A Gelatin/Alginate Double Network Hydrogel Nerve Guidance Conduit Fabricated by a Chemical-Free Gamma Radiation for Peripheral Nerve Regeneration.

Nerve guidance conduits (NGCs) are widely developed using various materials for the functional repair of injured or diseased peripheral nerves. Especially, hydrogels are considered highly suitable for the fabrication of NGCs due to their beneficial tissue-mimicking characteristics (e.g., high water content, softness, and porosity). However, the practical applications of hydrogel-based NGCs are hindered due to their poor mechanical properties and complicated fabrication processes. To bridge this gap, a novel double-network (DN) hydrogel using alginate and gelatin by a two-step crosslinking process involving chemical-free gamma irradiation and ionic crosslinking, is developed. DN hydrogels (1% alginate and 15% gelatin), crosslinked with 30 kGy gamma irradiation and barium ions, exhibit substantially improved mechanical properties, including tensile strength, elastic modulus, and fracture stain, compared to single network (SN) gelatin hydrogels. Additionally, the DN hydrogel NGC exhibits excellent kink resistance, mechanical stability to successive compression, suture retention, and enzymatic degradability. In vivo studies with a sciatic defect rat model indicate substantially improved nerve function recovery with the DN hydrogel NGC compared to SN gelatin and commercial silicone NGCs, as confirm footprint analysis, electromyography, and muscle weight measurement. Histological examination reveals that, in the DN NGC group, the expression of Schwann cell and neuronal markers, myelin sheath, and exon diameter are superior to the other controls. Furthermore, the DN NGC group demonstrates increased muscle fiber formation and reduced fibrotic scarring. These findings suggest that the mechanically robust, degradable, and biocompatible DN hydrogel NGC can serve as a novel platform for peripheral nerve regeneration and other biomedical applications, such as implantable tissue constructs.

Effective BMP-2 Release and Mineralization on a Graphene Oxide/Polyvinylpyrrolidone Hydrogel Forming Poly (ε-Caprolactone) Nanofibrous Scaffolds.

PCL nanofibrous scaffolds are widely used as bone scaffolds, and they can increase the efficiency of bone regeneration by loading drugs and/or growth factors onto them. However, to obtain a more effective bone regeneration effect, it is necessary to increase drug loading and release efficiency. In this study, conductive hydrogel forming nanofibrous scaffolds were prepared to increase drug efficiency. GO has an excellent conductivity and biocompatibility, making it an efficient conductive polymer for bone differentiation. Electrospun PCL was immersed in a mixed solution of GO and PVP and then crosslinked using gamma-ray irradiation. It was confirmed that GO/PVP-PCL was successfully prepared through its characterization (morphology, thermal, chemical, electrical, and biological properties). In addition, drug-release efficiency was confirmed by electrical stimulation after loading the sample with BMP-2, a bone-regeneration growth factor. Compared to PCL, it was confirmed that GO/PVP-PCL has an approximately 20% improved drug-release efficiency and an excellent mineralization of the scaffolds using SBF. After culturing MG63 cells on GO/PVP-PCL, a high effect on osteodifferentiation was confirmed by ALP activity. Therefore, GO/PVP-PCL prepared by a gamma-ray-induced crosslinking reaction is expected to be used as biomaterial for bone-tissue engineering.

Optimization of the Physical Properties of HDPE/PU Blends through Improved Compatibility and Electron Beam Crosslinking.

Polymer blending is a method in which polymers with different properties are mixed so that each advantage appears in one polymer blend. Improved thermal and mechanical properties of blends can be prepared by blending with high-density polyethylene (HDPE) of a non-polar polymer and polyurethane (PU) of a polar polymer. However, a compatibilizer is required because it has the disadvantage that blending has low miscibility due to the different phases. In this study, HDPE/PU blends with new and excellent physical properties were developed through optimal composition with improved compatibility between the HDPE and PU. In addition, the effects of improving the physical properties through electron-beam crosslinking were confirmed. In general, a crosslinking structure of HDPE is formed by electron beam irradiation to increase its thermal stability and strength, but its elongation is rapidly decreased. In particular, the elongation of HDPE irradiated at 100 kGy was about 110%, which was decreased about five times compared to unirradiated HDPE (510%). However, the HDPE/PU blend with improved compatibility (PU 30) showed an elongation of about 450% while maintaining excellent strength (22.5 MPa), which was increased by about four times compared to the HDPE irradiated at 100 kGy. In particular, the thermal stability of PU 30 irradiated at 100 kGy at a high temperature (180 °C) was improved more than six times compared to the HDPE. Therefore, it is possible to develop HDPE/PU blends with new and excellent physical properties by improving compatibility and using electron beam crosslinking technology.

In Vivo Evaluation of Gamma-Irradiated and Heparin-Immobilized Small-Diameter Polycaprolactone Vascular Grafts with VEGF in Aged Rats.

The effectiveness of small-diameter vascular grafts depends on their antithrombogenic properties and ability to undergo accelerated endothelialization. The extreme hydrophobic nature of poly(ε-caprolactone) (PCL) hinders vascular tissue integration, limiting its use in medical implants. To enhance the antithrombogenicity of PCL as a biomaterial, we grafted 2-aminoethyl methacrylate (AEMA) hydrochloride onto the PCL surface using gamma irradiation; developed a biodegradable heparin-immobilized PCL nanofibrous scaffold using gamma irradiation and N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide hydrochloride/N-hydroxysuccinimide reaction chemistry; and incorporated vascular endothelial growth factor (VEGF) into the scaffold to promote vascular endothelial cell proliferation and prevent thrombosis on the vascular grafts. We assessed the physicochemical properties of PCL, heparin-AEMA-PCL (H-PCL), and VEGF-loaded heparin-AEMA-PCL (VH-PCL) vascular grafts using scanning electron microscopy, attenuated total reflection-Fourier transform infrared spectroscopy, toluidine blue O staining, and fibrinogen adsorption and surface wettability measurement. In addition, we implanted the vascular grafts into 24-month-old Sprague Dawley rats and evaluated them for 3 months. The H-PCL and VH-PCL vascular grafts improved the recovery of blood vessel function by promoting the proliferation of endothelial cells and preventing thrombosis in clinical and histological evaluation, indicating their potential to serve as functional vascular grafts in vascular tissue engineering.

Radiation-Based Crosslinking Technique for Enhanced Thermal and Mechanical Properties of HDPE/EVA/PU Blends.

Crosslinking of polyolefin-based polymers can improve their thermal and mechanical properties, which can then be used in various applications. Radiation-induced crosslinking can be done easily and usefully by irradiation without a crosslinking agent. In addition, polymer blending can improve thermal and mechanical properties, and chemical resistance, compared to conventional single polymers. In this study, high-density polyethylene (HDPE)/ethylene vinyl acetate (EVA)/polyurethane (PU) blends were prepared by radiation crosslinking to improve the thermal and mechanical properties of HDPE. This is because HDPE, a polyolefin-based polymer, has the weaknesses of low thermal resistance and flexibility, even though it has good mechanical strength and machinability. In contrast, EVA has good flexibility and PU has excellent thermal properties and wear resistance. The morphology and mechanical properties (e.g., tensile and flexure strength) were characterized using scanning electron microscopy (SEM) and a universal testing machine (UTM). The gel fraction, thermal shrinkage, and abrasion resistance of samples were confirmed. In particular, after storing at 180 °C for 1 h, the crosslinked HDPE-PU-EVA blends exhibited ~4-times better thermal stability compared to non-crosslinked HDPE. When subjected to a radiation dose of 100 kGy, the strength of HDPE increased, but the elongation sharply decreased (80%). On the other hand, the strength of the HDPE-PU-EVA blends was very similar to that of HDPE, and the elongation was more than 3-times better (320%). Finally, the abrasion resistance of crosslinked HDPE-PU-EVA was ~9-times better than the crosslinked HDPE. Therefore, this technology can be applied to various polymer products requiring high heat resistance and flexibility, such as electric cables and industrial pipes.

Gamma Ray-Induced Polymerization and Cross-Linking for Optimization of PPy/PVP Hydrogel as Biomaterial.

Conducting polymer (CP)-based hydrogels exhibit the behaviors of bending or contraction/relaxation due to electrical stimulation. They are similar in some ways to biological organs and have advantages regarding manipulation and miniaturization. Thus, these hydrogels have attracted considerable interest for biomedical applications. In this study, we prepared PPy/PVP hydrogel with different concentrations and content through polymerization and cross-linking induced by gamma-ray irradiation at 25 kGy to optimize the mechanical properties of the resulting PPy/PVP hydrogel. Optimization of the PPy/PVP hydrogel was confirmed by characterization using scanning electron microscopy, gel fraction, swelling ratio, and Fourier transform infrared spectroscopy. In addition, we assessed live-cell viability using live/dead assay and CCK-8 assay, and found good cell viability regardless of the concentration and content of Py/pTS. The conductivity of PPy/PVP hydrogel was at least 13 mS/cm. The mechanical properties of PPy/PVP hydrogel are important factors in their application for biomaterials. It was found that 0.15PPy/PVP20 (51.96 ± 6.12 kPa) exhibited better compressive strength than the other samples for use in CP-based hydrogels. Therefore, it was concluded that gamma rays can be used to optimize PPy/PVP hydrogel and that biomedical applications of CP-based hydrogels will be possible.

Preparation of Radiation Cross-Linked Poly(Acrylic Acid) Hydrogel Containing Metronidazole with Enhanced Antibacterial Activity.

Metronidazole (MD) is known as a periodontitis medicine and has been widely used in antibiotics for resistance to anaerobic bacteria, periodontal disease, and other threats. To treat diseases, drug delivery carriers are needed with a high bioadhesive property and enhanced drug penetration. Poly (acrylic acid) (PAA) hydrogel films have a good bioadhesive property and are able to localize the absorption site and increase the drug residence time. In this study, we fabricated a MD loaded PAA hydrogel with different MD content (0.1, 0.25, 0.5, and 1 wt%) using varying doses (25, 50, and 75 kGy) and the radiation doses (25, 50, or 75 kGy) in a one-step gamma-ray irradiation process. The chemical and physical structure were determined through a Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy, gel content, and compressive strength. In addition, MD loaded PAA hydrogels were performed to MD release behaviors and cytotoxicity. Finally, we conducted antibacterial activity to demonstrate the prevention of growth of bacteria as a therapeutic dressing. The basic chemical structure analysis of MD was changed greatly at radiation doses of 50 and 75 kGy due to degradation by gamma-ray irradiation. However, when the absorbed dose was 25 kGy, the chemical structure analysis of MD did not change significantly, and the gel content and compressive strength of MD/PAA hydrogel were approximately 80% and 130 kPa, respectively. The MD/PAA hydrogels exhibited no cytotoxicity and good antibacterial activity against Escherichia coli, Staphylococcus aureus, and Streptococcus mutans. These results provide good evidence that MD/PAA hydrogel prepared by gamma-ray irradiation has potential as a competitive candidate for the therapeutic dressing.

Effect of Titanium Implants Coated with Radiation-Crosslinked Collagen on Stability and Osseointegration in Rat Tibia.

This study aimed to evaluate the titanium (Ti) implants coated with collagen type Ⅰ crosslinked using gamma-irrigation or glutaraldehyde (GA). The in vitro surface observations, quantification assay, and cell studies using human mesenchymal stem cells (hMSCs) were conducted. For in vivo experiments, the implants were divided into three groups and inserted into the rat tibias: control group (non-treated Ti implant), GA group (Ti implants coated with GA-crosslinked collagen) and 25 kGy group (Ti implants coated with gamma-radiation-crosslinked collagen at dose of 25 kGy). The animals were sacrificed at 4 weeks after implantation and the tissue sections were obtained. New bone volume (mm³) and bone-to-implant contact (BIC, %) within the region of interest (ROI) was measured. The in vitro results showed the highest osteogenic differentiation and levels of osteogenesis-related gene expressions in the 25 kGy group without cytotoxicity. The new bone volume of GA group was significantly higher than the control (p < 0.05). In the result of the BIC, the 25 kGy group was significantly higher than the control (p < 0.05). However, there was no significant difference between the experimental groups. Within the limitations of this study, Ti implant coated with gamma-radiation-crosslinked collagen has potential utility without side effects from chemical agents.

Preparation and evaluation of ß-glucan hydrogel prepared by the radiation technique for drug carrier applications.

ß-Glucan can provide excellent environment to apply to drug carrier due to its immunological and anti-inflammatory effect. Minocycline hydrochloride (MH) has excellent oral bioavailability pharmacological properties. Specifically, MH is effectively absorbed into the gingiva for periodontal disease treatment. In this study, we attempt to develop MH loaded ß-glucan hydrogel for periodontal disease treatment through radiation-crosslinking technique. In addition, MH loaded ß-glucan hydrogels were tested for their cytotoxicity and antibacterial activity. Finally, we conducted an in vivo study to demonstrate the potential to prevent the invasion of bacteria to treat periodontal disease. The gel content and compressive strength of the ß-glucan hydrogels increased as the ß-glucan content and the absorbed dose (up to 7 kGy) increased. For a radiation dose of 7 kGy, the gelation and the compressive strength of a 6 wt% ß-glucan hydrogel were approximately 92% and 270 kPa, respectively. As a drug, MH was consistently released from ß-glucan hydrogels, reaching 80% at approximately 90 min. Furthermore, the MH loaded ß-glucan hydrogels showed no cytotoxicity. The MH loaded ß-glucan hydrogels exhibited good antibacterial activity against Porphyromonas gingivalis. In addition, MH loaded ß-glucan hydrogel demonstrated the potential of a good capability to prevent the invasion of bacteria and to treat wounds.

Effective gamma-ray sterilization and characterization of conductive polypyrrole biomaterials.

Conductive polymers, including polypyrrole (PPy), have been extensively explored to fabricate electrically conductive biomaterials for bioelectrodes and tissue engineering scaffolds. For their in vivo uses, a sterilization method without severe impairment of original material properties and performance is necessary. Gamma-ray radiation has been commonly applied for sterilization of medical products because of its simple and uniform sterilization without heat generation. Herein we describe the first study on gamma-ray sterilization of PPy bioelectrodes and its effects on their characteristics. We irradiated PPy bioelectrodes with different doses (0-75 kGy) of gamma-rays. Gamma-ray irradiation of the PPy (γ-PPy) increased the oxygenation and hydrophilicity of the surfaces. Interestingly, gamma-ray irradiation did not alter the electrical impedances and conductivities of the PPy substrates. Additionally, γ-PPy prepared with various dopants (e.g., para-toluene sulfonate, polystyrene sulfonate, and chlorine) showed the electrochemical properties similar to the non-irradiated control. Gamma-ray irradiation at doses of ≥15 kGy was required for effective sterilization as evidenced by complete eradication of gram positive and negative bacteria. γ-PPy substrates also showed cytocompatibility similar to untreated control PPy, indicating no substantial alteration of cytocompatibility. In conclusion, gamma ray sterilization is a viable method of sterilization of conducting polymer-based biomaterials for biomedical applications.

One-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy.

INTRODUCTION: Although numerous studies have been conducted with the aim of developing drug-delivery systems, chemically synthesized gene carriers have shown limited applications in the biomedical fields due to several problems, such as low-grafting yields, undesirable reactions, difficulties in controlling the reactions, and high-cost production owing to multi-step manufacturing processes. MATERIALS AND METHODS: We developed a 1-step synthesis process to produce 2-aminoethyl methacrylate-grafted water-soluble chitosan (AEMA-g-WSC) as a gene carrier, using gamma irradiation for simultaneous synthesis and sterilization, but no catalysts or photoinitiators. We analyzed the AEMA graft site on WSC using 2-dimensional nuclear magnetic resonance spectroscopy (2D NMR; 1H and 13C NMR), and assayed gene transfection effects in vitro and in vivo. RESULTS: We revealed selective grafting of AEMA onto C6-OH groups of WSC. AEMA-g-WSC effectively condensed plasmid DNA to form polyplexes in the size range of 170 to 282 nm. AEMA-g-WSC polyplexes in combination with psi-hBCL2 (a vector expressing short hairpin RNA against BCL2 mRNA) inhibited tumor cell proliferation and tumor growth in vitro and in vivo, respectively, by inducing apoptosis. CONCLUSION: The simple grafting process mediated via gamma irradiation is a promising method for synthesizing gene carriers.

Preparation and Characterization of Resorbable Bacterial Cellulose Membranes Treated by Electron Beam Irradiation for Guided Bone Regeneration.

Bacterial cellulose (BC) is an excellent biomaterial with many medical applications. In this study, resorbable BC membranes were prepared for guided bone regeneration (GBR) using an irradiation technique for applications in the dental field. Electron beam irradiation (EI) increases biodegradation by severing the glucose bonds of BC. BC membranes irradiated at 100 kGy or 300 kGy were used to determine optimal electron beam doses. Electron beam irradiated BC membranes (EI-BCMs) were evaluated by scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, thermal gravimetric analysis (TGA), and using wet tensile strength measurements. In addition, in vitro cell studies were conducted in order to confirm the cytocompatibility of EI-BCMs. Cell viabilities of NIH3T3 cells on 100k and 300k EI-BCMs (100 kGy and 300 kGy irradiated BC membranes) were significantly greater than on NI-BCMs after 3 and 7 days (p < 0.05). Bone regeneration by EI-BCMs and their biodegradabilities were also evaluated using in vivo rat calvarial defect models for 4 and 8 weeks. Histometric results showed 100k EI-BCMs exhibited significantly larger new bone area (NBA; %) than 300k EI-BCMs at 8 weeks after implantation (p < 0.05). Mechanical, chemical, and biological analyses showed EI-BCMs effectively interacted with cells and promoted bone regeneration.

The Effect of Thickness of Resorbable Bacterial Cellulose Membrane on Guided Bone Regeneration.

This study introduces the effect of the thickness of a bacterial cellulose membrane by comparing the bone regeneration effect on rat skulls when using a collagen membrane and different thicknesses of resorbable bacterial cellulose membranes for guided bone regeneration. Barrier membranes of 0.10 mm, 0.15 mm, and 0.20 mm in thickness were made using bacterial cellulose produced as microbial fermentation metabolites. Mechanical strength was investigated, and new bone formation was evaluated through animal experimental studies. Experimental animals were sacrificed after having 2 weeks and 8 weeks of recovery, and specimens were processed for histologic and histomorphometric analyses measuring the area of bone regeneration (%) using an image analysis program. In 2 weeks, bone-like materials and fibrous connective tissues were observed in histologic analysis. In 8 weeks, all experimental groups showed the arrangement of osteoblasts surrounding the supporting body on the margin and center of the bone defect region. However, the amount of new bone formation was significantly higher (p < 0.05) in bacterial cellulose membrane with 0.10 mm in thickness compared to the other experimental groups. Within the limitations of this study, a bacterial cellulose membrane with 0.10 mm thickness induced the most effective bone regeneration.

Chestnut Honey Impregnated Carboxymethyl Cellulose Hydrogel for Diabetic Ulcer Healing.

Honey-based wound dressings have attracted a lot of attention from modern scientists owing to their anti-inflammatory and antibacterial effects without antibiotic resistance. Such dressings also promote moist wound healing, and have been considered natural, abundant, and cheap materials for folk marketing. This study investigated the various behaviors and characteristics of chestnut honey-impregnated carboxymethyl cellulose sodium hydrogel paste (CH⁻CMC) as a therapeutic dressing, such as its moist retention, antibacterial activity for inhibiting the growth of Staphylococcus aureus and Escherichia coli, and the rate of wound healing in db/db mice. The results provide good evidence, suggesting that CH⁻CMC has potential as a competitive candidate for diabetic ulcer wound healing.

Preparation of Extracellular Matrix Developed Using Porcine Articular Cartilage and In Vitro Feasibility Study of Porcine Articular Cartilage as an Anti-Adhesive Film.

In this study, we examined whether porcine articular cartilage (PAC) is a suitable and effective anti-adhesive material. PAC, which contained no non-collagenous tissue components, was collected by mechanical manipulation and decellularization of porcine knee cartilage. The PAC film for use as an anti-adhesive barrier was easily shaped into various sizes using homemade silicone molds. The PAC film was cross-linked to study the usefulness of the anti-adhesive barrier shape. The cross-linked PAC (Cx-PAC) film showed more stable physical properties over extended periods compared to uncross-linked PAC (UnCx-PAC) film. To control the mechanical properties, Cx-PAC film was thermally treated at 45 °C or 65 °C followed by incubation at room temperature. The Cx-PAC films exhibited varying enthalpies, ultimate tensile strength values, and contact angles before and after thermal treatment and after incubation at room temperature. Next, to examine the anti-adhesive properties, human umbilical vein endothelial cells (HUVECs) were cultured on Cx-PAC and thermal-treated Cx-PAC films. Scanning electron microscopy, fluorescence, and MTT assays showed that HUVECs were well adhered to the surface of the plate and proliferated, indicating no inhibition of the attachment and proliferation of HUVECs. In contrast, Cx-PAC and thermal-treated Cx-PAC exhibited little and/or no cell attachment and proliferation because of the inhibition effect on HUVECs. In conclusion, we successfully developed a Cx-PAC film with controllable mechanical properties that can be used as an anti-adhesive barrier.

Engineered ECM-like microenvironment with fibrous particles for guiding 3D-encapsulated hMSC behaviours.

The alginate hydrogel has been used as an attractive scaffold for tissue regeneration. In particular, its simple cross-linking, high water absorption, and biocompatibility have facilitated its utility in regulating the interaction with cells or organs. However, three-dimensional (3D) networks of the alginate hydrogel do not provide fibrous anchorage sites such as the collagen fibres in the natural extracellular matrix (ECM). This has partially limited the survival of anchorage-dependent cells in the 3D hydrogel environment. In this report, we established a hybrid hydrogel containing fibrous particles (FP) that closely mimics the ECM. The RGD peptide-coupled FP (R-FP) has a wide range of distribution and was homogeneously dispersed in the hydrogel. The encapsulated human mesenchymal stem cells in the hydrogel could bind to the R-FP presenting remarkable spreading morphology, augmented viability and differentiation. These findings may elicit the significance of a physical interaction in which the R-FP provides structural and biological cues to the cells. This strategy can be widely applicable to a variety of hydrogel systems.

The effect of bacterial cellulose membrane compared with collagen membrane on guided bone regeneration.

PURPOSE: This study was to evaluate the effects of bacterial cellulose (BC) membranes as a barrier membrane on guided bone regeneration (GBR) in comparison with those of the resorbable collagen membranes. MATERIALS AND METHODS: BC membranes were fabricated using biomimetic technology. Surface properties were analyzed, Mechanical properties were measured, in vitro cell proliferation test were performed with NIH3T3 cells and in vivo study were performed with rat calvarial defect and histomorphometric analysis was done. The Mann-Whitney U test and the Wilcoxon signed rank test was used (α<.05). RESULTS: BC membrane showed significantly higher mechanical properties such as wet tensile strength than collagen membrane and represented a three-dimensional multilayered structure cross-linked by nano-fibers with 60 % porosity. In vitro study, cell adhesion and proliferation were observed on BC membrane. However, morphology of the cells was found to be less differentiated, and the cell proliferation rate was lower than those of the cells on collagen membrane. In vivo study, the grafted BC membrane did not induce inflammatory response, and maintained adequate space for bone regeneration. An amount of new bone formation in defect region loaded with BC membrane was significantly similar to that of collagen membrane application. CONCLUSION: BC membrane has potential to be used as a barrier membrane, and efficacy of the membrane on GBR is comparable to that of collagen membrane.

Efficacy of rhBMP-2 loaded PCL/PLGA/ß-TCP guided bone regeneration membrane fabricated by 3D printing technology for reconstruction of calvaria defects in rabbit.

We successfully fabricated a three-dimensional (3D) printing-based PCL/PLGA/ß-TCP guided bone regeneration (GBR) membrane that slowly released rhBMP-2. To impregnate the GBR membrane with intact rhBMP-2, collagen solution encapsulating rhBMP-2 (5 µg ml(-1)) was infused into pores of a PCL/PLGA/ß-TCP membrane constructed using a 3D printing system with four dispensing heads. In a release profile test, sustained release of rhBMP-2 was observed for up to 28 d. To investigate the efficacy of the GBR membrane on bone regeneration, PCL/PLGA/ß-TCP membranes with or without rhBMP-2 were implanted in an 8 mm calvaria defect of rabbits. Bone formation was evaluated at weeks 4 and 8 histologically and histomorphometrically. A space making ability of the GBR membrane was successfully maintained in both groups, and significantly more new bone was formed at post-implantation weeks 4 and 8 by rhBMP-2 loaded GBR membranes. Interestingly, implantation with rhBMP-2 loaded GBR membranes led to almost entire healing of calvaria defects within 8 weeks.

Synergistic effect of dual-functionalized fibrous scaffold with BCP and RGD containing peptide for improved osteogenic differentiation.

Over the last decade, bone tissue engineering scaffolds have been advanced owing to the bioceramic incorporation and biomimetic modification. In this report, a dual-functional fibrous scaffold with a bioceramic and biomolecule is developed, and a combined effect of a dual-modification is investigated. Biphasic calcium phosphate (BCP) is incorporated in electrospun poly (L-lactide) scaffolds, and Arg-Gly-Asp (RGD) peptide is then conjugated through the graft polymerization of acrylic acid by γ-ray irradiation. The scaffolds exhibit the intrinsic properties of BCP as well as RGD peptide, and only RGD peptide improves an adhesion and proliferation of the human mesenchymal stem cell. However, alkaline phosphatase activity and calcium formation are synergistically improved by the BCP and RGD peptide indicating that a favorable microenvironment is constructed for bone formation. Therefore, this combination strategy with bioceramic and biomolecule can be a useful tool for the bone tissue engineering.

The effect of alendronate-loaded polycarprolactone nanofibrous scaffolds on osteogenic differentiation of adipose-derived stem cells in bone tissue regeneration.

The osteogenic effect of culturing adipose-derived stem cells (ADSCs) on alendronate (Aln)-loaded polycarprolactone (PCL) nanofibrous scaffolds was evaluated by examining alkaline phosphatase (ALP) activity, calcium content, and expression of osteogenic differentiation genes in vitro. The 10% Aln/PCL nanofibrous scaffolds showed more ALP activity, mineralization, and osteocalcin and osteopontin mRNA than the 1% or 5% Aln/PCL nanofibrous scaffolds. The capacity of Aln/PCL nanofibrous scaffolds to regenerate new bone was studied in a rat calvarial defect model. New bone formation in vivo was evaluated by radiography, micro-computed tomography, and histological analysis. At 8 weeks after implantation, Aln/PCL scaffolds had a positive effect on bone regeneration and matrix formation. These results suggested that Aln/PCL nanofibrous scaffolds enhanced the osteogenic differentiation of ADSCs in vitro and bone formation in vivo.