Potential Bone Tissue Engineering Research Articles

Sr-Mg co-doped Hardystonite/Polycaprolactone electrospun scaffolds: Fabrication and Characterization for enhanced bone regeneration

The production of scaffolds is a primary objective in tissue engineering for treating bone defects and diseases. The electrospinning process offers a promising technique to create structures resembling the extracellular matrix. Artificial polymeric grafts, such as poly(caprolactone) (PCL), often face issues of low strength and degradation. To overcome these limitations, we introduce ceramic reinforcing particles, specifically hardystonite (Ca2ZnSi2O7), known for its benefits in tissue regeneration. Considering the undeniable role of strontium and magnesium in bone regeneration, the aim of this study was to investigate and compare produced scaffolds with and without dopant elements, incorporated into hardystonite. Initially, strontium-magnesium-doped hardystonite (DHT) nanopowder was synthesized through mechanical milling followed by thermal treatment. The successful formation of a single-phase hardystonite structure was verified by X-ray diffraction (XRD), with estimated crystallite and particle sizes of approximately 41.6nm and 77.23 ± 36.60 nm, respectively. Subsequently, PCL/DHT composite scaffolds were fabricated with 3 wt%, 5 wt%, and 10 wt% bioceramic content. These scaffolds were assessed for fiber morphology, physical and chemical properties, hydrophilicity, surface roughness, mechanical characteristics, degradation, and biocompatibility. The results indicate that PCL/5 wt% DHT scaffolds exhibit superior biological, physical, and mechanical properties. Across all these tests, the PCL/5 wt% DHT scaffold consistently outperformed the others, suggesting its promising potential in bone tissue engineering.

Role of crosslinkers in advancing chitosan-based biocomposite scaffolds for bone tissue engineering: A comprehensive review.

Bone tissue engineering (BTE) aims to repair and regenerate damaged bone tissue by combining cells, scaffolds, and signaling molecules. Various macromolecules, including natural polymers like chitosan (CS), collagen, hyaluronic acid, and alginate, as well as synthetic polymers such as polyethylene glycol and polylactic acid, are used in scaffold fabrication. Among these, CS holds significant potential in BTE due to its biocompatibility, biodegradability, and other features. The inherent mechanical weaknesses of CS-based scaffolds require the implementation of crosslinking strategies to improve their stability and overall performance. Physical crosslinkers like ultra-violet irradiation and freeze-thaw cycles are biocompatible but offer limited mechanical strength. Chemical crosslinkers like glutaraldehyde significantly improve mechanical strength, but they may induce cytotoxicity. We briefly outline here the critical role of physical and chemical crosslinkers in improving the physicochemical properties, mechanical strength, biocompatibility, and biological functions of CS-based scaffolds, including effective bone regeneration. The influence of crosslinking on the CS-based scaffolds' bioactivity, including the controlled release of bioactive molecules, is also discussed. A thorough understanding of crosslinker chemistry and application in CS-based scaffolds is essential for advancing bone regeneration therapies.

Polyurethanes and Their Biomedical Applications.

The tunable mechanical properties of polyurethanes (PUs), due to their extensive structural diversity and biocompatibility, have made them promising materials for biomedical applications. Scientists can address PUs' issues with platelet absorption and thrombus formation owing to their modifiable surface. In recent years, PUs have been extensively utilized in biomedical applications because of their chemical stability, biocompatibility, and minimal cytotoxicity. Moreover, addressing challenges related to degradation and recycling has led to a growing focus on the development of biobased polyurethanes as a current focal point. PUs are widely implemented in cardiovascular fields and as implantable materials for internal organs due to their favorable biocompatibility and physicochemical properties. Additionally, they show great potential in bone tissue engineering as injectable grafts or implantable scaffolds. This paper reviews the synthesis methods, physicochemical properties, and degradation pathways of PUs and summarizes recent progress in applying different types of polyurethanes in various biomedical applications, from wound repair to hip replacement. Finally, we discuss the challenges and future directions for the translation of novel polyurethane materials into biomedical applications.

Stem Cells in Bone Tissue Engineering: Progress, Promises and Challenges.

Bone defects from accidents, congenital conditions, and age-related diseases significantly impact quality of life. Recent advancements in bone tissue engineering (TE) involve biomaterial scaffolds, patient-derived cells, and bioactive agents, enabling functional bone regeneration. Stem cells, obtained from numerous sources including umbilical cord blood, adipose tissue, bone marrow, and dental pulp, hold immense potential in bone TE. Induced pluripotent stem cells and genetically modified stem cells can also be used. Proper manipulation of physical, chemical, and biological stimulation is crucial for their proliferation, maintenance, and differentiation. Stem cells contribute to osteogenesis, osteoinduction, angiogenesis, and mineralization, essential for bone regeneration. This review provides an overview of the latest developments in stem cell-based TE for repairing and regenerating defective bones.

Tantalum granules with hierarchical pore structure for bone regeneration: Porous tantalum granules repair bone

Tantalum (Ta) has good potential for bone tissue engineering due to its excellent corrosion resistance and biocompatibility. However, the customization of Ta-based bone repair materials for irregularly shaped bone defects has been challenging due to their high melting point and hardness. In this work, porous tantalum granules (PTaG) were developed for the first time to repair irregularly shaped bone defects, inspired by the natural phenomenon of sand flow. PTaG were designed as a hierarchical porous structure to regulate the mechanical properties and provide a favorable space for inward growth of cells and tissues. Commercial porous titanium granules (PTiG) and Bio-Oss were used as positive controls to explore the potential of PTaG as bone substitute. The morphology, three-dimensional structure, composition, and mechanical properties of PTaG and PTiG were evaluated by SEM, X-Ray 3D imaging system, 3D laser confocal microscope, EDS, XRD, XPS, and nanoindentation. In vitro, cell compatibility and mineralization ability were evaluated for both materials. Furthermore, PTaG, PTiG, and Bio-Oss were filled in the rabbit femoral defect, and micro-CT and histological analysis were performed after 8 weeks. The results showed that the PTaG had the best bone healing effect due to the hierarchical porous structure, excellent three-dimensional connectivity and chemical stability, suitable mechanical properties and surface roughness, good biocompatibility and mineralization osteogenic activity. This work indicates that PTaG may have a positive potential for filling and repairing irregularly shaped bone defects.

Mg alloy scaffold with spherical/cubic hybrid pores for orthopedic repair

Biodegradable Mg-based scaffolds are regarded as potential bone tissue engineering materials for a promising approach to bone repair. In this work, the spherical/cubic hybrid pore-forming agents were introduced to prepare a porous Mg-based alloy scaffold by the negative salt pattern molding method. The porous Mg-Zn-Ca alloy scaffold containing spherical/cubic hybrid pores exhibited a porosity of about 68.60 % and a surface area ratio of about 7.88 cm2/cm3. The compressive elastic modulus was about 0.32 GPa and the compressive strength was about 4.22 MPa, close to cancellous bone. However, the rapid degradation of Mg alloy scaffold was inadaptive to orthopedic repair. Thus, a calcium phytate coating was prepared on the Mg-based scaffold for surface modification to retard rapid corrosion.

Development of injectable microgel-based scaffolds via enzymatic cross-linking of hyaluronic acid-tyramine/gelatin-tyramine for potential bone tissue engineering

Currently, the healing of large bone defects relies on invasive surgeries and the transplantation of autologous bone. As a less invasive treatment option, the provision of microenvironments that promote the regeneration of defective bones holds great promise. Here, we developed hyaluronic acid (HA)/gelatin (Ge) microgel-based scaffolds to guide bone regeneration. To enable the formation of microgels by enzymatic cross-linking in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2), we modified the polymers with tyramine (TA). Spectrophotometry and proton nuclear magnetic resonance (1H NMR) spectroscopy analysis confirmed successful tyramine substitution on polymer backbones. To enable the formation of microgels by a water-in-oil emulsion approach, the HRP and H2O2 concentrations were tuned to achieve the gelation in a few seconds. By varying the stirring speed from 600 to 1000 rpm, spherical microgels were produced with an average size of 116 ± 8.7 and 68 ± 4.7 μm, respectively. The results showed that microgels were injectable through needles and showed good biocompatibility with the cultured human osteosarcoma cell line (MG-63). HA/Ge-TA microgels served as a promising substrate for MG-63 cells since they improved the alkaline phosphatase activity and level of calcium deposition. In summary, the developed HA/Ge-TA microgels are promising injectable microgel-based scaffolds in bone tissue engineering.

Incorporation of calcium phosphate cement into decellularized extracellular matrix enhances its bone regenerative properties

Decellularized extracellular matrix (dECM) hydrogels are engineered constructs that are widely-used in the field of regenerative medicine. However, the development of ECM-based hydrogels for bone tissue engineering requires enhancement in its osteogenic properties. For this purpose, we initially employed bone-derived dECM hydrogel (dECM-Hy) in combination with calcium phosphate cement (CPC) paste to improve the biological and structural properties of the dECM hydrogel. A decellularization protocol for bovine bone was developed to prepare dECM-Hy, and the mechanically-tuned dECM/CPC-Hy was built based on both rheological and mechanical characteristics. The dECM/CPC-Hy displayed a double swelling ratio and compressive strength. An interconnected structure with distinct hydroxyapatite crystals was evident in dECM/CPC-Hy. The expression levels of Alp, Runx2 and Ocn genes were upregulated in dECM/CPC-Hy compared to the dECM-Hy. A 14-day follow-up of the rats receiving subcutaneous implanted dECM-Hy, dECM/CPC-Hy and mesenchymal stem cells (MSCs)-embedded (dECM/CPC/MSCs-Hy) showed no toxicity, inflammatory factor expression or pathological changes. Radiography and computed tomography (CT) of the calvarial defects revealed new bone formation and elevated number of osteoblasts-osteocytes and osteons in dECM/CPC-Hy and dECM/CPC/MSCs-Hy compared to the control groups. These findings indicate that the dECM/CPC-Hy has substantial potential for bone tissue engineering.

Polydopamine Applications in Biomedicine and Environmental Science.

This manuscript explores the multifaceted applications of polydopamine (PDA) across various scientific and industrial domains. It covers the chemical aspects of PDA and its potential in bone tissue engineering, implant enhancements, cancer treatment, and nanotechnology. The manuscript investigates PDA's roles in tissue engineering, cell culture technologies, surface modifications, drug delivery systems, and sensing techniques. Additionally, it highlights PDA's contributions to microfabrication, nanoengineering, and environmental applications. Through detailed testing and assessment, the study identifies limitations in PDA-related research, such as synthesis complexity, incomplete mechanistic understanding, and biocompatibility variability. It also proposes future research directions aimed at improving synthesis techniques, expanding biomedical applications, and enhancing sensing technologies to optimize PDA's efficacy and scalability.

Nanoclay-Composite Hydrogels for Bone Tissue Engineering.

Nanoclay-composite hydrogels represent a promising avenue for advancing bone tissue engineering. Traditional hydrogels face challenges in providing mechanical strength, biocompatibility, and bioactivity necessary for successful bone regeneration. The incorporation of nanoclay into hydrogel matrices offers a potential unique solution to these challenges. This review provides a comprehensive overview of the fabrication, physico-chemical/biological performance, and applications of nanoclay-composite hydrogels in bone tissue engineering. Various fabrication techniques, including in situ polymerization, physical blending, and 3D printing, are discussed. In vitro and in vivo studies evaluating biocompatibility and bioactivity have demonstrated the potential of these hydrogels for promoting cell adhesion, proliferation, and differentiation. Their applications in bone defect repair, osteochondral tissue engineering and drug delivery are also explored. Despite their potential in bone tissue engineering, nanoclay-composite hydrogels face challenges such as optimal dispersion, scalability, biocompatibility, long-term stability, regulatory approval, and integration with emerging technologies to achieve clinical application. Future research directions need to focus on refining fabrication techniques, enhancing understanding of biological interactions, and advancing towards clinical translation and commercialization. Overall, nanoclay-composite hydrogels offer exciting opportunities for improving bone regeneration strategies.

Synthesis and characterization of injectable thermosensitive hydrogel based on Pluronic-grafted silk fibroin copolymer containing hydroxyapatite nanoparticles as potential for bone tissue engineering

Injectable hydrogels are promising for bone tissue engineering due to their minimally invasive application and adaptability to irregular defects. This study presents the development of pluronic grafted silk fibroin (PF-127-g-SF), a temperature-sensitive graft copolymer synthesized from SF and modified PF-127 via a carbodiimide coupling reaction. The PF-127-g-SF copolymer exhibited a higher sol-gel transition temperature (34 °C at 16 % w/v) compared to PF-127 (23 °C), making it suitable for injectable applications. It also showed improved flexibility and strength, with a yielding point increase from <10 % to nearly 30 %. Unlike PF-127 gel, which degrades within 72 h in aqueous media, the PF-127-g-SF copolymer maintained a stable gel structure for over two weeks due to its robust crosslinked hydrogel network. Incorporating hydroxyapatite nanoparticles (n-HA) into the hydrogel reduced pore size and decreased swelling and degradation rates, extending structural stability to four weeks. Increasing n-HA concentration from 0 % to 20 % reduced porosity from 80 % to 66 %. Rheological studies indicated that n-HA enhanced the scaffold's strength and mechanical properties without altering gelation temperature. Cellular studies with MG-63 cells showed that n-HA concentration influenced cell viability and mineralization, highlighting the scaffold's potential in bone tissue engineering.

Osteoconductive composite membranes produced by rotary jet spinning bioresorbable PLGA for bone regeneration

Bone defects and injuries are common, and better solutions are needed for improved regeneration and osseointegration. Bioresorbable membranes hold great potential in bone tissue engineering due to their high surface area and versatility. In this context, polymers such as poly(lactic-co-glycolic acid) (PLGA) can be combined with osteoconductive materials like hydroxyapatite (HA) nanoparticles (NPs) to create membranes with enhanced bioactivity and bone regeneration. Rotary Jet spinning (RJS) is a powerful technique to produce these composite membranes. This study presents an innovative and efficient method to obtain PLGA-HA(NPs) membranes with continuous fibers containing homogeneous HA(NPs) distribution. The membranes demonstrated stable thermal degradation, allowing HA(NPs) quantification. In addition, the PLGA-HA(NPs) presented osteoconductivity, were not cytotoxic, and had high cell adhesion when cultured with pre-osteoblastic cells. These findings demonstrate the potential of RJS to produce PLGA-HA(NPs) membranes for easy and effective application in bone regeneration.

Design of gelatin cryogel scaffolds with the ability to release simvastatin for potential bone tissue engineering applications

Tissue engineering aims to improve or restore damaged tissues by using scaffolds, cells and bioactive agents. In tissue engineering, one of the most important concepts is the scaffold because it has a key role in keeping up and promoting the growth of the cells. It is also desirable to be able to load these scaffolds with drugs that induce tissue regeneration/formation. Based on this, in our study, gelatin cryogel scaffolds were developed for potential bone tissue engineering applications and simvastatin loading and release studies were performed. Simvastatin is lipoliphic in nature and this form is called inactive simvastatin (SV). It is modified to be in hydrophilic form and converted to the active form (SVA). For our study's drug loading and release process, simvastatin was used in both inactive and active forms. The blank cryogels and drug-loaded cryogels were prepared at different glutaraldehyde concentrations (1, 2, and 3%). The effect of the crosslinking agent and the amount of drug loaded were discussed with morphological and physicochemical analysis. As the glutaraldehyde concentration increased gradually, the pores size of the cryogels decreased and the swelling ratio decreased. For the release profile of simvastatin in both forms, we can say that it depended on the form (lipophilic and hydrophilic) of the loaded simvastatin.

Effect of DNA methylation on the osteogenic differentiation of mesenchymal stem cells: concise review.

Mesenchymal stem cells (MSCs) have promising potential for bone tissue engineering in bone healing and regeneration. They are regarded as such due to their capacity for self-renewal, multiple differentiation, and their ability to modulate the immune response. However, changes in the molecular pathways and transcription factors of MSCs in osteogenesis can lead to bone defects and metabolic bone diseases. DNA methylation is an epigenetic process that plays an important role in the osteogenic differentiation of MSCs by regulating gene expression. An increasing number of studies have demonstrated the significance of DNA methyltransferases (DNMTs), Ten-eleven translocation family proteins (TETs), and MSCs signaling pathways about osteogenic differentiation in MSCs. This review focuses on the progress of research in these areas.

Physical, mechanical characterization, and artificial neural network modeling of biodegradable composite scaffold for biomedical applications

The performance of substitute osteoconductive scaffolds in guiding new bone formation and creating vital biological conditions in living organisms is of crucial importance. In this study, bioresorbable scaffolds were synthesized by incorporating polyvinyl alcohol (PVA) with hydroxyapatite nanoparticles (n-HAP) and Iron oxide (Fe3O4) nanoparticles (NPs) (MNPs) using a freeze-drying technique. Subsequently, the magnetic nanocomposite scaffolds were immersed in a phosphate-buffered saline (PBS) solution for 24 days to assess their degradability percentage. The physicochemical and morphological properties of the magnetic nanocomposite scaffolds were evaluated using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Furthermore, the mechanical behavior was examined, while the pore dimensions and porosity were determined using immersion-based techniques. Noteworthy attributes of the magnetic nanocomposite scaffolds were observed, including a maximum swelling capacity of 176 %, a substantial porosity of 72.7%, and impressive mechanical characteristics, such as a compressive strength of 4.61 MPa and an elastic modulus of 2.13 GPa. The degradation study conducted in a PBS solution revealed that the scaffold with the highest n-HAP content (20 wt%) exhibited a degradation rate of approximately 21% after a 24-day period. The influence of environmental conditions, including time, temperature, and salt-containing environments, on the swelling behavior and bio-resorption of the scaffolds was examined. Additionally, an artificial neural network (ANN) was developed to forecast the impact of weight percentages of n-HAP and MNPs on various scaffold properties. According to the ANN predictions, increasing the weight percentages of n-HAP and MNPs resulted in a reduction in pore size, an increase in porosity, and an improvement in the mechanical properties of the scaffolds. Moreover, the incorporation of a higher number of nanoparticles led to increased absorption and swelling, facilitating bone tissue formation. Satisfactory accuracy in predicting scaffold properties was demonstrated through error analysis and linear regression plots, aiding designers in selecting appropriate weight percentages of nanoparticles for future designs. The findings indicate that the synthesized magnetic nanocomposite scaffold closely resembles the physical and mechanical characteristics of natural bone tissue. The utilization of an ANN for performance assessment demonstrated favorable efficiency and effectiveness. Therefore, the significance of the current study lies in the comprehensive investigation of the synthesis and characterization of a biodegradable magnetic nanocomposite scaffold, as well as the utilization of an ANN-based approach to predict and optimize its properties for potential bone tissue engineering applications.

Enhancing Osteogenic Potential in Bone Tissue Engineering: Optimizing Pore Size in Alginate–Gelatin Composite Hydrogels

Bone tissue engineering relies on crucial scaffolds for tissue formation and stem cell differentiation. A composite scaffold of alginate‐gelatin effectively supports these processes. This study aims to design a porous alginate‐gelatin hydrogel and assess pore size effects on cell behavior, focusing on morphology, adhesion, and proliferation in distinct osteogenic environments. Hydrogels are prepared using various alginate‐gelatin concentrations: 4% alginate and 6% gelatin (4A6G) or 3% alginate and 5% gelatin (3A5G), cross‐linked with 2% CaCl2. Pore size optimization employs simple freezing and thawing cycles. Scanning electron microscopy reveals varying pore sizes: 340 µm ± 30 µm for 4A6G and 635 µm ± 25 µm for 3A5G. Stiffness measurements indicate significant differences: ≈26.3 kPa ± 0.6 KPa for 4A6G and 21.6 kPa ± 0.2 KPa for 3A5G. Cell interaction studies demonstrate higher adhesion and proliferation rates in larger‐pored hydrogels. Evaluation of bone tissue formation, including RT‐PCR, ALP activity, and ARS staining, reveal superior osteogenic potential in the 3A5G hydrogel compared to 4A6G. In conclusion, the 3A5G hydrogel (3% alginate and 5% gelatin) holds promise for bone tissue regeneration due to its biodegradability and favorable bone‐forming properties.

Customized 3D‐printed heterogeneous porous titanium scaffolds for bone tissue engineering

AbstractBone defect is a common clinical disease. Due to the uncertainty of trauma or infection areas, customized size features are often required for bone substitutes. By inspiration of the natural bone structure, this study designs porous scaffolds with a biomimetic design perspective by using different inner and outer pore units. The outer pore units adopt body‐centered cubic (BCC) structure to simulate the weight‐bearing function of human cortical bone, while inner pore units using I‐Wrapped Package structure, a kind of three periods minimum surface, to obtain a good permeability and simulates the inner layer of cancellous bone. To further regulate the overall modulus of the scaffold within the range of natural bone modulus in the human body, the scaffold was designed to axial gradient structure. Compression experiments were conducted, and the results indicated that when the volume fraction linearly increased from 20% to 50%, the Young's modulus was close to the cortical bone modulus in the human body. In vitro cell experiments further proved that osteoblasts have good cellular activity and spreading morphology on the surface of this scaffold. The customized 3D‐printed heterogeneous porous titanium scaffold has great application potential in bone tissue engineering.

Integration of BMP-2/PLGA microspheres with the 3D printed PLGA/CaSO4 scaffold enhances bone regeneration

Treatment of large and complex irregular bone defects is a major clinical challenge in orthopedic surgery. The current treatment includes bone transportation using the Ilizarov technique and bone cement repair using the Masquelet technique, but they require long-term manual intervention or secondary operation. To improve this situation, we compared the different implanting materials in the literature published in the past 10 years, finding that glycolic acid copolymer (PLGA) and Calcium sulfate (CaSO4) are appropriated to be used as synthetic bone materials due to their advantages of easy-availability, nontoxicity, osteogenic properties and rapid degradation. Meanwhile, the development of 3D printing technique and devices makes it relatively easier to synthetize customized bio-mimetic porous scaffolds, thus facilitating the release of modified protein. In this study, we compounded BMP-2/PLGA microspheres with polylactic glycolic acid copolymer/CaSO4 (PC) 3D printed scaffold to improve the osteogenic properties of the scaffold. The result of our in vitro experiment demonstrated that the prepared PCB scaffold not only had satisfactory bio-compatibility, but also promoted osteogenic differentiation. This 3D printed scaffold is capable to accelerate the repair of complex bone defects by promoting new bone formation, suggesting that it may prove to be a potential bone tissue engineering substitute.

A Hierarchical Hydrogel Impregnation Strategy Enables Brittle-Failure-Free 3D-Printed Bioceramic Scaffolds.

3D-printed bioceramic scaffolds offer great potential for bone tissue engineering (BTE) but their inherent brittleness and reduced mechanical properties at high porosities can easily result in catastrophic fractures. Herein, this study presents a hierarchical hydrogel impregnation strategy, incorporating poly(vinyl alcohol) (PVA) hydrogel into the macro- and micropores of bioceramic scaffolds and synergistically reinforcing it via freeze-casting assisted solution substitution (FASS) in a tannic acid (TA)-glycerol solution. By effectively mitigating catastrophic brittle failures, the hydrogel-impregnated scaffolds showcase three- and 100-fold enhancement in mechanical energy absorption under compression (5.05MJm-3) and three-point bending (3.82MJm-3), respectively. The reinforcement mechanisms are further investigated by experimental and simulation analyses, revealing a multi-scale synergy of fracture and fragmentation resistance through macro and micro-scale fiber bridging, and nano and molecular-scale hydrogel reinforcement. Also, the scaffolds acquire additional antibacterial and drug-loading capabilities from the hydrogel phase while maintaining favorable cell biocompatibility. Therefore, this study demonstrates a facile yet effective approach for preparing brittle-failure-free bioceramic scaffolds with enhanced biological functionalities, showcasing immense potential for BTE applications.

Impact of ZrO2 Content on the Formation of Sr-Enriched Phosphates in Al2O3/ZrO2 Nanocomposites for Bone Tissue Engineering.

This study investigates the profound impact of the ZrO2 inclusion volume on the characteristics of Al2O3/ZrO2 nanocomposites, particularly influencing the formation of calcium phosphates on the surface. This research, aimed at advancing tissue engineering, prepared nanocomposites with 5, 10, and 15 vol% ZrO2, subjecting them to chemical surface treatment for enhanced calcium phosphate deposition sites. Biomimetic coating with Sr-enriched simulated body fluid (SBF) further enhanced the bioactivity of nanocomposites. While the ZrO2 concentration heightened the oxygen availability on nanocomposite surfaces, the quantity of Sr-containing phosphate was comparatively less influenced than the formation of calcium phosphate phases. Notably, the coated nanocomposites exhibited a high cell viability and no toxicity, signifying their potential in bone tissue engineering. Overall, these findings contribute to the development of regenerative biomaterials, holding promise for enhancing bone regeneration therapies.