Drug discovery of N-methyl-pyrazole derivatives as potent selective estrogen receptor degrader (SERD) for the treatment of breast cancer.

Nowadays, ERα is considered to be a primary target for the treatment of breast cancer, and selective estrogen receptor degraders (SERDs) are emerging as promising antitumor agents. By analysing ERα-SERDs complexes, the pharmacophore features of SERDs and the crucial protein-ligand interactions were identified. Then, by utilizing the scaffold-hopping and bioisosteres strategy, 23 novel derivatives were designed, synthesized and biologically evaluated. Among these derivatives, A20 exhibited potent ERα binding affinity (IC50 = 24.0 nM), degradation ability (EC50 = 5.3 nM), excellent ER selectivity, and outstanding anti-proliferative effects on MCF-7 cells (IC50 = 0.28 nM). Further biological studies revealed that A20 could degrade ERα through proteasome-mediated pathway, suppress signal transduction of MCF-7 cells, and arrest the cell cycle in G1 phase. Moreover, A20 showed excellent antitumor effect (TGI = 92.98 %, 30 mg kg-1 day-1) in the MCF-7 xenograft model in vivo with good safety and favorable pharmacokinetics (F = 39.6 %), making it a promising candidate for the treatment of breast cancer.

A bioengineered tumor matrix-based scaffold for the evaluation of melatonin efficacy on head and neck squamous cancer stem cells.

Head and neck squamous cell carcinoma (HNSCC) presents a significant challenge worldwide due to its aggressiveness and high recurrence rates post-treatment, often linked to cancer stem cells (CSCs). Melatonin shows promise as a potent tumor suppressor; however, the effects of melatonin on CSCs remain unclear, and the development of models that closely resemble tumor heterogeneity could help to better understand the effects of this molecule. This study developed a tumor scaffold based on patient fibroblast-derived decellularized extracellular matrix that mimics the HNSCC microenvironment. Our study investigates the antitumoral effects of melatonin within this context. We validated its strong antiproliferative effect on HNSCC CSCs and the reduction of tumor invasion and migration markers, even in a strongly chemoprotective environment, as it is required to increase the minimum doses necessary to impact tumor viability compared to the non-scaffolded tumorspheres culture. Moreover, melatonin exhibited no cytotoxic effects on healthy cells co-cultured in the tumor hydrogel. This scaffold-based platform allows an in vitro study closer to HNSCC tumor reality, including CSCs, stromal component, and a biomimetic matrix, providing a new valuable research tool in precision oncology.

Efficacy and Safety of Cell-Assisted Acellular Adipose Matrix Transfer for Volume Retention and Regeneration Compared to Hyaluronic Acid Filler Injection.

BACKGROUND: Cell-assisted acellular adipose matrix (AAM) transfer is a novel technique for soft tissue volume restoration, where AAM acts as a scaffold for tissue proliferation and promotes host cell migration, vascularization, and adipogenesis. This study aimed to evaluate the efficacy and safety of in vivo cell-assisted AAM transfer compared to hyaluronic acid (HA) filler injection. METHODS: Human adipose tissue was used to manufacture AAM, and murine adipose-derived stem cells (ASCs) were prepared. Nude mice were divided into four groups: AAM transfer (AT), ASC-assisted AAM transfer (CAT), HA filler injection (HI), and ASC-assisted HA filler injection (CHI). Eight weeks post-transfer, in vivo graft volume/weight, histology, and gene expression were analyzed to assess efficacy and safety. RESULTS: The AAM retained its three-dimensional scaffold structure without cellular components. AT/CAT showed lower volume retention than HA/CHA; however, CAT maintained a similar volume to HA. Histologically, adipogenesis and collagen formation were increased in AT/CAT compared to HA/CHA, with CAT showing the highest levels. CAT also demonstrated superior angiogenesis, adipogenesis, and gene expression (Vegf and Pparg), along with lower Il-6 expression, higher Il-10 expression, and reduced capsule formation, indicating better biocompatibility. CONCLUSIONS: Cell-assisted AAM transfer is a promising technique for volume retention and tissue regeneration, offering a safe and effective alternative to HA filler injections. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Combining human liver ECM with topographically featured electrospun scaffolds for engineering hepatic microenvironment.

Liver disease cases are rapidly expanding worldwide, and transplantation remains the only effective cure for end-stage disease. There is an increasing demand for developing potential drug treatments, and regenerative therapies using in-vitro culture platforms. Human decellularized extracellular matrix (dECM) is an appealing alternative to conventional animal tissues as it contains human-specific proteins and can serve as scaffolding materials. Herein we exploit this with human donor tissue from discarded liver which was not suitable for transplant using a synergistic approach to combining biological and topographical cues in electrospun materials as an in-vitro culture platform. To realise this, we developed a methodology for incorporating human liver dECM into electrospun polycaprolactone (PCL) fibres with surface nanotopographies (230-580 nm). The hybrid scaffolds were fabricated using varying concentrations of dECM; their morphology, mechanical properties, hydrophilicity and stability were analysed. The scaffolds were validated using HepG2 and primary mouse hepatocytes, with subsequent results indicating that the modified scaffolds-maintained cell growth and influenced cell attachment, proliferation and hepatic-related gene expression. This work demonstrates a novel approach to harvesting the potential from decellularized human tissues in the form of innovative in-vitro culture platforms for liver.

Advances in Tissue Engineering and Its Future in Regenerative Medicine Compared to Traditional Reconstructive Techniques: A Comparative Analysis.

Tissue engineering represents a revolutionary approach in regenerative medicine, offering promising alternatives to traditional reconstructive techniques. This systematic review explores recent advances in tissue engineering, comparing their efficacy, postoperative outcomes, and patient satisfaction to conventional methods. A comprehensive literature search was conducted across PubMed, Cochrane Library, and Google Scholar, covering studies published from 2000 to 2024. Fourteen studies were selected for final analysis based on inclusion criteria focusing on outcomes such as scar quality, postoperative pain, and patient satisfaction. The review demonstrated that tissue engineering techniques consistently provided superior cosmetic outcomes with minimal scarring compared to traditional methods. Patients undergoing tissue-engineered procedures experienced mild-to-moderate postoperative pain with rapid resolution, whereas traditional techniques resulted in moderate to severe pain requiring extended management. Furthermore, patients treated with tissue engineering reported high satisfaction rates due to improved cosmetic and functional outcomes. Despite challenges such as ensuring adequate vascularization, controlling scaffold degradation, and overcoming regulatory and cost barriers, ongoing research and development are essential to fully realize the potential of these innovative therapies. Tissue engineering offers significant advantages over traditional reconstructive techniques and has the potential to profoundly improve patient care in regenerative medicine.

Synthesis, structures, and cytotoxicity insights of organotin(IV) complexes with thiazole-appended pincer ligand.

Diorganotin complexes of the compositions [Me2Sn(L)] (1), [n-Bu2Sn(L)] (2), [Ph2Sn(L)]⋅C6H6 (3), [Bz2Sn(L)]⋅C6H6 (4) and [n-Oct2Sn(L)] (5) were synthesized by reacting R2SnO (R = Me, n-Bu, Ph, Bz or n-Oct) with the N2,N6-di(thiazol-2-yl)pyridine-2,6-dicarboxamide (H2L, where H2 denotes the two acidic protons) in refluxing toluene. Additionally, the mono-n-butyltin complex [n-BuSn(HL)Cl2]·H2O (6) was synthesized from n-BuSnCl3 and H2L in acetonitrile. Compounds were characterized by FT-IR, 1H, 13C and 119Sn NMR spectroscopy, while their solid-state structures were examined using single-crystal X-ray diffraction studies. In diorganotin compounds 1-5, the dianionic tridentate ligands (Npy, N-, N-) act as κ-N3 chelators. In 6, the L moiety (O, Npy, N-) acts as a κ-ON2 tridentate chelator, with involvement of one of the carboxamide oxygen atoms. The coordination polyhedron around the Sn(IV) ion is completed either by two axial Sn-R ligands in compounds 1-5 or by n-Bu and Cl ligands in compound 6, giving rise to distorted trigonal bipyramid or octahedral structures, respectively. The tin NMR results show that the penta-coordinated structures of compounds 1-5 and the hexacoordinated structure of compound 6, observed in the solid-state, are retained in solution. The in vitro antitumor activities of 1-5 were tested on T-47D breast cancer cells. Of these, diphenyltin compound 3 showed the highest anti-proliferative effect, with an IC50 of 10 ± 1.60 µM. Compound 3 exhibited selective toxicity, potentially inducing apoptosis via reactive oxygen species generation and nuclear changes, indicating promise as a breast cancer treatment. This study is the first to explore thiazole-appended organotin compounds for cytotoxicity.

Potential Role of Benzoic Acid and its Synthetic Derivatives to Alleviate Cancer: An Up-to-Date Review.

Unregulated cell division is one of the main causes of cancer. These cancerous cells negatively impact nearby healthy cells. Cancer can occur anywhere in the body. Normal cell division occurs when cells grow, reproduce, and divide as the body needs. As a normal cascade of cell growth and division, when the cells get damaged, they undergo death, and normal cells develop. However, sometimes, this process is not followed, and abnormal or damaged cells start to grow and multiply several times more than normal. This particular process may form the basis of cancer. There is a research gap in terms of identifying personalized synthetic anticancer therapy, which may be based on individual patient characteristics with an aim to optimize treatment efficacy and minimize adverse effects. While searching for new bioactive compounds, it has been observed that organic molecules with benzoic acid (BA) moiety possess significant anticancer potential. Several works of literature reported the use of BA from natural or synthetic sources to synthesize bioactive chemicals. It has been observed that several natural products also contain BA moiety, and the presence of this moiety is considered responsible for several important biological activities. Therefore, in order to chemically synthesize a wide variety of potent biologically active compounds, benzoic acid as a basic moiety in the form of a scaffold can be employed. Other synthetic compounds with BA scaffolds include furosemide, tetracaine, and bumetanide. The current article aims to focus on past and present work done on BA derivatives and to emphasize the molecular pathways involved in cancer treatment. The future prospects for research in this area are encouraging as researchers are striving to advance synthetic BA derivatives. This could possibly contribute to more efficient treatments and better results for cancer patients.

Mechanical deviation in 3D-Printed PLA bone scaffolds during biodegradation.

Large or carcinogenic bone defects may require a challenging bone tissue scaffold design ensuring a proper mechanobiological setting. Porosity and biodegradation rate are the key parameters controlling the bone-remodeling process. PLA presents a great potential for geometrically flexible 3-D scaffold design. This study aims to investigate the mechanical variation throughout the biodegradation process for lattice-type PLA scaffolds using both experimental observations and simulations. Three different unit-cell geometries are used for creating the scaffolds: basic cube (BC), body-centered structure (BCS), and body-centered cube (BCC). Three different porosity ratios, 50 %, 62.5 %, and 75 %, are assigned to all three structures by altering their strut dimensions. 3-D printed scaffolds are soaked in PBS solution at 37 °C for 15, 30, 60, 90, and 120 days both unloaded and under dead load. Water absorption, weight loss, and compression stiffness are measured to characterize the first-stage degradation and investigate the possible influences of these parameters on the whole biodegradation process. The strength reduction stage of biodegradation is simulated by solving pseudo-first-order kinetics-based molecular weight change equation using FEA with equisized cubic (voxel-like) elements. For the first stage, mechanical load does not have a statistically significant effect on biodegradation. BCC with 62.5 % porosity shows a maximum water absorption rate of around 25 % by the 60th day which brings an advantage in creating an aquatic environment for cell growth. Results indicate a significant water deposition inside almost all scaffolds and water content is determined to be the main reason for the retained or increased compression stiffness. A distinguishable stiffness increase in the initial degradation process occurs for 75 % porous BC and 50 % porous BCC scaffolds. Following the quasi-stable stage of biodegradation, almost all scaffolds lost their rigidity by around 44-48 % within 120 days based on numerical results. Therefore, initial stiffness increase in the quasi-stable stage of biodegradation can be advantageous and BCC geometry with a porosity between 50% and 62 % is the optimum solution for the whole biodegradation process.

Laser powder bed fusion printed poly-ether-ether-ketone/bioactive glass composite scaffolds with dual-scale pores for enhanced osseointegration and bone ingrowth.

Although poly-ether-ether-ketone (PEEK) implants hold significant medical promise, their bioinert nature presents challenges in osseointegration and bone ingrowth within clinical contexts. To mitigate these challenges, the present study introduces Diamond PEEK/bioactive glass (BG) composite scaffolds, characterized by macro/micro dual-porous structures, precisely fabricated via laser powder bed fusion (LPBF) technology. The findings indicate that an increase in BG content within these scaffolds significantly augments their hydrophilicity and hydroxyapatite formation capacities. Stress-strain curve analysis demonstrates reliable load-bearing stability across all scaffold types. In vitro assessments confirmed the non-cytotoxicity of PEEK/BG samples and demonstrated improved osteogenic differentiation and mineralization with increased BG incorporation. Further, in vivo experiments illustrated that the Diamond porous structure of these scaffolds facilitated bone growth, an effect notably amplified with higher BG content. Particularly in groups with 15 wt% and 25 wt% BG scaffolds, new bone formation was observed not only within the macropores of the Diamond structure but also within the micropores inside the scaffold rod, suggesting an almost seamless fusion with the new bone. This demonstrates the scaffolds' effective osteointegration and bone ingrowth properties. This study conclusively established the effectiveness of Diamond-structured PEEK/BG composite scaffolds, fabricated via LPBF, in bone repair. It highlights the crucial role of BG in enhancing osteogenic potential through interaction with the macro/micro pores of the scaffold. STATEMENT OF SIGNIFICANCE: This study addresses the bioinert nature of PEEK implants by developing Diamond-structured PEEK/bioactive glass (BG) composite scaffolds by laser powder bed fusion. The dual-porous macro/microstructure enhances hydrophilicity and hydroxyapatite formation, vital for bone regeneration. By adjusting the BG content, we controlled the melt viscosity and sintering rate, leading to the formation of beneficial microscale pores. These pores resolve the issue of ineffective bioactive fillers in previous LPBF-fabricated scaffolds, enhancing the osteogenic potential of BG and inducing superior bone ingrowth and osseointegration. In vitro and in vivo analyses show enhanced osteogenic differentiation, mineralization, and bone growth, underscoring the clinical potential of these scaffolds for bone repair.

Role of scaffold proteins in the heterogeneity of glioblastoma.

Glioblastoma (GB) is a highly heterogeneous type of incurable brain cancer with a low survival rate. Intensive ongoing research has identified several potential targets; however, GB is marred by the activation of multiple pathways, and thus common targets are highly sought. The signal regulatory scaffold IQGAP1 is an oncoprotein implicated in GB. IQGAP1 nucleates a myriad of pathways in a contextual manner and modulates many of the targets altered in GB like MAPK, NF-κB, and mTOR/PI3K/Akt1, thus positioning it as a plausible common therapeutic target. Here, we review the targets that are subjects of GB treatment clinical trials and the commonly used animal models that facilitate target identification. We propose a model in which the dysfunction of various IQGAP1 pathways can explain to a larger extent some of the GB heterogeneity and offer a platform for personalized medicine.

Targeting Bcl-2 with Indole Scaffolds: Emerging Drug Design Strategies for Cancer Treatment.

The B-cell lymphoma-2 (Bcl-2) protein family plays a crucial role as a regulator in the process of apoptosis. There is a substantial body of evidence indicating that the upregulation of antiapoptotic Bcl-2 proteins is prevalent in several cancer cell lines and original tumour tissue samples. This phenomenon plays a crucial role in enabling tumour cells to avoid apoptosis, hence facilitating the development of resistant cells against chemotherapy. Therefore, the success rate of chemotherapy for cancer can be enhanced by the down-regulation of anti-apoptotic Bcl-2 proteins. Furthermore, the indole structural design is commonly found in a variety of natural substances and biologically active compounds, particularly those that possess anti-cancer properties. Due to its distinctive physicochemical and biological characteristics, it has been highly regarded as a fundamental framework in the development and production of anti-cancer drugs. As a result, a considerable range of indole derivatives, encompassing both naturally occurring and developed compounds, have been identified as potential candidates for the treatment of cancer. Several of these derivatives have advanced to clinical trials, while others are already being used in clinical settings. This emphasizes the significant role of indole in the field of research and development of anti-cancer therapeutics. This study provides an overview of apoptosis and the structural characteristics of Bcl-2 family proteins, and mainly examines the present stage and recent developments in Bcl-2 inhibitors with an indole scaffold embedded in their structure.

Design of novel potent selective survivin inhibitors using 2D-QSAR modeling, molecular docking, molecular dynamics, and ADMET properties of new MX-106 hydroxyquinoline scaffold derivatives.

Given the critical role of survivin (BIRC5) in tumor cell regulation, developing novel inhibitors represents a promising approach for cancer therapy. This study details the design of innovative survivin inhibitors based on the hydroxyquinoline scaffold of our previously reported lead compound, MX-106. Our study identified nine compounds whose inhibitory activity is expected to be superior to that of the most active molecule in the series. These compounds demonstrated potent suppression of MDA-MB-435 breast cancer cell proliferation in vitro and exhibited enhanced metabolic stability compared to the series' most active member. To evaluate these derivatives as potential survivin inhibitors, we employed a multi-faceted approach combining 2D-QSAR methods, molecular docking, molecular dynamics, and ADMET property assessment. Our molecular modeling studies led to the design of nine novel compounds (Pred1-Pred9) predicted to exhibit potent survivin inhibitory activity based on MLR models. To assess their suitability as drug candidates, we recommend a thorough evaluation of their ADMET properties. These compounds hold promise as innovative anticancer agents targeting survivin, similar to the established MX-106.

Polyglycerol Sebacate/polycaprolactone/reduced graphene oxide composite scaffold for myocardial tissue engineering.

The aim of this research was to fabricate and evaluate polyglycerol sebacate/polycaprolactone/reduced graphene oxide (PGS-PCL-RGO) composite scaffolds for myocardial tissue engineering. Polyglycerol sebacate polymer was synthesized using glycerol and sebacic acid prepolymers, confirmed by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Six PGS-PCL-RGO composite scaffolds (S1-S6) with various weight ratios were prepared in chloroform (CF) and acetone (Ace) solvents at 8 CF:2Ace and 9 CF:1Ace volume ratios, using the electrospinning method at a rate of 1 ml/h and a voltage of 18 kV. The scaffolds' chemical composition and microstructure were characterized by FTIR, XRD, and scanning electron microscopy (SEM). Further investigations included tensile testing, contact angle testing, four-point probe testing for electrical conductivity, degradation testing, and cytotoxicity testing (MTT). The results showed that adding 2%wt RGO to the composite scaffold decreased fiber diameter and degradation rate, while increasing electrical conductivity and ductility. The 33%PGS-65%PCL-2%RGO (S3) composite scaffold exhibited the lowest degradation rate (23.87 % over 60 days) and the highest electrical conductivity (51E-3 S/m). Mechanical evaluations revealed an elastic modulus of 2.46 MPa and elongation of 62.43 %, aligning closely with the heart muscle's elastomeric properties. The contact angle test indicated that the scaffold was hydrophilic, with a water contact angle of 61 ± 2°. Additionally, the cell toxicity test confirmed that scaffolds containing RGO were non-toxic and supported good cell viability. In conclusion, the 33%PGS-65%PCL-2%RGO composite scaffold exhibits mechanical and structural properties similar to heart tissue, making it an ideal candidate for myocardial tissue engineering.

Application of polydopamine-modified triphasic PLA/PCL-PLGA/Mg(OH)2-velvet antler polypeptides scaffold loaded with fibrocartilage stem cells for the repair of osteochondral defects.

Articular cartilage defects often involve damage to both the cartilage and subchondral bone, requiring a scaffold that can meet the unique needs of each tissue type and establish an effective barrier between the bone and cartilage. In this study, we used 3D printing technology to fabricate a tri-phasic scaffold composed of PLA/PCL-PLGA/Mg(OH)2, which includes a cartilage layer, an osteochondral interface, and a bone layer. The scaffold was filled with Velvet antler polypeptides (VAP), and its characterization was assessed using compression testing, XRD, FTIR, SEM, fluorescence microscopy, and EDS. In vitro investigation demonstrated that the scaffold not only supported osteogenesis but also promoted chondrogenic differentiation of fibrocartilage stem cells (FCSCs). n vivo experiments showed that the tri-phasic PLA/PCL-PLGA/Mg(OH)2-VAP scaffold together with FCSC, when transplanted to animal models, increased the recovery of osteochondral defects. Those results demonstrate the promising future of illustrated tri-phasic PLA/PCL-PLGA/Mg(OH)2-VAP scaffold loaded with FCSCs as a new bone and cartilage tissue engineering approach for osteochondral defects treatment.

3D Scaffold-Based Culture System Enhances Preclinical Evaluation of Natural Killer Cell Therapy in A549 Lung Cancer Cells.

Cell-based immunotherapies have emerged as promising cancer treatment modalities, demonstrating remarkable clinical efficacy. As interest in applying immune cell-based therapies to solid tumors has gained momentum, experimental models that enable long-term monitoring and mimic clinical administration are increasingly necessary. This study explores the potential of scaffold-based cell culture technologies, specifically three-dimensional (3D) extracellular matrix (ECM)-like frameworks, as promising solutions. These frameworks facilitate unhindered immune cell growth and enable continuous cancer cell culture. The three-dimensional (3D) cell culture model was developed using tailored scaffolds for natural killer (NK) cell culture. Within this framework, A549 lung cancer cells were cocultured with NK cells, allowing real-time monitoring for up to 28 days. The expression of critical markers associated with anticancer drug resistance and epithelial-mesenchymal transition (EMT) was evaluated in cancer cells within this 3D culture context. Compared to conventional 2D monolayer cultures, this 3D scaffold-based culture revealed that solid tumor cells, specifically A549 cells, exhibited heightened resistance to anticancer drugs. Additionally, the 3D culture environment upregulated the expression of EMT markers namely vimentin, N-cadherin, and fibronectin, while NK and zEGFR-CAR-NK cells displayed anticancer effects. In the two-dimensional (2D) coculture, only zEGFR-CAR-NK cells exhibited such effects in the 3D coculture system, highlighting an intriguing inconsistency with the 2D culture model, further confirmed by in vivo experiments. This in vitro 3D cell culture model reliably predicts outcomes in NK immunotherapy experiments. Thus, it represents a valuable tool for investigating drug resistance mechanisms and assessing the efficacy of immune cell-based therapies. By bridging the gap between in vitro and in vivo investigations, this model effectively translates potential treatments into animal models and facilitates rigorous preclinical evaluations.

Advanced Biomaterials Derived from Functional Polyphosphoesters: Synthesis, Properties, and Biomedical Applications.

Polyphosphoesters (PPEs) represent an innovative class of biodegradable polymers, with the phosphate ester serving as the core repeating unit of their polymeric backbone. Recently, biomaterials derived from functionalized PPEs have garnered significant interest in biomedical applications because of their commendable biocompatibility, biodegradability, and the capacity for functional modification. This review commences with a brief overview of synthesis methodologies and the distinctive properties of PPEs, including thermoresponsiveness, degradability, stealth effect, and biocompatibility. Subsequently, the review delves into the latest applications of PPEs-based nanocarriers for drug or gene delivery and PPEs-based polymeric prodrugs and scaffolds in the biomedical field, presenting several illustrative examples for each application. By encapsulating the advancements of recent years, this review aims to offer an enhanced understanding and serve as a reference for the synthesis and biomedical applications of functional PPEs.

Graphene Oxide/Black Phosphorus Functionalized Collagen Scaffolds with Enhanced Near-Infrared Controlled In Situ Biomineralization for Promoting Infectious Bone Defect Repair through PI3K/Akt Pathway.

Infectious bone defects resulting from surgery, infection, or trauma are a prevalent clinical issue. Current treatments commonly used include systemic antibiotics and autografts or allografts. Nevertheless, therapies come with various disadvantages, including multidrug-resistant bacteria, complications arising from the donor site, and immune rejection, which makes artificial implants desirable. However, artificial implants can fail due to bacterial infections and inadequate bone fusion after implantation. Thus, the development of multifunctional bone substitutes that are biocompatible, antibacterial, osteoconductive, and osteoinductive would be of great clinical importance. This study designs and prepares 2D graphene oxide (GO) and black phosphorus (BP) reinforced porous collagen (Col) scaffolds as a viable strategy for treating infectious bone defects. The fabricated Col-GO@BP scaffold exhibited an efficient photothermal antibacterial effect under near-infrared (NIR) irradiation. A further benefit of the NIR-controlled degradation of BP was to promote biomineralization by phosphorus-driven and calcium-extracted phosphorus in situ. The abundant functional groups in GO could synergistically capture the ions and enhance the in situ biomineralization. The Col-GO@BP scaffold facilitated osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSC) by leveraging its mild photothermal effect and biomineralization process, which upregulated heat shock proteins (HSPs) and activated PI3K/Akt pathways. Additionally, systematic in vivo experiments demonstrated that the Col-GO@BP scaffold obviously promotes infectious bone repair through admirable photothermal antibacterial performance and enhanced vascularization. As a result of this study, we provide new insights into the photothermal activity of GO@BP nanosheets, their degradation, and a new biological application for them.

Bioengineered larynx and vocal folds: where are we today? A review.

The larynx is responsible for breathing, producing sound, and protecting the trachea against food aspiration through the cough reflex. Nowadays, scaffolding surgery has made it easier to regenerate damaged tissues by facilitating the influx of cells and growth factors. This review provides a comprehensive overview of the current knowledge on tissue engineering of the larynx and vocal folds. It also discusses the achievements and challenges of data sources. In conducting a literature search for relevant papers, we included 68 studies from January 2000 to November 2023, sourced from PubMed and Scholar Google databases. We found a need for collaboration between voice care practitioners, voice scientists, bioengineers, chemists, and biotechnologists to develop safe and clinically valid solutions for patients with laryngeal and vocal fold injuries. It is crucial for patients to be knowledgeable about the available choices of laryngeal tissue engineering for successful tissue repair. Although few human trials have been conducted, future works should build upon previously completedin-vivostudies in an effort to move towards more human models.

Direct extrusion of multifascicle prevascularized human skeletal muscle for volumetric muscle loss surgery.

Skeletal muscle is composed of multiple fascicles, which are parallel bundles of muscle fibers surrounded by connective tissues that contain blood vessels and nerves. Here, we fabricated multifascicle human skeletal muscle scaffolds that mimic the natural structure of human skeletal muscle bundles using a seven-barrel nozzle. For the core material to form the fascicle structure, human skeletal myoblasts were encapsulated in Matrigel with calcium chloride. Meanwhile, the shell that plays a role as the connective tissue, human fibroblasts and human umbilical vein endothelial cells within a mixture of porcine muscle decellularized extracellular matrix and sodium alginate at a 95:5 ratio was used. We assessed four types of extruded scaffolds monolithic-monoculture (Mo-M), monolithic-coculture (Mo-C), multifascicle-monoculture (Mu-M), and multifascicle-coculture (Mu-C) to determine the structural effect of muscle mimicking scaffold. The Mu-C scaffold outperformed other scaffolds in cell proliferation, differentiation, vascularization, mechanical properties, and functionality. In an in vivo mouse model of volumetric muscle loss, the Mu-C scaffold effectively regenerated the tibialis anterior muscle defect, demonstrating its potential for volumetric muscle transplantation. Our nozzle will be further used to produce other volumetric functional tissues, such as tendons and peripheral nerves.

Phloridzin functionalized gelatin-based scaffold for bone tissue engineering.

Polyphenol-functionalized biomaterials are significant in the field of bone tissue engineering (BTE) due to their antioxidant, anti-inflammatory, and osteoinductive properties. In this study, a gelatin (Gel)-based scaffold was functionalized with phloridzin (Ph), the primary polyphenol in apple by-products, to investigate its influence on physicochemical and morphological, properties of the scaffold for BTE application. A preliminary assessment of the biological properties of the functionalized scaffold was also undertaken. The Ph-functionalized scaffold (Gel/Ph) exhibited a porous structure with high porosity (71.3 ± 0.3 %), a pore size of 206.5 ± 1.7 µm, and a radical scavenging activity exceeding 70 %. This scaffold with Young's modulus of 10.8 MPa was determined to support cell proliferation and exhibited cytocompatibility with mesenchymal stem cells (MSCs). Incorporating hydroxyapatite nanoparticle (HA) in the Gel/Ph scaffold stimulated the osteogenic differentiation of key osteogenic genes, including Runx2, ALPL, COL1A1, and OSX ultimately promoting mineralization. This research highlights the promising potential of utilizing polyphenolic compounds derived from fruit waste to functionalize scaffolds for BTE applications.