Scaffolds For Bone Tissue Regeneration Research Articles

Functional Scaffolds for Bone Tissue Regeneration: A Comprehensive Review of Materials, Methods, and Future Directions.

Bone tissue regeneration is a rapidly evolving field aimed at the development of biocompatible materials and devices, such as scaffolds, to treat diseased and damaged osseous tissue. Functional scaffolds maintain structural integrity and provide mechanical support at the defect site during the healing process, while simultaneously enabling or improving regeneration through amplified cellular cues between the scaffold and native tissues. Ample research on functionalization has been conducted to improve scaffold-host tissue interaction, including fabrication techniques, biomaterial selection, scaffold surface modifications, integration of bioactive molecular additives, and post-processing modifications. Each of these methods plays a crucial role in enabling scaffolds to not only support but actively participate in the healing and regeneration process in bone and joint surgery. This review provides a state-of-the-art, comprehensive overview of the functionalization of scaffold-based strategies used in tissue engineering, specifically for bone regeneration. Critical issues and obstacles are highlighted, applications and advances are described, and future directions are identified.

3D-printed polycaprolactone-magnetic nanoparticles composite multifunctional scaffolds for bone tissue regeneration and hyperthermia treatment

Cancer management after tumor resection is characterized by two critical needs: (i) rehabilitation of the resected tissue and (ii) preventing post-surgical tumor recurrence by destroying any residual tumors. The state of the art in literature is limited because it tackles these two major priorities individually, it achieves tissue regeneration via autologous grafting and prevents tumor recurrence through chemotherapy. In this paper, extrusion 3D printing has been employed to manufacture composite multi-functional scaffolds with polycaprolactone (PCL) as a polymeric matrix and magnetic nanoparticles (MNPs) in a 0 to 50 wt% ratio, that would aid in bone regeneration and cancer management via magnetic hyperthermia treatment. The fabricated scaffolds were evaluated for their mechanical, magnetic and thermal characteristics. The Young’s modulus of the scaffolds increased multi-fold with increasing concentration of MNPs added to PCL (26.88±9.02 MPa for pure PCL to 229.06±37.05 MPa for PCL/50 wt% MNP scaffolds). PCL/MNP scaffolds displayed a directly proportional correlation between MNP concentration and saturation magnetization. While the in vitro tests showed a statistically significant cell growth of human Mesenchymal Stem Cells (hMSCs) over 7 days for all MNP concentrations, only the 50% MNP scaffold showed an increase in temperature over 41oC when subjected to an alternating magnetic field making it suitable for the hyperthermia treatment. On application of alternating magnetic fields to PCL and PCL/50 wt% MNP scaffolds, there was an increase in hMSCs proliferation and decrease in Bone cancer cells proliferation, thus proving the potential to be used as a multi-functional scaffold for post-surgical bone cancer management.  

Synthesis and Characterization of Nano Calcium Phosphates Extracted from Biogenic Cancellous Bovine Bone in Polymeric Scaffolds for Bone Tissue Regeneration: In Vitro Study

Synthesis and Characterization of Nano Calcium Phosphates Extracted from Biogenic Cancellous Bovine Bone in Polymeric Scaffolds for Bone Tissue Regeneration: In Vitro Study

Bone Regeneration Capabilities of Scaffolds Containing Chitosan and Nanometric Hydroxyapatite-Systematic Review Based on In Vivo Examinations.

In this systematic review, the authors aimed to investigate the state of knowledge on in vivo evaluations of chitosan and nanometric hydroxyapatite (nanohydroxyapatite, nHAp) scaffolds for bone-tissue regeneration. In March 2024, an electronic search was systematically conducted across the PubMed, Cochrane, and Web of Science databases using the keywords (hydroxyapatite) AND (chitosan) AND (scaffold) AND (biomimetic). Methodologically, the systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol to the letter. Initially, a total of 375 studies were screened, and 164 duplicates were removed. A further 188 articles were excluded because they did not correspond to the predefined topics, and an additional 3 articles were eliminated due to the inability to obtain the full text. The final compilation included 20 studies. All publications indicated a potential beneficial effect of the scaffolds in in vivo bone defect repair. A beneficial effect of hydroxyapatite as a scaffold component was observed in 16 studies, including greater mechanical resistance, cellular differentiation, and enhanced bone damage regeneration. The addition of chitosan and apatite ceramics, which combined the strengths of both materials, had the potential to become a useful bone-tissue engineering material.

Production of platelet-rich plasma (PRP)-enriched scaffolds for bone tissue regeneration with 3D printing technology

Bone disorders signify diverse abnormalities in the structure, development, and functions of bone tissue in the human body, with a significant correlation to ageing, insufficient physical activity, and escalating obesity. Recent advancements in bone tissue engineering aim to enhance bone tissue formation through the use of biomaterials, growth factors, and cells. The present study focuses on the fabrication and characterisation of scaffolds with a composition of gelatin (GEL) / sodium alginate (SA) / hydroxyapatite (HA) / platelet-rich plasma (PRP) using the 3D printing process. The inclusion of PRP, derived from blood, is of particular interest due to its potential to enhance bone regeneration through various growth factors. Scanning electron microscope (SEM) analysis revealed average pore sizes ranging from 481.50 ± 7.65 to 623.96 ± 11.54 µm. SEM images also showed that scaffold surfaces became smooth as the concentration of PRP increased. The mechanical test results demonstrated that as the PRP increased, the compressive strength decreased. When the swelling and degradation behaviours of scaffolds were examined, it was observed that GEL/SA/HA/3PRP scaffolds exhibited approximately 200 % swelling capability until the 4th day. GEL/SA/HA scaffolds showed a degradation behaviour about 70 % higher compared to other groups. A controlled release profile of PRP was maintained up to the 144th, 216th, and 240th hours from the scaffolds. According to the highest correlation coefficients (R2) in the release kinetics of scaffolds, GEL/SA/HA/0.5PRP and GEL/SA/HA/1PRP scaffolds were explained by the first-order model. In contrast, the GEL/SA/HA/3PRP scaffold was described using the Korsmeyer–Peppas model. The MTT analysis conducted with osteoblast cells showed that scaffolds did not demonstrate any toxic effects and facilitated cell adhesion by inducing the formation of extensions. These findings underscore the potential of PRP-incorporated GEL/SA/HA composites as a promising approach for bone tissue engineering, offering significant advancements in the treatment of bone disorders. This could lead to more effective treatments for bone disorders and injuries, reducing the need for more invasive procedures and improving patient recovery times.

Fibroin-Based Porous Scaffolds for Bone Tissue Regeneration

Fibroin-Based Porous Scaffolds for Bone Tissue Regeneration

3D-Bioprinted Gelatin Methacryloyl-Strontium-Doped Hydroxyapatite Composite Hydrogels Scaffolds for Bone Tissue Regeneration.

New gelatin methacryloyl (GelMA)-strontium-doped nanosize hydroxyapatite (SrHA) composite hydrogel scaffolds were developed using UV photo-crosslinking and 3D printing for bone tissue regeneration, with the controlled delivery capacity of strontium (Sr). While Sr is an effective anti-osteoporotic agent with both anti-resorptive and anabolic properties, it has several important side effects when systemic administration is applied. Multi-layer composite scaffolds for bone tissue regeneration were developed based on the digital light processing (DLP) 3D printing technique through the photopolymerization of GelMA. The chemical, morphological, and biocompatibility properties of these scaffolds were investigated. The composite gels were shown to be suitable for 3D printing. In vitro cell culture showed that osteoblasts can adhere and proliferate on the surface of the hydrogel, indicating that the GelMA-SrHA hydrogel has good cell viability and biocompatibility. The GelMA-SrHA composites are promising 3D-printed scaffolds for bone repair.

Biomimetic short fiber reinforced 3-dimensional scaffold for bone tissue regeneration

Bone defects caused by diseases and trauma are considered serious clinical challenges. Autologous and allogeneic transplantations are the most widely used methods to mitigate bone defects. However, transplantation poses risks such as secondary trauma, immune rejection, and disease transmission to patients. Preparing a biologically active bone tissue engineering scaffold as a bone substitute can overcome this problem. In the current study, a PLGA/gelatin (Gel) short fiber-reinforced composite three-dimensional (3D) scaffold was fabricated by electrospinning for bone tissue defect repair. A hybrid scaffold adding inorganic materials hydrotalcite (CaAl-LDH) and osteogenic factors deferoxamine (DFO) based on PLGA and Gel composite filaments was prepared. The structure, swelling, drug release, and compressive resilience performance of the 3D scaffolds in a wet state were characterized and the osteogenic effect of the crosslinked scaffold (C-DLPG) was also investigated. The scaffold has shown the optimum physicochemical attributes which still has 380 kPa stress after a 60% compression cycle and sustainedly released the drug for about twenty days. Moreover, a promising In vivo osteogenic performance was noted with better tissue organization. At 8 weeks after implantation, the C-DLPG scaffold could fill the bone defect site, and the new bone area reached 19 mm2. The 3D microfiber scaffold, in this study, is expected to be a promising candidate for the treatment of bone defects in the future.

Biomechanically tunable scaffolds for bone tissue regeneration and testbeds of cancer bone metastasis

Current challenges in bone regeneration and design of humanoid 3D bone metastases cancer testbeds can be overcome by designing bone-mimetic tissue engineering scaffolds with tunable mechanical and biological properties. This study employs three unnatural amino acids to modify montmorillonite clay (MMT), producing polymer clay nanocomposites (PCNs) to construct 3D bone-mimetic scaffolds. The modification of MMT clay with 5-aminovaleric acid, (±)-2-aminopimelic acid, and 4-(4-Aminophenyl) butyric acid is analyzed through x-ray diffraction (XRD) and fourier-transform infrared spectroscopy (FTIR), revealing changes in the interlayer spacing and functional groups. Molecular modeling elucidates the interaction energies in the amino acid intercalated nanoclays that influence the mechanical properties of the scaffolds. 4-(4-Aminophenyl) butyric acid-modified scaffolds exhibited the highest compressive strength, highlighting the critical influence of molecular interactions on the mechanical properties of the PCN. Despite being a small fraction of the scaffold, the presence and type of amino acids significantly affect the scaffold mechanical properties. Cell viability assays affirm biocompatibility of scaffolds. The amino acids within the nanoclays also impact mineralization on scaffolds seeded with human mesenchymal stem cells (hMSCs). Amino acid type also influences the amount of mineralization in the scaffolds. A sequential culture involving hMSCs and breast cancer cells (MCF-7) on the scaffold mimics breast cancer metastasis to bone. Enhanced mineralization by bone cells in the presence of MCF-7 cells is observed, emphasizing their osteoblastic characteristics. Hence, 3D scaffolds for bone regeneration and bone metastasis cancer testbeds can exhibit tunable mechanical properties and biological responses though a simulation guided choice of unnatural amino acids.

Stereolithography of ceramic scaffolds for bone tissue regeneration: Influence of hydroxyapatite/silica ratio on mechanical properties

In this paper, the results obtained in the development of ceramic resin feedstock for stereolithography are shown. Hydroxyapatite and silica are used as source of ceramic. Hydroxyapatite is extracted from bovine bone, which enhances bioactivity of ceramic scaffold. The influence of hydroxyapatite amount in polymer-based slurry on the viscosity and printability of feedstock is explored. Hydroxyapatite and silica containing scaffolds are successfully obtained by stereolithography. Influence of hydroxyapatite/silica ratio on the bioactivity, biodegradability and mechanical properties of the scaffolds is also studied. It was observed that higher concentrations of hydroxyapatite led to improved mechanical strength of the scuffolds but increased viscosity of the slurry, affecting printability. Cell viability assays and cell visualization experiments indicated that the scaffolds not cause significant cell toxicity.

Gelatin-coated mesoporous forsterite scaffold for bone tissue engineering

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.

Electrospun nanofibers: building blocks for the repair of bone tissue.

Bone, one of the hardest structures of the body, is the basic constituent of the skeletal system, which gives the shape to the body, provides mechanical support for muscles and soft tissues, and provides movement. Even if there is no damage, bone remodeling is a permanent process to preserve and renew the structural, biochemical, and biomechanical integrity of bone tissue. Apart from the remodeling, bone healing is the highly complicated process of repairing deficiencies of bone tissue by the harmonious operation of osteoblasts, osteocytes, osteoclasts, and bone lining cells. Various materials can be used to both trigger the bone healing process and to provide mechanical support to damaged bone. Nanofiber scaffolds are at the forefront of these types of systems because of their extremely large surface area-to-volume ratio, small pore size, and high porosity. Nanofibers are known to be highly functional systems with the ability to mimic the structure and function of the natural bone matrix, facilitating osteogenesis for cell proliferation and bone regeneration. Electrospinning is an easy and fast method to produce non-woven structures consisting of continuous ultrafine fibers with diameters ranging from micrometers down to nanometers. The simplicity and cost-effectiveness of the electrospinning technique, its ability to use a wide variety of synthetic, natural, and mixed polymers, and the formation of highly porous and continuous fibers are the remarkable features of this method. The importance of nanofiber-based scaffolds in bone tissue regeneration is increasing because of suitable pore size, high porosity, osteoinduction, induction of bone growth with osteoconduction, adaptability to the target area, biodegradation, and appropriate mechanical properties, which are among the main parameters that are important in the design of polymeric bone grafts. The aim of this review is to cast light on the increasing use of nanofiber-based scaffolds in bone tissue regeneration and give an insight about bone regeneration, production techniques of the electrospun nanofibers, and varying formulation parameters in order to reach different drug delivery goals. This review also provides an extensive market research of electrospun nanofibers and an overview on scientific research and patents in the field.

Biocompatible, porous hydrogels composed of aliphatic polyesters and poly(2-isopropenyl-2-oxazoline). Their application as scaffolds for bone tissue regeneration.

In this study, porous networks were efficiently prepared by crosslinking hydrophilic poly(2-isopropenyl-2-oxazoline) (PiPOx) with dicarboxylic polyesters (HOOC-PLA-COOH or HOOC-PCL-COOH) in the presence of sodium chloride as a water-soluble porogen. Importantly, by using a relatively simple synthetic protocol, the resulting spongy materials were freely formed to the desired size and shape while maintaining stable dimensions. According to the SEM data, the porous 3D structure can be altered by the pore dimensions, which are dependent on the porogen crystal size. After porosity characterization, the mechanical properties were also evaluated via uniaxial compression and tensile tests. The porous networks formed hydrogels with a high water absorption capacity. Finally, after showing cytocompatibility by the MTT assay, we also demonstrated the applicability of the porous hydrogels as scaffolds for cell cultivation. The presented results suggest that this type of hydrogels is a promising material for tissue engineering.

Effect of Gelatin Coating and GO Incorporation on the Properties and Degradability of Electrospun PCL Scaffolds for Bone Tissue Regeneration.

Polymer-based nanocomposites such as polycaprolactone/graphene oxide (PCL/GO) have emerged as alternatives for bone tissue engineering (BTE) applications. The objective of this research was to investigate the impact of a gelatin (Gt) coating on the degradability and different properties of PCL nanofibrous scaffolds fabricated by an electrospinning technique with 1 and 2 wt% GO. Uniform PCL/GO fibers were obtained with a beadless structure and rough surface. PCL/GO scaffolds exhibited an increase in their crystallization temperature (Tc), attributed to GO, which acted as a nucleation agent. Young's modulus increased by 32 and 63% for the incorporation of 1 and 2 wt% GO, respectively, in comparison with neat PCL. A homogeneous Gt coating was further applied to these fibers, with incorporations as high as 24.7 wt%. The introduction of the Gt coating improved the hydrophilicity and degradability of the scaffolds. Bioactivity analysis revealed that the hydroxyapatite crystals were deposited on the Gt-coated scaffolds, which made them different from their uncoated counterparts. Our results showed the synergic effect of Gt and GO in enhancing the multifunctionality of the PCL, in particular the degradability rate, bioactivity, and cell adhesion and proliferation of hGMSC cells, making it an interesting biomaterial for BTE.

Hybrid implants based on calcium-magnesium silicate ceramic diopside as a carrier of recombinant BMP-2 and demineralized bone matrix as a scaffold: ectopic osteogenesis in intramuscular implantation in mice

High efficiency of hybrid implants based on calcium-magnesium silicate ceramic diopside as a carrier of recombinant BMP-2 and xenogenic demineralized bone matrix (DBM) as a scaffold for bone tissue regeneration was demonstrated previously on the model of critical size cranial defects in mice. In order to investigate the possibility of using these implants for growing autologous bone tissue using the in vivo bioreactor principle in the patient’s own body, the effectiveness of the ectopic osteogenesis induced by them in intramuscular implantation in mice was studied. At 7 µg dose of BMP-2 per implant, after 1 week we observed a dense agglomeration of cells, probably skeletal muscle satellite precursor cells, with areas of intense chondrogenesis, the initial stage of indirect osteogenesis, around the implants. After 12 weeks, a dense bone capsule of trabecular structure was formed, covered with periosteum, with mature bone marrow located in the spaces between the trabeculae. The capsule volume was about 8-10 times the volume of the original implant. There were practically no signs of inflammation and foreign body reaction. Microcomputer tomography data showed a significant increase of the relative bone volume, number of trabeculae and bone tissue density in the group with BMP-2 in comparison with the group without BMP-2. Considering that DBM can be obtained in practically unlimited quantities, of the required size and shape, and the BMP-2 used, which is obtained by synthesis in E. coli cells, is relatively inexpensive, further development of the in vivo bioreactor model based on hybrid implants from BMP-2, diopside and xenogenic DBM seems promising.

In situ forming alginate/gelatin hydrogel scaffold through Schiff base reaction embedded with curcumin-loaded chitosan microspheres for bone tissue regeneration

In this study, we developed a biocompatible composite hydrogel that incorporates microspheres. This was achieved using a Schiff base reaction, which combines the amino and aldehyde groups present in gelatin (Gel) and oxidized alginate (OAlg). We suggest this hydrogel as a promising scaffold for bone tissue regeneration. To further boost its osteogenic capabilities and mechanical resilience, we synthesized curcumin (Cur)-loaded chitosan microspheres (CMs) and integrated them into the Gel-OAlg matrix. This formed a robust composite gel framework. We conducted comprehensive evaluations of various properties, including gelation time, morphology, compressive strength, rheological behavior, texture, swelling rate, in vitro degradation, and release patterns. A remarkable observation was that the inclusion of 30 mg/mL Cur-CMs significantly enhanced the hydrogel's mechanical and bioactive features. Over three weeks, the Gel-OAlg/Cur-CMs (30) composite showed a cumulative curcumin release of 35.57%. This was notably lower than that observed in standalone CMs and Gel-OAlg hydrogels. Additionally, the Gel-OAlg/Cur-CMs (30) hydrogel presented a reduced swelling rate and weight loss relative to hydrogels devoid of Cur-CMs. On the cellular front, the Gel-OAlg/Cur-CMs (30) hydrogel showcased superior biocompatibility. It also displayed increased calcium deposition, alkaline phosphatase (ALP) activity, and elevated osteogenic gene expression in human bone marrow mesenchymal stem cells (hBMSCs). These results solidify its potential as a scaffold for bone tissue regeneration.

Ion—modified optimization of smart scaffolds in bone tissue regeneration

Bioactive glasses and Calcium Phosphate bioceramics have emerged as promising scaffold biomaterials for bone tissue engineering. These materials possess inherent osteoinductive properties that work to create a more suitable environment for bone tissue formation. Additionally, these scaffolds exhibit dissolution properties when submerged in physiological fluids in vivo and therefore can release different ions. Incorporating therapeutic ion-modifiers that have independently demonstrated their osteogenic favorability to these scaffolds can further increase environmental suitability. This review discusses the favorable properties of bioactive glasses and Calcium Phosphate bioceramics in the context of Bone Tissue Engineering as well as potential incorporable metal ion-modifiers.

Preparation and characterization of novel poly (lactic acid)/calcium oxide nanocomposites by electrospinning as a potential bone tissue scaffold

Calcium oxide nanoparticles (n-CaO) ca. 22 nm were obtained from eggshell waste. The n-CaO was incorporated into the PLA matrix in 10 and 20 wt% of filler content by electrospinning process to get PLA/n-CaO fibers with homogenous morphology and diameter as a potential use in scaffold for bone tissue regeneration. The incorporation of n-CaO into PLA modifies the mechanical properties, having a reinforcement effect on the matrix. The Young modulus for PLA/n-CaO nanocomposites increased between 122 and 138 % concerning neat PLA fibers, showing a more rigid behavior. The PLA/n-CaO nanocomposite fibers showed in vitro bioactivity, capable of inducing the precipitation of hydroxyapatite (HA) layer in the fiber surface after seven days in SBF solution. The biocidal and biological properties of PLA/n-Cao with 20 wt% showed a 30 % reduction in bacterial viability against S. aureus and 11 % against E. coli after 6 h of bacterial exposure. Furthermore, the fibers did not show a cytotoxic effect on the bone marrow ST-2 cell line, allowing cell adhesion and proliferation in the RPMI medium. The PLA/n-CaO with 20 wt% of nanoparticles showed a higher capacity to promote osteogenic differentiation, significantly increasing the alkaline phosphatase (ALP) expression after seven days compared to PLA and cell control. The in vivo analysis corroborated the biocompatibility of the prepared scaffolds; the presence of n-CaO in PLA reduced the formation of fibrous encapsulation of the material, improving the healing process. These results validated using n-CaO to enhance the functionality of polymer matrices as a PLA, bringing bioactive, biocide, and biocompatible properties, opening a new and interesting route to develop new biomaterials as a scaffold for bone tissue engineering.

Hybrid Implants Based on Calcium-Magnesium Silicate Ceramic Diopside as a Carrier of Recombinant BMP-2 and Demineralized Bone Matrix as a Scaffold: Ectopic Osteogenesis in Intramuscular Implantation in Mice

High efficiency of hybrid implants based on calcium-magnesium silicate ceramic, diopside, as a carrier of recombinant BMP-2 and xenogenic demineralized bone matrix (DBM) as a scaffold for bone tissue regeneration was demonstrated previously using the model of critical size cranial defects in mice. In order to investigate the possibility of using these implants for growing autologous bone tissue using in vivo bioreactor principle in the patient’s own body, effectiveness of ectopic osteogenesis induced by them in intramuscular implantation in mice was studied. At the dose of 7 μg of BMP-2 per implant, dense agglomeration of cells, probably skeletal muscle satellite precursor cells, was observed one week after implantation with areas of intense chondrogenesis, initial stage of indirect osteogenesis, around the implants. After 12 weeks, a dense bone capsule of trabecular structure was formed covered with periosteum and mature bone marrow located in the spaces between the trabeculae. The capsule volume was about 8-10 times the volume of the original implant. There were practically no signs of inflammation and foreign body reaction. Microcomputed tomography data showed significant increase of the relative bone volume, number of trabeculae, and bone tissue density in the group of mice with BMP-2-containing implant in comparison with the group without BMP-2. Considering that DBM can be obtained in practically unlimited quantities with required size and shape, and that BMP-2 is obtained by synthesis in E. coli cells and is relatively inexpensive, further development of the in vivo bioreactor model based on the hybrid implants constructed from BMP-2, diopside, and xenogenic DBM seems promising.

Fabrication and Characterization of 3D Nanostructured Polycaprolactone-Gelatin/Nanohydroxyapatite-Nanoclay Scaffolds for Bone Tissue Regeneration

Fabrication and Characterization of 3D Nanostructured Polycaprolactone-Gelatin/Nanohydroxyapatite-Nanoclay Scaffolds for Bone Tissue Regeneration