Tissue Scaffolds Research Articles

Preparation of disulfiram-Cu2+-polylactide nanofibrous membranes via electrostatic spinning and evaluation of their in vitro anticancer effects

The antitumor effects of disulfiram (DSF) —a conventional medication used to treat alcohol dependence—have been documented in numerous studies. However, because of its low water solubility and Cu2+-dependent anticancer effects, the application of DSF in cancer therapy has been limited. Nanofibrous membranes produced via electrospinning have large specific surface areas. Consequently, they have been extensively used in biomedical applications, such as tissue scaffolding, drug delivery. In this study, a polylactic acid nanofibrous membrane was designed to encapsulate Cu2+ and DSF. The encapsulated drug was released when the membranes came into contact with the tumor tissue. DSF functioned as a Cu-ion carrier and combined with Cu2+ to induce tumor-cell apoptosis. The anticancer properties of the drug-loaded nanofibrous membrane were verified at the cellular level using in vitro experiments with cells. The results indicated that DSF and Cu2+ were released from the fiber membrane, and the combination of DSF and Cu2+ exhibited a better of cancer are proposed.

Fabrication, characterisation, physicochemical and biological studies of gelatin/PVA/ silk fibre with manganese substituted hydroxyapatite scaffold for bone tissue engineering application

In recent years, researchers have been aiming for the development of multifunctional materials to repair bone tissue. The development of metal, ceramic, glass, and composite implants is the subject of interest in bone tissue engineering. Among these, HAP (ceramic) is either combined with other components, such as polymers or doped with ions to give improved properties or to add novel characteristics. The present study is focused on fabricating a novel scaffold with the required properties. Here gelatin/PVA/SF-Mn-HAP (MGPS) was fabricated by electrospinning to prepare a nano-level scaffold. The manganese-hydroxyapatite (Mn-HAP) was prepared by hydrothermal method. The nano scaffold was fabricated using various wt % (20, 40, 60) of Mn-HAP (Ca5-x Mnx (PO4)3 OH) (x = 0.1, 0.5) with gelatin/PVA/silk fibre. The fabricated nano scaffold phase formation was confirmed by X-ray diffraction (XRD), the functional group belonging to the nano scaffold was confirmed by Fourier transform infrared spectroscopy (FTIR), the topography of the nano scaffold was seen by scanning electron microscopy and the composition of elements was noted from energy dispersive X-ray analysis (EDAX). From the results, the fabricated scaffold MGPS 16 (60 wt% of Mn-HAP (x = 0.5 M) with gelatin-PVA-silk fibre) showed the highest tensile strength of 95.61 MPa. The antimicrobial activity of MGPS 16 showed the zone of inhibition against S. aureus – 62 ± 1.36 mm,E. coli – 71 ± 1.24 mm and C. albicans – 70 ± 1.22 mm. The hemolytic (%) of the MGPS 16 was 1.86 %. The SEM images of biomineralized samples showed the formation of apatite on the surface of the nano-composite.

Antibacterial Properties of PCL@45s5 Composite Biomaterial Scaffolds Based on Additive Manufacturing

This study focuses on the development of polymer–bioglass composite bone scaffolds for the treatment of bone defects. PCL particles and 45s5 bioglass powder were employed as raw materials to fabricate PCL/45s5 composite wires with mass fractions of 5 wt%, 10 wt%, and 20 wt% via the twin-screw extrusion method. A cylindrical porous model was established using 3D modeling software, and a porous composite scaffold was constructed through the melt deposition manufacturing process. The macroscopical characterization of composite stock and composite powder was analyzed. The melt flow rate, water contact angle, elastic modulus, in vitro degradation rate, and antibacterial property of composite scaffold were measured. The experimental results showed that the incorporation of 45s5 bioglass into PCL material gave the composite better antibacterial properties, effectively reduced the flow rate of the material, increased the hydrophobicity of the material, and improved the rigidity and biocompatibility of the PCL material. This study offers initial insights into the use of synthetic bone tissue engineering scaffolds for clinical bone repair treatments.

Models to study myelodysplastic syndrome and acute myeloid leukaemia.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematological malignancies characterized by complex genetic alterations, leading to poor clinical outcomes. Despite advances in treatment, there is an urgent need for novel therapeutic approaches. This review outlines recent progress in humanized models of MDS and AML and highlight their role in advancing our understanding of these diseases. Patient derived xenografts (PDXs) were among the first humanized models for studying MDS and AML, allowing researchers to analyze patient-specific cancer properties in vivo. However, they face challenges related to sample availability and consistent engraftment in mice. New methods, including specialized mouse strains and human tissue scaffolds, have been developed to address these issues. Induced pluripotent stem cells (iPSCs) offer the advantage of indefinite expansion and genetic modification, making them valuable for in vitro research, though protocols to enhance their engraftment in vivo are still being refined. Genetically engineered human primary hematopoietic stem and progenitor cells (HSPCs) provide reliable in vivo models with good engraftment in mice, and recent advancements in culture systems and gene-editing techniques are helping to overcome challenges related to ex vivo expansion and genetic modification. PDXs, iPSCs, and genetically engineered HSPCs are crucial models for the study of MDS and AML. This review discusses strengths, limitations, and recent advancements of these humanized models, which provide insights into human-specific disease biology and therapeutic development.

Rapid curing dynamics of PEG-thiol-ene resins allow facile 3D bioprinting and in-air cell-laden microgel fabrication

Thiol-norbornene photoclick hydrogels are highly efficient in tissue engineering applications due to their fast gelation, cytocompatibility, and tunability. In this work, we utilized the advantageous features of polyethylene glycol (PEG)-thiol-ene resins to enable fabrication of complex and heterogeneous tissue scaffolds using 3D bioprinting and in-air drop encapsulation techniques. We demonstrated that photoclickable PEG-thiol-ene resins could be tuned by varying the ratio of PEG-dithiol to PEG norbornene to generate a wide range of mechanical stiffness (0.5-12 kPa) and swelling ratios. Importantly, all formulations maintained a constant, rapid gelation time (<0.5 s). We used this resin in biological projection microstereolithography (BioPµSL) to print complex structures with geometric fidelity and demonstrated biocompatibility by printing cell-laden microgrids. Moreover, the rapid gelling kinetics of this resin permitted high-throughput fabrication of tunable, cell-laden microgels in air using a biological in-air drop encapsulation apparatus (BioIDEA). We demonstrated that these microgels could support cell viability and be assembled into a gradient structure. This PEG-thiol-ene resin, along with BioPµSL and BioIDEA technology, will allow rapid fabrication of complex and heterogeneous tissues that mimic native tissues with cellular and mechanical gradients. The engineered tissue scaffolds with a controlled microscale porosity could be utilized in applications including gradient tissue engineering, biosensing, andin vitrotissue models.

Research progress on the repair of tendon injuries with Tissue Engineering Technology

Tendon injuries are frequently encountered in clinical practice, and traditional repair methods rarely achieve complete restoration of the tendon's original structure and functionality. The challenges of accelerating and optimizing the healing of injured tendons, enhancing the strength of the regenerated tendon, and preventing adhesion remain significant in clinical settings. Tendon tissue engineering, which combines material science, cell biology, and molecular biology, involves the synergistic application of multiple factors to create functional constructs and has become an emerging technique with promise for repair. The maximization of the regenerative potential of these elements is a critical research question. Future research should concentrate on discovering the optimal combinations of cells, biosignals, and scaffolds to produce tissue that emulates the characteristics of an undamaged, natural tendon. This review will cover various aspects, including the fabrication of tendon tissue scaffolds, the selection of seed cells, strategies for the modulation of healing-related biosignals, and provide a summary with prospective insights, aiming to enhance the comprehension of tissue engineering techniques in tendon injury repair and to inspire innovative applications in this domain.

Recent Development of Fibrous Hydrogels: Properties, Applications and Perspectives.

Fibrous hydrogels (FGs), characterized by a 3D network structure made from prefabricated fibers, fibrils and polymeric materials, have emerged as significant materials in numerous fields. However, the challenge of balancing mechanical properties and functions hinders their further development. This article reviews the main advantages of FGs, including enhanced mechanical properties, high conductivity, high antimicrobial and anti-inflammatory properties, stimulus responsiveness, and an extracellular matrix (ECM)-like structure. It also discusses the influence of assembly methods, such as fiber cross-linking, interfacial treatments of fibers with hydrogel matrices, and supramolecular assembly, on the diverse functionalities of FGs. Furthermore, the mechanisms for improving the performance of the above five aspects are discussed, such as creating ion carrier channels for conductivity, in situ gelation of drugs to enhance antibacterial and anti-inflammatory properties, and entanglement and hydrophobic interactions between fibers, resulting in ECM-like structured FGs. In addition, this review addresses the application of FGs in sensors, dressings, and tissue scaffolds based on the synergistic effects of optimizing the performance. Finally, challenges and future applications of FGs are discussed, providing a theoretical foundation and new insights for the design and application of cutting-edge FGs.

MICROWAVE REFLECTOMETRY CIRCUITS INTEGRATION WITH COAXIAL PROBE FOR INITIAL BREAST TUMOR DETECTION

A six-port reflectometry (SPR) system was developed to predict the dielectric properties of both tumor and normal breast tissue, intended for medical diagnostic applications. Ensuring precise measurements, the SPR underwent calibration using a well-established four-step procedure, which will be briefly outlined. Afterward, the investigated coaxial probe was connected to the SPR through the calibrated measurement port. Subsequently, the exposed end of the probe aperture was immersed into synthetic samples representing both healthy and cancerous breast tissue to assess the dielectric constant, εrʹ and loss factor, εrʺ across frequencies ranging from 1.5 GHz to 3.3 GHz. The dielectric constant, εrʹ and loss factor, εrʺ were derived from the measured reflection coefficient using a closed-form equation associated with the coaxial probe. An examination was undertaken to compare the performance of a commercially available vector network analyzer (VNA) outfitted with a Keysight 85070E dielectric probe against an SPR-probe system. The comparison was based on analyzing the reflection coefficient magnitude, phase shift, dielectric constant, and loss factor of synthetic breast tissue samples. The study revealed maximum absolute errors of 0.01, 1.07°, 1.12, and 0.75 for the measured reflection coefficient magnitude, phase shift, dielectric constant, and loss factor, respectively. The calibrated reflection coefficient and predicted relative permittivity, εr can be effectively utilized to distinguish between normal (εrʹ &lt; 50) and tumor (εrʹ &gt; 50) breast tissue.

CytoSpatio: Learning cell type spatial relationships using multirange, multitype point process models.

Recent advances in multiplexed fluorescence imaging have provided new opportunities for deciphering the complex spatial relationships among various cell types across diverse tissues. We introduce CytoSpatio, open-source software that constructs generative, multirange, and multitype point process models that capture interactions among multiple cell types at various distances simultaneously. On analyzing five cell types across five tissues, our software showed consistent spatial relationships within the same tissue type, with certain cell types like proliferating T cells consistently clustering across tissue types. It also revealed that the attraction-repulsion relationships between cell types like B cells and CD4-positive T cells vary with tissue type. CytoSpatio can also generate synthetic tissue structures that preserve the spatial relationships seen in training images, a capability not provided by previous descriptive, motif-based approaches. This potentially allows spatially realistic simulations of how cell relationships affect tissue biochemistry.

Electroactive covalent linkers for enhancing conducting polymer adhesion, charge transfer, and biological integration of PEDOT-coated carbon microfibers

Poly(3,4-ethylenedioxythiophene) (PEDOT)-coated carbon microfibers (PCMFs) are a key technology for developing advanced neuroprosthetic electrodes and electroactive tissue scaffolds. However, for their successful application in human therapeutics, PEDOT adhesion to the carbon substrate must be enhanced without compromising electric charge transfer. Here, electrically functional linkers are synthesized to modify the surface at the nanoscale, facilitating the covalent bonding of EDOT to carbon. The properties of the resulting microfibers are compared before and after PEDOT polymerization. PCMFs deterioration is studied by applying controlled mechanical stress in vitro or by implanting them in the rodent spinal cord in vivo. Amino phenyl-EDOT derivatives allow for efficient covalent carbon surface functionalization and PEDOT electropolymerization but substantially reduce charge transfer as assessed by chronopotentiometry, electrochemical impedance spectroscopy, and cyclic voltammetry. Nevertheless, the azido-EDOT (EDOT-Ph-N3) derivative is similarly effective for carbon surface modification, enabling PEDOT polymerization to develop a nanostructured CMF surface based on robust covalent bonds, and enhancing both electric charge transfer and PEDOT adhesion to the carbon substrate. This makes PCMFs more resistant to polymer delamination when assessed in vitro or when implanted into the neural tissue. Azido-EDOT modified PCMFs also show excellent biological integration within the spinal cord, causing negligible tissue damage and cell reactivity. Overall, azido-EDOT provides a superior electroconducting linker for anchoring PEDOT and optimizes the electrical, mechanical, and biological performance of PCMFs.

Extracellular vesicle-laden hybrid cryogel-interpenetrating network scaffold for improved osteogenesis in bone tissue engineering

Bone tissue engineering (BTE) aims to regenerate the damaged or diseased bone by combining cells, growth factors, and biomaterials. Synthetic bone tissue, which is widely available, is a promising alternative to autografts, allografts, and natural fillers. Biomaterials like 3D scaffolds mimic the extracellular matrix, supporting cell growth and tissue regeneration. However, clinical applications face challenges such as limited osteogenic and angiogenic capabilities, weak mechanical strength, and risks of infection and immune reactions. The current work introduces a mechanically robust cryogel-hydrogel hybrid scaffold, loaded with extracellular vesicles (EVs) and cell secretomes as osteoinductive cues. The scaffold’s mechanical strength was assessed against its individual components. Its physical characteristics, including swelling capacity and porous structure, were analyzed using field emission scanning electron microscopy (FESEM), and the incorporation of nano-hydroxyapatite (nHAp) was confirmed through Fourier transform infrared (FTIR) spectroscopy. Three scaffolds were tested: a cryogel scaffold of gelatin and nano-hydroxyapatite (nHAp), a hydrogel scaffold of poly(ethylene glycol) diacrylate (PEGDA), and a hybrid cryogel scaffold of gelatin and nano-hydroxyapatite with a PEGDA interpenetrating network (IPN). The results indicated that the hybrid cryogel scaffold with IPN had the greatest normalized ALP content and lowest cytotoxicity, making it the best choice for further study. To explore the osteoinductive potential of Mesenchymal Stem Cell-derived EVs, three scaffold variations were tested: a hybrid IPN scaffold, IPN + nHAp scaffold, and IPN + nHAp + EVs scaffold. These were evaluated for viable cell count, ALP activity, DNA content, and calcium accumulation. The IPN + nHAp + EVs scaffold demonstrated the greatest potential for BTE, with the highest mechanical strength—20.82-fold greater than the single-network cryogel and 1.75-fold stronger than the PEGDA hydrogel. It also showed the highest normalized ALP content, 3.39-fold and 1.47-fold greater than the IPN and IPN + nHAp scaffolds, respectively, and the highest calcium deposition, 1.30-fold higher than the IPN + nHAp scaffold. In conclusion, this study successfully developed a hybrid scaffold system with improved mechanical characteristics and osteogenesis potential, advancing the field of bone tissue engineering.

Advanced functional polymer materials for biomedical applications

AbstractPolymer structures are essential in biomedical applications due to their biocompatibility, biodegradability, and ability to form intricate structures on micro‐ to nanometer scales. This review, emphasizing electrospinning and phase inversion techniques, examines the fabrication strategies and chemical design of polymer structures for biomedical use. Electrospinning, particularly needleless electrospinning, produces nanofibres with high porosity and flexibility and is widely applied in tissue engineering and drug delivery. Phase inversion, including thermal, nonsolvent‐, vapor‐ and evaporation‐induced phase separation, allows precise control over polymer properties but faces challenges in terms of cooling rates and solvent characteristics. Chemical design through doping, functionalization, cross‐linking and copolymerization enhances the biocompatibility, biodegradability and mechanical properties of polymers, facilitating advanced applications in drug delivery, tissue scaffolding and biosensors. Advanced functional polymers are revolutionizing biomedical fields, offering innovative solutions for therapeutic medicine delivery, disease detection, diagnostics, and regenerative medicine. Despite remarkable progress, challenges, such as scalability, cost‐effectiveness, and environmental impact, persist. This review underscores the transformative potential of advanced polymer materials in medical treatments and advocates for continuous research and interdisciplinary collaboration to overcome existing challenges and fully exploit the capabilities of these materials in improving patient care and medical outcomes. Future perspectives highlight enhancing precision control mechanisms, integrating phase inversion with other techniques and developing large‐scale production methods to advance the field further.

Electrospinning Aligned SF/Magnetic Nanoparticles-Blend Nanofiber Scaffolds for Inducing Skeletal Myoblast Alignment and Differentiation.

In the realm of skeletal muscle tissue engineering, anisotropic materials that emulate natural tissues show substantial promise. Electrospun scaffolds, mimicking the fibrillar structure of the extracellular matrix, are commonly employed but often fall short in achieving optimal alignment and mechanical strength. Silk fibroin has emerged as a versatile material in tissue engineering, valued for its biocompatibility, mechanical robustness, and biodegradability. However, conventional electrospinning methods of SF result in randomly oriented fibers, limiting their efficacy. In this work, we developed a straightforward method to fabricate directional tissue scaffolds using silk fibroin. By integrating a magnetic field collecting device and incorporating Fe3O4 nanoparticles into the spinning solution, we successfully produced well-aligned silk nanofiber scaffolds. These aligned fibers not only improved scaffold orientation and mechanical properties but also exhibited magnetic responsiveness. The aligned SF scaffolds effectively guided the adhesion, proliferation, and differentiation of mesenchymal stem cells along the fiber direction. Cultured on these scaffolds, myoblast C2C12 cells demonstrated oriented growth, highlighting the potential of aligned SF fibers in advancing skeletal muscle engineering for biomedical applications.

Application of electrospinning and 3D-printing based bilayer composite scaffold in the skull base reconstruction during transnasal surgery

Skull base defects are a common complication after transsphenoidal endoscopic surgery, and their commonly used autologous tissue repair has limited clinical outcomes. Tissue-engineered scaffolds prepared by advanced techniques of electrostatic spinning and three-dimensional (3D) printing was an effective way to solve this problem. In this study, soft tissue scaffolds consisting of centripetal nanofiber mats and 3D-printed hard tissue scaffolds consisting of porous structures were prepared, respectively. And the two layers were combined to obtain bilayer composite scaffolds. The physicochemical characterization proved that the nanofiber mat prepared by polylactide-polycaprolactone (PLCL) electrospinning had a uniform centripetal nanofiber structure, and the loaded bFGF growth factor could achieve a slow release for 14 days and exert its bioactivity to promote the proliferation of fibroblasts. The porous scaffolds prepared with polycaprolactone (PCL), and hydroxyapatite (HA) 3D printing have a 300 μm macroporous structure with good biocompatibility. In vivo experiments results demonstrated that the bilayer composite scaffold could promote soft tissue repair of the skull base membrane through the centripetal nanofiber structure and slow-release of bFGF factor. It also played the role of promoting the regeneration of the skull base bone tissue. In addition, the centripetal nanofiber structure also had a promotional effect on the regeneration of skull base bone tissue.

A biodegradable piezoelectric scaffold promotes spinal cord injury nerve regeneration

Neural repair and regeneration remain one of the greatest challenges in regenerative medicine. The incorporation of intelligent scaffolds with noninvasive in vivo electrical stimulation illustrates considerable potential for tissue repair and regeneration. Nevertheless, the development of biomaterials that possess both biodegradable tissue scaffolds and electrical stimulation capabilities at a high level remains a significant obstacle. In this study, we effectively integrated the organic piezoelectric material poly-L-lactic acid (PLLA) with inorganic piezoelectric nanowires (potassium sodium niobate coated with polydopamine, KNN@PDA) to fabricate PLLA/KNN@PDA piezoelectric composite fibers. These fibers exhibit in-situ electrical stimulation capabilities, rendering them suitable for direct application in living tissues. The PLLA/KNN@PDA piezoelectric composite fibers not only function as biodegradable scaffolds for regenerative tissue engineering and platforms for in-situ electrical stimulation to enhance dorsal root ganglion axon growth, proliferation, and neuronal differentiation but also serve as versatile scaffolds for broader tissue engineering applications. In the complete spinal cord transection rat model, the piezoelectric scaffold enabled the recovery of rat motor function, indicating its significant ability to promote tissue formation and regeneration. Therefore, combining biodegradable piezoelectric tissue scaffolds with in situ electrical stimulation has significant therapeutic advantages for spinal cord injury repair and may be extended to other damaged tissues regeneration.

Folic acid modified silver nanoparticles promote endothelialization and inhibit calcification of decellularized heart valves by immunomodulation with anti-bacteria property

Xenogeneic decellularized heart valves (DHVs) have become one of the most commonly used scaffolds for tissue engineered heart valves (TEHVs) due to extensive resources and possessing the distinct three-layer structure similar to native heart valves. However, DHVs as scaffolds face the shortages such as poor mechanical properties, proneness to thrombosis and calcification, difficulty in endothelialization and chronic inflammatory responses etc., which limit their applications in clinic. In this work, we constructed a novel TEHV with immunomodulatory functions by loading folic acid modified silver nanoparticles (FS NPs) on DHVs to overcome these issues. The FS NPs preferentially targeted M1 macrophages and reduced their intracellular H2O2 level, resulting in polarizing them into M2 phenotype. The increased M2 macrophages facilitated to eliminate inflammation, recruit endothelial cells, and promote their proliferation and endothelialization by secreting relative factors. We founded that FS NPs with the size of 80 nm modified DHVs (FSD-80) performed optimally on cytocompatibility and regulating macrophage phenotype ability in vitro. In addition, the FSD-80 had excellent mechanical properties, hemocompatibility and anti-bacteria property. The results of the subcutaneous implantation in rats revealed that the FSD-80 also had good performance in regulating macrophage phenotype, promoting endothelialization, remolding the extracellular matrix and anti-calcification in vivo. Therefore, FS NPs-loaded DHVs possess immunomodulatory functions, which is a feasible and promising strategy for constructing TEHVs with excellent comprehensive performance.

3D Bioprinted Chondrogenic Gelatin Methacrylate-Poly(ethylene glycol) Diacrylate Composite Scaffolds for Intervertebral Disc Restoration

Abstract Degenerative spine pathologies, including intervertebral disc (IVD) degeneration, present a significant healthcare challenge due to their association with chronic pain and disability. This study explores an innovative approach to IVD regeneration utilizing 3D bioprinting technology, specifically visible light-based digital light processing (VL-DLP), to fabricate tissue scaffolds that closely mimic the native architecture of the IVD. Utilizing a hybrid bioink composed of gelatin methacrylate (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) at a 10% concentration, we achieved enhanced printing fidelity and mechanical properties suitable for load-bearing applications such as the IVD. Preconditioning rat bone marrow-derived mesenchymal stem cell (rBMSC) spheroids with chondrogenic media before incorporating them into the GelMA-PEGDA scaffold further promoted the regenerative capabilities of this system. Our findings demonstrate that this bioprinted scaffold not only supports cell viability and integration but also contributes to the restoration of disc height in a rat caudal disc model without inducing adverse inflammatory responses. The study underscores the potential of combining advanced bioprinting techniques and cell preconditioning strategies to develop effective treatments for IVD degeneration and other musculoskeletal disorders, highlighting the need for further research into the dynamic interplay between cellular migration and the hydrogel matrix.

Meniscal scaffolds based on self-healable elastomer-hydrogel composites with biomimetic structure and tribological properties for repairing meniscal injuries

Meniscal injuries are increasing dramatically with the aging of the population and the prevalence of sports. Tissue engineering technology is the most promising method for the treatment of meniscal injuries, but the preparation of long-term and durable meniscal scaffolds with mechanical and tribological properties like natural articular cartilage remains a great challenge. Here, inspired by the structure and lubrication mechanism of the meniscus, a durable meniscus scaffold with bionic 3D structure, self-lubrication, and intelligent drug release function is prepared. An elastomer-hydrogel composite consisting of a direct ink writing (DIW) printed elastomer skeleton and a hydrogel matrix is prepared for the meniscus scaffold. The bionic 3D structure of the scaffolds is realized by combining computer-aided structural design and 3D printing technology. The self-healing ability obtained by incorporating dynamic covalent bonds, and the robust interface achieved by co-curing of the elastomer and hydrogel resins, ensure the stability and durability of the composite meniscal scaffolds. Taking advantage of the coexistence of aqueous and oily phases in the emulsion-type hydrogel resin, a hydrophobic phospholipid is loaded into the hydrogel, and achieves excellent boundary lubrication of the composite through its fiction-response release and self-assembly. Moreover, the meniscus scaffolds enable intelligent drug release to adapt to the physiological characteristics during inflammation. In vivo tests in rabbit models validate the protective effect of the scaffold on cartilage. These methods and concepts provide a solid foundation for the preparation of bionic tissue scaffolds.

An in vivo screen for proteolytic switch domains that can mediate Notch activation by force.

Notch proteins are single pass transmembrane receptors activated by sequential extracellular and intramembrane cleavages that release their cytosolic domains to function as transcription factors in the nucleus. Upon binding, Delta/Serrate/LAG-2 (DSL) ligands activate Notch by exerting a "pulling" force across the intercellular ligand/receptor bridge. This pulling force is generated by Epsin-mediated endocytosis of ligand into the signal-sending cell, and results in the extracellular cleavage of the force-sensing Negative Regulatory Region (NRR) of the receptor by an ADAM10 protease [Kuzbanian (Kuz) in Drosophila ]. Here, we have used chimeric Notch and DSL proteins to screen for other domains that can function as ligand-dependent proteolytic switches in place of the NRR in the developing Drosophila wing. While many of the tested domains are either refractory to cleavage or constitutively cleaved, we identify several that mediate Notch activation in response to ligand. These NRR analogues derive from widely divergent source proteins and have strikingly different predicted structures. Yet, almost all depend on force exerted by Epsin-mediated ligand endocytosis and cleavage catalyzed by Kuz. We posit that the sequence space of protein domains that can serve as force-sensing proteolytic switches in Notch activation is unexpectedly large, a conclusion that has implications for the mechanism of target recognition by Kuz/ADAM10 proteases and is consistent with a more general role for force dependent ADAM10 proteolysis in other cell contact-dependent signaling mechanisms. Our results also validate the screen for increasing the repertoire of proteolytic switches available for synthetic Notch (synNotch) therapies and tissue engineering.

Nanozyme-enhanced enzyme control: Computational strategies for precise and sustained enzymatic activity in tissue engineering

Nanomaterials are revolutionizing tissue engineering by significantly enhancing enzyme-mediated chemical processes and cellular activities, thereby advancing the development of more effective therapeutic strategies. This research delves into the intricate dynamics of enzyme diffusion within tissue matrices, providing a comprehensive computational modeling framework aimed at optimizing enzyme concentration control in tissue scaffolds. Through advanced numerical algorithms and computational analysis, the study simulates optimal control strategies for regulating nanozyme levels, ensuring precise and sustained enzymatic activity within the scaffolds. A novel aspect of this work is the integration of videographic records, which offers an enriched understanding of the complex interactions between nanomaterials and biological tissues, providing detailed insights into the system’s operational dynamics. The study bridges the gap between experimental methodologies and theoretical models, aligning with the cutting-edge research in chemical physics and physical chemistry by offering novel approaches to tissue engineering challenges. The findings underscore the critical role of nanomaterials in achieving precise enzymatic control, which is pivotal for the development of advanced biomimetic systems and improved therapeutic outcomes. This work contributes to the ongoing frontier research in physical phenomena within chemistry, biology, and materials science, by providing significant new insights into enzyme delivery mechanisms and their application in biomedical contexts. The research not only highlights the importance of innovative methodologies in tissue engineering but also sets the stage for future experimental validations and potential clinical applications