Catechol-Modified and MnO2-Nanozyme-Reinforced Hydrogel with Improved Antioxidant and Antibacterial Capacity for Periodontitis Treatment.

Periodontitis is an inflammatory disease characterized by tooth loss and alveolar bone resorption. Bacteria are the original cause of periodontitis, and excess reactive oxygen species (ROS) encourage and intensify inflammation. In this study, a mussel-inspired and MnO2 NPs-reinforced adhesive hydrogel capable of alleviating periodontitis with improved antibacterial and antioxidant abilities was developed. The hydrogel was created by combining polyvinyl alcohol (PVA), 3,4-dihydroxy-d-phenylalanine (DOPA), and MnO2 nanoparticles (NPs) (named PDMO hydrogel). The hydrogel was demonstrated to be able to scavenge various free radicals (including total ROS─O2•- and OH•) and relieve the hypoxia in an inflammatory microenvironment by scavenging excess ROS and generating O2 due to its superoxide dismutase (SOD)/catalase (CAT)-like activity. Besides, under 808 nm near-infrared (NIR) light, the photothermal performance of the PDMO hydrogel displayed favorable antibacterial and antibiofilm effects toward Escherichia coli, Staphylococcus aureus, and Porphyromonas gingivalis (up to nearly 100% antibacterial rate). Furthermore, the PDMO hydrogel exhibited favorable therapeutic efficacy in alleviating gingivitis in Sprague-Dawley rats, even comparable to or better than the commercial PERIO. In addition, in the periodontitis models, the PDMO2 group showed the height of the residual alveolar bone and the smallest shadow area of low density among other groups, indicating the positive role of the PDMO2 hydrogel in bone regeneration. Finally, the biosafety of the PDMO hydrogel was comprehensively investigated, and the hydrogel was demonstrated to have good biocompatibility. Therefore, the developed PDMO hydrogel provided an effective solution to resolve biofilm recolonization and oxidative stress in periodontitis and could be a superior candidate for local drug delivery system in the clinical management of periodontitis with great potential for future clinical translation.

The effect of GelMA/alginate interpenetrating polymeric network hydrogel on the performance of porous zirconia matrix for bone regeneration applications.

Bone tissue is a natural composite, exhibiting complicated structures and unique mechanical/biological properties. With an attempt of mimicking the bone tissue, a novel inorganic-organic composite scaffolds (ZrO2-GM/SA) was designed and prepared via the vacuum infiltration method and the single/double cross-linking strategy by blending GelMA/alginate (GelMA/SA) interpenetrating polymeric network (IPN) into the porous zirconia (ZrO2) scaffold. The structure, morphology, compressive strength, surface/interface properties, and biocompatibility of the ZrO2-GM/SA composite scaffolds were characterized to evaluate the performance of the composite scaffolds. Results showed that compared to ZrO2 bare scaffolds with well-defined open pores, the composite scaffolds prepared by double cross-linking of GelMA hydrogel and sodium alginate (SA) presented a continuous, tunable and honeycomb-like microstructure. Meanwhile, GelMA/SA showed favorable and controllable water-uptake capacity, swelling property and degradability. After the introduction of IPN components, the mechanical strength of composite scaffolds was further improved. The compressive modulus of composite scaffolds was significantly higher than the bare ZrO2 scaffolds. In addition, ZrO2-GM/SA composite scaffolds had highly biocompatibility and displayed a potent proliferation and osteogenesis of MC3T3-E1 pre-osteoblasts compared to bare ZrO2 scaffolds and ZrO2-GelMA composite scaffolds. At the same time, ZrO2-10GM/1SA composite scaffold regenerated significantly greater bone than other groups in vivo. This study demonstrated that the proposed ZrO2-GM/SA composite scaffolds had great research and application potential in bone tissue engineering.

Hydroxysafflor Yellow A-Induced Osteoblast Differentiation and Proliferation of BM-MSCs by Up-Regulating Nuclear Vitamin D Receptor.

BACKGROUND: Vitamin D receptor (VDR) is critical for mineral and bone homeostasis since it plays an essential role in the osteoblast differentiation of bone marrow mesenchymal stem cells (BM-MSCs). Hydroxysafflor yellow A (HSYA) has the potential to promote bone mineralization and inhibit bone resorption, while its detailed mechanism needs to be elaborated. OBJECTIVE: This study intends to explore the action of HSYA on the proliferation and differentiation of BM-MSC and the underlying mechanism. METHODS: Different concentrations of HSYA to BM-MSC and CCK-8, and EdU were used to detect cell viability and proliferation. The alkaline phosphatase (ALP) was used to observe the differentiation ability of BM-MSC osteoblasts. The calcium uptake and mineralization of osteoblast-like cells were observed by alizarin red staining. The level of calcium ion uptake in cells was detected by flow cytometry. AutoDock was performed for molecular docking of HSYA to VDR protein. Immunofluorescence and western blotting were performed to detect the expression of VDR expression levels. Finally, the effect of VDR was verified by a VDR inhibitor. RESULTS: After treatment with HSYA, the proliferation and calcium uptake of BM-MSC were increased. The level of ALP increased significantly and reached its peak on the 12th day. HSYA promoted calcium uptake and calcium deposition, and mineralization of osteoblasts. The western blotting and immunofluorescence showed that HSYA increased the expression of VDR in the osteoblast-like cell's nucleus and upregulated Osteocalcin, S100 calcium-binding protein G, and CYP24A1. In addition, HYSA treatment increased the expression of osteopontin and the synthesis of osteogenic proteins, such as Type 1 collagen. After the addition of the VDR inhibitor, the effect of HSYA was weakened. CONCLUSION: HSYA could significantly promote the activity and proliferation of osteoblasts and increase the expression level of VDR in osteoblasts. HSYA may also improve calcium absorption by osteoblasts by regulating the synthesis of calciumbinding protein and vitamin D metabolic pathway-related proteins.

Diabetic bone regeneration with nanoceria-tailored scaffolds by recapitulating cellular microenvironment: Activating integrin/TGF-ß co-signaling of MSCs while relieving oxidative stress.

Regenerating defective bone in patients with diabetes mellitus remains a significant challenge due to high blood glucose level and oxidative stress. Here we aim to tackle this issue by means of a drug- and cell-free scaffolding approach. We found the nanoceria decorated on various types of scaffolds (fibrous or 3D-printed one; named nCe-scaffold) could render a therapeutic surface that can recapitulate the microenvironment: modulating oxidative stress while offering a nanotopological cue to regenerating cells. Mesenchymal stem cells (MSCs) recognized the nanoscale (tens of nm) topology of nCe-scaffolds, presenting highly upregulated curvature-sensing membrane protein, integrin set, and adhesion-related molecules. Osteogenic differentiation and mineralization were further significantly enhanced by the nCe-scaffolds. Of note, the stimulated osteogenic potential was identified to be through integrin-mediated TGF-ß co-signaling activation. Such MSC-regulatory effects were proven in vivo by the accelerated bone formation in rat calvarium defect model. The nCe-scaffolds further exhibited profound enzymatic and catalytic potential, leading to effectively scavenging reactive oxygen species in vivo. When implanted in diabetic calvarium defect, nCe-scaffolds significantly enhanced early bone regeneration. We consider the currently-exploited nCe-scaffolds can be a promising drug- and cell-free therapeutic means to treat defective tissues like bone in diabetic conditions.

3D Printed Poly(𝜀-caprolactone)/Hydroxyapatite Scaffolds for Bone Tissue Engineering: A Comparative Study on a Composite Preparation by Melt Blending or Solvent Casting Techniques and the Influence of Bioceramic Content on Scaffold Properties.

Bone tissue engineering has been developed in the past decades, with the engineering of bone substitutes on the vanguard of this regenerative approach. Polycaprolactone-based scaffolds are fairly applied for bone regeneration, and several composites have been incorporated so as to improve the scaffolds' mechanical properties and tissue in-growth. In this study, hydroxyapatite is incorporated on polycaprolactone-based scaffolds at two different proportions, 80:20 and 60:40. Scaffolds are produced with two different blending methods, solvent casting and melt blending. The prepared composites are 3D printed through an extrusion-based technique and further investigated with regard to their chemical, thermal, morphological, and mechanical characteristics. In vitro cytocompatibility and osteogenic differentiation was also assessed with human dental pulp stem/stromal cells. The results show the melt-blending-derived scaffolds to present more promising mechanical properties, along with the incorporation of hydroxyapatite. The latter is also related to an increase in osteogenic activity and promotion. Overall, this study suggests polycaprolactone/hydroxyapatite scaffolds to be promising candidates for bone tissue engineering, particularly when produced by the MB method.

Bone tissue engineering: Anionic polysaccharides as promising scaffolds.

Bone repair is a self-healing process. However, critical-sized bone defects need bone augmentation where bone tissue engineering plays vital role. Bone tissue Engineering (BTE) requires unique combinations of scaffolds, cells, and bio-signal molecules. Bone scaffold materials should be biocompatible, bioresorbable and exhibit biomimetic properties. Natural polymers, acquiring cell binding motives, producing nontoxic degradation products and tunable properties are ideal materials. Anionic polysaccharides of natural origin mimic mammalian ECM components and even the group called GAGs (Glycosaminoglycan) are actual components of ECM possessing various functions including cell adhesion, cell signaling, maintenance of homeostasis and inflammation control. Among them, anionic polysaccharides provide stabilization and sustained release of growth factors (GFs), porosity, calcium phosphate nucleation site, viscoelasticity, and water retention. Therefore, anionic polysaccharides are unique biomaterials for BTE. In this review, we have summarized the highlights of bone tissue engineering and recent applications of anionic polysaccharides in BTE.

3D Printable Composite Biomaterials Based on GelMA and Hydroxyapatite Powders Doped with Cerium Ions for Bone Tissue Regeneration.

The main objective was to produce 3D printable hydrogels based on GelMA and hydroxyapatite doped with cerium ions with potential application in bone regeneration. The first part of the study regards the substitution of Ca2+ ions from hydroxyapatite structure with cerium ions (Ca10-xCex(PO4)6(OH)2, xCe = 0.1, 0.3, 0.5). The second part followed the selection of the optimal concentration of HAp doped, which will ensure GelMA-based scaffolds with good biocompatibility, viability and cell proliferation. The third part aimed to select the optimal concentrations of GelMA for the 3D printing process (20%, 30% and 35%). In vitro biological assessment presented the highest level of cell viability and proliferation potency of GelMA-HC5 composites, along with a low cytotoxic potential, highlighting the beneficial effects of cerium on cell growth, also supported by Live/Dead results. According to the 3D printing experiments, the 30% GelMA enriched with HC5 was able to generate 3D scaffolds with high structural integrity and homogeneity, showing the highest suitability for the 3D printing process. The osteogenic differentiation experiments confirmed the ability of 30% GelMA-3% HC5 scaffold to support and efficiently maintain the osteogenesis process. Based on the results, 30% GelMA-3% HC5 3D printed scaffolds could be considered as biomaterials with suitable characteristics for application in bone tissue engineering.

Role of Macrophages and Plasminogen Activator Inhibitor-1 in Delayed Bone Repair Induced by Glucocorticoids in Mice.

Glucocorticoids delay fracture healing and induce osteoporosis. However, the mechanisms by which glucocorticoids delay bone repair have yet to be clarified. Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of plasminogen activators and an adipocytokine that regulates metabolism. We herein investigated the roles of macrophages in glucocorticoid-induced delays in bone repair after femoral bone injury using PAI-1-deficient female mice intraperitoneally administered with dexamethasone (Dex). Dex significantly decreased the number of F4/80-positive macrophages at the damaged site two days after femoral bone injury. It also attenuated bone injury-induced decreases in the number of hematopoietic stem cells in bone marrow in wild-type and PAI-1-deficient mice. PAI-1 deficiency significantly weakened Dex-induced decreases in macrophage number and macrophage colony-stimulating factor (M-CSF) mRNA levels at the damaged site two days after bone injury. It also significantly ameliorated the Dex-induced inhibition of macrophage phagocytosis at the damaged site. In conclusion, we herein demonstrated that Dex decreased the number of macrophages at the damaged site during early bone repair after femoral bone injury partly through PAI-1 and M-CSF in mice.

Antibacterial Honeycomb Scaffolds for Achieving Infection Prevention and Bone Regeneration.

Surgical site infection (SSI) is a severe complication associated with orthopedic bone reconstruction. For both infection prevention and bone regeneration, the framework surface of osteoconductive and bioresorbable scaffolds must be locally modified by minimum antibacterial substances, without sacrificing the osteoconductivity of the scaffold framework. In this study, we fabricated antibacterial honeycomb scaffolds by replacing carbonate apatite, which is the main component of the scaffold, with silver phosphate locally on the scaffold surface via dissolution-precipitation reactions. When the silver content was 9.9 × 10-4 wt %, the honeycomb scaffolds showed antibacterial activity without cytotoxicity and allowed cell proliferation, differentiation, and mineralization. Furthermore, the antibacterial honeycomb scaffolds perfectly prevented bacterial infection in vivo in the presence of methicillin-resistant Staphylococcus aureus, formed new bone at 2 weeks after surgery, and were gradually replaced with a new bone. Thus, the antibacterial honeycomb scaffolds achieved both infection prevention and bone regeneration. In contrast, severe infection symptoms, including abscess formation, osteolytic lesions, and inflammation, occurred 2 weeks after surgery when honeycomb scaffolds without silver phosphate modification were implanted. Nevertheless, the unmodified honeycomb scaffolds eliminated bacteria and necrotic bone through their scaffold channels, resulting in symptom improvement and bone formation. These results suggest that the honeycomb structure is inherently effective in hindering bacterial growth. This novel insight may contribute to the development of antibacterial scaffolds. Moreover, our modification method is useful for providing antibacterial activity to various biomaterials.

Biomimetic porous scaffolds containing decellularized small intestinal submucosa and Sr2+/Fe3+co-doped hydroxyapatite accelerate angiogenesis/osteogenesis for bone regeneration.

The design of bone scaffolds is predominately aimed to well reproduce the natural bony environment by imitating the architecture/composition of host bone. Such biomimetic biomaterials are gaining increasing attention and acknowledged quite promising for bone tissue engineering. Herein, novel biomimetic bone scaffolds containing decellularized small intestinal submucosa matrix (SIS-ECM) and Sr2+/Fe3+co-doped hydroxyapatite (SrFeHA) are fabricated for the first time by the sophisticated self-assembled mineralization procedure, followed by cross-linking and lyophilization post-treatments. The results indicate the constructed SIS/SrFeHA scaffolds are characterized by highly porous structures, rough microsurface and improved mechanical strength, as well as efficient releasing of bioactive Sr2+/Fe3+and ECM components. These favorable physico-chemical properties endow SIS/SrFeHA scaffolds with an architectural/componential biomimetic bony environment which appears to be highly beneficial for inducing angiogenesis/osteogenesis bothin vitroandin vivo. In particular, the cellular functionality and bioactivity of endotheliocytes/osteoblasts are significantly enhanced by SIS/SrFeHA scaffolds, and the cranial defects model further verifies the potent ability of SIS/SrFeHA to acceleratein vivovascularization and bone regeneration following implantation. In this view these results highlight the considerable angiogenesis/osteogenesis potential of biomimetic porous SIS/SrFeHA scaffolds for inducing bone regeneration and thus may afford a new promising alternative for bone tissue engineering.

Chrysin Attenuates High Glucose-Induced BMSC Dysfunction via the Activation of the PI3K/AKT/Nrf2 Signaling Pathway.

PURPOSE: High glucose environment in diabetes mellitus induces the dysfunction of bone marrow-derived mesenchymal stromal cells (BMSCs) and impairs bone regeneration. Chrysin is a natural polyphenol with outstanding anti-inflammation and anti-oxidation ability. However, whether and how chrysin affects BMSCs in high glucose conditions remain poorly understood. The present study aimed to explore the effects and underlying mechanisms of chrysin on the BMSCs exposed to high glucose environment. MATERIALS AND METHODS: Cell viability was detected by cell counting kit 8 assay and 5-ethynyl-2'-deoxyuridine staining, while cell apoptosis was determined through flow cytometry using Annexin V-FITC/PI kit. The oxidative stress in BMSCs was evaluated by detecting the reactive oxygen species production, malondialdehyde content, and superoxide dismutase activity. Alkaline phosphatase staining, Alizarin Red staining, and quantitative real-time PCR were performed to determine the osteogenic differentiation. Western blot was used to examine the expression of the PI3K/ATK/Nrf2 signaling pathway. Furthermore, chrysin was injected into calvarial defects of type 1 diabetic SD rats to assess its in vivo bone formation capability. RESULTS: Chrysin reduced oxidative stress, increased cell viability, and promoted osteogenic differentiation in BMSCs exposed to high glucose. Blocking PI3K/ATK/Nrf2 signaling pathway weakened the beneficial effects of chrysin, indicating that chrysin at least partly worked through the PI3K/ATK/Nrf2 pathway. CONCLUSION: Chrysin can protect BMSCs from high glucose-induced oxidative stress via the activation of the PI3K/AKT/Nrf2 pathway, and promote bone regeneration in type 1 diabetic rats.

Using scaffolds as drug delivery systems to treat bone tumor.

Surgery is the principal strategy to treat osteosarcoma and other types of bone tumors, but it causes bone defects that cannot be healed spontaneously. After surgery, patients still need to receive radiotherapy and/or chemotherapy to prevent tumor recurrence and metastasis, which leads to systemic side effects. Bone scaffolds exhibit the potentials to load cargos (drugs or growth factors) and act as drug delivery systems (DDSs) in the osteosarcoma postoperative treatment. This review introduces current types of bone scaffolds and highlights representative works using scaffolds as DDSs to treat osteosarcomas. Challenges and perspectives in the scaffold-based DDSs are also discussed. This review may provide references to develop effective and safe strategies for osteosarcoma postoperative treatment.

Monocytes and pyrophosphate promote mesenchymal stem cell viability and early osteogenic differentiation.

Pyrophosphate-containing calcium phosphate implants promote osteoinduction and bone regeneration. The role of pyrophosphate for inflammatory cell-mesenchymal stem cell (MSC) cross-talk during osteogenesis is not known. In the present work, the effects of lipopolysaccharide (LPS) and pyrophosphate (PPi) on primary human monocytes and on osteogenic gene expression in human adipose-derived MSCs were evaluated in vitro, using conditioned media transfer as well as direct effect systems. Direct exposure to pyrophosphate increased nonadherent monocyte survival (by 120% without LPS and 235% with LPS) and MSC viability (LDH) (by 16-19% with and without LPS). Conditioned media from LPS-primed monocytes significantly upregulated osteogenic genes (ALP and RUNX2) and downregulated adipogenic (PPAR-γ) and chondrogenic (SOX9) genes in recipient MSCs. Moreover, the inclusion of PPi (250 µM) resulted in a 1.2- to 2-fold significant downregulation of SOX9 in the recipient MSCs, irrespective of LPS stimulation or culture media type. These results indicate that conditioned media from LPS-stimulated inflammatory monocytes potentiates the early MSCs commitment towards the osteogenic lineage and that direct pyrophosphate exposure to MSCs can promote their viability and reduce their chondrogenic gene expression. These results are the first to show that pyrophosphate can act as a survival factor for both human MSCs and primary monocytes and can influence the early MSC gene expression. Graphical abstract.

Informative title: Guided bone regeneration with and without rhBMP-2: 17-year results of a randomized controlled clinical trial.

OBJECTIVES: To assess long-term outcomes of implants placed in conjunction with guided bone regeneration (GBR) with or without recombinant human bone morphogenetic protein-2 (rhBMP-2). MATERIALS AND METHODS: Eleven patients with at least two lateral bone defects (split-mouth design) received a total of 34 implants. The defects were treated with a xenogenic bone substitute with (test) or without (control) rhBMP-2 and covered with a collagen membrane. Eight patients could be reexamined after at least 17 years. Wilcoxon signed-rank tests were performed to assess differences between test and control groups. RESULTS: The implant survival rate was 100% for all test and control sites. Mean marginal bone levels were 2.51 mm (SD ±1.64) (mesial test), 1.83 mm (SD ±0.93) (mesial control) (p = .055), 2.36 mm (SD ±1.70) (distal test), and 2.13 mm (SD ±0.84) (distal control) (p = 1.000). Compared with the mean values at baseline, a mean bone loss of 1.16 mm (SD ±1.60) (test) and 0.70 mm (SD ±1.02) (control) was found. The mean buccal bone gain after 17 years was 5.38 mm (test) and 3.14 mm (control) based on the comparison between the measurements at the cone beam CT after 17 years and the data from the intraoperative measurements at baseline. Further, mean values for (i) bone thickness ranged from 1.36 to 3.09 mm (test) and 1.18 to 3.39 mm (control) and for (ii) mucosal thickness of 1.24 mm (test) and 1.26 mm (control). CONCLUSION: Implants placed in conjunction with GBR applying a xenogenic bone substitute and a collagen membrane with and without the addition of rhBMP-2 demonstrate excellent clinical and radiographic results after at least 17 years.

Enhanced bone formation in rat critical-size tibia defect by a novel quercetin-containing alpha-calcium sulphate hemihydrate/nano-hydroxyapatite composite.

We developed an innovative method to include quercetin into alpha-calcium sulphate hemihydrate/nano-hydroxyapatite (α-CSH/n-HA), to prepare a novel quercetin-containing α-CSH/n-HA composite (Q-α-CSH/n-HA). The physicochemical properties, and ability of Q-α-CSH/n-HA to promote cell proliferation, migration, and osteogenic differentiation of bone marrow stem cells (BMSCs) in vitro were examined. Further, the potential of Q-α-CSH/n-HA to promote bone defect repair was studied using a Sprague-Dawley rat model of critical tibial defects. Imaging was conducted by radiography and micro-CT, and bone defect repairs were observed by histopathological staining. Addition of quercetin clearly increased the porosity of the degraded composite, which elevated the cell proliferation rate, migration ability, osteogenesis differentiation, and mineralisation of BMSCs. Further, quercetin-containing composite increased the expression levels of OSX, RUNX2, OCN, ALP, BMP-2, OPN, BSP, SMAD2, and TGF-ß in BMSCs, while it downregulated TNF-α. X-ray and micro-CT imaging showed that the quercetin-containing composite significantly enhanced bone defect repair and new bone in formation. Haematoxylin and eosin, Goldner, and Safranin O staining also showed that quercetin significantly increased new bone generation and promoted composite degradation and absorption. Moreover, immunofluorescence assay revealed that quercetin significantly increased the number of RUNX2/OSX/OCN-positive cells. Overall, our data demonstrate that Q-α-CSH/n-HA has excellent biocompatibility, bone conductivity, and osteo-induction performance in vitro and mediates enhanced overall repair effects and bone reconstruction in vivo, indicating that it is a promising artificial bone graft to promote bone regeneration.

Metal Phenolic Nanodressing of Porous Polymer Scaffolds for Enhanced Bone Regeneration via Interfacial Gating Growth Factor Release and Stem Cell Differentiation.

Porous polymer scaffolds are essential materials for tissue engineering because they can be easily processed to deliver stem cells or bioactive factors. However, scaffolds made of synthetic polymers normally lack a bioactive cell-material interface and undergo a burst release of growth factors, which may hinder their further application in tissue engineering. In this paper, a metal-phenolic network (MPN) was interfacially constructed on the pore surface of a porous poly(dl-lactide) (PPLA) scaffold. Based on the molecular gating property of the MPN supramolecular structure, the PPLA@MPN scaffold achieved the sustained release of the loaded molecules. In addition, the MPN coating provided a bioactive interface, thus encouraging the migration and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The PPLA@MPN scaffolds exhibited enhanced bone regeneration in a rat femoral defect model in vivo compared to PPLA, which is ascribed to the combined effect of sustained bone morphogenetic protein-2 (BMP-2) release and the osteogenic ability of MPN. This nanodressing technique provides a viable and straightforward strategy for enhancing the performance of porous polymer scaffolds in bone tissue engineering.

Functional Macromolecular Adhesives for Bone Fracture Healing.

Compared with traditional internal fixation devices, bone adhesives are expected to exhibit remarkable advantages, such as improved fixation of comminuted fractures and maintained spatial location of fractured scattered bone pieces in treating bone injuries. In this review, different bone adhesives are summarized from the aspects of bone tissue engineering, and the applications of bone adhesives are emphasized. The concepts of "liquid scaffold" and "liquid plate" are proposed to summarize two different research directions of bone adhesives. Furthermore, significant advances of bone adhesives in recent years in mechanical strength, osseointegration, osteoconductivity, and osteoinductivity are discussed. We conclude this topic by providing perspectives on the state-of-the-art research progress and future development trends of bone adhesives. We hope this review will provide a comprehensive summary of bone adhesives and inspire more extensive and in-depth research on this subject.

Osteogenic growth peptide (OGP)-loaded amphiphilic peptide (NapFFY) supramolecular hydrogel promotes osteogenesis and bone tissue reconstruction.

Efficient bone reconstruction after bone injury remains a great challenge. Injectable supramolecular hydrogels based on amphiphilic peptide have been widely used due to their good biocompatability, non-immunogenicity, and manipulable physicochemical properties by sequence design. Herein, we used a well-studied hydrogelator, NapFFY, to coassemble with osteogenic growth peptide (OGP) to prepare a supramolecular hydrogel, NapFFY-OGP. Both in vitro and in vivo studies demonstrate that OGP was ideally synchronously, and continuously released from the hydrogel to effectively promote the regeneration and reconstruction of skull bone defects. More specifically, after the embedding the rat skull defect area with NapFFY-OGP hydrogels, a bone regeneration rate of 37.54% bone volume fraction (BV/TV) was achieved compared to that of NapFFY hydrogel group (25.09%). NapFFY-OGP hydrogel shows great promise in the clinic repair of bone defects in the future.

Collagen and nano-hydroxyapatite interactions in alginate-based microcapsule provide an appropriate osteogenic microenvironment for modular bone tissue formation.

The addition of nano-hydroxyapatite (nHA) and collagen (Col) to the alginate (Alg) microcapsule hydrogel reduced swelling and degradation ratios while the compressive strength increased compared to Alg, Alg-Col, and Alg-nHA groups. MTT assay and Calcein-AM staining revealed an enhanced MG-63 osteoblasts viability in the Alg-nHA-Col hydrogel compared to the other groups. SEM showed the attachment of MG-63 osteoblasts inside Alg-Col hydrogels. Non-significant differences were found in antioxidant capacity of cells inside the Alg-nHA-Col hydrogel compared to the Alg group. Hematoxylin-Eosin staining showed the distribution of MG-63 osteoblasts inside microspheres. Calcium deposits, alkaline phosphatase (ALP) activity with the increase of intracellular calcium were found in Alg-nHA-Col group. Western blotting showed that levels of osteocalcin, ColA2, Sox-9, and ColA1 also significantly increased compared to the Alg, Alg-Col, Alg-nHA groups. The present study demonstrated that the addition of mineral nHA and protein (Col) into the Alg improves osteogenic potential and provides a 3D platform for modular bone tissue engineering.

Polydopamine treatment of chitosan nanofibers for the conception of osteoinductive scaffolds for bone reconstruction.

We report the influence of treatment time of electrospun chitosan nanofibers (CHT NFs) in dopamine hydrochloride bath (2 mg.mL-1 in 10 mM Tris buffer, pH 8.5) on the extent of the polydopamine (pDA) coating on NFs surface. The reaction was characterized by FTIR and SEM analysis and the cytocompatibility of the scaffolds toward MT3C3-E1 cells was assessed. Biomimetic deposition of hydroxyapatite (HA) in 1.5xSBF batch was investigated by SEM-EDS and XRD. Samples treated in dopamine bath during 2 h promoted the structural stability of NFs in PBS, provided optimal cytocompatibility and induced the in vitro biomineralization from 6 days in 1.5xSBF. The XRD and SEM-EDS investigations confirmed formation of spherical-shaped particles composed of apatitic phase. Finally, this study shows that these NFs-pDA scaffolds prepared in the optimal experimental conditions defined here are promising candidates for application as osteoinductive scaffolds for bone regeneration applied to orthopedic and dental applications.