Critical-sized bone defects require advanced grafts that simultaneously address regeneration, vascularization, and infection. This study presents a multifunctional 3D-printed scaffold designed for coordinated bone healing, composed of alginate reinforced with copper-doped hydroxyapatite (Cu-HA) nanoparticles and postfunctionalized with L-arginine (Arg). Physicochemical analyses confirmed successful fabrication of scaffolds with controlled porosity and a compressive modulus of 1.6-2.6 GPa, suitable for cancellous bone. Furthermore, the Cu-HA composition endowed the scaffold with a significant and controllable photothermal response under 808 nm irradiation, producing a temperature rise of up to 26 degrees C in the hydrated state. The scaffolds also demonstrated enhanced protein adsorption and a potent, copper-dependent antibacterial effect. In vitro biological evaluation revealed a multifaceted pro-angiogenic response: scaffold extracts significantly stimulated endothelial cell migration in a scratch assay and potently enhanced tubulogenesis on Matrigel; the addition of Arg induced a distinct morphological shift towards elongated, stabilized cellular networks. Regarding osteogenesis, elevated Cu2+ levels accelerated the differentiation timeline, and the combination of Arg and Cu2+ robustly upregulated expression of collagen I and osteopontin. By integrating structural support with demonstrated antibacterial, angiogenic, osteogenic, and photothermal functionalities, this scaffold represents a promising multi-stimuli platform for complex bone tissue engineering applications.

The treatment of extensive bone defects involves the use of multicomponent scaffolds where different components can be precisely controlled according to specific conditions. Therefore, hybridizing biomaterials within cell-laden osteogenic bioscaffolds provides promising opportunities for clinical applications. In this study, a cell-laden, photocrosslinkable hydrogels composed of methacrylated chitosan (MECs) and silk fibroin (SF) fibers was developed to induce osteogenesis, and its structural and biological properties was investigated. SF fibers were mineralized with a hydroxyapatite (HAp) layer using a modified alternate soaking followed by heat treatment. Optimal photocrosslinking conditions were determined using the Taguchi method. SF fibers were incorporated into MECs at varying concentrations, and the resulting hydrogel structure was assessed with and without fibers under different ionic conditions. Adipose-derived stem cells (ADSCs) were encapsulated into hydrogels, and their morphology, viability, and osteogenic gene expression were analyzed. FTIR, XRD, and SEM confirmed successful mineralization of SF, with heat treatment enhancing HAp crystallinity. SF addition effectively prevented hydrogel shrinkage and promoted a porous structure due to fiber enrichment and double crosslinking. Encapsulated ADSCs remained viable after 14 days, and mineralized fibers significantly upregulated bone-related gene expression compared to controls. This study introduces a biomimetic, fiber-enriched, osteoinductive hydrogel with strong potential for the repair and regeneration of large bone defects.

The development of multifunctional scaffolds capable of promoting bone regeneration while preventing infection remains a major challenge in bone tissue engineering. Herein, we report a 3D-printed polycaprolactone/nano-hydroxyapatite (PCL/HA) scaffold coated with zein for the sustained release of tetracycline hydrochloride (TCH). The optimized scaffold containing 20 wt% HA exhibited enhanced apparent mechanical performance while maintaining an interconnected porosity of approximately 51%, providing a physiologically relevant mechanical and structural context for trabecular bone tissue engineering applications. Zein coating at 7 wt/v% produced a uniform, crack-free surface without pore obstruction, significantly reducing the initial burst release of TCH and enabling controlled drug release for up to 14 days. The scaffold demonstrated antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli ), and supported adhesion, spreading, and viability of MG-63 osteoblast-like cells, particularly at 10 wt% TCH loading. These findings highlight the synergistic effects of the PCL/HA framework, zein coating, and localized antibiotic delivery, providing a cost-effective and clinically translatable platform for bone regeneration in infection-prone environments.

Gelatin methacryloyl (GelMA) and bioactive glasses (BGs) have attracted considerable scientific interest as scaffold materialsin bone tissue engineering, particularly for their structural applications in bone repair procedures. Cerium (Ce) can be incorporated into BGs, demonstrating beneficial effects on osteogenesis and regenerative processes. In this study, we fabricated GelMA-Gel scaffolds using a 3D printing method and evaluated the impact of BG and BG/Ce inclusion through in vitro and in vivo assessments. Scanning electron microscopy images revealed an interconnected porous structure within the scaffolds. The incorporation of Ce appeared to enhance the mechanical properties of the scaffolds. Additionally, the inclusion of Ce did not induce cytotoxicity and positively influenced the viability and proliferation of human bone marrow-derived mesenchymal stem cells while enhancing alkaline phosphatase secretion compared to other samples. No edema or erythema response was observed in the Guinea Pig Maximization Test (GPMT) following the implantation of GelMA-Gel-BG/Ce scaffolds. Implantation of the scaffolds into cranial bone defects in rats over 12 weeks demonstrated enhanced bone formation and mineralization, as evidenced by histological staining. The results indicate that the GelMA-Gel-BG/Ce scaffold is biocompatible and capable of promoting bone regeneration, highlighting its potential as an effective implant for addressing bone injuries.

Articular cartilage has limited self-healing capacity, driving the need for biomaterial scaffolds that replicate its hierarchical architecture and mechanical resilience. In this study, we present a dual-crosslinked hydrogel system for 3D bioprinting, composed of gellan gum (GG), oxidized GG (OGG), decellularized human amniotic membrane (dHAM), and aminolyzed polycaprolactone nanofibers (A-PCL NFs). Schiff base linkages between OGG aldehydes and amine groups in dHAM/A-PCL NFs, combined with Ca2+-mediated ionic gelation, provided a reinforced hydrogel network with tunable physicochemical properties. The resulting scaffolds exhibited high structural fidelity, a compressive modulus of 232.6 kPa, controlled swelling, and sustained degradation (30 % mass loss over 21 days). The integration of A-PCL NFs significantly enhanced mechanical performance and stabilized the hydrogel matrix, while dHAM supplied native extracellular matrix (ECM) cues. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) encapsulated in the bioink showed >85 % viability after 7 days and underwent robust chondrogenic differentiation, as confirmed by histology and increased glycosaminoglycan deposition. This biomimetic design-combining dynamic crosslinking, ECM-derived bioactivity, and NF reinforcement-demonstrates how structural and biochemical synergies can be harnessed to advance functional cartilage scaffolds. The platform shows strong potential for translational application in articular cartilage repair and may be extended to other load-bearing tissues requiring both mechanical integrity and biological functionality.

Bone tissue engineering requires scaffolds that synergize mechanical strength with bioactivity. This study aimed to develop and characterize 3D-printed zinc (Zn)- and cobalt (Co)-doped 45S5 bioactive glass (BG)/β-tricalcium phosphate (TCP) composite scaffolds for enhanced bone regeneration. Sol-gel-synthesized BG powders, doped with 3–15

As a naturally occurring mineral component of bone, hydroxyapatite (HA) is a preferred bone-repair material in clinical medicine. This adaptable biomaterial is developed from synthetic or biological sources. The goal of this study was to investigate the physicochemical and biological properties of scaffolds made from diverse hydroxyapatite sources. We prepared hydroxyapatite powders either from naturally occurring sources, using decellularized bone extracellular matrix (DBECM) and deproteinized bovine bone (DBB), or in the laboratory using the co-precipitation method. Although XRD analysis confirmed the pure phase of HA in all three powders, XRF data found some other trace elements in bone-derived biomaterials, such as magnesium and strontium. Further, FTIR spectra showed DBECM-associated macromolecule peaks. In the second phase of this study, the particles were mixed with sodium alginate to produce bioink for 3D printing via extrusion. SEM photographs of the printed scaffolds showed a grid-like porous structure with large, interconnected pores. Although all of the scaffolds retained their structural integrity after 28 days submerged in the culture medium, DBECM-based scaffolds degraded the most. The test of Young's modulus and compressive strength of scaffolds revealed that all scaffolds are strong enough to be employed in non-weight-bearing applications. The biological characteristics of the scaffolds were then evaluated via cytotoxicity analysis, SEM examination of cell attachment, MTT assay, ALP activity assessment, immunofluorescence staining, and Alizarin red staining. The results indicated that all three scaffolds provided a surface that promoted adhesion and proliferation of rat bone marrow mesenchymal stem cells (rMSCs), as well as stimulated the production of mineralized extracellular matrices. Additionally, our findings showed that scaffolds made from DBECM powders offer the best environment for cell activity. This is most likely due to the presence of trace elements and protein macromolecules in DBECM powders that are not found in DBB and synthetic HA. In conclusion, our comparative study revealed that while all three scaffolds are suitable for bone tissue engineering, DBECM-based scaffolds outperform DBB and synthetic HA.

Mesenchymal stromal cells (MSCs) and chimeric antigen receptor (CAR)-T cells are two core elements in cell therapy procedures. MSCs have significant immunomodulatory effects that alleviate inflammation in the tissue regeneration process, while administration of specific chemokines and adhesive molecules would primarily facilitate CAR-T cell trafficking into solid tumors. Multiple parameters affect cell homing, including the recipient's age, the number of cell passages, proper cell culture, and the delivery method. In addition, several chemokines are involved in the tumor microenvironment, affecting the homing procedure. This review discusses parameters that improve the efficiency of cell homing and significant cell therapy challenges. Emerging comprehensive mechanistic strategies such as non-systemic and systemic homing that revealed a significant role in cell therapy remodeling were also reviewed. Finally, the primary implications for the development of combination therapies that incorporate both MSCs and CAR-T cells for cancer treatment were discussed.

Due to the characteristics of electrospun nanofibers (NFs), they are considered a suitable substrate for the adsorption and removal of heavy metals. Electrospun nanofibers are prepared based on optimized polycaprolactone (PCL, 12 wt%) and polyacrylic acid (PAA, 1 wt%) polymers loaded with graphene oxide nanoparticles (GO NPs, 1 wt%). The morphological, molecular interactions, crystallinity, thermal, hydrophobicity, and biocompatibility properties of NFs are characterized by spectroscopy (scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Thermogravimetric analysis), contact angle, and MTT tests. Finally, the adsorption efficacy of NFs to remove lead (Pb2+) from water and apple juice samples was determined using inductively coupled plasma optical emission spectroscopy (ICP-OES). The average diameter for PCL, PCL/PAA, and PCL/PAA/GO NFs was 137, 500, and 216 nm, respectively. Additionally, the contact angle for PCL, PCL/PAA, and PCL/PAA/GO NFs was obtained at 74.32º, 91.98º, and 94.59º, respectively. The cytotoxicity test has shown non-toxicity for fabricated NFs against the HUVEC endothelial cell line by more than 80% survival during 72 h. Under optimum conditions including pH (= 6), temperature (25 °C), Pb concentration (25 to 50 mg/L), and time (15 to 30 min), the adsorption efficiency was generally between 80 and 97%. The adsorption isotherm model of PCL/PAA/GO NFs in the adsorption of lead metal follows the Langmuir model, and the reaction kinetics follow the pseudo-second-order. PCL/PA/GO NFs have shown adsorption of over 80% in four consecutive cycles. The adsorption efficacy of NFs to remove Pb in apple juice has reached 76%. It is appropriate and useful to use these nanofibers as a high-efficiency adsorbent in water and food systems based on an analysis of their adsorption properties and how well they work.

Dealing with spinal cord injuries presents problematic due to multiple secondary mechanisms. Beyond primary concerns like paralysis and disability, complications including urinary, gastrointestinal, cardiac, and respiratory disorders, along with substantial economic burdens may occur. Limited research focuses on modeling and treating contusion and compression injuries. Tissue engineering emerges as an innovative treatment, targeting lesion pathophysiology. This study was evaluated implanting injectable biomaterials into injury-induced cavity before glial scar formation, avoiding tissue incisions and minimizing further damage. The efficacy of injectable alginate/thiolated chitosan hydrogel was investigated for acute spinal cord injury induced by Vanick & yacute; method in Wistar rats. Three days post-injury, hydrogel was administrated through microinjection after laminectomy. After 60 days, the hydrogel group demonstrated notable motor function enhancement compared to the control by the BBB locomotor test (P < 0.05). However, no statistically significant differences were observed in MRI assessment concerning lesion severity. Stereological and histopathological evaluations revealed a reduction in vacuole volume and the presence of axon profiles within the scaffold (P < 0.05), alongside reduced infiltration of inflammatory and Gitter cells in the hydrogel group, although the latter was not statistically significant compared to the control. Thiolated chitosan/ alginate hydrogel implantation may be regarded as a promising treatment to enhance motor function by restraining destructive processes post-acute spinal cord injury.

In this study, carboxymethyl chitosan/gelatin/Akermanite (CMC/GEL/AK)-based scaffolds were prepared for bone tissue regeneration via 3D printing method. The bioactive AK was synthesized and used to fabricate the scaffolds. The AK powder was analysed through scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and X-ray diffraction (XRD). The porous scaffolds were fabricated and characterized to show their ability in bone tissue engineering (BTE). Degradation rate, swelling ratio, and mechanical properties of the scaffolds containing AK have been significantly increased. The scaffolds possess the interconnected networks with the pore size of about 300–900 μm. The mechanical strength increased up to 2.6 MPa by adding 20

Adding foreign ions to hydroxyapatite (HAp) is a popular approach for improving its properties. This study focuses on the effects of calcium substitution with copper in HAp. Instead of calcium, copper ions were doped into the structure of hydroxyapatite nanoparticles at 1%, 3%, and 5% concentrations. XRD analysis showed that the amount of substituted copper was less than needed to generate a distinct phase, yet its lattice parameters and crystallinity slightly decreased. Further, the results of degradation tests revealed that copper doping in hydroxyapatite doubled calcium ion release in water. The incorporation of copper into the apatite structure also boosted the HAp zeta potential and FBS protein adsorption onto powders. According to antibacterial investigations, a concentration of 200 mg/ml of hydroxyapatite containing 5% copper was sufficient to effectively eradicate E. coli and S. aureus bacteria. Furthermore, copper improved hydroxyapatite biocompatibility. Alkaline phosphatase activity and alizarin red tests showed that copper in hydroxyapatite did not inhibit stem cell differentiation into osteoblasts. Also, the scratch test demonstrated that copper-containing hydroxyapatite extract increased HUVEC cell migration. Overall, our findings demonstrated the utility of incorporating copper into the structure of hydroxyapatite from several perspectives, including the induction of antibacterial characteristics, biocompatibility, and angiogenesis.

The use of porous scaffolds with appropriate mechanical and biological features for the host tissue is one of the challenges in repairing critical-size bone defects. With today's three-dimensional (3D) printing technology, scaffolds can be customized and personalized, thereby eliminating the problems associated with conventional methods. In this work, after preparing Ti6Al4V/Calcium phosphate (Ti64@CaP) core-shell nanocomposite via a solution-based process, by taking advantage of fused deposition modeling (FDM), porous poly(lactic acid) (PLA)-Ti64@CaP nanocomposite scaffolds were fabricated. Scanning electron microscope (SEM) showed that nanostructured calcium phosphate was distributed uniformly on the surface of Ti64 particles. Also, X-ray diffraction (XRD) indicated that calcium phosphate forms an octacalcium phosphate (OCP) phase. As a result of incorporating 6 wt% Ti64@CaP into the PLA, the compressive modulus and ultimate compressive strength values increased from 1.4 GPa and 29.5 MPa to 2.0 GPa and 53.5 MPa, respectively. Furthermore, the differential scanning calorimetry results revealed an increase in the glass transition temperature of PLA, rising from 57.0 to 62.4 °C, due to the addition of 6 wt% Ti64@CaP. However, it is worth noting that there was a moderate decrease in the crystallization and melting temperatures of the nanocomposite filament, which dropped from 97.0 to 89.5 °C and 167 to 162.9 °C, respectively. The scaffolds were seeded with human adipose tissue-derived mesenchymal stem cells (hADSCs) to investigate their biocompatibility and cell proliferation. Calcium deposition, ALP activity, and bone-related proteins and genes were also used to evaluate the bone differentiation potential of hADSCs. The obtained results showed that introducing Ti64@CaP considerably improved in vitro biocompatibility, facilitating the attachment, differentiation, and proliferation of hADSCs. Considering the findings of this study, the 3D-printed nanocomposite scaffold could be considered a promising candidate for bone tissue engineering applications.

Physiochemical tissue inducers and mechanical stimulation are both efficient variables in cartilage tissue fabrication and regeneration. In the presence of biomolecules, decellularized extracellular matrix (ECM) may trigger and enhance stem cell proliferation and differentiation. Here, we investigated the controlled release of transforming growth factor beta (TGF-β1) as an active mediator of mesenchymal stromal cells (MSCs) in a biocompatible scaffold and mechanical stimulation for cartilage tissue engineering. ECM-derived hydrogel with TGF-β1-loaded alginate-based microspheres (MSs) was created to promote human MSC chondrogenic development. Ex vivo explants and a complicated multiaxial loading bioreactor replicated the physiological conditions. Hydrogels with/without MSs and TGF-β1 were highly cytocompatible. MSCs in ECM-derived hydrogel containing TGF-β1/MSs showed comparable chondrogenic gene expression levels as those hydrogels with TGF-β1 added in culture media or those without TGF-β1. However, constructs with TGF-β1 directly added within the hydrogel had inferior properties under unloaded conditions. The ECM-derived hydrogel group including TGF-β1/MSs under loading circumstances formed better cartilage matrix in an ex vivo osteochondral defect than control settings. This study demonstrates that controlled local delivery of TGF-β1 using MSs and mechanical loading is essential for neocartilage formation by MSCs and that further optimization is needed to prevent MSC differentiation towards hypertrophy.

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

Current bioadhesive dressings, though potential in wound care, often exhibit inadequate adhesion and lack essential properties for optimal wound healing, such as being antibacterial, hemostatic, and angiogenic. While various scaffolds containing natural adhesive molecules such as 3,4-dihydroxyphenyl-l-alanine (DOPA) and tannic acid (TA) have been individually assessed, the comparison of adhesives containing these molecules are scarcely studied. This study addresses these limitations by developing two innovative composite hydrogel adhesives, based on DOPA and TA, which are integrated with novel multi-metal bioactive glass nanoparticles (BGNs). A comprehensive comparison of their properties was conducted to evaluate their potential in improving wound healing outcomes.BGNs were synthesized using sol-gel approach, yielding an amorphous and porous structure. Incorporation of 10% w/w BGNs with uniform distribution enhanced the mechanical and adhesive properties of both hydrogels, with TA-based dressings demonstrating superior performance. While both dressings demonstrated biocompatibility and hemocompatibility, TA-based adhesive outperformed DOPA-based adhesive in cell viability and antibacterial activity against Staphylococcus aureus and Escherichia coli, while DOPA-based composites showed better in vitro angiogenic and hemostatic capabilities.Regarding in vivo investigations, conducted on mice model of full-thickness skin wounds, DOPA- incorporated adhesive dressing which contained 10% BGN exhibited slightly superior performance in re-epithelialization, collagen formation and blood vessel density, indicating its potential for acute wound healing applications.

This research aimed to develop and evaluate various multi-layer nanofiber scaffolds using different scaffold compounds, including Silk fibroin, Silk fibroin/Collagen, Silk fibroin/collagen/Aloe vera, silk fibroin/Collagen/Aloe vera/ epithelial growth factor, for tissue engineering of the corneal epithelial layer. The scaffolds were characterized from both engineering and biological perspectives. The study successfully prepared nanofiber scaffolds with appropriate thickness and structure, possessing desirable engineering and biological properties for corneal repair. The scaffolds were based on silk fibroin and collagen, supplemented with aloe vera and Epithelial Growth Factor (EGF) to enhance corneal regeneration. The fabrication involved a combination of electrospinning and electrospraying techniques to create three-layer nanofiber scaffolds. Engineering properties, such as degradability (weight loss), water contact angle, growth factor release, and static and dynamic mechanical properties, were evaluated using Scanning Electron Microscopy (SEM). Biological characteristics, including cell binding, cell viability, and the scaffold differentiation potential, were also investigated. The obtained results demonstrated the successful development of nanofiber scaffolds with suitable thickness, structure, and desirable engineering and biological properties for corneal tissue engineering. The developed scaffold holds potential as a viable alternative for repairing damaged corneal epithelial layers, offering a promising solution for corneal regeneration.