Materials For Bone Regeneration Research Articles

Genesis of osteoclasts on calcium phosphate ceramics and their role in material-induced bone formation.

Innate immune responses play important roles in material-induced bone formation and such roles were further explored in the current study with an emphasis on M2 macrophages and osteoclastogenesis. With the presence of M-CSF and RANKL, M0 macrophages from FVB mouse bone marrow-derived monocytes (BMMs) fused to osteoclasts with both M2 marker and osteoclast marker at day 5, and such osteoclast formation at day 5 was enhanced when the cells were treated with IL-4 at day 3. With IL-4 treatment alone for 24 h, M0 polarized into M2 macrophages. Conditioned medium of M2 macrophages enhanced osteogenic differentiation of MC3T3-E1 (pre-osteoblasts) while osteoclast conditioned medium enhanced osteogenic differentiation of CRL-12424 (osteogenic precursors). TCPs (a typical osteoinductive material) supported M2 macrophage polarization at day 4 and osteoclast formation at day 5, while TCPb (a typical non-osteoinductive material) was less effective. Moreover, osteoclasts formed on TCPs produced osteogenic factors including S1P, Wnt10B and BMP-6, resulting osteogenic differentiation of CRL-12424 cells. Similar to in vitro testing, TCPs favored M2 macrophage polarization followed by the formation of osteoclasts in vivo, as compared to TCPb. The overall data provided evidence of a coupling between M2 macrophages, osteoclasts and material-induced bone formation: osteoclasts formed from M2 macrophages secrete osteogenic cytokines to induce osteogenic differentiation of osteogenic precursor cells to finally form bone. The current findings outlined a biological mechanism of material-induced bone formation and further rationalized the use of osteoinductive materials for bone regeneration. STATEMENT OF SIGNIFICANCE: This paper provides evidence for finding out the relationship between M2 macrophages, osteoclasts and osteogenesis in material-induced bone formation. It suggested that osteoinductive materials enhanced macrophage polarization to M2 macrophages which fuses to osteoclasts, osteoclasts subsequently secret osteogenic cytokines to differentiate finally osteogenic precursors to form bone in osteoinductive materials. The data supports scientifically the superiority of osteoinductive materials for bone regeneration in clinics.

Scaffold Guided Bone Regeneration for the Treatment of Large Segmental Defects in Long Bones.

Bone generally displays a high intrinsic capacity to regenerate. Nonetheless, large osseous defects sometimes fail to heal. The treatment of such large segmental defects still represents a considerable clinical challenge. The regeneration of large bone defects often proves difficult, since it relies on the formation of large amounts of bone within an environment impedimental to osteogenesis, characterized by soft tissue damage and hampered vascularization. Consequently, research efforts have concentrated on tissue engineering and regenerative medical strategies to resolve this multifaceted challenge. In this review, we summarize, critically evaluate, and discuss present approaches in light of their clinical relevance; we also present future advanced techniques for bone tissue engineering, outlining the steps to realize for their translation from bench to bedside. The discussion includes the physiology of bone healing, requirements and properties of natural and synthetic biomaterials for bone reconstruction, their use in conjunction with cellular components and suitable growth factors, and strategies to improve vascularization and the translation of these regenerative concepts to in vivo applications. We conclude that the ideal all-purpose material for scaffold-guided bone regeneration is currently not available. It seems that a variety of different solutions will be employed, according to the clinical treatment necessary.

Effect of Alleviating Fibrosis with EGCG-Modified Bone Graft in Murine Model Depended on Less Accumulation of Inflammatory Macrophage.

In response to current trends in the modification of guided bone regeneration (GBR) materials, we aimed to build upon our previous studies on epigallocatechin-3-gallate (EGCG) by immersing a commonly used bone graft primarily composed of hydroxyapatite (HA) in EGCG solution, expecting to obtain superior bone material integration after implantation. Bone grafts are commonly used for bone repair, in which the bone extracellular matrix is stimulated to promote osteogenesis. However, due to its profibrosis effect, this osteoconductive material commonly exhibits implant failure. In addition to providing a basic release profile of EGCG-modified bone graft (E-HA) to clarify the relationship between this material and the environment, we have examined the integration effect via subcutaneous implantation experiments. In this manner, we have assessed the aggregation of proinflammatory macrophages, the formation of fibrous capsules, and an enhanced cell viability observed in cultured RAW 264.7 cells. Among these results, we focus on proinflammatory macrophages due to their close relationship with fibrosis, which is the most important process in the immune response. Immunofluorescent staining results showed that E-HA substantially compromised the formation of fibrous capsules in hematoxylin-eosin-stained sections, which exhibited less proinflammatory macrophage recruitment; meanwhile, the cell viability was improved. This work lays the foundation for future studies on GBR.

A novel peptide hydrogel of metal ion clusters for accelerating bone defect regeneration.

In the absence of adequate treatment, effective bone regeneration remains a great challenge. Exploring hydrogels with properties of excellent bioactivity, stability, non-immunogenicity, and commercialization is an important step to develop hydrogel-based bone regeneration materials. In this study, we engineered a self-assembled chelating peptide hydrogel loaded with an osteogenic metal ion cluster extracted from the processed pyritum decoction, including Fe2+, Cu2+, Zn2+, Mn2+, Mg2+, and Ca2+ ions, named processed pyritum hydrogel (PPH). We demonstrated that as a reservoir of beneficial metal ion clusters in bone regeneration, PPH has been shown to regulate a variety of genes in the process of bone regeneration. These genes are mainly involved in extracellular matrix synthesis, cell adhesion and migration, cytokine expression, antimicrobial and inflammation. Therefore, PPH accelerated the progress of various bone healing stages, and shortened the bone healing cycle by 4weeks. Our investigation outcomes showed that the engineered metal ion cluster hydrogel is a novel, simple, and commercializable bone-regenerating hydrogel with potential clinical use.

Alveolar ridge preservation in rat tooth extraction model by chitosan-derived epigenetic modulation scaffold.

Alveolar ridge preservation is a surgical technique used to prevent dimensional changes in the alveolar bone by dressing biomaterials in the extraction socket. Recently, a chitosan biphasic calcium phosphate loaded with trichostatin A (CS/BCP/TSA) scaffold was introduced as an excellent bone-regeneration material. This study aimed to explore the biological properties of released trichostatin A (TSA) and evaluate the potential of the CS/BCP/TSA scaffold in preserving the alveolar ridge in a rat tooth extraction model. In vitro biocompatibility, histone deacetylase (HDAC) activity, and osteogenic differentiation of MC3T3-E1 cells were tested. For in vivo studies, the maxillary first molars (M1) of Wistar rats were extracted, and alveolar ridge preservation was performed using a CS/BCP/TSA scaffold or commercial bone graft. Micro-Computed Tomography (micro-CT), polyfluorochrome labeling, and histological analysis were used to evaluate the ridge-preservation ability. The released TSA was cytocompatible. Inhibition of histone deacetylase (HDAC) activity and induction of osteogenic differentiation in MC3T3-E1 cells were confirmed. The socket dressing with the CS/BCP/TSA scaffold showed increased socket bone fill and preserved the buccal and middle aspects of the alveolar ridge compared with the conventional graft. Further analysis of the bone regeneration ability by histomorphometric and histological analyses demonstrated that CS/BCP/TSA showed a significantly higher potential to induce bone formation and complete healing in the extraction socket than the other groups. The CS/BCP/TSA scaffold is a novel candidate for alveolar ridge preservation.

<i>In Vivo</i> Evaluation of Calcium-Phosphate Ceramics with Highly-Interconnected Pores Using Porcine Tibia Defect Model

The aim of this study was to compare the difference in bone formation between hydroxyapatite (HAp) and β-tricalcium phosphate (β-TCP) ceramics with similar porous structure. Porous HAp and β-TCP ceramics (total porosity: ~70%) with highly-interconnected structure were fabricated by firing calcium-phosphate fiber mixed with carbon beads (~150 μm). The size of highly-interconnected pores was measured by mercury intrusion technique. Each sample (ϕ4 mm × 8 mm) was implanted into the tibial bone defect (ϕ4.2 mm × 8 mm) of a pig (2 years old, male). After 6 weeks of implantation, undecalcified section was prepared and stained with hematoxylin and eosin (HE) stain. New bone area and remaining material area were evaluated.Interconnection sizes of HAp and β-TCP ceramics were 23.0 µm and 15.6 µm, respectively. New bone area of β-TCP ceramics was significantly higher compared to HAp ceramics. Remaining material ratio was 77.1 ± 3.3% for β-TCP ceramics whereas HAp ceramics remained stable. Bone formation in HAp ceramics was inhomogeneous compared to β-TCP ceramics in HE stained section. Although the β-TCP ceramics interconnection size was smaller, higher resorption may have played a positive role in homogeneous bone formation. According to the result of the study, it is suggested that highly-interconnected porous ceramics made by β-TCP could be a suitable material for bone regeneration.

Chitosan as Bone Scaffold and Graft Materials for Bone Regeneration: A Systematic Review

Chitosan is a natural biodegradable polymer made from crustacean exoskeletons (shrimp and crab). Recently, natural material is preferably used in order to prevent any side effects from synthetic material. Previous research showed that chitosan has anti-bacterial properties, which can act as a bone graft scaffold material to increase in bone regeneration process. This article discusses the antibacterial effect of chitosan in the bone regeneration process. Bone graft consists of many primary graft materials which focus on alloplastic graft composite type. Bone graft is related to bone regeneration which associated with the process of secondary/indirect bone healing. The main trait of bone graft material is that it is not toxic to the chitosan’s host cell. Chitosan’s anti-bacterial effects can be associated with one of the three phases of bone defect healing, which is inflammation phase that acts to prevent bacterial invasion as an infectious disease in bone injury. Because of this, it can accelerate the polarization of macrophage M1 (secrete pro-inflammatory cytokine) to macrophage M2 (secrete anti-inflammatory cytokine) that relates to osteoblastogenesis. Osteoblastogenesis relates to the increase of osteoblast synthesis, deposition and mineralization of extracellular matrix leading to the maturation of osteoblast become osteocyte called ossification process.

Application of Piezoelectric Material and Devices in Bone Regeneration.

Bone injuries are common in clinical practice. Given the clear disadvantages of autologous bone grafting, more efficient and safer bone grafts need to be developed. Bone is a multidirectional and anisotropic piezoelectric material that exhibits an electrical microenvironment; therefore, electrical signals play a very important role in the process of bone repair, which can effectively promote osteoblast differentiation, migration, and bone regeneration. Piezoelectric materials can generate electricity under mechanical stress without requiring an external power supply; therefore, using it as a bone implant capable of harnessing the body's kinetic energy to generate the electrical signals needed for bone growth is very promising for bone regeneration. At the same time, devices composed of piezoelectric material using electromechanical conversion technology can effectively monitor the structural health of bone, which facilitates the adjustment of the treatment plan at any time. In this paper, the mechanism and classification of piezoelectric materials and their applications in the cell, tissue, sensing, and repair indicator monitoring aspects in the process of bone regeneration are systematically reviewed.

Bioactive Nanocomposite Microsponges for Effective Reconstruction of Critical-Sized Calvarial Defects in Rat Model.

Micro-sized sponge particulates have attracted extensive attention because of their potential to overcome the intrinsic limitations of conventional monolithic scaffolds in tissue engineering. Bioactive nanocomposite microsponges are regarded as potential bone substitute materials for bone regeneration. Based on a combination of microfluidic emulsion with further freezing and in situ thawing, chitosan (CS)-hydroxyapatite (HAP) microsponges were prepared and characterized in terms of their morphology and elemental distribution using a scanning electron microscope equipped with an X-ray detector. The swelling ratio, porosity, degradability, antibacterial activity, and bioactivity were detected and analyzed. The biological functions of the CS-HAP microsponges were examined to assess the adhesion, proliferation, and differentiation of in vitro co-cultured rat bone marrow mesenchymal stem cells (rBMSCs). Furthermore, the CS-HAP microsponges were used as cell-free scaffolds and implanted into calvarial defects in a rat model to evaluate the in vivo osteogenesis. The CS-HAP microsponges have a porous structure with high porosity (~76%), good swelling capacity (~1900%), and shape-memory properties. The results of in vitro experiments show that the CS-HAP microsponges achieve good bioactivity and promote osteogenic differentiation of rBMSCs. Furthermore, the CS-HAP microsponges significantly promote bone regeneration in rat calvarial defects. The bioactive CS-HAP microsponges have the potential to be used as bone substitute materials for bone tissue engineering.

Clindamycin-Loaded Halloysite Nanotubes as the Antibacterial Component of Composite Hydrogel for Bone Repair.

A new drug delivery system consisting of clindamycin phosphate entrapped in acid-etched halloysite nanotubes was successfully prepared and characterized. It was then used as an antibacterial component of the multicomponent hydrogel designed as a material for bone regeneration. First, halloysite (HNT) was etched and clindamycin phosphate (CP) was entrapped in both raw and modified nanotubes, resulting in HNT-CP and EHNT-CP systems. They were characterized using SEM, TEM, TGA and FTIR; the entrapment efficiency and release of CP from both systems were also studied. EHNT-CP was then used as an antibacterial component of the two hydrogels composed of alginate, collagen and β-TCP. The hydrogels were prepared using different crosslinking procedures but had the same composition. The morphology, porosity, degradation rate, CP release profile, cytocompatibility, antibacterial activity and ability to induce biomineralization were studied for both materials. The hydrogel obtained by a chemical crosslinking with EDC followed by the physical crosslinking with calcium ions had better properties and was shown to have potential as a bone repair material.

Application to open wound extraction socket of new bone regenerative material

ObjectiveNew bone regenerative material of octacalcium phosphate and collagen composite (OCPcol) has exhibited excellent operability and the bone regeneration surpassed other bone substitutes. However, it has never been to elucidate the application of OCPcol for open wound extraction socket, although the previous studies suggested that OCPcol inhibited bone resorption if implanted into the closed wound extraction sockets. Therefore, the present study investigated whether OCPcol would be applicable for open wound extraction sockets. MethodsThe prepared OCPcol disks or nothing was implanted into the canine mandibular extraction sockets, and each group was closed watertight or left as an open wound. That is, the experimental groups were divided into four groups; OCPcol closed wound (OCPcol-C), OCPcol open wound (OCPcol-O), untreated closed wound (Unt-C), and untreated open wound (Unt-O). After 3 months of operation, radiomorphometric analyses was conducted by measuring alveolar cross-sectional areas of the 1/4 (Sq) and 1/2 (Sh) of the mandibular height near the alveolar apex. During the experimental periods, all animals were generally well and no eating disorders nor postoperative infections were observed including OCPcol-O. ResultsThe radiographic findings of prepared extraction sockets in each group were similarly occupied by uniform radiopaque images. However, the Sq of OCPcol-O was significantly more than other three groups, and the Sh of OCPcol-O and OCPcol-C were significantly more than those of Unt-C and Unt-O. ConclusionsThese results suggest that it would be applicable to OCPcol for extraction sockets with an open wound.

The durability of resin-dentine bonds are enhanced by epigallocatechin-3-gallate-encapsulated nanohydroxyapatite/mesoporous silica.

Biomimetic nanohydroxyapatite (nHAp) has long been used as a biocompatible material for bone repair, bone regeneration, and bone reconstruction due to its low toxicity to local or systemic tissues. Various cross-linkers have been employed to maintain the structure of collagen; these include epigallocatechin-3-gallate (EGCG), which can fortify the mechanical properties of collagen and withstand the degradation of collagenase. We hypothesized that EGCG combined with nHAp may promote resin-dentin bonding durability. Here, we examined the effect of epigallocatechin-3-gallate-encapsulated nanohydroxyapatite/mesoporous silica (EGCG@nHAp@MSN) on thermal stability and remineralization capability of dentin collagen. Dentin slices (2 × 2 × 1 mm3 ) were obtained and completely demineralized in a 10% phosphoric acid water solution. The resulting dentin collagen matrix was incubated with deionized water, EGCG, nHAp@MSN, and EGCG@nHAp@MSN. The collagen thermal degradation temperature was assessed utilizing differential scanning calorimetry analysis, which indicated that EGCG, nHAp@MSN, and EGCG@nHAp@MSN reinforced collagen's capability to resist thermal degradation. EGCG@nHAp@MSN resulted in the highest increase in denaturation temperature. Thermogravimetric analysis showed that both nHAp@MSN and EGCG@nHAp@MSN achieved a higher residual mass than the EGCG and control groups. Fourier transform infrared spectroscopy was performed to examine the interaction between EGCG@nHAp@MSN and dentin collagen. The EGCG@nHAp@MSN sample exhibited stronger dentin microhardness and uppermost bond strength after thermocycling. EGCG significantly enhanced collagen's capability to resist thermal degradation. In summary, EGCG and nHAp@MSN may work together to assist the exposed collagen to improve resistance to thermal cycling and promote remineralization while also strengthening the durability of resin-dentin bonds.

Eco-friendly fabricated multibioactive Ca(II)-antibiotic coordination framework coating on zinc towards improved bone tissue regeneration

Zinc is a biodegradable candidate material for bone regeneration; however, concomitant implant-related infection and rejection require new solutions to raise the biomedical potential of zinc. Functionalization towards localized drug administration with bioactive frameworks can be a solution. It is herein reported for the first time an eco-friendly approach for coating zinc with multibioactive antibiotic coordination frameworks (ACF). ACF1, a new 1D framework with deprotonated nalidixic and salicylic acids, obtained by mechanochemistry, results from the coordination of Ca(II) centers to the organic acids anions. To maximize ACF1 loading and cells’ adhesion, the surface area was increased by creating a porous 3D Zn layer. A coverage of ∼70% of the surface with ACF1, achieved by electrophoretic deposition in an aqueous solution, preserved the desired Zn degradation as |Z| in the order of 103 Ω.cm2 is attained for both bare and coated samples in physiological conditions. The bioactivities of the ACF1 powder are a strong antibacterial activity against Escherichia coli (MIC of 1.95 µg/mL) and weaker against Staphylococcus aureus (MIC of 250 µg/mL), while osteoblasts’ cytocompatibility is achieved for concentration ranging between 10 and 100 μg/mL. In its coating form, the degradation of Zn coated with ACF1 results in nalidixic acid release, which may convey antibacterial activity to the implant. The osteoinduction observe over this new biomaterial relates to the precipitation of an apatite layer built from the Ca(II) of ACF1.The work described herein, where unexplored eco-friendly approaches were used, presents a new trend for the design of multibioactive coatings on bioresorbable metallic materials.

In Vitro and In Vivo Response of Zinc-Containing Mesoporous Bioactive Glasses in a Sheep Animal Model.

Zinc-enriched mesoporous bioactive glasses (MBGs) are bioceramics with potential antibacterial and osteogenic properties. However, few assays have been performed to study these properties in animal models. In this study, MBGs enriched with up to 5% ZnO were synthesized, physicochemically characterized, and evaluated for their osteogenic activity both in vitro and in vivo. The ZnO MBGs showed excellent textural properties despite ZnO incorporation. However, the release of Zn2+ ions inhibited the mineralization process when immersed in simulated body fluid. In vitro assays showed significantly higher values of viability and expression of early markers of cell differentiation and angiogenesis in a ZnO-content-dependent manner. The next step was to study the osteogenic potential in a sheep bone defect model. Despite their excellent textural properties and cellular response in vitro, the ZnO MBGs were not able to integrate into the bone tissue, which can be explained in terms of inhibition of the mineralization process caused by Zn2+ ions. This work highlights the need to develop nanostructured materials for bone regeneration that can mineralize to interact with bone tissue and induce the processes of implant acceptance, cell colonization by osteogenic cells, and regeneration of lost bone tissue.

Surface modification of activated carbon cloth with calcium silicate and hydroxyapatite: bioactive composite material

In this study new compounds consisting of activated carbon cloths (ACC) modified with calcium silicate (CaSiO3) were prepared for hydroxyapatite (HAP) generation. ACC samples were oxidized with 8 M HNO3 at different times (15 min and 2 h), to increase oxygenated functional groups. The CaSiO3 fine powders were prepared by chemical coprecipitation using Ca(NO3)2∙4H2O and Si(OC2H5)4, and 5 M NaOH was used as precipitant. The resulting powders were mixed with ethanol by ultrasound stirring and the previously oxidized activated carbon fibers were placed leaving under stirring for 30 min to allow particle dispersion. Once the formed compounds were dried, the samples were immersed in a simulated body fluid (SBF) solution for 21 days in conical tubes at 36.5 °C to allow the HAP formation on the ACC/CaSiO3 composite surface. The results indicated that the increase in oxidation time improves HAP formation on the surface from ACC/CaSiO3 compounds and this bioactive composite may be a potential material for bone regeneration.

Bioderived amorphous calcium phytate as artificial bone substitute

Calcium phosphates have been widely used in clinics as bone substitutes due to their excellent biocompatibility and similar chemical compositions to bone minerals. The best-known commercial products are hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), however, their degradation rates do not match well with the formation of new bone, making them somehow unsatisfactory. A degradation rate between these two would be more suitable for bone regeneration and such materials are consistently sought. In this study, we developed a bioderived amorphous calcium phytate (a-CP). Compared with HA and β-TCP, a-CP showed similar effects on proliferation, better effects on differentiation and mineralization of osteogenic related cells. The degradation rate of a-CP fell between β-TCP and HA: In vivo, β-TCP was found to degrade in 4 weeks, while no sign of degradation was observed for HA groups in 8 weeks; the degradation rate of a-CP appeared to be more appropriate. Consequently, a-CP showed better curative effect than both HA and β-TCP in femoral condyle defects: 51±4% of new bone formation was observed on the site of a-CP, while 34±3% and 40±4% of HA and β-TCP groups, respectively. This article is the first to explore the potential of a-CP as a bone substitute, and the in vitro and in vivo performances indicate it to be a promising candidate for bone defect repairing.

Developing Porous Ortho- and Pyrophosphate-Containing Glass Microspheres; Structural and Cytocompatibility Characterisation.

Phosphate-based glasses (PBGs) are promising materials for bone repair and regeneration as they can be formulated to be compositionally similar to the inorganic components of bone. Alterations to the PBG formulation can be used to tailor their degradation rates and subsequent release of biotherapeutic ions to induce cellular responses, such as osteogenesis. In this work, novel invert-PBGs in the series xP2O5·(56 - x)CaO·24MgO·20Na2O (mol%), where x is 40, 35, 32.5 and 30 were formulated to contain pyro (Q1) and orthophosphate (Q0) species. These PBGs were processed into highly porous microspheres (PMS) via flame spheroidisation, with ~68% to 75% porosity levels. Compositional and structural analysis using EDX and 31P-MAS NMR revealed that significant depolymerisation occurred with reducing phosphate content which increased further when PBGs were processed into PMS. A decrease from 50% to 0% in Q2 species and an increase from 6% to 35% in Q0 species was observed for the PMS when the phosphate content decreased from 40 to 30 mol%. Ion release studies also revealed up to a four-fold decrease in cations and an eight-fold decrease in phosphate anions released with decreasing phosphate content. In vitro bioactivity studies revealed that the orthophosphate-rich PMS had favourable bioactivity responses after 28 days of immersion in simulated body fluid (SBF). Indirect and direct cell culture studies confirmed that the PMS were cytocompatible and supported cell growth and proliferation over 7 days of culture. The P30 PMS with ~65% pyro and ~35% ortho phosphate content revealed the most favourable properties and is suggested to be highly suitable for bone repair and regeneration, especially for orthobiologic applications owing to their highly porous morphology.

Mg2+-doped carbon dots synthesized based on Lycium ruthenicum in cell imaging and promoting osteogenic differentiation in vitro

The construction of biomaterials suitable for bone regeneration has been a serious challenge in the medical field. Considering that the process of bone regeneration is difficult to monitor, the application of fluorescent carbon dots (CDs) materials for bone regeneration has received much attention. Here, we developed a Mg2+-doped biogenic carbon dot material and characterized it to determine the optimal ratio of carbon and magnesium sources in the synthesis of the material. Subsequently, its biocompatibility with MC3T3-E1 Subclone 4 (MC3T3) was investigated, and its high biocompatibility was supported by the preparation of biocarbon dots using natural lycium ruthenicum as the carbon source. In addition, our experimental results showed that the appropriate concentration of Mg-CDs was suitable for long-term cell growth and the cells had better growth, proliferation, and osteogenic differentiation ability. This Mg2+-doped biomass carbon dot shows great potential in bone tissue regeneration.

Novel Epigenetic Modulation Chitosan-Based Scaffold as a Promising Bone Regenerative Material.

Bone tissue engineering is a complicated field requiring concerted participation of cells, scaffolds, and osteoactive molecules to replace damaged bone. This study synthesized a chitosan-based (CS) scaffold incorporated with trichostatin A (TSA), an epigenetic modifier molecule, to achieve promising bone regeneration potential. The scaffolds with various biphasic calcium phosphate (BCP) proportions: 0%, 10%, 20%, and 40% were fabricated. The addition of BCP improved the scaffolds’ mechanical properties and delayed the degradation rate, whereas 20% BCP scaffold matched the appropriate scaffold requirements. The proper concentration of TSA was also validated. Our developed scaffold released TSA and sustained them for up to three days. The scaffold with 800 nM of TSA showed excellent biocompatibility and induced robust osteoblast-related gene expression in the primary human periodontal ligament cells (hPDLCs). To evaluate in vivo bone regeneration potential, the scaffolds were implanted in the mice calvarial defect model. The excellent bone regeneration ability was further demonstrated in the micro-CT and histology sections compared to both negative control and commercial bone graft product. New bone formed in the CS/BCP/TSA group revealed a trabeculae-liked characteristic of the mature bone as early as six weeks. The CS/BCP/TSA scaffold is an up-and-coming candidate for the bone tissue engineering scaffold.

Engineering elastic bioactive composite hydrogels for promoting osteogenic differentiation of embryonic mesenchymal stem cells.

The development of bioactive materials with good mechanical properties and promotion of stem cell osteogenic differentiation has important application prospects in bone tissue engineering. In this paper, we designed a novel organic‒inorganic composite hydrogel (FPIGP@BGN-Sr) utilizing diacrylated F127 (DA-PF127), β-glycerophosphate-modified polyitaconate (PIGP) and strontium-doped bioactive glass nanoparticles (BGN-Sr) through free radical polymerization and coordination interactions and then evaluated its promoting effect on the osteogenic differentiation of mouse embryonic mesenchymal stem cells in detail. The results showed that the FPIGP@BGN-Sr hydrogel exhibited a controlled storage modulus by changing the amount of BGN-Sr. Notably, the FPIGP@BGN-Sr hydrogel possessed excellent elastic ability with a compressive strain of up to 98.6% and negligible change in mechanical properties after 10 cycles of compression. In addition, the FPIGP@BGN-Sr hydrogel had good cytocompatibility, maintained the activity and proliferation of mouse embryonic mesenchymal stem cells (C3H10T1/2), and effectively enhanced the activity of alkaline phosphatase, osteogenic gene expression and biomineralization ability of the cells. In conclusion, the excellent mechanical properties and osteogenic biological activity of the FPIGP@BGN-Sr hydrogel make it a promising organic‒inorganic composite bioactive material for stem cell-based bone regeneration.