Lanthanum phosphate/chitosan scaffolds enhance cytocompatibility and osteogenic efficiency via the Wnt/ß-catenin pathway.

BACKGROUND: Fabrication of porous scaffolds with great biocompatibility and osteoinductivity to promote bone defect healing has attracted extensive attention. METHODS: In a previous study, novel lanthanum phosphate (LaPO4)/chitosan (CS) scaffolds were prepared by distributing 40- to 60-nm LaPO4 nanoparticles throughout plate-like CS films. RESULTS: Interconnected three dimensional (3D) macropores within the scaffolds increased the scaffold osteoconductivity, thereby promoting cell adhesion and bone tissue in-growth. The LaPO4/CS scaffolds showed no obvious toxicity and accelerated bone generation in a rat cranial defect model. Notably, the element La in the scaffolds was found to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) through the Wnt/ß-catenin signalling pathway and induced high expression of the osteogenesis-related genes alkaline phosphatase, osteocalcin and Collagen I (Col-I). Moreover, the LaPO4/CS scaffolds enhanced bone regeneration and collagen fibre deposition in rat critical-sized calvarial defect sites. CONCLUSION: The novel LaPO4/CS scaffolds provide an admirable and promising platform for the repair of bone defects.

Construction of a composite hydrogel of silk sericin via horseradish peroxidase-catalyzed graft polymerization of poly-PEGDMA.

Silk sericin (SS), which is one of the main components of Bombyx mori silk fibers, has attracted increasing attentions as functional biomaterials due to its diverse biological activities as well as excellent biocompatibility. However, the poor formability and weak mechanical properties of SS materials severely limit their practical applications in biomedical field. To address this issue, in this study poly(ethylene glycol)dimethacrylate (PEGDMA) modified sericin were prepared by graft polymerization of poly-PEGDMA (pPEGDMA) onto sericin chains in the presence of horseradish peroxidase and hydrogen peroxide under mild condition. The composite hydrogels obtained from the modified SS not only exhibit much improved formability and excellent mechanical properties, but also high possess porosity and swelling ratios up to 63 and 1,250%, respectively, at the optimized formulation. Moreover, the composite hydrogels also reveal sustained drug release behavior and acceptable cytotoxicity, which endow them with vast application as biomaterials. It is envisioned that the method presented in this study would expand the application of SS in biomedical filed.

Biofunctionalized chondrogenic shape-memory ternary scaffolds for efficient cell-free cartilage regeneration.

Cartilage defect repair remains a great clinical challenge due to the limited self-regeneration capacity of cartilage tissue. Surgical treatment of injured cartilage is rather difficult due to the narrow space in the articular cavity and irregular defect area. Herein, we designed and fabricated chondrogenic and physiological-temperature-triggered shape-memory ternary scaffolds for cell-free cartilage repair, where the poly (glycerol sebacate) (PGS) networks ensured elasticity and shape recovery, crystallized poly (1,3-propylene sebacate) (PPS) acted as switchable phase, and immobilized bioactive kartogenin (KGN) endowed the scaffolds with chondrogenic capacity. The resultant scaffolds exhibited shape-memory properties with shape-memory fixed ratio of 98% and recovered ratio of 97% at 37°C for PPS/PGS/KGN-100, indicating a good potential for minimally invasive implantation. The scaffolds gradually degraded in Dulbecco's phosphate-buffered saline and released KGN up to 12 weeks in vitro. In addition, the scaffolds promoted chondrogenic differentiation while inhibiting osteogenic differentiation of bone marrow-derived mesenchymal stem cells in a concentration-dependent manner and cartilage regeneration in full-thickness defects of rat femoropatellar groove for 12 weeks. Consequently, the PPS/PGS/KGN-100 scaffolds stimulated the formation of an overlying layer of neocartilage mimicking the characteristic architecture of native articular cartilage even in the absence of exogenous growth factors and seeded cells. This study provides much inspiration for future research on cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: There are two crucial challenges for cartilage defect repair: the lack of self-regeneration capacity of cartilage tissue and difficult scaffold implantation via traditional open surgery due to space-limited joints. Herein, bioactive body-temperature-responsive shape memory scaffolds are designed to simultaneously address the challenges. The scaffolds can be readily implanted by minimally invasive approach and recover by body-temperature of patient. The integration of kartogenin endows scaffolds the bioactivity, leading to the first example of bulk shape-memory scaffolds for cell-free cartilage repair. These characteristics make the scaffolds advantageous for clinical translation. Moreover, our developed material is easy to be functionalized due to the presence of extensive free hydroxyl groups and provides a versatile platform to design diverse functional shape memory biomaterials.

Chemically and physically cross-linked polyvinyl alcohol-borosilicate gel hybrid scaffolds for bone regeneration.

The composite scaffolds of bioactive glasses and polymers are often used in bone regeneration which could improve the stiffness, compressive strength and bioactivity of polymers while maintaining the osteoconductivity and osteoinductivity of bioactive glasses. But due to complicated situations and limitations of compositing process, the prepared composite materials have low uniformity and obvious phase separation, leading to problems such as poor mechanical properties and inferior new bone formation capacity. In this paper, a modified sol-gel processing technique was used to realize the homogeneous inorganic-organic composites. After hydrolysis of the metal alkoxide, the sol was mixed with the aqueous solution of polyvinyl alcohol (PVA), and through gelation and chemical reaction, the mixture was solidified into the inorganic-organic composite hydrogel. The composites showed as a uniform single phase with interpenetrating networks of PVA gel and borosilicate gel (BG) that chemically and physically interacted at the scale of molecular or nanometer, therefore PVA-BG hybrids were obtained. When immersed in phosphate-buffered saline, the PVA-BG hybrid-derived scaffolds released beneficial ions into the medium and converted to hydroxyapatite. The scaffolds were not toxic to the rat bone marrow-derived mesenchymal stem cells (rBMSCs), and supported rBMSCs proliferation. Furthermore, the alkaline phosphatase activity of the rBMSCs and the expression levels of osteogenic-related genes (alkaline phosphatase, osteocalcin and runt-related transcription factor 2) increased significantly with increasing amount of BG in the hybrid scaffolds. Finally, the bone defect repair results of critical-sized femoral condyle defect rat model demonstrated that PVA-BG hybrid scaffolds could enhance bone regeneration compared with PVA scaffolds. The results suggested that PVA-BG hybrid scaffolds may be a promising biomaterial for bone regeneration.

Cytocompatibility and Bone-Formation Potential of Se-Coated 316L Stainless Steel with Nano-Pit Arrays.

316L stainless steel is still widely applied in joint replacement and orthopedic surgery due to its mechanical properties, corrosion resistance and relatively low price. In this study, electrochemical oxidation and nanoscale coating were used to fabricate Se-coated 316L stainless steel with nano-pit arrays to enhance its surface characteristics, biocompatibility and osseointegration ability. The modified 316L stainless steel was tested via field emission scanning microscopy (FESEM), energy-dispersive X-ray spectrometry (EDS), X-ray photoelectron spectroscopy (XPS) and Se release studies. The results of this study showed that the nano-pit arrays were 50 nm in diameter and that the Se coating consisted primarily of elemental Se and exhibited sustained release. The biological response of the samples was evaluated using in vitro rat bone marrow mesenchymal stem cell (rBMSCs) experiments and in vivo animal experiments. The modified 316L stainless steel displays enhanced abilities of cell adhesion, proliferation and osteogenic activity, as shown by FESEM, CCK-8 assay, immunofluorescence microscopy (IF) and alkaline phosphatase (ALP) activity assay in vitro and additional new bone formation in vivo, indicating its outstanding cytocompatibility and osteogenic differentiation ability. More importantly, the Se coating can upregulate gene expression of OPN, RUNX-2 and ALP, indicating that the nano-Se-coated 316L stainless steel with nano-pit arrays is a promising biomedical material for implants in orthopedic or dental clinic applications.

Preparation of a bio-composite of sericin-g-PMMA via HRP-mediated graft copolymerization.

Silk sericin (SS) derived from silkworms has the characteristics of anti-oxidation, antibacterial, and biocompatibility, however, high solubility in water restricted its applications in biomedical fields. In the present work, SS was enzymatically graft-copolymerized with a hydrophobic vinyl monomer of methyl methacrylate (MMA), through a free radical reaction, through the combination use of hydrogen peroxide and horseradish peroxidase (HRP). Efficacy of the HRP-mediated reaction was examined by means of FTIR, SDS-PAGE, and SEC chromatogram. A bio-composite of SS-graft-polymethyl methacrylate (SS-g-PMMA) was constructed subsequently, the corresponding wettability, thermal behavior, and biocompatibility of the obtained composite were examined, respectively. The data reveal that MMA was successfully copolymerized with the reactive sites in sericin chains, resulting in a noticeable increase in the molecular weight. For the membrane of SS-g-PMMA, the surface hydrophobicity was evidently improved compared to that of the untreated, according to the determined data of water contact angle and dissolution ratio. The current work develops an eco-friendly technique for reuse of the industrial waste like sericin, and provides a novel method for preparation of the sericin-based biomaterials as well.

Angiogenesis and Full-Thickness Wound Healing Efficiency of a Copper-Doped Borate Bioactive Glass/Poly(lactic- co-glycolic acid) Dressing Loaded with Vitamin E in Vivo and in Vitro.

There is an urgent demand for wound healing biomaterials because of the increasing frequency of traffic accidents, industrial contingencies, and natural disasters. Borate bioactive glass has potential applications in bone tissue engineering and wound healing; however, its uncontrolled release runs a high risk of rapid degradation and transient biotoxicity. In this study, a novel organic-inorganic dressing of copper-doped borate bioactive glass/poly(lactic- co-glycolic acid) loaded with vitamin E (0-3.0 wt % vitamin E) was fabricated to evaluate its efficiency for angiogenesis in cells and full-thickness skin wounds healing in rodents. In vitro results showed the dressing was an ideal interface for the organic-inorganic mixture and a controlled release system for Cu2+ and vitamin E. Cell culture suggested the ionic dissolution product of the copper-doped and vitamin E-loaded dressing showed the best migration, tubule formation, and vascular endothelial growth factor (VEGF) secretion in human umbilical vein endothelial cells (HUVECs) and higher expression levels of angiogenesis-related genes in fibroblasts in vitro. Furthermore, this dressing also suggested a significant improvement in the epithelialization of wound closure and an obvious enhancement in vessel sprouting and collagen remodeling in vivo. These results indicate that the copper-doped borate bioactive glass/poly(lactic- co-glycolic acid) dressing loaded with vitamin E is effective in stimulating angiogenesis and healing full-thickness skin defects and is a promising wound dressing in the reconstruction of full-thickness skin injury.