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Tissue engineering applications in bone defect treatment have shown promising outcomes over the past decade. In this context, taking advantage of bioactive scaffolds mimicking the intrinsic composition of bone has resulted in remarkable effects on bone regeneration. In this study, Zirconium-based metal-organic framework, known as MOF 801, was synthesized and incorporated into the gelatin matrix as an osteoconductive agent to fabricate a nanocomposite bone scaffold by freeze-drying method. Physical and chemical characteristics of MOF 801 and nanocomposite scaffolds were analyzed using FE-SEM, EDS, XRD, ICP and FTIR. Besides, the biological activity of the prepared scaffolds was evaluated by MTT, alizarin red staining, crystal violet staining, and ALP assays. Inclusion of MOF 801 NPs into the scaffolds resulted in enhancement of their compressive strength up to 15 ± 0.05 MPa. The nanocomposite samples containing MOF 801 NPs also exhibited favorable bioactive feature that was confirmed by their apatite-forming ability on their surfaces upon immersion in SBF solution. The Zr ion and fumarate release studies illustrated sustained release profiles from the gelatin matrix, leading to both antioxidant and anti-inflammatory properties. MTT assay results affirmed biocompatibility of scaffolds containing up to 5 % w/w MOF 801, besides the crystal violet assay exhibited proper cell confluency and adhesion. Eventually, Alizarin red and ALP activity assays revealed that an increment of MOF 801 could induce calcium mineralization and Alkaline Phosphatase enzyme production in MG-63 cells confirming the potential of prepared scaffolds for related bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

Background: In bone tissue engineering segment, numerous approaches have been investigated to address critically sized bone defects via 3D scaffolds, as the amount of autologous bone grafts are limited, accompanied with complications on harvesting. Moreover, the use of bone-marrow-derived stem cells is also a limiting factor owing to the invasive procedures involved and the low yield of stem cells. Hence, research is ongoing on the search for an ideal bone graft system promoting bone growth and regeneration. Purpose of the Study: This study aims to develop a unique platform for tissue development via stem cell differentiation towards an osteogenic phenotype providing optimum biological cues for cell adhesion, differentiation and proliferation using biomimetic gelatin-based scaffolds. The use of adipose-derived mesenchymal stem cells in this study also offers an ideal approach for the development of an autologous bone graft. Methods: A gelatin-vinyl acetate-based 3D scaffold system incorporating Bioglass was developed and the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs) on the highly porous freeze-dried gelatin-vinyl acetate/ Bioglass scaffold (GB) system was analyzed. The physicochemical properties, cell proliferation and viability were investigated by seeding rat adipose tissue-derived mesenchymal stem cells (ADSCs) onto the scaffolds. The osteogenic differentiation potential of the ADMSC seeded GeVAc/bioglass system was assessed using calcium deposition assay and bone-related protein and genes and comparing with the 3D Gelatin vinyl acetate coppolymer (GeVAc) constructs. Results and Conclusion: According to the findings, the 3D porous GeVAc/bioglass scaffold can be considered as a promising matrix for bone tissue regeneration and the 3D architecture supports the differentiation of the ADMSCs into osteoblast cells and enhances the production of mineralized bone matrix. [ABSTRACT FROM AUTHOR]

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are non-coding RNAs involved in the regulation of gene expression associated with cell differentiation, proliferation, adhesion, and important biological functions such as inflammation. miRNAs play roles associated with the pathogenesis of chronic degenerative disorders including cardiovascular diseases. Understanding the influence of miRNAs and their target genes can effectively streamline the identification of key biologically active pathways that are important in the development of vascular grafts through the tissue engineering of blood vessels. To determine miRNA expression levels and identify miRNA target genes and pathways with biological roles in scaffolds that have been repopulated with adipose-derived stem cells (ASCs) generated through tissue engineering for the construction of blood vessels. miRNA quantification assays were performed in triplicate to determine miRNA expression in a total of 20 samples: five controls (natural inferior vena cava), five scaffolds recellularized with ASCs and differentiated into the endothelium (luminal layer), five samples of complete scaffolds seeded with ASCs differentiated into the endothelium (luminal layer) and smooth muscle (extraluminal layer), and five samples of ASC without cell differentiation. Several differentially expressed miRNAs were identified and predicted to modulate target genes with roles in key pathways associated with angiogenesis, vascular system control, and endothelial and smooth muscle regulation, including migration, proliferation, and growth. These findings underscore the involvement of these pathways in the regulatory mechanisms that are essential for vascular scaffold production through tissue engineering. Our research contributes to the knowledge of miRNA-regulated mechanisms, which may impact the design of vascular substitutes, and provide valuable insights for enhancing clinical practice. The molecular pathways regulated by miRNAs in tissue engineering of blood vessels (TEBV) allowed us to elucidate the main phenomena involved in cellular differentiation to constitute a blood vessel, with the main pathways being essential for angiogenesis, cellular differentiation, and differentiation into vascular smooth muscle. [ABSTRACT FROM AUTHOR]

3D printing technology is a powerful tool in scaffold engineering for biomedical applications, especially in anticancer activities and drug delivery. The present study developed a 3D-printed gelatin–alginate scaffold incorporating letrozole-loaded niosomes (Let/Nio@Gel-AL-SC) as a more effective drug delivery system. The findings showed that the fabricated niosomes appeared spherical. 3D-printed scaffolds exhibited biodegradability and sustained drug-release properties. The drug release from the scaffold was less prominent under acidic conditions than physiological ones. Cytotoxicity analysis showed that the engineered Let/Nio@Gel-AL-SC scaffold exhibited significant cytotoxicity against MCF-7 cancer cells. Gene expression analysis demonstrated a significant decrease in the expression of BCL2, CCND1, MMP2, and CDK4 genes and a notable increase in the expression of BAX and P53 genes, as well as the activity of Caspase 3/7 enzyme following treatment with Let/Nio@Gel-AL-SC. In addition, flow cytometry analysis revealed that Let/Nio@Gel-AL-SC significantly reduced necrosis and dramatically increased apoptosis. Also, the Let/Nio@Gel-AL-SC formulation exhibited a significantly greater increase in ROS values. The incorporation of letrozole-loaded niosomes into 3D printing gelatin/alginate scaffold has enhanced the efficacy of anticancer therapy. This is demonstrated by the sustained release of drugs, which indicates a promising potential for effective anticancer activity. Consequently, this combination holds promise as a potential future cancer therapy strategy. [ABSTRACT FROM AUTHOR]

In the context of tissue engineering, biofabrication techniques are employed to process cells in hydrogel-based matrices, known as bioinks, into complex 3D structures. The aim is the production of functional tissue models or even entire organs. The regenerative production of biological tissues adheres to a multitude of criteria that ultimately determine the maturation of a functional tissue. These criteria are of biological nature, such as the biomimetic spatial positioning of different cell types within a physiologically and mechanically suitable matrix, which enables tissue maturation. Furthermore, the processing, a combination of technical procedures and biological materials, has proven highly challenging since cells are sensitive to stress, for example from shear and tensile forces, which may affect their vitality. On the other hand, high resolutions are pursued to create optimal conditions for subsequent tissue maturation. From an analytical perspective, it is prudent to first investigate the printing behavior of bioinks before undertaking complex biological tests. According to our findings, conventional shear rheological tests are insufficient to fully characterize the printing behavior of a bioink. For this reason, we have developed optical methods that, complementarily to the already developed tests, allow for quantification of printing quality and further viscoelastic modeling of bioinks. [ABSTRACT FROM AUTHOR]

Chemobrionic systems have attracted great attention in material science for development of novel biomimetic materials. This study aims to design a new bioactive material by integrating biosilica into chemobrionic structure, which will be called biochemobrionic, and to comparatively investigate the use of both chemobrionic and biochemobrionic materials as bone scaffolds. Biosilica, isolated from Amphora sp. diatom, was integrated into chemobrionic structure, and a comprehensive set of analysis was conducted to evaluate their morphological, chemical, mechanical, thermal, and biodegradation properties. Then, the effects of both scaffolds on cell biocompatibility and osteogenic differentiation capacity were assessed. Cells attached to the scaffolds, spread out, and covered the entire surface, indicating the absence of cytotoxicity. Biochemobrionic scaffold exhibited a higher level of mineralization and bone formation than the chemobrionic structure due to the osteogenic activity of biosilica. These results present a comprehensive and pioneering understanding of the potential of (bio)chemobrionics for bone regeneration. [ABSTRACT FROM AUTHOR]

The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 μm). It was found that scaffolds with a mesh size of 500 μm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration. [ABSTRACT FROM AUTHOR]

3D bioprinting techniques have enabled the fabrication of irregular large‐sized tissue engineering scaffolds. However, complicated customized designs increase the medical burden. Meanwhile, the integrated printing process hinders the cellular uniform distribution and local angiogenesis. A novel approach is introduced to the construction of sizable tissue engineering grafts by employing hydrogel 3D printing for modular bioadhesion assembly, and a poly (ethylene glycol) diacrylate (PEGDA)‐gelatin‐dopamine (PGD) hydrogel, photosensitive and adhesive, enabling fine microcage module fabrication via DLP 3D printing is developed. The PGD hydrogel printed micocages are flexible, allowing various shapes and cell/tissue fillings for repairing diverse irregular tissue defects. In vivo experiments demonstrate robust vascularization and superior graft survival in nude mice. This assembly strategy based on scalable 3D printed hydrogel microcage module could simplify the construction of tissue with large volume and complex components, offering promise for diverse large tissue defect repairs. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing is dramatically improving breast reconstruction by offering customized and precise interventions at various stages of the surgical process. In preoperative planning, 3D imaging techniques, such as computer-aided design, allow the creation of detailed breast models for surgical simulation, optimizing surgical outcomes and reducing complications. During surgery, 3D printing makes it possible to customize implants and precisely shape autologous tissue flaps with customized molds and scaffolds. This not only improves the aesthetic appearance, but also conforms to the patient's natural anatomy. In addition, 3D printed scaffolds facilitate tissue engineering, potentially favoring the development and integration of autologous adipose tissue, thus avoiding implant-related complications. Postoperatively, 3D imaging allows an accurate assessment of breast volume and symmetry, which is crucial in assessing the success of reconstruction. The technology is also a key educational tool, enhancing surgeon training through realistic anatomical models and surgical simulations. As the field evolves, the integration of 3D printing with emerging technologies such as biodegradable materials and advanced imaging promises to further refine breast reconstruction techniques and outcomes. This study aims to explore the various applications of 3D printing in breast reconstruction, addressing current challenges and future opportunities. [ABSTRACT FROM AUTHOR]

Triply periodic minimal surface microarchitectures (TPMS) were developed by mathematicians and evolved in all kingdoms of living organisms. Renowned for their lightweight yet robust attributes, TPMS structures find application in diverse fields, such as the construction of satellites, aircrafts, and electric vehicles. Moreover, these microarchitectures, despite their intricate geometric patterns, demonstrate potential for application as bone substitutes, despite the inherent gothic style of natural bone microarchitecture. Here, we produced three TPMS microarchitectures, D-diamond, G-gyroid, and P-primitive, by 3D printing from hydroxyapatite. We explored their mechanical characterization and, further, implanted them to study their bone augmentation and osteoconduction potential. In terms of strength, the D-diamond and G-gyroid performed significantly better than the P-primitive. In a calvarial defect model and a calvarial bone augmentation model, where osteoconduction is determined as the extent of bony bridging of the defect and bone augmentation as the maximal vertical bone ingrowth, the G-gyroid performed significantly better than the P-primitive. No significant difference in performance was observed between the G-gyroid and D-diamond. Since, in real life, the treatment of bone deficiencies in patients comprises elements of defect bridging and bone augmentation, ceramic scaffolds with D-diamond and G-gyroid microarchitectures appear as the best choice for a TPMS-based scaffold in bone tissue engineering. [ABSTRACT FROM AUTHOR]

In exploring the challenges of bone repair and regeneration, this review evaluates the potential of bone tissue engineering (BTE) as a viable alternative to traditional methods, such as autografts and allografts. Key developments in biomaterials and scaffold fabrication techniques, such as additive manufacturing and cell and bioactive molecule-laden scaffolds, are discussed, along with the integration of bio-responsive scaffolds, which can respond to physical and chemical stimuli. These advancements collectively aim to mimic the natural microenvironment of bone, thereby enhancing osteogenesis and facilitating the formation of new tissue. Through a comprehensive combination of in vitro and in vivo studies, we scrutinize the biocompatibility, osteoinductivity, and osteoconductivity of these engineered scaffolds, as well as their interactions with critical cellular players in bone healing processes. Findings from scaffold fabrication techniques and bio-responsive scaffolds indicate that incorporating nanostructured materials and bioactive compounds is particularly effective in promoting the recruitment and differentiation of osteoprogenitor cells. The therapeutic potential of these advanced biomaterials in clinical settings is widely recognized and the paper advocates continued research into multi-responsive scaffold systems. [ABSTRACT FROM AUTHOR]

The piezoelectric property and biocompatibility of barium titanate (BTO) is exceptional, whereas its biological activity is limited. Bioactive glasses (BG) are widely recognized for osteoinductive bioactivities. Hence, it is meaningful to explore the reasonable design of BTO and BG combinations to achieve bioactive piezoelectric tissue engineering scaffolds that mimic natural bone. In this study, homogeneous core-shell particles of BTO wrapped in BG layer were firstly fabricated via a sol-gel process. Various BG weight ratios (5 wt%, 10 wt%, and 15 wt%) in BTO@BG particles have been able to achieve the shell thickness in the range of 4 nm–16 nm. Furthermore, the composite particles were three-dimensionally printed into porous scaffolds through gas extrusion using polyvinyl pyrrolidone as binders. The composite scaffolds have been extensively characterized with respect to their physical and functional properties. Desirable piezoelectric scaffolds (BTO@15BG-S) with compressive strength at ∼66 MPa, and piezoelectric constant (d 33) of ∼1.1 pC/N were obtained after sintering and polarization. Our findings indicated that higher sintering temperatures led to denser scaffolds with reduced porosity, increased compressive strength and higher d 33 constant. Additionally, an increase in the amount of BG coating promoted scaffold calcination via melt filling in pores, while reduced the piezoelectric constant d 33. Among all scaffolds, BTO@15BG-S exhibited superior ability to induce apatite formation when sintered at 1250 °C and soaked in simulated body fluid for 7 days. In vitro culture rat bone marrow mesenchymal stem cells (rBMSCs) and cellular assessments confirmed that polarized piezoelectric ceramic scaffolds could effectively enhance cell adhesion, proliferation, and osteogenic differentiation compared to unpolarized scaffolds. An increase in BG coating amount enhanced the capacity of piezoelectric ceramic scaffolds to upgrade osteogenesis activities of rBMSCs. These results rendered BTO@BG-S composite scaffolds promising candidate in the field of bone repair. [ABSTRACT FROM AUTHOR]

The choice of sterilization method for hydrogels used for cell culture influences the ease of preparing the gel. We prepared interpenetrating gelatin/calcium alginate hydrogels containing 1% (w/v) alginate and 1–16% (w/v) gelatin by molding with the mixture of gelatin/sodium alginate solution, followed by the addition of calcium ions by incubation in calcium chloride solution. It is the simplest method to prepare autoclavable gelatin/sodium hydrogel. We measured various properties of the hydrogels including volume, Young's modulus in the compression test, storage modulus, and loss modulus in the dynamic viscoelasticity measurement. The gelatin/alginate hydrogel can be easily fabricated into any shape by this method. After autoclave treatment, the hydrogel was shrunk to smaller than the original shape in similar figures. The shape of the gelatin/alginate hydrogel can be designed into any shape with the reduction ratio of the volume. Human osteosarcoma (HOS) cells adhered to the gelatin/alginate hydrogel and then proliferated. Gelatin/calcium alginate hydrogels with a high concentration are considered to be autoclavable culture substrates because of their low deformation and gelatin elution rate after autoclaving and the high amount of cells attached to the hydrogels. [Display omitted] • We prepared an autoclavable gelatin/alginate hydrogel by molding. • The gelatin/alginate hydrogel can be designed to any 2D/3D shape. • The gelatin/alginate hydrogel has good cell adhesion property and heat stability. • The gelatin/alginate hydrogel is useful as a scaffold in tissue engineering. [ABSTRACT FROM AUTHOR]

A challenge in tissue engineering and the pharmaceutical sector is the development of controlled local release of drugs that raise issues when systemic administration is applied. Strontium is an example of an effective anti-osteoporotic agent, used in treating osteoporosis due to both anti-resorptive and anabolic mechanisms of action. Designing bone scaffolds with a higher capability of promoting bone regeneration is a topical research subject. In this study, we developed composite multi-layer three-dimensional (3D) scaffolds for bone tissue engineering based on nano-hydroxyapatite (HA), Sr-containing nano-hydroxyapatite (SrHA), and poly-ε-caprolactone (PCL) through the material extrusion fabrication technique. Previously obtained HA and SrHA with various Sr content were used for the composite material. The chemical, morphological, and biocompatibility properties of the 3D-printed scaffolds obtained using HA/SrHA and PCL were investigated. The 3D composite scaffolds showed good cytocompatibility and osteogenic potential, which is specifically recommended in applications when faster mineralization is needed, such as osteoporosis treatment. [ABSTRACT FROM AUTHOR]

Extensive research and practical applications have been conducted within the biomaterials domain, focusing on polylactic acid (PLA) based composite. These composites have been explored for their favorable attributes, such as excellent processability, biodegradability, and bioactivity properties, but still lack mechanical properties. In this work, PLA-based nanocomposites were prepared by incorporating hydroxyapatite (HA) and graphene oxide (GO) via melt mixing (extruder). Filaments were obtained to develop scaffolds through 3D printing, utilizing the fused deposition method (FDM). The GO was produced using Hummer’s method and characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), and Raman Spectroscopy. The composites were analyzed using Fourier-transform infrared spectroscopy (FTIR), molecular weight, contact angle measurements, and thermal, mechanical, and rheological analysis. Adding only 0.05 wt% of GO to both PLA and PLA/HA resulted in enhancements in mechanical properties, particularly tensile strength, and significantly modified the surface properties of the materials studied. Specifically, formulation involving PLA/HA/GO was the only one to exhibit rheological properties compatible with the scaffold production process via FDM. These specific formulations were also investigated regarding cytotoxicity, and the presence of GO induces good cytocompatibility in mouse osteoblast cells (MC3T3). These results suggest that FDM technology can be used to fabricate higher-performance (mechanical and biological) scaffolds for tissue engineering. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing is an emerging technology for the construction of complex 3D constructs used for tissue engineering applications. In this study, we are proposing the preparation of 3D printing hydrogel inks consisting of the synthetic polymers poly(caprolactone) and poly(lactic acid), the biopolymer chitosan, and naturally derived gelatin. In addition, pluronic F-127 was used to improve the miscibility between the hydrophobic and hydrophilic components due to its amphiphilic character, as well as for its good 3D printability. The printability of the hydrogel inks was optimized by varying the composition, the extrusion nozzle, and the temperature, while the integrity of the 3D scaffolds was secured via sol–gel transition. The produced hydrogels with PCL-pluronic-chitosan-gelatin/15-20-4-2 wt% (PC3.75-Pl5-CG) and PLA-pluronic-chitosan-gelatin/10-20-4-2 wt% (PL2.5-Pl5-CG) presented the best printability, producing smooth and uniform porous scaffolds. The prepared hydrogels were formed via the interactions between the polymers through hydrogen bonding. Additionally, the produced hydrogels exhibited temperature-dependent swelling behavior, and the scaffolds with PCL presented lower swelling capacity than the scaffolds with PLA. The produced scaffolds presented slower hydrolyzation rate in simulated body fluid (SBF) at 25 °C compared to 37 °C. Biological studies proved that the 3D-printed porous scaffolds were non-cytotoxic and promoted human adipose-derived mesenchymal stem cell adhesion. [ABSTRACT FROM AUTHOR]

In the field of metal-based bone tissue engineering scaffolds, porous Zn-based scaffolds are expected to be one of the most promising biodegradable bone tissue engineering scaffolds due to their acceptable biocompatibility and more suitable degradation rate compared with Mg-based and Fe-based scaffolds. However, the poor mechanical strength of porous pure Zn scaffolds limits their clinical applications. To improve the mechanical properties of porous Zn scaffolds, alloying treatment has become a feasible method. In this work, porous Zn-Mg-Y alloy scaffolds were prepared by an air pressure infiltration (API) method using NaCl particles as spacing holders. The phase structures, microstructures, compressive mechanical properties, degradation properties, antibacterial abilities as well as cytotoxicity of the obtained porous Zn-Mg-Y alloy scaffolds were investigated. The experimental results suggest that the alloy scaffolds contain strengthening phases such as MgZn2 and/or Mg2Zn11 as well as Y-rich phases. Under the action of these strengthening phases, the porous Zn-Mg-Y alloy scaffolds exhibit better mechanical properties. In vitro degradation tests indicate that the strengthening phases such as MgZn2 and Mg2Zn11 in the alloy scaffolds can be preferentially degraded as sacrificial anodes. Correspondingly, the degradation rates of the porous Zn-Mg-Y alloy scaffolds in simulated body fluid (SBF) have been accelerated. Antibacterial tests imply that the porous Zn-Mg-Y alloy scaffolds possess excellent antibacterial ability against Escherichia coli similar to the porous pure Zn scaffolds. Cytotoxicity tests show that the Zn2+ concentrations in the 100% extracts prepared from the porous Zn-Mg-Y alloy scaffolds (not including Zn-3Mg-0.5Y alloy scaffold) were all lower than that prepared from the porous pure Zn scaffold. The 25% and 10% extracts prepared from all the porous Zn-Mg-Y alloy scaffolds exhibit excellent cellular activity on MC3T3-E1 cells. In summary, the porous Zn-Mg-Y alloy scaffolds have the potential to be used as bone tissue engineering scaffolds to withstand relatively large loads. [ABSTRACT FROM AUTHOR]

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2-/- mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life. [ABSTRACT FROM AUTHOR]

In the development of bone graft substitutes, a fundamental step is the use of scaffolds with adequate composition and architecture capable of providing support in regenerative processes both on the tissue scale, where adequate resistance to mechanical stress is required, as well as at the cellular level where compliant chemical–physical and mechanical properties can promote cellular activity. In this study, based on a previous optimization study of this group, the potential of a three-dimensional construct based on polycaprolactone (PCL) and a novel biocompatible Mg- and Sr-containing glass named BGMS10 was explored. Fourier-transform infrared spectroscopy and scanning electron microscopy showed the inclusion of BGMS10 in the scaffold structure. Mesenchymal stem cells cultured on both PCL and PCL-BGMS10 showed similar tendencies in terms of osteogenic differentiation; however, no significant differences were found between the two scaffold types. This circumstance can be explained via X-ray microtomography and atomic force microscopy analyses, which correlated the spatial distribution of the BGMS10 within the bulk with the elastic properties and topography at the cell scale. In conclusion, our study highlights the importance of multidisciplinary approaches to understand the relationship between design parameters, material properties, and cellular response in polymer composites, which is crucial for the development and design of scaffolds for bone regeneration. [ABSTRACT FROM AUTHOR]

The evaluation of nanostructured biomaterials and medicines is associated with 2D cultures that provide insight into biological mechanisms at the molecular level, while critical aspects of the tumor microenvironment (TME) are provided by the study of animal xenograft models. More realistic models that can histologically reproduce human tumors are provided by tissue engineering methods of co-culturing cells of varied phenotypes to provide 3D tumor spheroids that recapitulate the dynamic TME in 3D matrices. The novel approaches of creating 3D tumor models are combined with tumor tissue engineering (TTE) scaffolds including hydrogels, bioprinted materials, decellularized tissues, fibrous and nanostructured matrices. This review focuses on the use of nanostructured materials in cancer therapy and regeneration, and the development of realistic models for studying TME molecular and immune characteristics. Tissue regeneration is an important aspect of TTE scaffolds used for restoring the normal function of the tissues, while providing cancer treatment. Thus, this article reports recent advancements in the development of 3D TTE models for antitumor drug screening, studying tumor metastasis, and tissue regeneration. Also, this review identifies the significant opportunities of using 3D TTE scaffolds in the evaluation of the immunological mechanisms and processes involved in the application of immunotherapies. [ABSTRACT FROM AUTHOR]

This systematic review aims to gather evidence on the mechanisms triggered by diverse preconditioning strategies for mesenchymal stem cells (MSCs) and their impact on their potential to treat ischemic and traumatic injuries affecting the nervous system. The 52 studies included in this review report nine different types of preconditioning, namely, manipulation of oxygen pressure, exposure to chemical substances, lesion mediators or inflammatory factors, usage of ultrasound, magnetic fields or biomechanical forces, and culture in scaffolds or 3D cultures. All these preconditioning strategies were reported to interfere with cellular pathways that influence MSCs' survival and migration, alter MSCs' phenotype, and modulate the secretome and proteome of these cells, among others. The effects on MSCs' phenotype and characteristics influenced MSCs' performance in models of injury, namely by increasing the homing and integration of the cells in the lesioned area and inducing the secretion of growth factors and cytokines. The administration of preconditioned MSCs promoted tissue regeneration, reduced neuroinflammation, and increased angiogenesis and myelinization in rodent models of stroke, traumatic brain injury, and spinal cord injury. These effects were also translated into improved cognitive and motor functions, suggesting an increased therapeutic potential of MSCs after preconditioning. Importantly, none of the studies reported adverse effects or less therapeutic potential with these strategies. Overall, we can conclude that all the preconditioning strategies included in this review can stimulate pathways that relate to the therapeutic effects of MSCs. Thus, it would be interesting to explore whether combining different preconditioning strategies can further boost the reparative effects of MSCs, solving some limitations of MSCs' therapy, namely donor-associated variability. [ABSTRACT FROM AUTHOR]

Nervous system traumatic injuries are prevalent in our society, with a significant socioeconomic impact. Due to the highly complex structure of the neural tissue, the treatment of these injuries is still a challenge. Recently, 3D printing has emerged as a promising alternative for producing biomimetic scaffolds, which can lead to the restoration of neural tissue function. The objective of this work was to compare different biomaterials for generating 3D-printed scaffolds for use in neural tissue engineering. For this purpose, four thermoplastic biomaterials, ((polylactic acid) (PLA), polycaprolactone (PCL), Filaflex (FF) (assessed here for the first time for biomedical purposes), and Flexdym (FD)) and gelatin methacrylate (GelMA) hydrogel were subjected to printability and mechanical tests, in vitro cell–biomaterial interaction analyses, and in vivo biocompatibility assessment. The thermoplastics showed superior printing results in terms of resolution and shape fidelity, whereas FD and GelMA revealed great viscoelastic properties. GelMA demonstrated a greater cell viability index after 7 days of in vitro cell culture. Moreover, all groups displayed connective tissue encapsulation, with some inflammatory cells around the scaffolds after 10 days of in vivo implantation. Future studies will determine the usefulness and in vivo therapeutic efficacy of novel neural substitutes based on the use of these 3D-printed scaffolds. [ABSTRACT FROM AUTHOR]

Chitosan, a versatile biopolymer derived from chitin, has garnered significant attention in various biomedical applications due to its unique properties, such as biocompatibility, biodegradability, and mucoadhesiveness. This review provides an overview of the diverse applications of chitosan and its derivatives in the antibacterial, anticancer, wound healing, and tissue engineering fields. In antibacterial applications, chitosan exhibits potent antimicrobial properties by disrupting microbial membranes and DNA, making it a promising natural preservative and agent against bacterial infections. Its role in cancer therapy involves the development of chitosan-based nanocarriers for targeted drug delivery, enhancing therapeutic efficacy while minimising side effects. Chitosan also plays a crucial role in wound healing by promoting cell proliferation, angiogenesis, and regulating inflammatory responses. Additionally, chitosan serves as a multifunctional scaffold in tissue engineering, facilitating the regeneration of diverse tissues such as cartilage, bone, and neural tissue by promoting cell adhesion and proliferation. The extensive range of applications for chitosan in pharmaceutical and biomedical sciences is not only highlighted by the comprehensive scope of this review, but it also establishes it as a fundamental component for forthcoming research in biomedicine. [ABSTRACT FROM AUTHOR]

The integration of microfabrication and microfluidics techniques into cell culture technology has significantly transformed cell culture conditions, scaffold architecture, and tissue biofabrication. These tools offer precise control over cell positioning and enable high-resolution analysis and testing. Culturing cells in 3D systems, such as spheroids and organoids, enables recapitulating the interaction between cells and the extracellular matrix, thereby allowing the creation of human-based biomimetic tissue models that are well-suited for pre-clinical drug screening. Here, we demonstrate an innovative microfluidic device for the formation, culture, and testing of hepatocyte spheroids, which comprises a large array of patterned microwells for hosting hepatic spheroid culture in a reproducible and organized format in a dynamic fluidic environment. The device allows maintaining and characterizing different spheroid sizes as well as exposing to various drugs in parallel enabling high-throughput experimentation. These liver spheroids exhibit physiologically relevant hepatic functionality, as evidenced by their ability to produce albumin and urea at levels comparable to in vivo conditions and the capability to distinguish the toxic effects of selected drugs. This highlights the effectiveness of the microenvironment provided by the chip in maintaining the functionality of hepatocyte spheroids. These data support the notion that the liver-spheroid chip provides a favorable microenvironment for the maintenance of hepatocyte spheroid functionality. [ABSTRACT FROM AUTHOR]

This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to the low micrometric size range. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in the secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. In more detail, the dimer formation achieved by molecular self-docking showed two distinct poses, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior. [ABSTRACT FROM AUTHOR]

Silk fibroin (SF), a natural protein derived from silkworms, has emerged as a promising biomaterial due to its biocompatibility, biodegradability, degradation rate, and tunable mechanical properties. This review delves into the intrinsic attributes of SF that make it an attractive candidate for scaffold development in tissue engineering and regenerative medicine. The distinctiveness of this comprehensive review resides in its detailed exploration of recent advancements in the fabrication techniques of SF‐based fibrous scaffolds, namely electrospinning, freeze‐drying, and 3D printing. An in‐depth analysis of these fabrication techniques is conducted to illustrate their versatility in customizing essential scaffold characteristics, such as porosity, fiber diameter, and mechanical strength. The article meticulously discusses process parameters, advantages, and challenges of each fabrication technique, highlighting the innovative advancements made in the respective field. Furthermore, the review goes beyond fabrication techniques to provide an overview of the latest biomedical applications and research endeavors utilizing SF‐derived scaffolds. From nerve regeneration and wound healing to drug delivery, bone regeneration, and vascular tissue engineering, the diverse applications underscore the versatility of SF in adopting various biomedical challenges. Finally, the article emphasizes the need for standardized characterization techniques, scalable manufacturing processes, and long‐term in vivo studies. [ABSTRACT FROM AUTHOR]

3D inkjet printing is a fast, reliable, and non‐contact bottom–up approach to printing small and large models and is one of the fastest additive manufacturing technologies available. These attributes position inkjet printing as a promising tool for the additive manufacturing of biomaterials, for example, tissue engineering scaffolds. However, due to the stringent technical rheological requirements of current inkjet technologies, there is a lack of photopolymer resins suitable for the inkjet printing of biomaterials. Hence, a novel ink engineered for 3D piezoelectric inkjet printing of biomaterials is designed and developed. The novel resin leverages a biodegradable amino acid phosphorodiamidate matrix copolymerized with a dialkyne ether to modulate the viscosity. Copolymerization with commercially available thiols facilitates the photochemical thiol‐yne curing reaction. The ink exhibits optimal viscosity, eliminating the need for solvents, as well as reliable jetting and sufficiently swift curing kinetics. Furthermore, the formulation is successfully demonstrated in an industrial inkjet printhead. Notably, the resulting materials have low cytotoxicity and, hence, have significant promise in advancing the applications of 3D inkjet printing of biological scaffolds. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) are well known for their outstanding field emission (FE) performance, facilitated by their unique combination of electrical, mechanical, and thermal properties. However, if the substrate of choice is a poor conductor, the electron supply towards the CNTs can be limited, restricting the FE current. Furthermore, ineffective heat dissipation can lead to emitter–substrate bond degradation, shortening the field emitters' lifetime. Herein, temperature-stable titanium nitride (TiN) was deposited by plasma-enhanced atomic layer deposition (PEALD) on different substrate types prior to the CNT growth. A turn-on field reduction of up to 59% was found for the emitters that were generated on TiN-coated bulk substrates instead of on pristine ones. This observation was attributed exclusively to the TiN layer as no significant change in the emitter morphology could be identified. The fabrication route and, consequently, improved FE properties were transferred from bulk substrates to free-standing, electrically insulating nanomembranes. Moreover, 3D-printed, polymeric microstructures were overcoated by atomic layer deposition (ALD) employing its high conformality. The results of our approach by combining ALD with CNT growth could assist the future fabrication of highly efficient field emitters on 3D scaffold structures regardless of the substrate material. [ABSTRACT FROM AUTHOR]

Currently, a major challenge in material engineering is to develop a cell-safe biomaterial with significant utility in processing technology such as 3D bioprinting. The main goal of this work was to optimize the composition of a new graphene oxide (GO)-based bioink containing additional extracellular matrix (ECM) with unique properties that may find application in 3D bioprinting of biomimetic scaffolds. The experimental work evaluated functional properties such as viscosity and complex modulus, printability, mechanical strength, elasticity, degradation and absorbability, as well as biological properties such as cytotoxicity and cell response after exposure to a biomaterial. The findings demonstrated that the inclusion of GO had no substantial impact on the rheological properties and printability, but it did enhance the mechanical properties. This enhancement is crucial for the advancement of 3D scaffolds that are resilient to deformation and promote their utilization in tissue engineering investigations. Furthermore, GO-based hydrogels exhibited much greater swelling, absorbability and degradation compared to non-GO-based bioink. Additionally, these biomaterials showed lower cytotoxicity. Due to its properties, it is recommended to use bioink containing GO for bioprinting functional tissue models with the vascular system, e.g., for testing drugs or hard tissue models. [ABSTRACT FROM AUTHOR]

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

This document provides an introduction to biomimetic scaffolds for hard tissue surgery, specifically focusing on bones and teeth. It explains that three-dimensional biomaterial scaffolds are being used to repair damaged hard tissues by providing mechanical stability and a porous network for cell growth and tissue regeneration. The document also introduces a special issue that discusses the latest advances in this field, including design strategies, fabrication techniques, biomaterials, and clinical applications. The special issue includes contributions from scholars in the field, with articles covering bone and joint surgery, maxillofacial and oral surgery, and general surgery. The document provides an overview of the published papers in the special issue, highlighting review articles on biomimetic silk-based materials and scaffolds, as well as the evolution of designs in arthroplasty endoprostheses. It also summarizes research articles on personalized biomimetic scaffolds, drug-releasing scaffolds, composite materials, ceramic biocomposites, and highly porous scaffolds. Overall, the contributions demonstrate advancements in the field and the potential for biomimetic scaffolds to assist in tissue regeneration. [Extracted from the article]

Background: Complex graft bioengineering is an actual topic in bone defects' repair. For those, different scaffolds may be seeded with mesenchymal stromal cells and growth / differentiation factors. The natural role of platelet factors in reparative processes justifies the possibility of its usage for mesenchymal stromal cell proliferation and differentiation into osteoblasts in vitro in terms of the scaffold-based bioengineering. To develop and evaluate in vitro biocompatibility and osteoconductivity of a complex biograft based on a bioorganic scaffold seeded with human bone marrow mesenchymal stromal cells and saturated with growth and differentiation factors of allogeneic platelet-rich plasma. Results: The properties of viability and adhesion of human bone marrow mesenchymal stromal cells in four types of bioorganic scaffolds were evaluated with biochemical and immunomorphological methods. Scaffold with the least cytotoxicity was used as a basis for complex biograft formation, so as a carrier for cells and platelet-derived factors. Then, cell proliferation activity and osteogenic differentiation were estimated with biochemical, morphological, histochemical and molecular-biological methods. The study showed high viability of cells in all bioorganic scaffolds but the least cytotoxicity was the one based on xenogeneic collagen sponge. We also found that allogeneic platelet-rich plasma positively affects the proliferation and osteogenic differentiation of bone marrow mesenchymal stromal cells in a complex biograft in vitro. Conclusions: The properties of the developed complex biograft characterize its biocompatibility and osteoconductivity and make it potentially suitable for regenerative medicine, particularly for reconstructive surgery of bone defects. [ABSTRACT FROM AUTHOR]

This study explores an approach to design and prepare a multilayer scaffold mimicking interstratified natural tissue. This multilayer construct, composed of chitosan matrices with graded nanohydroxyapatite concentrations, was achieved through an in situ biomineralization process applied to individual layers. Three distinct precursor concentrations were considered, resulting in 10, 20, and 30 wt% nanohydroxyapatite content in each layer. The resulting chitosan/nanohydroxyapatite (Cs/n-HAp) scaffolds, created via freeze-drying, exhibited nanohydroxyapatite nucleation, homogeneous distribution, improved mechanical properties, and good cytocompatibility. The cytocompatibility analysis revealed that the Cs/n-HAp layers presented cell proliferation similar to the control in pure Cs for the samples with 10% n-HAp, indicating good cytocompatibility at this concentration, while no induction of apoptotic death pathways was demonstrated up to a 20 wt% n-Hap concentration. Successful multilayer assembly of Cs and Cs/n-HAp layers highlighted that the proposed approach represents a promising strategy for mimicking multifaceted tissues, such as osteochondral ones. [ABSTRACT FROM AUTHOR]

Type I collagen, prevalent in the extracellular matrix, is biocompatible and crucial for tissue engineering and wound healing, including angiogenesis and vascular maturation/stabilization as required processes of newly formed tissue constructs or regeneration. Sometimes, improper vascularization causes unexpected outcomes. Vascularization failure may be caused by extracellular matrix collagen and non-collagen components heterogeneously. This study compares the angiogenic potential of collagen type I-based scaffolds and collagen type I/glycosaminoglycans scaffolds by using the chick embryo chorioallantoic membrane (CAM) model and IKOSA digital image analysis. Two clinically used biomaterials, Xenoderm (containing type I collagen derived from decellularized porcine extracellular matrix) and a dual-layer collagen sponge (DLC, with a biphasic composition of type I collagen combined with glycosaminoglycans) were tested for their ability to induce new vascular network formation. The AI-based IKOSA app enhanced the research by calculating from stereomicroscopic images angiogenic parameters such as total vascular area, branching sites, vessel length, and vascular thickness. The study confirmed that Xenoderm caused a fast angiogenic response and substantial vascular growth, but was unable to mature the vascular network. DLC scaffold, in turn, produced a slower angiogenic response, but a more steady and organic vascular maturation and stabilization. This research can improve collagen-based knowledge by better assessing angiogenesis processes. DLC may be preferable to Xenoderm or other materials for functional neovascularization, according to the findings. [ABSTRACT FROM AUTHOR]

Polycrystalline metal‐organic framework (MOF) membrane films prepared on ceramic supports can separate gases with high energy efficiency. They generally exhibit very high permeance and selectivity but suffer from cost issues through the required ceramic supports. Increasing the area and reducing the ceramic component to a minimum can be a strategy to enabling neat membranes of MOFs. In a rapid prototyping approach using 3D‐printed porous scaffolds with a double‐helical channel geometry, an increased active membrane area‐to‐volume ratio is shown. Following stereolithographic printing and debinding of a ceramic slurry, an adapted sintering protocol is employed to sinter commercially available alumina slurries into porous scaffolds. The 3D‐printed scaffolds are optimized at a porosity of 40%, with satisfying mechanical stability. Furthermore, synthetic procedures yielding omnidirectional, homogeneous coatings on the outside and inside of the tubular scaffolds are developed. Membrane films of zeolitic imidazolate framework 8 and Hong Kong University of Science and Technology 1 covering a huge 50 cm2 membrane area are produced in this way by applying a counter‐diffusion methodology. Gas‐separation performance is evaluated for H2, CO2, N2, and CH4, in single‐gas measurements and on their binary‐gas mixtures. [ABSTRACT FROM AUTHOR]

In response to the urgent demand for innovative bone regeneration solutions, the focus of this study is to develop and characterize Mg, Sr, Zn-substituted calcium phosphate scaffolds that replicate the trabecular architecture of cancellous bone. Ion substitution represents a promising approach to improve the biological effectiveness of calcium phosphates and composite materials used in bone tissue engineering applications. Porous scaffolds mimicking the natural bone structure were additively manufactured from the photosensitive ceramic suspensions for vat photopolymerization using digital light processing. The impact of the selected trace elements (0, 1 and 5 mol.% substitution) and the sintering temperature (900, 1000, 1100, 1200, and 1300 °C) was investigated in relation to the obtained crystalline phase content, microstructure, elemental distribution, thermal stability, and mechanical properties. After sintering, in addition to hydroxyapatite, β -tricalcium phosphate was detected as a result of the added trace elements in the calcium-deficient hydroxyapatite used as a starting powder. The obtained scaffolds exhibited uniform distribution of the trace elements, and they feature 3D-designed porosity predominantly ranged from 10 to 900 μm in diameter, with an average pore size of 546.25 ± 10.95 μm. The total porosity of scaffolds was 76.24 ± 1.32 vol% and an average wall thickness of 217.03 ± 8.98 μm, closely resembling the morphology of cancellous bone tissue. The mechanical properties of the scaffolds sintered at 1100 °C, 1200 °C, and 1300 °C were in line with those typically observed in trabecular bone. The study demonstrates the feasibility of using custom made bioactive hydroxyapatite powders together with vat photopolymerization to design the porosity and properties of the bone scaffolds on demand, based on the requirements of individual bone defects. [ABSTRACT FROM AUTHOR]

This study aims to develop a mesoporous forsterite spheres-based scaffold for bone tissue regeneration. To achieve this goal, mesoporous forsterite spheres were fabricated using alginate (gel-forming agent) and activated charcoal (porogen). The impact of carbon concentration (2, 5, 10, and 20 wt %) and sintering temperature (1100 and 1200 °C) on the structural properties of mesoporous forsterite spheres was investigated. Additionally, gelatin coatings were applied to modify these spheres. Forsterite microspheres with a particle size of 2.43 ± 0.22 mm were successfully produced, exhibiting varying pore sizes based on the sintering temperature and carbon content. Notably, mesoporous forsterite spheres synthesized using 5 wt% carbon and sintered at 1200 °C displayed uniform morphology, a minor average diameter (2.4 ± 0.3 mm(, and an average pore size of 2.7 ± 0.9 μm. These optimized forsterite spheres exhibited mesoporous structures with superior surface area (2.93 m2g-1) and pore volume (0.009–0.048 cm3g-1). Furthermore, the gelatin coating, with an average thickness of 160 μm, was effectively applied to the forsterite spheres. The gelatin coating reduced the surface area (1.40 m2g-1), pore volume (0.003 cm3g-1), and average pore diameter to 9.26 nm, maintaining the mesoporous structure. Both mesoporous forsterite spheres successfully induced bone-like apatite formation in vitro during a 21-day immersion in simulated body fluid. Moreover, while both forsterite-based spheres exhibited cytocompatibility with MG63 cells (cell viability >80 %), the gelatin coating significantly enhanced osteogenic differentiation (1.29 times). In conclusion, gelatin-coated mesoporous forsterite spheres exhibit promising potential as bioactive filling scaffolds for bone tissue regeneration. [ABSTRACT FROM AUTHOR]

The influence of cobalt ion dopant on the in vitro biological properties of biphasic calcium phosphate (BCP) was investigated with an aim to develop an effective scaffold for bone tissue engineering applications. Cost-efficient wet chemical method was used to prepare in-situ cobalt doped BCP and XRD, FTIR, Raman spectroscopy, FESEM analyses were performed for detailed physico-chemical characterizations. It has been observed that pure BCP is comprised of 98 vol% of β-TCP and 2 vol% of β-CPP, whereas incorporation of cobalt leads to 58.8 vol% of β-TCP and 41.4 vol% of β-CPP. Moreover, Co-doped BCP exhibited relatively larger particle size when compared to pure BCP as observed in FESEM analysis. Furthermore, cobalt doped BCP showed enhanced antibacterial activity and the zone of inhibition was prominent compared to pure BCP. The release of cobalt ions from doped BCP was analyzed by Inductively Coupled Plasma (ICP) mass spectrometry at different time points (up to 28 days) and sustained release of cobalt ions warrants its benefits in native tissue regeneration. Both pure and Co-doped BCP showed excellent hemocompatibility as the percentage of hemolysis was below 2 %. Cell viability was found to be marginally higher with incorporation of trace amount of cobalt in BCP. Notably, in vitro angiogenic activity assessment results confirmed that VEGF-A and HIF-1α gene expression was significantly enhanced in case of doped BCP compared to pure BCP, signifying that the cobalt doping considerably improved the expression of angiogenic factors. Over the study, results demonstrated that incorporation of cobalt as dopants can effectively improve the in vitro biological properties of biphasic calcium phosphate based bioceramics and might be considered as a new generation bone grafts in bone regeneration applications. [ABSTRACT FROM AUTHOR]

Recent advancements in the field of biomedical engineering have underscored the pivotal role of biodegradable materials in addressing the challenges associated with tissue regeneration therapies. The spectrum of biodegradable materials presently encompasses ceramics, polymers, metals, and composites, each offering distinct advantages for the replacement or repair of compromised human tissues. Despite their utility, these biomaterials are not devoid of limitations, with issues such as suboptimal tissue integration, potential cytotoxicity, and mechanical mismatch (stress shielding) emerging as significant concerns. To mitigate these drawbacks, our research collective has embarked on the development of protein-based composite materials, showcasing enhanced biodegradability and biocompatibility. This study is dedicated to the elaboration and characterization of an innovative suture fabricated from human serum albumin through an extrusion methodology. Employing a suite of analytical techniques—namely tensile testing, scanning electron microscopy (SEM), and thermal gravimetric analysis (TGA)—we endeavored to elucidate the physicochemical attributes of the engineered suture. Additionally, the investigation extends to assessing the influence of integrating biodegradable organic modifiers on the suture's mechanical performance. Preliminary tensile testing has delineated the mechanical profile of the Filament Suture (FS), delineating tensile strengths spanning 1.3 to 9.616 MPa and elongation at break percentages ranging from 11.5 to 146.64%. These findings illuminate the mechanical versatility of the suture, hinting at its applicability across a broad spectrum of medical interventions. Subsequent analyses via SEM and TGA are anticipated to further delineate the suture's morphological features and thermal resilience, thereby enriching our comprehension of its overall performance characteristics. Moreover, the investigation delves into the ramifications of incorporating biodegradable organic constituents on the suture's mechanical integrity. Collectively, the study not only sheds light on the mechanical and thermal dynamics of a novel suture material derived from human serum albumin but also explores the prospective enhancements afforded by the amalgamation of biodegradable organic compounds, thereby broadening the horizon for future biomedical applications. [ABSTRACT FROM AUTHOR]

Reference genome assemblies have been created from multiple lineages within the Canidae family; however, despite its phylogenetic relevance as a basal genus within the clade, there is currently no reference genome for the gray fox (Urocyon cinereoargenteus). Here, we present a chromosome-level assembly for the gray fox (U. cinereoargenteus), which represents the most contiguous, non-domestic canid reference genome available to date, with 90% of the genome contained in just 34 scaffolds and a contig N50 and scaffold N50 of 59.4 and 72.9 Megabases, respectively. Repeat analyses identified an increased number of simple repeats relative to other canids. Based on mitochondrial DNA, our Vermont sample clusters with other gray fox samples from the northeastern United States and contains slightly lower levels of heterozygosity than gray foxes on the west coast of California. This new assembly lays the groundwork for future studies to describe past and present population dynamics, including the delineation of evolutionarily significant units of management relevance. Importantly, the phylogenetic position of Urocyon allows us to verify the loss of PRDM9 functionality in the basal canid lineage, confirming that pseudogenization occurred at least 10 million years ago. [ABSTRACT FROM AUTHOR]

With its exceptional biocompatibility, alginate emerged as a highly promising biomaterial for a large range of applications in regenerative medicine. Whether in the form of microparticles, injectable hydrogels, rigid scaffolds, or bioinks, alginate provides a versatile platform for encapsulating cells and fostering an optimal environment to enhance cell viability. This review aims to highlight recent studies utilizing alginate in diverse formulations for cell transplantation, offering insights into its efficacy in treating various diseases and injuries within the field of regenerative medicine. [ABSTRACT FROM AUTHOR]

Biomaterials play an important role in the development of advancing three dimensional (3D) in vitro skin models, providing valuable insights for drug testing and tissue-specific modeling. Commercial materials, such as collagen, fibrin or alginate, have been widely used in skin modeling. However, they do not adequately represent the molecular complexity of skin components. On this regard, the development of novel biomaterials that represent the complexity of tissues is becoming more important in the design of advanced models. In this study, we have obtained aged human decellularized dermal extracellular matrix (dECM) hydrogels extracted from cadaveric human skin and demonstrated their potential as scaffold for advanced skin models. These dECM hydrogels effectively reproduce the complex fibrillar structure of other common scaffolds, exhibiting similar mechanical properties, while preserving the molecular composition of the native dermis. It is worth noting that fibroblasts embedded within human dECM hydrogels exhibit a behavior more representative of natural skin compared to commercial collagen hydrogels, where uncontrolled cell proliferation leads to material shrinkage. The described human dECM hydrogel is able to be used as scaffold for dermal fibroblasts in a skin aging-on-a-chip model. These results demonstrate that dECM hydrogels preserve essential components of the native human dermis making them a suitable option for the development of 3D skin aging models that accurately represent the cellular microenvironment, improving existing in vitro skin models and allowing for more reliable results in dermatopathological studies. [ABSTRACT FROM AUTHOR]

Presently, millions worldwide suffer from degenerative and inflammatory bone and joint issues, comprising roughly half of chronic ailments in those over 50, leading to prolonged discomfort and physical limitations. These conditions become more prevalent with age and lifestyle factors, escalating due to the growing elderly populace. Addressing these challenges often entails surgical interventions utilizing implants or bone grafts, though these treatments may entail complications such as pain and tissue death at donor sites for grafts, along with immune rejection. To surmount these challenges, tissue engineering has emerged as a promising avenue for bone injury repair and reconstruction. It involves the use of different biomaterials and the development of three-dimensional porous matrices and scaffolds, alongside osteoprogenitor cells and growth factors to stimulate natural tissue regeneration. This review compiles methodologies that can be used to develop biomaterials that are important in bone tissue replacement and regeneration. Biomaterials for orthopedic implants, several scaffold types and production methods, as well as techniques to assess biomaterials' suitability for human use—both in laboratory settings and within living organisms—are discussed. Even though researchers have had some success, there is still room for improvements in their processing techniques, especially the ones that make scaffolds mechanically stronger without weakening their biological characteristics. Bone tissue engineering is therefore a promising area due to the rise in bone-related injuries. [ABSTRACT FROM AUTHOR]

The functionalization of bone substitutes with exosomes appears to be a promising technique to enhance bone tissue formation. This study investigates the potential of exosomes derived from bone marrow mesenchymal stromal cells (BMSCs) to improve bone healing and bone augmentation when incorporated into wide open-porous 3D-printed ceramic Gyroid scaffolds. We demonstrated the multipotent characteristics of BMSCs and characterized the extracted exosomes using nanoparticle tracking analysis and proteomic profiling. Through cell culture experimentation, we demonstrated that BMSC-derived exosomes possess the ability to attract cells and significantly facilitate their differentiation into the osteogenic lineage. Furthermore, we observed that scaffold architecture influences exosome release kinetics, with Gyroid scaffolds exhibiting slower release rates compared to Lattice scaffolds. Nevertheless, in vivo implantation did not show increased bone ingrowth in scaffolds loaded with exosomes, suggesting that the scaffold microarchitecture and material were already optimized for osteoconduction and bone augmentation. These findings highlight the lack of understanding about the optimal delivery of exosomes for osteoconduction and bone augmentation by advanced ceramic scaffolds. [ABSTRACT FROM AUTHOR]

Medicinal properties of naturally sourced biomolecules, such as ginger (Zingiber officinale) extract, are documented in the traditional Indian and Chinese medical systems. However, limited work is performed to assess the potential of ginger extracts for bone--tissue engineering. Our work demonstrates the direct incorporation of ginger extract on iron oxide--magnesium oxide (Fe2O3 and MgO) co-doped hydroxyapatite (HA) for enhancement in the biological properties. The addition of Fe2O3 and MgO co-doping system and ginger extract with HA increases the osteoblast viability up to ~1.4 times at day 11. The co-doping does not adversely affect the release of ginger extract from the graft surface in the biological medium at pH 7.4 for up to 28 days. Assessment of antibacterial efficacy according to the modified ISO 22196: 2011 standard method indicates that the combined effects of Fe2O3, MgO, and ginger extract lead to ~82% more bacterial cell reduction, compared to the control HA against Staphylococcus aureus. These ginger extract-loaded artificial bone grafts with enhanced biological properties may be utilized as an on-site delivery vehicle for various bone--tissue engineering applications. [ABSTRACT FROM AUTHOR]

In recent years, polyelectrolytes have been successfully used as an alternative to non-collagenous proteins to promote interfibrillar biomineralization, to reproduce the spatial intercalation of mineral phases among collagen fibrils, and to design bioinspired scaffolds for hard tissue regeneration. Herein, hybrid nanofibers were fabricated via electrospinning, by using a mixture of Poly ɛ-caprolactone (PCL) and cationic cellulose derivatives, i.e., cellulose-bearing imidazolium tosylate (CIMD). The obtained fibers were self-assembled with Sodium Alginate (SA) by polyelectrolyte interactions with CIMD onto the fiber surface and, then, treated with simulated body fluid (SBF) to promote the precipitation of calcium phosphate (CaP) deposits. FTIR analysis confirmed the presence of SA and CaP, while SEM equipped with EDX analysis mapped the calcium phosphate constituent elements, estimating an average Ca/P ratio of about 1.33—falling in the range of biological apatites. Moreover, in vitro studies have confirmed the good response of mesenchymal cells (hMSCs) on biomineralized samples, since day 3, with a significant improvement in the presence of SA, due to the interaction of SA with CaP deposits. More interestingly, after a decay of metabolic activity on day 7, a relevant increase in cell proliferation can be recognized, in agreement with the beginning of the differentiation phase, confirmed by ALP results. Antibacterial tests performed by using different bacteria populations confirmed that nanofibers with an SA-CIMD complex show an optimal inhibitory response against S. mutans, S. aureus, and E. coli, with no significant decay due to the effect of CaP, in comparison with non-biomineralized controls. All these data suggest a promising use of these biomineralized fibers as bioinspired membranes with efficient antimicrobial and osteoconductive cues suitable to support bone healing/regeneration. [ABSTRACT FROM AUTHOR]

The treatment of bone defects is a clinical challenge. Bone tissue engineering is gaining interest as an alternative to current treatments, with the development of 3D porous structures (scaffolds) helpful in promoting bone regeneration by ensuring temporary functional support. In this work, methacrylated silk fibroin (SilMA) sponges were investigated as scaffolds for bone tissue engineering by exploiting the combination of physical (induced by NaCl salt during particulate leaching) and chemical crosslinking (induced by UV-light exposure) techniques. A biomimetic approach was adopted to better simulate the extracellular matrix of the bone by introducing either natural (mussel shell-derived) or synthetic-origin hydroxyapatite nanoparticles into the SilMA sponges. The obtained materials were characterized in terms of pore size, water absorption capability and mechanical properties to understand both the effect of the inclusion of the two different types of nanoparticles and the effect of the photocrosslinking. Moreover, the SilMA sponges were tested for their bioactivity and suitability for bone tissue engineering purposes by using osteosarcoma cells, studying their metabolism by an AlamarBlue assay and their morphology by scanning electron microscopy. Results indicate that photocrosslinking helps in obtaining more regular structures with bimodal pore size distributions and in enhancing the stability of the constructs in water. Moreover, the addition of naturally derived hydroxyapatite was observed to be more effective at activating osteosarcoma cell metabolism than synthetic hydroxyapatite, showing a statistically significant difference in the AlamarBlue measurement on day 7 after seeding. The methacrylated silk fibroin/hydroxyapatite nanocomposite sponges developed in this work were found to be promising tools for targeting bone regeneration with a sustainable approach. [ABSTRACT FROM AUTHOR]

This study investigated six-month outcomes of first models of ascending aortic replacement. The molds used to produce the Biotube were implanted subcutaneously in goats. After 2–3 months, the molds were explanted to obtain the Biotubes (inner diameter, 12 mm; wall thickness, 1.5 mm). Next, we performed ascending aortic replacement using the Biotube in five allogenic goats. At 6 months, the animals underwent computed tomography (CT) and histologic evaluation. As a comparison, we performed similar surgeries using glutaraldehyde-fixed autologous pericardial rolls or pig-derived heterogenous Biotubes. At 6 months, CT revealed no aneurysmalization of the Biotube or pseudoaneurysm formation. The histologic evaluation showed development of endothelial cells, smooth muscle cells, and elastic fibers along the Biotube. In the autologous pericardium group, there was no evidence of new cell development, but there was calcification. The histologic changes observed in the heterologous Biotube group were similar to those in the allogenic Biotube group. However, there was inflammatory cell infiltration in some heterologous Biotubes. Based on the above, we could successfully create the world's first Biotube-based ascending aortic replacement models. The present results indicate that the Biotube may serve as a scaffold for aortic tissue regeneration. [ABSTRACT FROM AUTHOR]

The three-dimensional (3D) printing of biomaterials, cells, and bioactive components, including growth factors, has gained interest among researchers in the field of tissue engineering (TE) with the aim of developing many scaffolds to sustain size, shape fidelity, and structure and retain viable cells inside a network. The biocompatible hydrogel employed in 3D printing should be soft enough to accommodate cell survival. At the same time, the gel should be mechanically strong to avoid the leakage of cells into the surrounding medium. Considering these basic criteria, researchers have developed nanocomposite-based printable inks with suitable mechanical and electroconductive properties. These nanomaterials, including carbon family nanomaterials, transition metal dichalcogenides, and polymeric nanoparticles, act as nanofillers and dissipate stress across polymeric networks through their electroactive interactions. Nanofiber-reinforced printable ink is one kind of nanocomposite-based ink that comprises dispersed nanofiber components in a hydrogel matrix. In this current review, we compile various TE applications of nanofiber-reinforced printable ink and describe the 3D-printing parameters, classification, and impact of cross-linkage. Furthermore, we discuss the challenges and future perspectives in this field. [ABSTRACT FROM AUTHOR]