanical test, the TFBC+C+M group exhibited higher failure strength compared with other repair techniques. The most common failure mode was avulsion fracture in the TFBC+C+M group, but tendon-bone junction rupture was observed predominantly in different groups. Engineered TFBC with mechanical stimulation showed over 70% relative failure strength compared with normal ISP, and the other groups showed about 50% relative failure strength. Histological analysis revealed less fat infiltration and closer-to-normal muscle fiber structure in the mechanical stimulation group. Conclusion: This study provides evidence that mechanical stimulation of engineered TFBC promotes rotator cuff regeneration, thus supporting its potential for rotator cuff repair augmentation. Clinical Relevance: This study provides valuable evidence supporting the use of a novel tissue-engineered material (TFBC) in rotator cuff repair and paves the way for advancements in the field of rotator cuff regeneration. [ABSTRACT FROM AUTHOR]

Taking inspiration from diverse interlocking and adhesion structures found in nature, a biaxially interlocking interface is developed in this work. This interface is formed by interconnecting two electrostatically flocked substrates and its mechanical strength is enhanced through the incorporation of enoki‐mushroom‐shaped microfibers and deposited extracellular matrix (ECM). Tips of flocked straight fibers can be transformed into mushroom shapes through thermal treatment. The tensile strength of interlocked scaffolds with mushroom‐shaped tips drastically increases when compared to scaffolds made of straight fibers, which is not reported previously. More cells proliferate within interlocked scaffolds with mushroom‐shaped tips than scaffolds with straight fibers. Additionally, the mechanical strength (e.g., compressive, tensile, and shear) of cell‐seeded interlocked scaffolds increases proportionally to the amount of ECM deposited by dermal fibroblasts. The biaxially interlocking interface developed in this study holds promise for applications in engineering interfacial tissues, modeling tissue interfaces, investigating tissue–tissue interactions, and facilitating tissue bridging or binding. [ABSTRACT FROM AUTHOR]

The utilization of lattice-based scaffolds emerging as an advance technique over conventional bio-implants in Bone Tissue Engineering. In this study, totally six lattice structures are considered for permeability and wall shear stress (WSS) investigation. Namely triply periodic minimal surfaces (TPMS)-based Gyroid, Schwarz-P, Schwarz-D, and two beam-based structure—Cubic and Fluorite are compared with the proposed new lattice structure at porosity level of 80%, 75%, and 70%. The proposed new lattice has combine characteristic of Gyroid and Schwarz-D TPMS lattice. The permeability is determined through Darcy's law, where the pressure drop across the lattice structure is calculated using a computational fluid dynamics (CFD) tool at flowrate between 0.2 and 10 ml/min. The Cubic and Schwarz-P lattice structures exhibited the highest permeability but at the cost of a lower active surface area for WSS, measuring below 155 mm², means least cell proliferation occurs while the permeability value in New Lattice structure is in the ideal range with the enhanced active surface area for WSS (514 mm²). The complex internal curvatures of New Lattice promote the cell proliferation while the through-pore holes allow the efficient cell seeding.The utilization of lattice-based scaffolds emerging as an advance technique over conventional bio-implants in Bone Tissue Engineering. In this study, totally six lattice structures are considered for permeability and wall shear stress (WSS) investigation. Namely triply periodic minimal surfaces (TPMS)-based Gyroid, Schwarz-P, Schwarz-D, and two beam-based structure—Cubic and Fluorite are compared with the proposed new lattice structure at porosity level of 80%, 75%, and 70%. The proposed new lattice has combine characteristic of Gyroid and Schwarz-D TPMS lattice. The permeability is determined through Darcy's law, where the pressure drop across the lattice structure is calculated using a computational fluid dynamics (CFD) tool at flowrate between 0.2 and 10 ml/min. The Cubic and Schwarz-P lattice structures exhibited the highest permeability but at the cost of a lower active surface area for WSS, measuring below 155 mm², means least cell proliferation occurs while the permeability value in New Lattice structure is in the ideal range with the enhanced active surface area for WSS (514 mm²). The complex internal curvatures of New Lattice promote the cell proliferation while the through-pore holes allow the efficient cell seeding. [ABSTRACT FROM AUTHOR]

In this study, polycaprolactone (PCL) scaffolds have been employed as structural framework scaffolds for patellofemoral cartilage tissue regeneration. The biomechanical and biological properties of different scaffolds were investigated by varying alginate concentrations and the number of scaffold layers. Patellofemoral cartilage defects result in knee pain and reduced mobility, and they are usually treated with conventional methods, often with limited success. Generally, tissue-engineered PCL-alginate scaffolds fabricated by bioprinting technology show promise for enhanced cartilage regeneration due to the biocompatibility and mechanical stability of PCL. In addition, alginate is known for its cell encapsulation capabilities and for promoting cell viability. Biological and morphological assessments, utilizing water contact angle, cell adhesion tests, MTT assays, and scanning electron microscopy (SEM), informed the selection of the optimized scaffold. Comparative analyses between the initial optimal scaffolds with the same chemical composition also included flexural and compression tests and fracture surface observations using SEM. The controlled integration of PCL and alginate offers a hybrid approach, that assembles the mechanical strength of PCL and the bioactive properties of alginate for tissue reconstruction potential. This study aims to identify the most effective scaffold composition for patellofemoral articular cartilage tissue engineering, emphasizing cell viability, structural morphology, and mechanical integrity. The results showed that the optimum biomechanical and biological properties of scaffolds were obtained with a 10% alginate concentration in the monolayer of PCL structure. The findings contribute to regenerative medicine by advancing the understanding of functional tissue constructs, bringing us closer to addressing articular cartilage defects and related clinical challenges. [ABSTRACT FROM AUTHOR]

Hybrid organic–inorganic nanomaterials made of various types of organosilanes display very promising applications in a variety of fields, including biocompatible materials. Currently, these types of nanomaterials are studied in various physical forms due to the tunable combination of organic and inorganic parts bringing numerous properties into the field of medicine. Particularly, in the field of regenerative medicine, nanofibrous organosilane scaffolds are under wide investigation due to their morphological similarity to the extracellular matrix. Here, we describe the economically and procedurally simple synthesis and successful preparation of pure organosilane nanofibres (NFs) using only an N,N´-bis(3-(triethoxysilyl)propyl)oxamide precursor via a one-pot synthesis process utilising the acid-catalysed sol–gel process. Unlike established practices, the organosilane scaffolds proposed in this work are prepared thanks to the conscious and precise setting of the sol–gel process parameters without the need for any potentially harmful additives such as co-polymers, surfactants, and/or alkoxides. In addition, the synthesis of the precursor (BTPO) contains silicates for the polymerisation and a simple organic alkyl linker with amide bonds being akin to the biological friendly peptide bond. BTPO NFs were successfully electrospun on a large scale using a Nanospider™ and fully characterised and analysed for cytocompatibility using 3T3 fibroblasts. Formed organosilane NFs displaying negligible cytotoxicity, along with good cell proliferation and metabolic activity, open up the possibility of introducing various organic structures, using the synthetic strategies presented here, for inherent functional properties which could be exploited further in tissue engineering. [ABSTRACT FROM AUTHOR]

Carotenoids are especially hydrophobic and dissolve poorly in water. Encapsulation is used to increase their solubility in water-based food products. However, it is not yet known whether encapsulation with a combination of lecithin and medium-chain triglycerides improves carotenoid bioaccessibility and intestinal cell uptake. The relative bioaccessibility and Caco-2 cell uptake of two water-soluble carotenoid (i.e. lutein and astaxanthin) dispersions in a liquid form (VitaSperse®) and a powdered form (VitaDry®) were compared to the carotenoid ingredient alone. An in vitro digestion model was used to assess bioaccessibility, measuring the micellarized fraction postdigestion. The micelle fraction was incubated with Caco-2 cells to assess intestinal uptake of carotenoids. Encapsulation (by either VitaDry® or Vitasperse®) increased total astaxanthin bioaccessibility 2-2.4× and cell uptake by ∼2× relative to control. Encapsulation also increased total lutein bioaccessibility by 3–5× and cell uptake 2.3× relative to control. There was no significant difference between VitaDry® and VitaSperse® products in regards to Caco-2 cell uptake. Increased bioaccessibility largely drove increased carotenoid cell uptake from the encapsulated formulations. These results suggest further study is warranted to determine if this encapsulation approach increases carotenoid bioavailability in human studies. [ABSTRACT FROM AUTHOR]

Background: Stress urinary incontinence (SUI) is a widespread condition affecting more than 200 million people worldwide. Common treatments for this condition include retropubic colposuspension, and pelvic sling methods, which use autologous grafts or synthetic materials to support the bladder neck and urethral sphincter. Although these treatments have a cure rate of over 80%, adverse effects and recurrence may still occur. Several studies have focused on the potential of cell therapy. Muscle-derived cells (MDCs) can be easily obtained from small biopsied striated muscular tissues and possess superior multi-lineage differentiation and self-renewal capacity. Methods: Based on the unique characteristics of MDCs and previous favorable results in muscle regeneration, we fabricated a chitosan-gelatin hydrogel sling loaded with MDCs in a rat model of SUI. Leak point pressure and histological indices regarding inflammation, muscular atrophy, and collagen density were assessed to compare the effectiveness of cell injection and cell-laden sling. Results: The level of LPP was significantly reduced in the MODEL group versus the control animals. The LPP level was considerably higher in CELL INJECTION, SLING, and CELL/SLING groups compared to the MODEL group but did not reach the significance threshold. The inflammation rate was significantly lower in the CELL/SLING group compared to the SLING group. Conclusion: The CELL/SLING group showed less atrophy compared to the other experimental groups, indicating that the cells may have higher viability on SLING than through injection. This also suggests that in long-term studies, as the degradation rate of hydrogels increases, the function of cells will become more apparent. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is incurable and raises growing concerns. The main barrier to nerve repair is the complicated inhibitory microenvironment, where single-targeted strategies are largely frustrated. Despite the progress in combinatory therapeutic systems, the development and translation of effective therapies remain a challenge with extremely limited clinical materials. In this study, mesenchymal stem cells are transplanted in combination with sustained release of methylprednisolone through delivery in one composite matrix of a microsphere-enveloped adhesive hydrogel. All the materials used, including the stem cells, drug, and the matrix polymers gelatin and hyaluronan, are clinically approved. The therapeutic effects and safety issues are evaluated on rat and canine SCI models. The implantation significantly promotes functional restoration and nerve repair in a severe long-span rat spinal cord transection model. Distant spinal cord segments and the urinary system are effectively protected against pathologic damage. Moreover, the local sustained drug delivery mitigates the inflammatory microenvironment when overcoming the clinical issue of systemic side effects. The study presents an innovative strategy to achieve safe and efficient combinatory treatment of SCI. [Display omitted] • An implant based on clinical materials elicit effective and safe spinal cord repair. • The therapy overcame the issue of systemic drug toxicity in clinical administration. • The composite carrier provided benefit niche for stem cell transplantation. • Severe rat spinal cord transection and canine models both showed inspiring results. [ABSTRACT FROM AUTHOR]

Objectives: Engineered Heart Tissue (EHT) is a promising tool to repair heart muscle defects and can additionally be used for drug testing. Due to the absence of an in vitro vascularization, EHT geometry crucially impacts nutrient and oxygen supply by diffusion capacity. We analyzed cardiomyocyte survival in different EHT geometries. Methods: Different geometries with varying surface‐area‐to‐volume‐ratios were calculated (structure A (Ring) AS/V = 58.47 mm2/440 μL3, structure B (Infinity) 25.86 mm2/440 μL3). EHTs were generated from hiPSC‐derived cardiomyocytes (4 × 106) and a fibrin/thrombin hydrogel. Cell viability was evaluated by RT‐PCR, cytometric studies, and Bioluminescence imaging. Results: Using 3D‐printed casting molds, spontaneously beating EHTs can be generated in various geometric forms. At day 7, the RT‐PCR analyses showed a significantly higher Troponin‐T value in ring EHTs, compared to infinity EHTs. In cytometric studies, we evaluated 15% more Troponin‐T positive cells in ring (73% ± 12%), compared to infinity EHTs (58% ± 11%, p = 0.04). BLI visualized significantly higher cell survival in ring EHTs (ROI = A: 1.14 × 106 p/s and B: 8.47 × 105 p/s, p < 0.001) compared to infinity EHTs during longitudinal cultivation process. Conclusion: Use of 3D‐printing allows the creation of EHTs in all desired geometric shapes. The geometry with an optimized surface‐area‐to‐volume‐ratio (ring EHT) demonstrated a significantly higher cell survival measured by RT‐PCR, Bioluminescence imaging, and cytometric studies using FACS analysis. [ABSTRACT FROM AUTHOR]

Osteochondral tissue engineering using layered scaffolds is a promising approach for treating osteochondral defects as an alternative to microfracture procedure, autologous chondrocyte implantation, and cartilage-bone grafting. The team previously investigated the chondrogenesis of mesenchymal stem cells (MSCs) on a polycaprolactone (PCL)/acetylated hyaluronic acid scaffold. The present study first focused on fabricating a novel osteoconductive scaffold utilizing bismuth-nanohydroxyapatite/reduced graphene oxide (Bi-nHAp/rGO) nanocomposite and electrospun PCL. The osteoconductive ability of the scaffold was investigated by evaluating the alkaline phosphatase (ALP) activity and the osteogenic genes expression in the adipose-derived MSCs. The expression of Runx2, collagen I, ALP, and osteocalcin as well as the result of ALP activity indicated the osteoconductive potential of the Bi-nHA-rGO/PCL scaffold. In the next step, a bilayer scaffold containing Bi-nHAp/rGO/PCL as an osteogenic layer and acetylated hyaluronic acid/PCL as a chondrogenic layer was prepared by the electrospinning technique and transplanted into osteochondral defects of rats. The chondrogenic and osteogenic markers corresponding to the surrounding tissues of the transplanted scaffold were surveyed 60 days later by real-time polymerase chain reaction (PCR) and immunohistochemistry methods. The results showed increased chondrogenic (Sox9 and collagen II) and osteogenic (osteocalcin and ALP) gene expression and augmented secretion of collagens II and X after transplantation. The results strongly support the efficacy of this constructed cell-free bilayer scaffold to induce osteochondral defect regeneration. • Bi-nHA/rGO nanocomposite and PCL were used to create an osteogenic scaffold. • A bilayer scaffold consisting of Bi-nHA/rGO/PCL (osteogenic) and Ac-HA/PCL (chondrogenic) was fabricated. • The bilayer scaffold was implanted in rat knee defects. • Chondrogenic and osteogenic markers were assessed using real-time PCR and immunohistochemistry. • Increased osteogenic and chondrogenic markers indicated osteochondral defect regeneration. [ABSTRACT FROM AUTHOR]

Cross-linkers are pivotal to meliorate the attributes of the biopolymers, which are exploited in the biomedical industries, and also those intended as packaging supplies. Genipin (GN) is an efficacious cross-linker. Moreover, being naturally procured, biodegradable and biocompatible makes it an auspicious candidate for the biomedical and food industries. Accordingly, we attempted to provide a comprehensive review on GN as an efficient cross-linker for biopolymers. Initially, we presented the chief botanical sources of GN. The GN extraction strategies, which adopted safe solvents, were then discussed while highlighting their realized yields. The proposed GN structures, its possible modes of action, and the factors affecting its interactions, such as pH, temperature, and GN concentration were also reviewed. Afterward, the GN applications that mainly involved cross-linking biopolymers and biopolymers containing materials were discussed. These included tissue engineering, wound dressings, drug delivery, and packaging applications. GN capability to activate biopolymers, such as chitosan and gelatin, into covalently reactive enzyme immobilizers was also discussed. Moreover, other important GN applications, such as exploiting it as a colorant for foods and textiles and incorporating it in altered biosensors, were discussed. [ABSTRACT FROM AUTHOR]

The skin is a tissue constantly exposed to the risk of damage, such as cuts, burns, and genetic disorders. The standard treatment is autograft, but it can cause pain to the patient being extremely complex in patients suffering from burns on large body surfaces. Considering that there is a need to develop technologies for the repair of skin tissue like 3D bioprinting. Skin is a tissue that is approximately 1/16 of the total body weight and has three main layers: epidermis, dermis, and hypodermis. Therefore, there are several studies using cells, biomaterials, and bioprinting for skin regeneration. Here, we provide an overview of the structure and function of the epidermis, dermis, and hypodermis, and showed in the recent research in skin regeneration, the main cells used, biomaterials studied that provide initial support for these cells, allowing the growth and formation of the neotissue and general characteristics, advantages and disadvantages of each methodology and the landmarks in recent research in the 3D skin bioprinting. [ABSTRACT FROM AUTHOR]

The interactions of naturally occurring polymers and medicaments, sodium carboxymethyl cellulose (Na-CMC) and Paracetamol (PCM), have attracted the interest of researchers in a variety of biomedical and pharmaceutical applications areas, such as drug delivery, cosmetics and tissue engineering. In our research described here, the effects of temperature and concentration of Na-CMC/PCM/water (W) mixed solutions were studied at various temperatures ranging from 20 °C to 45 °C. We highlighted that different regions can be distinguished in the aqueous Na-CMC/PCM/W complexes, depending on the composition and electrostatic interactions of the solutions, which are associated with significantly different phase behaviors. [ABSTRACT FROM AUTHOR]

• Collagen type VIII is a non-fibrillar, short-chain, network-forming collagen expressed throughout the vasculature. • Collagen VIII is dysregulated in cardiovascular, lung, and renal diseases, as well as in certain cancers. • Collagen VIII plays active roles in angiogenesis, vessel compliance and repair, and atherosclerosis. • Collagen VIII modulates pathways involved in extracellular matrix remodeling. Collagens have dual functions in the extracellular matrix (ECM), acting as both structural components and signaling molecules in matricellular communication. Although collagen molecules share a common triple helix motif, the supramolecular organization helps classify them into nearly 30 different types of collagens. Collagen type VIII is a non-fibrillar, short-chain, network-forming collagen that is expressed throughout the vasculature. Collagen VIII expression is aberrant in cardiovascular, lung, and renal disease, as well as in several different types of cancer. It plays active roles in angiogenesis, vessel injury repair, maintenance of arterial compliance, atherosclerotic plaque formation and stability modulation, fibrosis, and ECM remodeling. This review presents an overview of the characteristics of collagen VIII in vascular-related disorders, from clinical significance to laboratory studies, with a major focus on highlighting the signaling properties of collagen VIII in the vascular ECM. The expression patterns of collagen VIII in human diseases and experimental animal models highlight the protein's important yet underexplored functions. A deeper understanding of its mechanisms and downstream signaling pathways may pave the way for translational and tissue engineering applications of collagen VIII. [ABSTRACT FROM AUTHOR]

Poly(vinyl alcohol) (PVA) based hydrogels have gained more interest in the field of biomaterials because of their many biomedical uses (i.e., wound healing, drug delivery, and tissue engineering) and intrinsic physicochemical and biological characteristics. They can be made using a variety of synthetic techniques, but all of them are very time-consuming. Among them, photopolymerization also referred to as light-induced polymerization, has drawn a lot of attention because of its benefits, which include not requiring the use of solvents, easy and quick network formation, energy efficiency, quick processing, control over both space and time and reliability of crosslinking density and matrix strength. Ultraviolet (UV)-curable hydrogels containing PVA as a main component are gaining interest because of their excellent properties, including biodegradability, biocompatibility, less cytotoxicity and remarkable mechanical strength. This review highlights the significance of UV curable systems and their components, types, advantages and disadvantages of photoinitiators (PIs), UV curable monomers and their structures, properties of UV-cured PVA hybrid hydrogels, and their characterizations and applications in different fields. The photopolymerization mechanisms, tunable properties, and unique advantages of these hydrogels have been explored in detail. Furthermore, it sheds light on recent advancements in PVA-based hydrogels research and future exploration in this domain. [ABSTRACT FROM AUTHOR]

There has been an important interest in to use of electrospun nanomaterials for tissue engineering applications due to the excellent scaffold-cell interaction provided by high interconnectivity and high porosity by electrospun nanofibers. In this study, Polyacrylonitrile (PAN) and carbon nanotube-inserted PAN (PAN/CNT) nanofibers were produced by the electrospinning method and characterized by SEM, FT-IR, and EIS spectroscopy. Both PAN and PAN/CNT nanofibers were obtained beadless and ordered with the average fiber diameters of 277.61 ± 43.6 and 171.01 ± 48.4, respectively. The influence of CNT addition on PAN nanofibers was observed with the decrease of diameter and increase of electrical conductivity of nanofibers. Then, the biocompatibility of PAN and PAN/CNT nanofibers was evaluated by the MTT and AO/EB double-staining experiments. It was observed that the nanofibers showed no cytotoxic effect on L929 fibroblast cells. In the docking experiments, while both PAN and PAN/CNT showed energetically favorable interactions (ΔG = −4.60 kcal/mol; −7.26 kcal/mol, respectively) with the membrane bilayer complex, PAN/CNT formed a more stable binding with the cellular membrane compared to PAN alone. Docking results mechanistically support the more effective increase in the proliferation of L929 fibroblasts at high concentrations in vitro, as PAN/CNT exhibits stronger binding affinity and interaction with the cellular membrane. The increase in electrical conductivity of nanofibers influenced the proliferation positively, as well. [ABSTRACT FROM AUTHOR]

A tri-layer scaffold was fabricated according to functionally graded materials (FGM) theory from poly(glycerol sebcate)/poly(L-lactic acid) blend by the increasing polylactic acid ratio from the inner to the outer layer. Heparin and platelet-rich plasma were loaded in separate layers to achieve proper remodeling and patency. The scaffold showed a linear degradation trend. The elastic modulus was 13.8 ± 1.11 Mpa that was in the favorable range for constructing artificial vessels. The integrity of the layers was preserved due to its FGM structure. The scaffold showed full blood compatibility by minimal platelet adhesion and hemolysis due to relatively slow release of Heparin. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a profound medical condition that significantly hampers motor function, imposing substantial limitations on daily activities and exerting a considerable financial burden on patients and their families. The constrained regenerative capacity of endogenous spinal cord tissue, exacerbated by the inflammatory response following the initial trauma, poses a formidable obstacle to effective therapy. Recent advancements in the field, stem cells, biomaterials, and molecular therapy, show promising outcomes. This review provides a comprehensive analysis of tissue engineering and regenerative medicine approaches for SCI treatment, including cell transplantation, tissue-engineered construct implantation, and other potential therapeutic strategies. Additionally, it sheds light on preclinical animal studies and recent clinical trials incorporating these modalities, providing a glimpse into the evolving landscape of SCI management. The investigation into spinal cord injury (SCI) treatments focuses on reducing long-term impacts by targeting scar inhibition and enhancing regeneration through stem cells, with or without growth factors. Induced pluripotent stem cells (iPSCs) show promise for autologous use, with clinical trials confirming their safety. Challenges include low cell viability and difficulty in targeted differentiation. Biomaterial scaffolds hold potential for improving cell viability and integration, and extracellular vesicles (EVs) are emerging as a novel therapy. While EV research is in its early stages, stem cell trials demonstrate safety and potential recovery. Advancing tissue engineering approaches with biomaterial scaffolds is crucial for human trials. [Display omitted] [ABSTRACT FROM AUTHOR]

Tissue engineering is a promising approach for generating or repairing living tissues. The development of innovative biomaterials for tissue engineering has the potential to address the unmet clinical needs in certain applications. However, before these biomaterials can be used in clinical settings, they must undergo preclinical testing to ensure safety and performance. The chicken chorioallantoic membrane (CAM) assay is a preferred screening tool for studying biocompatibility, angiogenesis, and inflammation induced by biomaterials owing to ethical and economic considerations. This CAM‐based platform increased the throughput of biomaterial testing for tissue engineering before in vivo testing. In this paper, we discuss the advantages of the CAM model. We also provided a step‐by‐step guide for implementing the CAM model in a research laboratory, along with tips and tricks for successfully running CAM assays. Finally, we present examples of biomaterials screened using CAM assays. CAM assay is a powerful in vivo model for assessing the angiogenic potential of tissue‐engineered scaffolds. This guide provides a framework for conducting the assay, but specific experimental conditions should be optimized based on the scaffold material and the research question. [ABSTRACT FROM AUTHOR]

Gelatin methacrylate (GelMA) is a photo-cross-linkable biopolymer. A combination of GelMA with biodegradable polyesters such as PCL (poly‐ε‐caprolactone) and their triblock derivatives improve the mechanical properties of GelMA. PCL-PEG-PCL (PCEC) was synthesized using ring-opening polymerization of ε-caprolactone in the presence of polyethylene glycol (PEG). The GelMA- PCEC was fabricated using freeze-drying and 3D printing and their porosity, mechanical properties, and swelling behavior were investigated. Human dental pulp stem cells were cultured on the scaffolds for a period of 14 days and cell adhesion was evaluated by scanning electron microscopy. Cell viability was analyzed by MTT and osteogenic differentiation was evaluated by Alizarin red S. Results showed that the 3D-printed scaffold had higher water absorption rate, retaining its structure up to a strain of 0.2 %, and a higher Young's modulus compared to the freeze-dried scaffold. In terms of cell viability, the 3D-printed scaffold outperformed the freeze-dried scaffold with a percentage of 86 % and 63 % viability respectively. Moreover, the 3D-printed scaffold exhibited better osteodifferentiation with calcium deposition. Overall, these findings suggest that the 3D-printed scaffold may have advantages over the freeze-dried scaffold in tissue engineering applications that require high water absorption, elasticity, and cell viability. The fabricated scaffolds provided suitable cell proliferation. [ABSTRACT FROM AUTHOR]

Polymer porous membranes are crucial in various applications, including water filtration, tissue engineering, and drug administration. Conventional far‐field electrospinning (FFES) is widely used for producing polymeric membranes due to its cost‐effectiveness, scalability, and flexibility in using many polymers. However, FFES has limitations in controlling pore form and size, as it produces randomly oriented fibers that lead to inconsistent and noncustomizable pore sizes. To address these limitations, this work combines near‐field electrospinning (NFES) with thermal treatment of polymer fibers and membranes. NFES offers more precise control over fiber placement and alignment, producing well‐defined fiber patterns with consistent and customizable pore sizes without compromising the thickness of membranes. By exploring the interplay between polymer behavior, thermal effects, and capillary action, the differences in pore area under various temperatures and fiber spacings are characterized. Additionally, this study investigates the influence of multilayer infusion on pore size and geometric arrangement by examining multilayer configurations stacked at various angles. The results indicate that increasing the number of layers leads to decreased pore size, while the alignment of infused fibers affects pore shape. This integrated approach enhances control over membrane characteristics, improving the performance and consistency of polymer porous membrane fabrication across various applications. [ABSTRACT FROM AUTHOR]

Recent progress in developing cardiac patches for regenerating the myocardium has opened a new hope after myocardial infarction (MI). Herein, we introduce a novel bilayer nanofiber cardiac patch composed of polycaprolactone (PCL), poly(xylitol sebacate) (PXS), and multi-walled carbon nanotubes (MWCNTs). First, we electrospun different monolayer scaffolds, including PCL, PCL/MWCNT, PCL/PXS, and PCL/PXS/MWCNTs, and characterized their physical, mechanical, and biological performance to determine the interaction effects of different material compositions on their scaffold properties. In vitro examinations confirmed the cooperative effect of PXS and MWCNT in blending with PCL to fabricate conductive and well-organized nanofibers with good biocompatibility. Subsequently, a bilayer nanofiber scaffold composed of PCL/PXS/MWCNT nanofibers electrospun over a PCL fibrous layer was fabricated to achieve an efficient structure capable of providing the desirable characteristics of a cardiac patch. The bilayer nature increased the mechanical performance of the PCL/PXS/MWCNT monolayer while preserving its appropriate wettability and acceptable conductivity. Excellent viability and proliferation of H9c2 cells on the bilayer scaffolds were observed in the live/dead assay. Moreover, cell-matrix interaction confirmed that bilayer nanofibers decrease myofibroblast differentiation of seeded NIH3T3 cells, which may be beneficial for cardiac repair post-MI. After transplantation of the bilayer nanofiber onto the infarcted heart of the MI rats for 4 weeks, the ischemic zone decreased, cardiac function significantly improved and very slightly activated macrophages were observed. These findings suggested a potentially durable nanofiber cardiac patch containing PXS for myocardial repair post-MI. [ABSTRACT FROM AUTHOR]

A complex of interrelated methods and means of analysis, clustering, segmentation and classification of objects on images obtained by sensors of different physical nature (with the help of modern methods of radiography, computer and magnetic resonance imaging) is proposed, which will allow modeling the optimal form of a bone substitute with functional properties by CAD/CAM/CAE design methods, depending on the anatomical data, the nature and localization of the cavity bone defect, its size, load conditions and patterns of bone tissue neoplasm. Methods for making multi-criteria decisions have been developed, which will allow for their implementation for a wide range of optimization tasks of researching the correlation of the shape and size of porosity with indicators of the stress-deformed state of bone substitutes in order to maintain the structural integrity of the biomaterial in the process of regeneration of hard tissue. [ABSTRACT FROM AUTHOR]