Bioactive Nanocomposite Scaffolds Research Articles

Cell-loaded genipin cross-linked collagen/gelatin skin substitute adorned with zinc-doped bioactive glass-ceramic for cutaneous wound regeneration

An optimal tissue-engineered dermal substitute should possess biocompatibility and cell adhesion conduction to facilitate fibroblast and keratinocyte infiltration and proliferation, as well as angiogenesis potential to escalate wound healing. Zinc was doped to bioactive glass-ceramic (Zn-BGC) to promote biocompatibility and angiogenesis properties. Zn-BGC was then incorporated into a collagen (Col) and gelatin (Gel) porous scaffold. The bioactive porous bionanocomposite exhibited biocompatibility along with improved cell attachment and proliferation. Scaffolds including Col-Gel/Zn-BGC with or without mouse embryonic fibroblasts were applied on full-thickness skin wounds on the BALB/c mice to assess their wound healing potential in vivo. The results indicated that the biodegradation rate of the Col-Gel/Zn-BGC nanocomposites was comparable to the rate of skin tissue regeneration in vivo. Macroscopic wound healing results showed that Col-Gel/Zn-BGC loaded with mouse embryonic fibroblast possesses the smallest wound size, indicating the fastest healing process. Histopathological evaluations displayed that the optimal wound regeneration was observed in Col-Gel/Zn-BGC nanocomposites loaded with mouse embryonic fibroblasts indicated by epithelialization and angiogenesis; besides the number of fibroblasts and hair follicles was increased. The bioactive nanocomposite scaffold of Col-Gel containing Zn-BGC nanoparticles loaded with mouse embryonic fibroblasts can be employed as a desirable skin substitute to ameliorate cutaneous wound regeneration.

L-cysteine aided polyaniline capped SrO2 nanoceramics: Assessment of MC3T3-E1-arbitrated osteogenesis and anti-bactericidal efficacy on the polyurethane 2D nanofibrous substrate

Fabricating bioartificial bone graft ceramics retaining structural, mechanical, and bone induction properties akin to those of native stem-cell niches is a major challenge in the field of bone tissue engineering and regenerative medicine. Moreover, the developed materials are susceptible to microbial invasion leading to biomaterial-centered infections which might limit their clinical translation. Here, we successfully developed biomimetic porous scaffolds of polyurethane-reinforcedL-cysteine-anchored polyaniline capped strontium oxide nanoparticles to improve the scaffold’s biocompatibility, osteo-regeneration, mechanical, and antibacterial properties. The engineered nanocomposite substrate PU/L-Cyst-SrO2 @PANI (0.4 wt%) significantly promotes bone repair and regeneration by modulating osteolysis and osteogenesis. ALP activity, collagen-I, ARS staining, as well as biomineralization of MC3T3-E1 cells, were used to assess the biocompatibility and cytocompatibility of the developed scaffolds in vitro, confirming that the scaffold provided a favorable microenvironment with a prominent effect on cell growth, proliferation, and differentiation. Furthermore, osteogenic protein markers were studied using qRT-PCR with expression levels of runt-related transcription factor 2 (RUNX2), secreted phosphoprotein 1 (Spp-I), and collagen type I (Col-I). The overall results suggest that PU/L-Cyst-SrO2 @PANI (0.4 wt%) scaffolds showed superior interfacial biocompatibility, antibacterial properties, load-bearing ability, and osteoinductivity as compared to pristine PU. Thus, prepared bioactive nanocomposite scaffolds perform as a promising biomaterial substrate for bone tissue regeneration.

Boosting cell proliferation in three-dimensional polyacrylates/nanohydroxyapatite scaffolds synthesized by deep eutectic solvent-based emulsion templating

Among three-dimensional (3D) scaffold fabrication methods, porous polymers templated using high internal phase emulsions (HIPEs) have emerged as an attractive method due to the facile generation of interconnected porosity through a variety of synthetic routes. These include a bottom-up approach to selectively incorporate nanomaterials onto the inner walls in a nonaqueous environment. In this work, novel nonaqueous HIPEs made of different (meth)acrylate monomers and a deep eutectic solvent (DES) were formulated with nonfunctionalized nanohydroxyapatite (NHA), which also played the role of cosurfactant. Free radical polymerization of HIPEs yielded free-standing nanocomposites with 3D interconnected macroporosity and nonfunctionalized NHA selectively decorating the scaffolds’ inner surface. The influence of different polymer functionalities, acrylate or methacrylate, their alkyl tail length, and the presence of NHA on MC3T3-E1 preosteoblast cell proliferation in vitro, reactive oxygen species (ROS) production and alkaline phosphatase (ALP) activity were evaluated. All materials presented promising biocompatibility, non-hemolytic activity, negligible inflammatory response along to remarkably enhanced cell proliferation (e.g., up to 160-fold cell proliferation increase compared with polystyrene plate) in vitro, which open the path for the development of scaffolds in regenerative medicine. It is noteworthy that polyHIPEs studied here were obtained using a green synthetic protocol where nonfunctionalized nanoparticles can be selectively incorporated into a scaffolds’ inner walls. This versatile technique allows for the simple construction of 3D bioactive nanocomposite scaffolds with varied compositions for cell culture.

Antioxidant, and enhanced flexible nano porous scaffolds for bone tissue engineering applications

AbstractThree‐dimensional bioactive, antioxidant, and porous nanocomposite scaffolds are inevitable to avoid dependency and disability in the life cycle. Herein, we develop a facile fabrication protocol of nano porous zinc doped hydroxyapatite (Zn‐HAp) scaffold enhanced by polysaccharide polymeric structure for bone tissue engineering applications. The bioactive nano scaffold exhibit opens porous assembly that sustains its flexible and robust nature and promotes efficient linking capability. Moreover, nano scaffold geometry and its porosity were controlled efficiently in various concentrations of zinc doped hydroxyapatite (Zn‐HAp) nanoparticles. Indeed, the composite scaffolds are retained in a dry shape with a suitable load‐bearing strength adjacent to the cancellous bone. The presence of zinc doped hydroxyapatite in the polymeric matrix of nano scaffold regulates its antibacterial response against different bacterial strains owing to its oxidative stress nature. The antioxidant and biocompatibility of nano‐scaffolds were investigated by DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) scavenging behavior, the scavenging activity of ABTS (2,2‐azino‐bis‐3‐ethylbenzthiazoline‐ 6‐sulphonic acid) radical, and iron‐chelating potential. The observed results reveal that polysaccharide‐dependent porous geometry possesses adequate biocompatibility, radical scavenging behavior, and excellent antibacterial properties that validate it as a suitable candidate material for bone tissue implantation. The unprecedented radical scavenging and antioxidant bioactive nanocomposite scaffold are all set to reshape the future bone tissue implantation.

Integrative 'Bricks‑And‑Mortar' Approach for the Fabrication of Poly( <sub>D,L</sub>‑Lactide)/Bioactive Glass Nanocomposite Scaffolds by Freeze‑Casting

Integrative 'Bricks‑And‑Mortar' Approach for the Fabrication of Poly( <sub>D,L</sub>‑Lactide)/Bioactive Glass Nanocomposite Scaffolds by Freeze‑Casting

Integrating cold atmospheric plasma with 3D printed bioactive nanocomposite scaffold for cartilage regeneration.

The progressive degeneration of articular cartilage or osteoarthritis of the knee is a serious clinical problem affecting patient quality of life. In recent years, artificially engineered cartilage scaffolds have been widely studied as a promising method to stimulate cartilage regeneration. In this study, a novel biomimetic cartilage scaffold was developed by integrating a cold atmospheric plasma (CAP) treatment with prolonged release of bioactive factors. Specifically, a surface of 3D printed hydrogel scaffold with drug-loaded nanoparticles was treated with CAP. Our results showed that the scaffolds with CAP treatment can improve hydrophilicity as well as surface nano-roughness and can thus facilitate stem cell adhesion. More importantly, this study demonstrated that integrating CAP treatment with drug-loaded nanoparticles can synergistically enhance chondrogenesis of human bone marrow mesenchymal stem cells when compared to control scaffolds. The results in this study indicate the great potential of applying CAP and drug-loaded nanoparticles into 3D printed tissue scaffolds for promoting cartilage regeneration.

Synthesis of Silver-Coated Bioactive Nanocomposite Scaffolds Based on Grafted Beta-Glucan/Hydroxyapatite via Freeze-Drying Method: Anti-Microbial and Biocompatibility Evaluation for Bone Tissue Engineering.

Advancement and development in bone tissue engineering, particularly that of composite scaffolds, are of great importance for bone tissue engineering. We have synthesized polymeric matrix using biopolymer (β-glucan), acrylic acid, and nano-hydroxyapatite through free radical polymerization method. Bioactive nanocomposite scaffolds (BNSs) were fabricated using the freeze-drying method and Ag was coated by the dip-coating method. The scaffolds have been characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction analysis (XRD) to investigate their functional groups, surface morphology, and phase analysis, respectively. The pore size and porosity of all BNS samples were found to be dependent on silver concentration. Mechanical testing of all BNS samples have substantial compressive strength in dry form that is closer to cancellous bone. The samples of BNS showed substantial antibacterial effect against DH5 alpha E. coli. The biological studies conducted using the MC3T3-E1 cell line via neutral red dye assay on the scaffolds have found to be biocompatible and non-cytotoxic. These bioactive scaffolds can bring numerous applications for bone tissue repairs and regenerations.

Arabinoxylan-co-AA/HAp/TiO2 nanocomposite scaffold a potential material for bone tissue engineering: An in vitro study

Arabinoxylan (AX) is a natural biological macromolecule with several potential biomedical applications. In this research, AX, nano-hydroxyapatite (n-HAp) and titanium dioxide (TiO2) based polymeric nanocomposite scaffolds were fabricated by the freeze-drying method. The physicochemical characterizations of these polymeric nanocomposite scaffolds were performed for surface morphology, porosity, swelling, biodegradability, mechanical, and biological properties. The scaffolds exhibited good porosity and rough surface morphology, which were efficiently controlled by TiO2 concentrations. MC3T3-E1 cells were employed to conduct the biocompatibility of these scaffolds. Scaffolds showed unique biocompatibility in vitro and was favorable for cell attachment and growth. PNS3 proved more biocompatible, showed interconnected porosity and substantial mechanical strength compared to PNS1, PNS2 and PNS4. Furthermore, it has also showed more affinity to cells and cell growth. The results illustrated that the bioactive nanocomposite scaffold has the potential to find applications in the tissue engineering field.

Reinforcement of electrospun polycaprolacton scaffold using KIT-6 to improve mechanical and biological performance

Electrospinning has been extensively accepted as one of most important techniques for fabrication of scaffolds for bone tissue engineering. Polycaprolactone is one of the most applied electro-spinned scaffolds. Since low mechanical strength of polycaprolactone scaffold leads to the limitation of its applications, composition of polycaprolactone with ceramic particles is of great interest. Several studies have been conducted on fabrication and characterization of polycaprolactone nanocomposite scaffolds, but none of these researches has used mesoporous silica particles (KIT-6). In this project, a high-strength and bioactive nanocomposite scaffold has been developed which consists of polycaprolactone and mesoporous silica particles. Results showed that increase of KIT-6 particles percentages up to 5% leads to the enhancement of tensile strength of scaffold from 1.8 ± 0.2 to 2.9 ± 1.0 MPa. Although wettability of scaffolds in presence of particles was totally lower than pure PCL scaffold, but increase of particles percentages led to enhancement of wettability and water absorption of scaffolds. On the other hand presence of KIT-6 particles increased specific surface area and also bioactivity of scaffold was increased by enhancement of ion exchange between surface and simulated body fluid. Finally it was concluded that PCL-KIT-6 scaffolds are a suitable candidate for application in tissue engineering.

Generation of bioactive nano-composite scaffold of nanobioglass/silk fibroin/carboxymethyl cellulose for bone tissue engineering

The development of bone tissue construct through tissue engineering approach offers a great promise in meeting the increasing demand for repair and regeneration of damaged and/or diseased bone tissue. For the generation of bone tissue engineered construct, polymer-ceramic composite matrices with nanostructure architecture and mesenchymal stem cells (hMSCs) of human origin are of prime requirement. Keeping these in view, in the present work a novel electrospun nanofibrous silk fibroin (SF)/carboxymethyl cellulose (CMC)/nano-bioglass (nBG) composite scaffold that mimics native bone extracellular matrix with appropriate composition was designed and fabricated by free liquid surface electrospinning technique. The scaffold possesses desired morphological, structural, biodegradability, bioactivity, surface roughness and mechanical properties thereby exhibited an excellent platform to support the growth of cells. The in-vitro culture of hMSCs over the developed scaffold has shown adhesion, proliferation and viability of cells, thus facilitated cell-scaffold construct generation and further extracellular bone matrix formation through osteogenic differentiation as evident from alkaline phosphatase activity, biomineralization, immunostaining and Runx2/osteocalcin expression assessment. Thus, the developed hMSCs seeded scaffold construct might be suitable for bone tissue engineering applications.

Feasibility of Defect Tunable Bone Engineering Using Electroblown Bioactive Fibrous Scaffolds with Dental Stem Cells.

Healing and repair of damaged bones with various geometries are challenging issues in personalized regenerative medicine. Herein, we examine if the engineered electroblown scaffolds can be suitable to this purpose with the ability to shape and fill defects, populate stem cells, and stimulate the regeneration process of defected bone. The electroblowing method could generate bioactive nanocomposite scaffolds made of poly(caprolactone) and bioactive glass nanoparticles, of which the macrostructure is highly spaced and fibrous networked. The scaffolds were easily formable to different shapes with space filling ability, and were hydrophilic to soak water and blood rapidly. Multipotent stem cells from dental pulp effectively infiltrated the scaffold networks, anchored the fiber surface within few hours, proliferated actively over weeks, and were stimulated to differentiate into osteogenic cells. The cell/scaffold constructs, implanted to tooth-extracted, irregular-shaped alveolar bone defects, were shown to fit the defect and to stimulate early new bone formation. Taken together, the electroblown bioactive fibrous scaffolds and their constructs with multipotent dental stem cells may be useful as a potential 3D platform for future personalized bone tissue engineering.

Preparation of poly(vinyl alcohol)/poly(lactic acid)/hydroxyapatite bioactive nanocomposites for fused deposition modeling

Poly(vinyl alcohol)/hydroxyapatite (PVA/HA) has excellent mechanical properties and osteoconductivity that allow it to be used for cartilage repair. However, nanofillers, such as HA, cause PVA to foam during the extrusion process, making it difficult to produce filament feedstocks with uniform diameters that are suitable for fused deposition modeling (FDM). In this article, a novel method was developed to prevent the foaming of PVA‐based nanocomposites during extrusion by selectively distributing HA in the poly(lactic acid) (PLA) phase. To achieve this, HA was treated with 3‐Glycidoxypropyltrimethoxysilane (KH560). The results showed that HA treated with KH560 was segregated from the PVA phase, thus preventing the foaming of PVA. Finally, filament feedstocks with a uniform diameter of 1.75 ± 0.05 mm, which is suitable for FDM, were successfully fabricated. Meanwhile, a mathematical equation for characterizing the printability of feedstock materials was improved. The results indicated that in combination with PLA, composites with a higher compressive modulus and better melt flowability were able to be processed by FDM. Finally, complex PVA‐based bioactive nanocomposite scaffolds with high dimensional accuracy, good mechanical properties, and biocompatibility were fabricated by the FDM machine. POLYM. COMPOS., 39:E508–E518, 2018. © 2017 Society of Plastics Engineers

Nanocomposite scaffolds with tunable mechanical and degradation capabilities: co-delivery of bioactive agents for bone tissue engineering

Novel multifunctional nanocomposite scaffolds made of nanobioactive glass and alginate crosslinked with therapeutic ions such as calcium and copper were developed for delivering therapeutic agents, in a highly controlled and sustainable manner, for bone tissue engineering. Alendronate, a well-known antiresorptive agent, was formulated into microspheres under optimized conditions and effectively loaded within the novel multifunctional scaffolds with a high encapsulation percentage. The size of the cation used for the alginate crosslinking impacted directly on porosity and viscoelastic properties, and thus, on the degradation rate and the release profile of copper, calcium and alendronate. According to this, even though highly porous structures were created with suitable pore sizes for cell ingrowth and vascularization in both cases, copper-crosslinked scaffolds showed higher values of porosity, elastic modulus, degradation rate and the amount of copper and alendronate released, when compared with calcium-crosslinked scaffolds. In addition, in all cases, the scaffolds showed bioactivity and mechanical properties close to the endogenous trabecular bone tissue in terms of viscoelasticity. Furthermore, the scaffolds showed osteogenic and angiogenic properties on bone and endothelial cells, respectively, and the extracts of the biomaterials used promoted the formation of blood vessels in an ex vivo model. These new bioactive nanocomposite scaffolds represent an exciting new class of therapeutic cell delivery carrier with tunable mechanical and degradation properties; potentially useful in the controlled and sustainable delivery of therapeutic agents with active roles in bone formation and angiogenesis, as well as in the support of cell proliferation and osteogenesis for bone tissue engineering.

Novel chitosan-sulfonated chitosan-polycaprolactone-calcium phosphate nanocomposite scaffold

New bioactive nanocomposite scaffolds from chitosan, sulfonated chitosan, and poly(ε-caprolactone) nanofibers were prepared. In this study, sulfonated chitosan was prepared using chlorosulfonic acid and combined with chitosan in order to improve the bioactivity of chitosan-based scaffolds. Meanwhile, different amounts of chopped-hydrophilic PCL nanofibers were incorporated into the fabricated scaffold in order to mimic extracellular matrix-like structure. In the end, apatite formed on/in the composite scaffolds through alternate dipping in calcium and phosphate rich solutions. The morphology, apatite forming ability, and mechanical properties of the scaffolds were evaluated. The results indicated that larger pore sizes, higher porosity and apatite deposition are obtained as a result of adding more PCL nanofibers. Contrary to the effects of increased pore size, addition of PCL nanofibers enhanced the mechanical properties. Cell culture experiments with osteoblast-like cells on the scaffolds demonstrated that incorporation of PCL nanofibers into the fabricated scaffolds improves cell viability and attachment.

Osteoblast-seeded bioglass/gelatin nanocomposite: a promising bone substitute in critical-size calvarial defect repair in rat.

Amid the plethora of methods to repair critical bone defects, there is no one perfect approach. In this study, we sought to evaluate a potent 3-dimensional (3D) bioactive SiO2-CaO-P2O5 glasses (bioglass)/gelatin (gel) scaffold for its biocompatibility by seeding cells as well as for its regenerative properties by animal implantation. Osteoblast cells were seeded onto nanocomposite scaffolds to investigate the process of critical-size calvarial defect via new bone formation. Scanning electron microscopy (SEM) was used to validate topography of the scaffolds, its homogeneity and ideal cellular attachment. Proliferation assay and confocal microscopy were used to evaluate its biocompatibility. To validate osteogenesis of the bioactive nanocomposite scaffolds, they were first implanted into rats and later removed and analyzed at different time points post mortem using histological, immunohistochemical and histomorphometric methods. Based on in vitro results, we showed that our nanocomposite is highly cell-compatible material and allows for osteoblasts to adhere, spread and proliferate. In vivo results indicate that our nanocomposite provides a significant contribution to bone regeneration and is highly biodegradable and biocompatible. So, seeded scaffolds with osteoblasts enhanced repair of critical bone defects via osteogenesis. We demonstrate the feasibility of engineering a nanocomposite scaffold with an architecture resembling the human bone, and provide proof-of-concept validation for our scaffold using a rat animal model.

Design of a Novel 3D Printed Bioactive Nanocomposite Scaffold for Improved Osteochondral Regeneration.

Chronic and acute osteochondral defects as a result of osteoarthritis and trauma present a common and serious clinical problem due to the tissue's inherent complexity and poor regenerative capacity. In addition, cells within the osteochondral tissue are in intimate contact with a 3D nanostructured extracellular matrix composed of numerous bioactive organic and inorganic components. As an emerging manufacturing technique, 3D printing offers great precision and control over the microarchitecture, shape and composition of tissue scaffolds. Therefore, the objective of this study is to develop a biomimetic 3D printed nanocomposite scaffold with integrated differentiation cues for improved osteochondral tissue regeneration. Through the combination of novel nano-inks composed of organic and inorganic bioactive factors and advanced 3D printing, we have successfully fabricated a series of novel constructs which closely mimic the native 3D extracellular environment with hierarchical nanoroughness, microstructure and spatiotemporal bioactive cues. Our results illustrate several key characteristics of the 3D printed nanocomposite scaffold to include improved mechanical properties as well as excellent cytocompatibility for enhanced human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation in vitro. The present work further illustrates the effectiveness of the scaffolds developed here as a promising and highly tunable platform for osteochondral tissue regeneration.

Fibronectin immobilization on to robotic-dispensed nanobioactive glass/polycaprolactone scaffolds for bone tissue engineering.

Bioactive nanocomposite scaffolds with cell-adhesive surface have excellent bone regeneration capacities. Fibronectin (FN)-immobilized nanobioactive glass (nBG)/polycaprolactone (PCL) (FN-nBG/PCL) scaffolds with an open pore architecture were generated by a robotic-dispensing technique. The surface immobilization level of FN was significantly higher on the nBG/PCL scaffolds than on the PCL scaffolds, mainly due to the incorporated nBG that provided hydrophilic chemical-linking sites. FN-nBG/PCL scaffolds significantly improved cell responses, including initial anchorage and subsequent cell proliferation. Although further in-depth studies on cell differentiation and the in vivo animal responses are required, bioactive nanocomposite scaffolds with cell-favoring surface are considered to provide promising three-dimensional substrate for bone regeneration.

Nanocomposite bioactive polymeric scaffold promotes adhesion, proliferation and osteogenesis of rat bone marrow stromal cells

Synthetic degradable polymer scaffolds have often shown poor cell affinity and bone bioactivity. Bioactive inorganic nanoadditives with the composition of calcium silicate in amorphous phase (CSN) were incorporated within poly (lactic acid) (PLA) to develop nanocomposite bone scaffolds. Nanocomposite solutions containing PLA with 10% CSN were porous-structured by a salt-impregnation / leaching method. The nanocomposite scaffold showed higher dynamical mechanical modulus values than the pure PLA equivalent, indicating a proper usage for hard tissue scaffolds. Rat bone marrow stromal cells (rBMSCs) were cultured on the scaffolds and the cell adhesion, proliferation and osteogenic differentiation at gene and protein levels were addressed. Cells adhered better on the nanocomposite scaffold with respect to PLA equivalent, and then proliferated more during the culture periods of up to 7 days. The expression of osteogenic genes, including collagen type I, osteopontin, osteocalcin and alkaline phosphatase, were significantly stimulated on the nanocomposite scaffold, as confirmed by a real time polymerase chain reaction. Furthermore, Western blot analysis indicated higher expression of osteopontin protein of cells by the nanocomposite scaffold. Results demonstrated the bioactive nanocomposite scaffolds provided appropriate matrix conditions for rBMSCs to populate on and to undergo osteogenic processes in vitro.

Preparation of laminated poly(ε-caprolactone)-gelatin-hydroxyapatite nanocomposite scaffold bioengineered via compound techniques for bone substitution

In this research, new bioactive nanocomposite scaffolds were successfully developed using poly(ε-caprolactone) (PCL), cross-linked gelatin and nanoparticles of hydroxyapatite (HAp) after testing different solvents and methods. First, HAp powder was synthesized via a chemical precipitation technique and characterized. Then, the nanocomposites were prepared through layer solvent casting combined with freeze-drying and lamination techniques. According to the results, the increasing of the PCL weight in the scaffolds led to the improvement of the mechanical properties. The amount of ultimate stress, stiffness and also elastic modulus increased from 8 MPa for 0% wt PCL to 23.5 MPa for 50% wt PCL. The biomineralization study revealed the formation of an apatite layer on the scaffolds after immersion in simulated body fluid (SBF). The Ca-P ratios were in accordance to nonstoichiometric biological apatite, which was approximately 1.67. The in vitro biocompatibility and cytocompatibility of the scaffolds were tested using mesenchymal stem cells (MSCs), and the results indicated no sign of toxicity, and cells were found to be attached to the scaffold walls. The in vivo biocompatibility and osteogenesis of these scaffolds in the animal experiments is also under investigation, and the result will be published at the end of the study.

Development of macroporous nanocomposite scaffolds of gelatin/bioactive glass prepared through layer solvent casting combined with lamination technique for bone tissue engineering

In this study, macroporous bioactive nanocomposite scaffolds were developed using cross-linked gelatin and bioactive glass (BaG) nanoparticles. First, BaG nanoparticles were synthesized via sol–gel method and characterized. Then, macroporous nanocomposites were prepared through layer solvent casting combined with freeze-drying and lamination techniques. This research has developed a new composition to produce a new bioactive nanocomposite which is porous with three-dimensional (3D) inter-connected microstructure, pore sizes are 200–500 μm, porosity are 72–86% and BaG nanoparticles are dispersed evenly among cross-linked gelatin matrices. It is mentionable that in this study, we have reported the formation of chemical bonds between BaG nanoparticles and gelatin for the first time. Finally, the in vitro cytocompatibility of the nanocomposite scaffolds was tested using SaOS-2 cell line.