Search

Osteonecrosis is a common orthopedic disease in clinic, resulting in joint collapse if no appropriate treatment is performed in time. Core decompression is a general treatment modality for early osteonecrosis. However, effective bone regeneration in the necrotic area is still a significant challenge. This study developed a biofunctionalized composite scaffold (PLGA/nHA30VEGF) for osteonecrosis therapy through potentiation of osteoconduction, angiogenesis, and a favorable metabolic microenvironment. The composite scaffold had a porosity of 87.7% and compressive strength of 8.9 MPa. PLGA/nHA30VEGF had an average pore size of 227.6 μm and a water contact angle of 56.5° with a sustained release profile of vascular endothelial growth factor (VEGF). After the implantation of PLGA/nHA30VEGF, various osteogenic and angiogenic biomarkers were upregulated by 2–9 fold compared with no treatment. Additionally, the metabolomic and lipidomic profiling studies demonstrated that PLGA/nHA30VEGF effectively regulated the multiple metabolites and more than 20 inordinate metabolic pathways in osteonecrosis. The excellent performances reveal that the biofunctionalized composite scaffold provides an advanced adjuvant therapy modality for osteonecrosis., Graphical abstract Image 1, Highlights • A biofunctionalized organic−inorganic composite scaffold is developed for osteonecrosis therapy. • The biofunctionalized composite scaffold potentiates osteoconduction and angiogenesis in osteonecrosis. • The biofunctionalized composite scaffold reverses the adverse microenvironments of osteonecrosis. • The biofunctionalized composite scaffold provides a promising clinical modality for treatment of early osteonecrosis.

India is the world’s 3rd largest shrimp producer at the same stint the shrimp industry generates 40%–70% waste of the catch volume. In this research, chitosan from shrimp (Penaeus indicus) waste wa...

Objective: Osteochondral defect presents a big challenge for clinical treatment. This study aimed at constructing a bi-layered composite chitosan/chitosan-β-tricalcium phosphate (CS/CS-β-TCP) scaffold and at repairing the rat osteochondral defect. Approach: The bi-layered CS/CS-β-TCP scaffold was fabricated by lyophilization, and its microstructure was observed by a scanning electron microscope. Chondrocytes and bone marrow stem cells (BMSCs) were seeded into the CS layer and the CS-β-TCP layer, respectively. Viability and proliferation ability of the cells were observed under a confocal microscope. After subcutaneous implantation, the chondrogenic ability of the CS layer and osteogenic ability of the CS-β-TCP layer were evaluated by immunofluorescence. Then, the bi-layered scaffolds were implanted into the rat osteochondral defects and the harvested samples were macroscopically and histologically evaluated. Results: The bi-layered CS/CS-β-TCP scaffold exhibited the distinctive microstructures for each layer. The seeded chondrocytes in the CS layer could maintain the chondrogenic lineage, whereas BMSCs in the CS-β-TCP layer could continually differentiate into the osteogenic lineage. Moreover, cells in both layers could maintain well viability and excellent proliferation ability. For the in vivo study, the newly formed tissues in the bi-layered scaffolds group were similar with the native osteochondral tissues, which comprised hyaline-like cartilage and subchondral bone, with better repair effects compared with those of the pure CS group and the blank control group. Innovation: This is the first time that the bi-layered composite CS/CS-β-TCP scaffold has been fabricated and evaluated with respect to osteochondral defect repair. Conclusion: The bi-layered CS/CS-β-TCP scaffolds could facilitate osteochondral defect repair and might be the promising candidates for osteochondral tissue engineering.

Biomimetic scaffolds loaded with drugs can be applied in bone tissue engineering. In this study, a series of three-dimensional polylactic acid/hydroxyapatite/graphene oxide (PLA/HA/GO) drug-loaded biomimetic composite scaffolds with different concentrations of aspirin (ASA; 0–50 wt%) was successfully prepared using the phase separation technique. ASA addition increased the scaffold pore size without destroying the biomimetic structure. The hydrophilicity of a PLA/HA/GO/ASA drug-loaded biomimetic composite scaffold is linked to the component and structure of the prepared scaffold. The porosity can reach >85% in all samples. A test to assess the apatite-formation ability confirmed that the prepared composite scaffold had good bioactivity and could induce the formation of spherical hydroxyapatites. The haemolysis rate, platelet adhesion and in vitro cell proliferation experiments showed that the prepared scaffold had good haemocompatibility and cytocompatibility. However, ASA addition demonstrated an inhibitory effect on MC3T3-E1 cells. The prepared PLA/HA/GO/ASA drug-loaded biomimetic composite scaffold revealed good sustained drug-release performance. Hence, different concentrations of ASA can be loaded onto the scaffold on the basis of therapy requirements.

Mussel-derived nacre and pearl, which are natural composites composed CaCO3 platelets and interplatelet organic matrix, have recently gained interest due to their osteogenic potential. The crystal form of CaCO3 could be either aragonite or vaterite depending on the characteristics of mineralization template within pearls. So far, little attention has been paid on the different osteogenic capacities between aragonite and vaterite pearl. In the current work, aragonite or vaterite pearl powders were incorporated into poly-l-lactic acid (PLLA) scaffold as bio-functional fillers for enhanced osteogenesis. In intro results revealed that PLLA/aragonite scaffold possessed stronger stimulatory effect on SaOS-2 cell proliferation and differentiation, evidenced by the enhanced cell viability, alkaline phosphatase activity, collagen synthesis and gene expressions of osteogenic markers including osteocalcin, osteopotin and bone sialoprotein. The bone regeneration potential of various scaffolds was evaluated in vivo employing a rabbit critical-sized radial bone defect model. The X-ray and micro-CT results showed that significant bone regeneration and bridging were achieved in defects implanted with composite scaffolds, while less bone formation and non-bridging were found for pure PLLA group. Histological evaluation using Masson's trichrome and hematoxylin/eosin (H&E) staining indicated a typical endochondral bone formation process conducted at defect sites treated with composite scaffolds. Through three-point bending test, the limbs implanted with PLLA/aragonite scaffold were found to bear significantly higher bending load compared to other two groups. Together, it is suggested that aragonite pearl has superior osteogenic capacity over vaterite pearl and PLLA/aragonite scaffold can be employed as a potential bone graft for bone regeneration., Graphical abstract Image 1, Highlights • PLLA/pearl powder composite scaffolds with interconnected pores were fabricated. • PLLA/aragonite scaffold stimulated SaOS-2 cell proliferation and differentiation. • PLLA/aragonite scaffold promoted bone regeneration in vivo.

Tooth loss due to periodontal disease, dental caries, trauma or a variety of genetic disorders causes an adverse inability in adult’s lives. It is proved that biodegradable composite scaffolds in dental tissue engineering could play crucial role. To inhibit bacterial colonization in dental structure noticeable research concerning the drug delivery approach has been administrated. Nanostructures retain and release drug molecules more efficiently and continuously than other microstructure. In the present research, composite electrospun nanofibers of polyurethane-Single-walled carbon nanotube (SWNT) by the different mass ratios of metronidazole benzoate were prepared. Physico-chemical characterization of scaffolds including Scanning electron microscopy (SEM), uniaxial tensile testing and Ultraviolet-Visible (UV-Vis) spectroscopy analysis was operated. Culture of dental pulp stem cells (DPSCs) to evaluate cells behavior was carried out. The role of nanofiber diameters and drug content on releasing profile of the scaffolds was investigated. The median diameter of the nanofibrous scaffold was reduced from 330 ± 4 to 120 ± 4 nm. Ultimate stress and Young modulus of the scaffolds by enhancement of drug content increased from 0.28 ± 0.05 up to the 1.8 ± 0.05 MPa and 0.87 ± 0.05 up to the 4.4 ± 0.05 Mpa respectively. According to the result, prolonged and continuous releasing profile of the drug molecules was achieved. As the content of the drug increased, the drug was released continuously. It means that two parameters of fiber's diameter and drug ratio affected the releasing behavior of composite structures. Polyurethane-SWNT scaffolds contained metronidazole benzoate presented appropriate support of DPSCs adhesion and proliferation and biomimetic architecture like the structure of dental ECM.

In this study, a novel hydroxyapatite (HA)/polyurethane (PU) composite porous 3D scaffold was developed by in situ polymerization. Aliphatic hexamethylene diisocyanate (HDI) as a nontoxic and safe ...

Three-dimensional (3D) printing technology provides an effective alternative for tissue engineering scaffold. In this paper, a composite scaffold composed of polylactic acid (PLA) film and 3D printing scaffold was fabricated which could provide structural and mechanical support for tissue application. The effects of PLA film/3D printing composite scaffold on scaffold morphology, average diameter, pore diameter, mechanical properties, themal conductivity, electrical conductivity, and surface hydrophilicity were characterized. PLA film/3D printing composite scaffold had larger thickness, better mechanical and thermal conductivity properties in comparison with pure PLA film and 3D printed scaffold. These results suggested that composite scaffold with relatively good overall performance could be a potential candidate for tissue engineering application.

In this work, doxorubicin (DOX) was intercalated into layered nanohydroxyapatite (LHAp). The drug loaded LHAp (DOX@LHAp) was then mixed with poly(lactic-co-glycolic acid) (PLGA) and electrospun to yield DOX@LHAp/PLGA composite scaffolds. As control, needle-like nanohydroxyapatite (nHAp) was also used to make an DOX@nHAp/PLGA composite scaffold and bare DOX was used to fabricate DOX/PLGA scaffold. The morphology, release behavior of DOX, and capability to inhibit cancer cells were assessed. The addition of DOX-loaded nHAp to PLGA causes a slight decrease in the average fiber diameter of DOX@LHAp/PLGA as compared to PLGA. The in vitro drug release tests reveal a much faster release of DOX from DOX/PLGA than DOX@LHAp/PLGA. Moreover, DOX@LHAp/PLGA displays a more sustainable release over DOX@nHAp/PLGA due to the storage of DOX in the gallery of LHAp, which is further proved by their cancer cell inhibition results. We believe that the DOX@LHAp/PLGA scaffold has potential as an implantable drug delivery system.

The development of a bone tissue engineering scaffold with a biologically active surface for fast bone cell adhesion, proliferation, and extracellular matrix mineralization has been hotly pursued in recent years. However, most substrate materials do not show enough biological activity. Here, polydopamine-assisted immobilization of strontium (Sr) endows a three-dimensional reduced graphene oxide/polypyrrole (3D rGO/PPY) composite scaffold with higher bioactivity. Compared to the bare 3D rGO/PPY scaffold, 3D rGO/PPY modified with Sr (3D rGO/PPY/PDA/Sr) has a higher surface roughness. Moreover, benefiting from the introduction of Sr, the 3D rGO/PPY/PDA/Sr scaffold can significantly enhance early adhesion and proliferation of MC3T3-E1 cells on the 2nd day of culture. Additionally, ALP activity and extracellular matrix mineralization are distinctly enhanced.

Simple Summary Polycaprolactone (PCL) is a bioresorbable and biocompatible polymer that has been widely used in long-term implants. However, when it comes to regenerative medicine, PCL suffers from some shortcomings such as a slow degradation rate, poor mechanical properties, and low cell adhesion. The incorporation of ceramics such as bioactive glasses into the PCL matrix has yielded a class of hybrid biomaterials with remarkably improved mechanical properties, controllable degradation rates, and enhanced bioactivity, which are suitable for bone tissue engineering. The use of conventional approaches (such as solvent casting and particulate leaching, phase separation, electrospinning, freeze drying, etc.) in realizing these composite scaffolds strongly affects the control of both the internal and the external architecture of scaffolds, including pore size, pore morphology, and overall structure porosity. Accordingly, 3D printing was used in this study because of the benefits offered over conventional methods, such as high flexibility in shape and size, high reproducibility, capabilities of precise control over internal architecture down to the microscale level, and a customized design that can be tailored to specific patient needs. The optimization of the scaffold structure was previously investigated in terms of architecture through the combination of the Taguchi method and CAD drawing, and, in this study, it was investigated by varying the composition of the composite material. Abstract Polycaprolactone (PCL) is widely used in additive manufacturing for the construction of scaffolds for tissue engineering because of its good bioresorbability, biocompatibility, and processability. Nevertheless, its use is limited by its inadequate mechanical support, slow degradation rate and the lack of bioactivity and ability to induce cell adhesion and, thus, bone tissue regeneration. In this study, we fabricated 3D PCL scaffolds reinforced with a novel Mg-doped bioactive glass (Mg-BG) characterized by good mechanical properties and biological reactivity. An optimization of the printing parameters and scaffold fabrication was performed; furthermore, an extensive microtopography characterization by scanning electron microscopy and atomic force microscopy was carried out. Nano-indentation tests accounted for the mechanical properties of the scaffolds, whereas SBF tests and cytotoxicity tests using human bone-marrow-derived mesenchymal stem cells (BM-MSCs) were performed to evaluate the bioactivity and in vitro viability. Our results showed that a 50/50 wt% of the polymer-to-glass ratio provides scaffolds with a dense and homogeneous distribution of Mg-BG particles at the surface and roughness twice that of pure PCL scaffolds. Compared to pure PCL (hardness H = 35 ± 2 MPa and Young’s elastic modulus E = 0.80 ± 0.05 GPa), the 50/50 wt% formulation showed H = 52 ± 11 MPa and E = 2.0 ± 0.2 GPa, hence, it was close to those of trabecular bone. The high level of biocompatibility, bioactivity, and cell adhesion encourages the use of the composite PCL/Mg-BG scaffolds in promoting cell viability and supporting mechanical loading in the host trabecular bone.

Bone scaffolds play an important role in promoting the healing of large bone defects. However, the type of scaffold material, type of drug loaded into the scaffold, and method of preparation have a significant impact on the scaffold's properties. In this study, we developed a composite scaffold comprising sodium alginate (SA), chitosan (CS), and hydroxyapatite (HA). The composite stent carries vascular endothelial growth factor (VEGF), wrapped in internal microspheres, and vancomycin (VAN). The microspheres are wrapped in an outer matrix formed by SA, CS, and HA, whereas the outer matrix carries VAN. Using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction, and scanning electron microscopy analyses, we studied the contraction rate, swelling, porosity, mechanical properties, degradation, and drug release ability of all the composite scaffolds. The best scaffold, as demonstrated by the results of these studies, was the HA6(SA/CS)4@VAN/VEGF scaffold. The antibacterial ability of the HA6(SA/CS)4@VAN/VEGF scaffold was determined using Staphylococcus aureus (S. aureus). Cytotoxicity, cell adhesion, and osteogenic properties of the HA6(SA/CS)4@VAN/VEGF scaffold were studied using bone marrow mesenchymal stem cells. The results indicate that the HA6(SA/CS)4@VAN/VEGF scaffold exhibits good physical, chemical, antibacterial, and osteogenic properties, and is, thus, a new type of bone scaffold composite material with good osteogenic potential.

To evaluate the performance of a composite scaffold of Wharton’s jelly (WJ) and chondroitin sulfate (CS) and the effect of the composite scaffold loaded with human umbilical cord mesenchymal stem cells (hUCMSCs) in repairing articular cartilage defects, two experiments were carried out. The in vitro experiments involved identification of the hUCMSCs, construction of the biomimetic composite scaffolds by the physical and chemical crosslinking of WJ and CS, and testing of the biomechanical properties of both the composite scaffold and the WJ scaffold. In the in vivo experiments, composite scaffolds loaded with hUCMSCs and WJ scaffolds loaded with hUCMSCs were applied to repair articular cartilage defects in the rat knee. Moreover, their repair effects were evaluated by the unaided eye, histological observations, and the immunogenicity of scaffolds and hUCMSCs. We found that in vitro, the Young’s modulus of the composite scaffold (WJ-CS) was higher than that of the WJ scaffold. In vivo, the composite scaffold loaded with hUCMSCs repaired rat cartilage defects better than did the WJ scaffold loaded with hUCMSCs. Both the scaffold and hUCMSCs showed low immunogenicity. These results demonstrate that the in vitro construction of a human-derived WJ-CS composite scaffold enhances the biomechanical properties of WJ and that the repair of knee cartilage defects in rats is better with the composite scaffold than with the single WJ scaffold if the scaffold is loaded with hUCMSCs.

There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide, and hence growing needs for hypopharyngeal and cervical esophageal tissue repair. This work produced a bi-layer composite scaffold with decellularized small intestine submucosa and polylactic-co-glycolic acid, which resembled the layered architectures of its intended tissues. The decellularized small intestine submucosa contained minimal residual DNA (52.5 ± 1.2 ng/mg) and the composite scaffold exhibited satisfactory mechanical properties (a tensile modulus of 21.1 ± 4.8 MPa, an ultimate tensile strength of 14.0 ± 2.9 MPa and a failure strain of 26.9 ± 5.1%). The interactions between cells and the respective layers of the scaffold were characterized by CCK-8 assays, immunostaining and Western blotting. Desirable cell proliferation and phenotypic behaviors were observed. These results have provided an important basis for the next-step in vivo studies of the scaffold, and bode well for its future clinical applications.

In this study, composite scaffolds based on poly(caprolactone) (PCL) and non-covalently functionalized few-layer graphene (FLG) were manufactured by an extrusion-based system for the first time. For that, functionalized FLG powder was obtained through the evaporation of a functionalized FLG aqueous suspension prepared from a graphite precursor. Cryomilling was shown to be an efficient mixing method, producing a homogeneous dispersion of FLG particles onto the PCL polymeric matrix. Thereafter, fused deposition modeling (FDM) was used to print 3D scaffolds and their morphology, thermal, biodegradability, mechanical, and cytotoxicity properties were analysed. The presence of functionalized FLG demonstrated to induce slight changes in the microstructure of the scaffold, did not affect the thermal stability and enhanced significantly the compressive modulus. The composite scaffolds presented a porosity of around 40% and a mean pore size in the range of 300 μm. The cell viability and proliferation of SaOs-2 cells were assessed and the results showed good cell viability and long-term proliferation onto produced composite scaffolds. Therefore, these new FLG/PCL scaffolds comprised adequate morphological, thermal, mechanical, and biological properties to be used in bone tissue regeneration., The authors acknowledge the Portuguese Foundation for Science and Technology (FCT), the European program FEDER/COMPETE for the financial support through project LA ICVS/3Bs - 2015-2017 and to IPC (UID/CTM/50025/2013 and UID/CTM/50025/2016), and the scholarship SFRH/BD/87214/2012 granted to Eunice Cunha. Daniela Dias acknowledges the mobility grant from the BEAM project- Biomedical Engineering-EU Australian cooperation at master level, ICIECP Education Cooperation Programme (388414-EM-January 1, 2014-IT-ERA MUNDUS-ICIJMP). We also acknowledge Prof. Dietmar W. Hutmacher that kindly hosts Daniela Dias in the IHBI laboratory.

Repair of articular cartilage defects is a challenging aspect of clinical treatment. Kartogenin (KGN), a small molecular compound, can induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Here, we constructed a scaffold based on chondrocyte extracellular matrix (CECM) and poly(lactic-co-glycolic acid) (PLGA) microspheres (MP), which can slowly release KGN, thus enhancing its efficiency. Cell adhesion, live/dead staining, and CCK-8 results indicated that the PLGA(KGN)/CECM scaffold exhibited good biocompatibility. Histological staining and quantitative analysis demonstrated the ability of the PLGA(KGN)/CECM composite scaffold to promote the differentiation of BMSCs. Macroscopic observations, histological tests, and specific marker analysis showed that the regenerated tissues possessed characteristics similar to those of normal hyaline cartilage in a rabbit model. Use of the PLGA(KGN)/CECM scaffold may mimic the regenerative microenvironment, thereby promoting chondrogenic differentiation of BMSCs in vitro and in vivo. Therefore, this innovative composite scaffold may represent a promising approach for acellular cartilage tissue engineering.

Background: Application of platelet-rich plasma (PRP) can improve tendon-bone healing (TBH) after rotator cuff surgical repair. Graphene Oxide (GO) is a steady, controlled, and sustained carrier. The purpose of this study is to determine whether GO/PRP Composite Scaffold enhances the TBH after RC surgical repair in a rabbit model.Methods: A full-thickness tear of the supraspinatus tendon was created and repaired in 36 adult male New Zealand rabbits. They were divided into three groups: Control group, PRP group, and GO/PRP Composite Scaffold group (GO group). The effect of GO/PRP Composite Scaffold on TBH was assessed using histological and biomechanical evaluations at 8 and 12 weeks postoperatively.Results: Histological analysis showed that greater continuity, better orientation, and more density of collagen fiber were detected in the GO group than PRP and Control groups at 8 and 12 weeks, respectively. Results of biomechanical evaluations showed that the load to failure and stiffness of the GO group were statistically higher than those of PRP and Control groups at both 8 and 12 weeks (P0.05), while the stiffness at 12 weeks was higher than that at 8 weeks (P Conclusions: These results demonstrated that GO/PRP Composite Scaffold enhanced the TBH following rotator cuff surgical repair in a rabbit model. The GO may be an effective carrier for PRP into repair sites.

Background Current strategies for craniofacial defect are faced with unmet outcome. Combining 3D-printing with safe, noninvasive magnetic therapy could be a promising breakthrough. Methods In this study, polylactic acid/hydroxyapatite (PLA/HA) composite scaffold was fabricated. After seeding rat bone marrow mesenchymal stem cells (BMSCs) on scaffolds, the effects of electromagnetic fields (EMF) on the proliferation and osteogenic differentiation capacity of BMSCs were investigated. Additionally, 6-mm critical-sized calvarial defect was created in rats. BMSC-laden scaffolds were implanted into the defects with or without EMF treatment. Results Our results showed that PLA/HA composite scaffolds exhibited uniform porous structure, high porosity (~ 70%), suitable compression strength (31.18 ± 4.86 MPa), modulus of elasticity (10.12 ± 1.24 GPa), and excellent cyto-compatibility. The proliferation and osteogenic differentiation capacity of BMSCs cultured on the scaffolds were enhanced with EMF treatment. Mechanistically, EMF exposure functioned partly by activating mitogen-activated protein kinase (MAPK) or MAPK-associated ERK and JNK pathways. In vivo, significantly higher new bone formation and vascularization were observed in groups involving scaffold, BMSCs, and EMF treatment, compared to scaffold alone. Furthermore, after 12 weeks of implanting, craniums in groups including scaffold, BMSCs, and EMF exposure showed the greatest biomechanical properties. Conclusion In conclusion, EMF treatment combined with 3D-printed scaffold has great potential applications in craniofacial regeneration.

In-vitro degradation behaviors of composite scaffold materials composed of 1,4-butanediamine modified poly(lactide-co-glycolide) (BMPLGA), nanobioactive glass (NBG) and β-tricalcium phosphate (β-TC...

The combination of double-fillers with synthetic polymers has been an attractive route for developing bone scaffolds. In this article, polycaprolactone (PCL) scaffolds were produced using a selective laser sintering (SLS) technique; multi-walled carbon nanotubes (MWCNTs) and eggshell (ES) were used as two fillers to improve their mechanical and osteogenic properties. The crystal phase, morphology, hydrophilicity, biocompatibility and mechanical properties of the composite scaffold were detected using X-ray diffraction, scanning electron microscope, water contact angle tester and in vitro cell test, respectively. Results show that ES improved the hydrophilicity and biocompatibility of the scaffolds obviously, whereas MWCNTs enhanced their compression and tensile strength. The PCL/ES/MWCNTs composited scaffold prepared by SLS possess excellent biocompatibility and mechanical strength, showing a potential application for bone repair.

Background Composite scaffolds of poly(lactic-co-glycolic acid) (PLGA) and PLGA/COL I were developed by a low-temperature deposition manufacturing (LDM) technique using three-dimensional printing technology. Their physical properties were tested, and the scaffolds were then used as cell culture platforms to prepare an ideal scaffold for cartilage tissue engineering. Methods The LDM technique was used to fabricate PLGA and PLGA/COL I composite scaffolds. The macrostructure, micromorphology, porosity, hydrophobicity, mechanical properties, and chemical structure of these scaffolds were examined. Primary chondrocytes were isolated and identified, second-passage cells were seeded onto the two scaffolds, and the adhesion and proliferation of the cells were determined. Results Both the PLGA and PLGA/COL I scaffolds prepared by LDM displayed a regular three-dimensional structure with high porosity. The PLGA scaffold had better mechanical properties than the PLGA/COL I scaffold, while the latter had significantly higher hydrophilicity than the former. The PLGA/COL I scaffold cultured with chondrocytes exhibited a higher adhesion rate and proliferation rate than the PLGA/COL I scaffold. Conclusion The novel PLGA/COL I composite scaffold printed by the LDM technique exhibited favourable biocompatibility and biomechanical characteristics and could be a good candidate for cartilage tissue engineering.

Glioblastoma (GBM), one of the most malignant types of human brain tumor, is resistant to conventional treatments and is associated with poor survival. Since the 3D extracellular matrix (ECM) of GBM microenvironment plays a significant role on the tumor behavior, the engineering of the ECM will help us to get more information on the tumor behavior and to define novel therapeutic strategies. In this study, polycaprolactone (PCL)/gelatin(Gel)/hyaluronic acid(HA) composite scaffolds with aligned and randomly oriented nanofibers were successfully fabricated by electrospinning for mimicking the extracellular matrix of GBM tumor. We investigated the effect of nanotopography and components of fibers on the mechanical, morphological, and hydrophilic properties of electrospun nanofiber as well as their biocompatibility properties. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) have been used to investigate possible interactions between components. The mean fiber diameter in the nanofiber matrix was increased with the presence of HA at low collector rotation speed. Moreover, the rotational velocity of the collector affected the fiber diameters as well as their homogenous distribution. Water contact angle measurements confirmed that hyaluronic acid-incorporated aligned nanofibers were more hydrophilic than that of random nanofibers. In addition, PCL/Gel/HA nanofibrous scaffold (7.9 MPa) exhibited a significant decrease in tensile strength compared to PCL/Gel nanofibrous mat (19.2 MPa). In-vitro biocompatibilities of nanofiber scaffolds were tested with glioblastoma cells (U251), and the PCL/Gel/HA scaffolds with random nanofiber showed improved cell adhesion and proliferation. On the other hand, PCL/Gel/HA scaffolds with aligned nanofiber were found suitable for enhancing axon growth and elongation supporting intracellular communication. Based on these results, PCL/Gel/HA composite scaffolds are excellent candidates as a biomimetic matrix for GBM and the study of the tumor.

Magnetic-responsive materials are promising for applications in various biomedical fields. Especially, superparamagnetic nanoparticles are widely used in magnetic system for bone tissue engineering owing to superior biocompatibility and long term stability. Based on the idea of in situ bionics, we successfully incorporate the nano-hydroxyapatite (nHAP) and Fe3O4 nanoparticles which were prepared by in situ crystallization and freeze-drying technique into the chitosan/collagen (CS/Col) organic matrix to achieve the uniform dispersion of inorganic substrate with nanometer-scale. The in vitro results of the physicochemical and biocompatibility tests showed that CS/Col/Fe3O4/nHAP magnetic scaffold possessed superior structural and mechanical performance for cell adhesion and proliferation, as well as the osteogenic differentiation. Mineralization experiments showed better bioactive and good ability of in situ biomimetic mineralization. Moreover, from the in vivo model of SD rats’ skull defects proved that the CS/Col/Fe3O4/nHAP hybrid scaffold had a better tissue compatibility and higher bone regeneration ability when implanted into the skull defects comparing to control group. Herein, the magnetic hybrid micro/nanostructured scaffold showed a potential application for bone defect repair.

The application of three-dimensional (3D) printed scaffolds for tissue engineering have gained significant attention in recent years. The biological activity of scaffolds used in tissue engineering applications depends on fabricating high-resolution patterns with fiber orientation and scale. In this study, Bacterial Cellulose (BC) and Polycaprolactone (PCL) composite scaffolds with the line spacing of 100 µm are produced using Electrohydrodynamic (EHD)-3D-bioprinting technique. The composite scaffolds exhibit enhanced biocompatibility with facilitated cell attachment and proliferation in vitro. The results of this work have demonstrated that EHD-3D-bioprinting method shows great potential for the preparation of BC/PCL composite scaffold and patterns for tissue engineering with enhanced bioactivity.

In this work, a novel ultralong hydroxyapatite microtube (HMT)–chitosan (CHS) composite scaffold has been successfully prepared. The mechanical properties of the HMT–CHS composite scaffold is greatly improved compared with the CHS–hydroxyapatite nanorod scaffold and the pure chitosan scaffold. By using gentamicin sulfate (GS) as the model drug, the GS-loaded HMT–CHS composite scaffold has a high drug loading capacity, sustained drug release behavior and high antibacterial activity. The as-prepared HMT–CHS composite scaffold has promising applications in various fields such as drug delivery and bone defect repair.

Alginate scaffold with high porosity has great potential in the field of tissue engineering due to its biocompatibility and degradability. However, the poor mechanical performance of pure alginate scaffold has limited its use in many applications. Cellulose nanofibers (CNFs) have attracted attention as reinforcing agents to fabricate composite scaffolds with alginate. In this paper, CNF obtained from raw ramie fibers was incorporated with sodium alginate to make a composite scaffold by the freeze-drying method. CNF contents of 0.025, 0.05, 0.1, 0.2, 0.4, 0.8, and 1.6% were selected to study the effect of CNF on scaffold characterization. The composite scaffold exhibited fewer pores but more compact structure than the pure alginate scaffold. Fourier transform infrared spectroscopy was used to study the changes in the functional groups between the ramie fiber and its CNF, pure alginate scaffold, and the composite scaffold. X-ray diffraction indicated that the crystallinity of scaffold increased with addition of CNF. The mechanical performance of scaffold was successfully improved by adding CNF, but the porosity and swelling ratio were decreased. Hence, by combining CNF with alginate, the porous structure, mechanical properties, and swelling behaviors could be tailored, which could expand its use in the field of tissue engineering.

Contractile behavior of cardiomyocytes relies on directed signal propagation through the electroconductive networks that exist within the native myocardium. Due to their unique electrical properties, electroactive materials, such as graphene, have recently emerged as promising candidate materials for cardiac tissue engineering applications. In this work, the potential of three-dimensional (3D) nanofibrous graphene and poly(caprolactone) (PCL + G) composite scaffold for cardiac tissue engineering has been explored for the first time. The addition of graphene into PCL led to an increased volume conductivity of scaffolds with an even distribution of graphene particles throughout the matrix. Graphene particles provided local conductive sites within the PCL matrix, which enabled application of external electrical stimulation throughout the scaffold using a custom point stimulation device. When mouse embryonic stem cell derived cardiomyocytes (mES-CM) were seeded on PCL + G scaffolds, cells adhered well, contracted spontaneously, and exhibited classical cardiomyocyte phenotype confirming the biocompatibility of electroactive PCL + G scaffolds. Further functional characterization demonstrated that graphene especially affected Ca2+ handling properties of mES-CM compared to that of cardiomyocytes cultured in 2D culture, highlighting the potential of PCL + G for in vitro cardiac tissue engineering. © 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part A: 106A: 2923-2933, 2018.

Ionic substitutions are a promising strategy to enhance the biological performance of calcium phosphates (CaP) and composite materials for bone tissue engineering applications. However, systematic studies have not been performed on multi-substituted organic/inorganic scaffolds. In this work, highly porous composite scaffolds based on CaPs substituted with Sr2+, Mg2+, Zn2+ and SeO32− ions, and chitosan have been prepared by freeze-gelation technique. The scaffolds have shown highly porous structure, with very well interconnected pores and homogeneously dispersed CaPs, and high stability during 28 days in the degradation medium. Osteogenic potential of human mesenchymal stem cells seeded on scaffolds has been determined by histological, immunohistochemical and RT-qPCR analysis of cultured cells in static and dynamic conditions. Results indicated that ionic substitutions have a beneficial effect on cells and tissues. The scaffolds with multi-substituted CaPs have shown increased expression of osteogenesis related markers and increased phosphate deposits, compared to the scaffolds with non-substituted CaPs.

In recent years, various composite scaffolds based on hydroxyapatite have been developed for bone tissue engineering. However, the poor cell survival micro-environment is still the major problem limiting their practical applications in bone repairing and regeneration. In this study, we fabricated a class of fluffy and porous three-dimensional composite fibrous scaffolds consisting of hydroxyapatite and polyacrylonitrile by employing an improved electrospinning technique combined with a bio-mineralization process. The fluffy structure of the hydroxyapatite/polyacrylonitrile composite scaffold ensured the cells would enter the interior of the scaffold and achieve a three-dimensional cell culture. Bone marrow mesenchymal stem cells were seeded into the scaffolds and cultured for 21 days in vitro to evaluate the response of cellular morphology and biochemical activities. The results indicated that the bone marrow mesenchymal stem cells showed higher degrees of growth, osteogenic differentiation and mineralization than those cultured on the two-dimensional hydroxyapatite/polyacrylonitrile composite membranes. The obtained results strongly supported the fact that the novel three-dimensional fluffy hydroxyapatite/polyacrylonitrile composite scaffold had potential application in the field of bone tissue engineering.

The aim of this study is to investigate the applicability of poly(lactic-co-glycolic acid) (PLGA)/collagen composite scaffold for skin tissue engineering. PLGA and collagen were dissolved in HFIP as a common solvent and fibrous scaffolds were prepared by electrospinning method. The scaffolds were characterized by scanning electron microscopy (SEM), FTIR spectroscopy, mercury porosimetry, tensile strength, biocompatibility assays and Biodegradation. Cytotoxicity and cell adhesion were tested for two cell line groups, human dermal fibroblast (HDF) and human keratinocyte (HaCat). SEM images showed appropriate cell adhesion to the scaffold for both cell lines. MTT assays indicated that the cell viability of HDF cells increased with time, but the number of HaCat cells decreased after 14 days. The ultimate tensile strength was suitable for skin substitute application, but its elongation at break was rather low. For successful clinical application of the PLGA/collagen scaffold, some properties especially mechanical strain needs to be improved.

Aim To determine the feasibility of using three-dimensional printed Biodentine/polycaprolactone composite scaffolds for orthopaedic and dental applications. The physicochemical properties and the odontogenic differentiation of human dental pulp cells (hDPCs) were investigated. Methodology Biodentine was well-suspended in ethanol and dropped slowly into molten polycaprolactone with vigorous stirring. The Biodentine/polycaprolactone composite scaffolds were then fabricated into controlled macropore sizes and structures using an extrusion-based three-dimensional (3D) printer. The mechanical properties, bioactivity, and the proliferation and odontogenic differentiation of human dental pulp cells (hDPCs) cultured on the scaffolds were evaluated. Results Biodentine/polycaprolactone scaffolds had uniform macropores 550 μm in size with established interconnections and a compressive strength of 6.5 MPa. In addition, the composite scaffolds exhibited a good apatite-forming ability and were capable of supporting the proliferation and differentiation of hDPCs. Conclusion The composite scaffolds fabricated by an extrusion-based 3D printing technique had similar characteristics to Biodentine cement, including bioactivity and the ability to promote the differentiation of hDPCs. These results indicate that the composite scaffold would be a candidate for dental and bone regeneration.

Yi-Hsun Yu,1,2 Demei Lee,2 Yung-Heng Hsu,1,2 Ying-Chao Chou,1,2 Steve WN Ueng,1 Che-Kang Chen,2 Shih-Jung Liu1,2 1Department of Orthopedic Surgery, Musculoskeletal Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Taoyuan, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Department of Mechanical Engineering, Chang Gung University, No. 259 Wen-Hwa 1st Road, Guishan District, Taoyuan 333, TaiwanTel +886 3 211 8166Fax +886 3 211 8558Email shihjung@mail.cgu.edu.twIntroduction: Masquelet proposed a new solution for the healing of segmental bone defects, thus minimizing the disadvantages associated with traditional bone grafting. However, a major factor leading to the failure of this technique pertains to be the residual infection. Accordingly, we developed an antibiotic- and osteo-inductive agent-loaded composite scaffold to solve this problem.Methods: A mesh-like polycaprolactone scaffold was prepared using a lab-exploited solution-type three-dimensional printer, and hybrid sheath-core structured poly(lactic-co-glycolic-acid) nanofibers were fabricated using co-axial electrospinning technology. Vancomycin, ceftazidime, and bone morphological protein (BMP)-2 were employed. The in vitro and in vivo (rabbit fracture model) release patterns of applied agents from the composite scaffold were investigated.Results: The results revealed that the drug-eluting composite scaffold enabled the sustainable release of the medications for at least 30 days in vitro. Animal tests demonstrated that a high concentration of medications was maintained. Abundant growth factors were induced within the bioactive membrane stimulated by the applied scaffold. Finally, satisfactory bone healing potential was observed on radiological examination and biomechanical evaluation.Discussion: The developed composite scaffold may facilitate bone healing by inducing bioactive membrane formation and yielding high concentrations of antibiotics and BMP-2 during the Masquelet procedure.Keywords: Masquelet procedure, composite scaffold, three-dimensional printing, co-axial electrospinning

Background/objectives For treatment of large bone defects challenging in orthopaedic clinics, bone graft substitutes are commonly used for the majority of surgeons. It would be proposed in the current study that our bioactive scaffolds could additionally serve as a local delivery system for therapeutic small molecule agents capable of providing support to enhance biological bone repair. Methods In this study, composite scaffolds made of poly (lactic-co-glycolic acid) (PLGA) and tricalcium phosphate (TCP) named by P/T was fabricated by a low-temperature rapid prototyping technique. For optimizing the scaffolds, the phytomolecule icaritin (ICT) was incorporated into P/T scaffolds called P/T/ICT. The osteogenic efficacies of the two groups of scaffolds were compared in a successfully established calvarial defect model in rats. Bone regeneration was evaluated by X-ray, micro-computerised tomography (micro-CT), and histology at weeks 4 and/or 8 post-implantation. In vitro induction of osteogenesis and osteoclastogenesis was established for identification of differentiation potentials evoked by icaritin in primary cultured precursor cells. Results The results of radiographies and decalcified histology demonstrated more area and volume fractions of newly formed bone within bone defect sites implanted with P/T/ICT scaffold than that with P/T scaffold. Undecalcified histological results presented more osteoid and mineralized bone tissues, and also more active bone remodeling in P/T/ICT group than that in P/T group. The results of histological staining in osteoclast-like cells and newly formed vessels indicated favorable biocompatibility, rapid bioresorption and more new vessel growth in P/T/ICT scaffolds in contrast to P/T scaffolds. Based on in vitro induction, the results presented that icaritin could significantly facilitate osteogenic differentiation, while suppressed adipogenic differentiation. Meanwhile, icaritin demonstrated remarkable inhibition of osteoclastogenic differentiation. Conclusion The finding that P/T/ICT composite scaffold can enhance bone regeneration in calvarial bone defects through facilitating effective bone formation and restraining excessive bone resorption. The translational potential of this article The osteogenic bioactivity of icaritin facilitated PLGA/TCP/icartin composite scaffold to exert significant bone regeneration in calvarial defects in rat model. It might form an optimized foundation for potential clinical validation in bone defects application.

Natural porous scaffolds have been studied and developed for decades in biomedical science in order to support cells with a simulated extracellular matrix in natural tissue as an ideal environment. Such three-dimensional scaffolds provide many degrees of freedom to modulate cell activity, such as porosity, pore size, mechanical strength, biodegradability, and biocompatibility. In this study, a porous, three-dimensional material of alginate incorporating tapioca starch was fabricated. A particular freeze-gelation method was applied to homogenously mix starch in the alginate, and the concentration was controllable. This pure natural composite porous scaffold was characterized physically and biologically. The synergistic functions, including biocompatibility, biodegradability, cell adhesion, and cell proliferation, were also investigated. A myogenic differentiation model further verified that the composite porous scaffold provided a suitable environment, supporting the differentiation effect in the myogenic process. The positive results demonstrated that this novel material has the potential to serve as a biomedical or clean meat appliance.

The aim of this study was to transform human hair keratin waste into a scaffold for soft tissue engineering to heal wounds. The keratin was extracted using the Shindai method. Keratin and polyvinyl alcohol (PVA) was cross-linked with alginate dialdehyde and converted into a scaffold by the freeze-drying method using gentamycin sulphate (GS) as a model drug. The scaffold was subjected to Fourier transform infrared spectra (FTIR), swelling index, porosity, water absorption, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), drug release, and cell viability (MTT) analysis. The scaffold was tested for keratinocyte growth using the murine fibroblast cell line (NIH 3T3 cells). The outcome from the keratin had a molecular weight band between 52–38 kDa in SDS-PAGE (Sodium dodecylsulfate-Polyacrylamide gel electrophoresis). A porous scaffold was capable of water absorption (73.64 ± 14.29%), swelling ability (68.93 ± 1.33%), and the release of GS shown as 97.45 ± 4.57 and 93.86 ± 5.22 of 1:4 and 1:3 scaffolds at 16 h. The physicochemical evaluation revealed that the prepared scaffold exhibits the proper structural integrity: partially crystalline with a strong thermal property. The scaffold demonstrated better cell viability against the murine fibroblast cell line (NIH 3T3 cells). In conclusion, we found that the prepared composite scaffold (1:4) can be used for wound healing applications.

The use of porous three-dimensional (3D) composite scaffolds has attracted great attention in bone tissue engineering applications because they closely simulate the major features of the natural extracellular matrix (ECM) of bone. This study aimed to prepare biomimetic composite scaffolds via a simple 3D printing of gelatin/hyaluronic acid (HA)/hydroxyapatite (HAp) and subsequent biomineralization for improved bone tissue regeneration. The resulting scaffolds exhibited uniform structure and homogeneous pore distribution. In addition, the microstructures of the composite scaffolds showed an ECM-mimetic structure with a wrinkled internal surface and a porous hierarchical architecture. The results of bioactivity assays proved that the morphological characteristics and biomineralization of the composite scaffolds influenced cell proliferation and osteogenic differentiation. In particular, the biomineralized gelatin/HA/HAp composite scaffolds with double-layer staggered orthogonal (GEHA20-ZZS) and double-layer alternative structure (GEHA20-45S) showed higher bioactivity than other scaffolds. According to these results, biomineralization has a great influence on the biological activity of cells. Hence, the biomineralized composite scaffolds can be used as new bone scaffolds in bone regeneration.

Chitosan/nanodiopside/nanohydroxyapatite (CS/nDP/nHAp) composite scaffolds were prepared from the mixture of chitosan, nDP, and nHAp in different inorganic/organic weight ratios by using the freeze-drying method. The prepared nHAp and composite scaffolds were investigated using BET, TG, FT-IR, SEM, EDS, and XRD techniques. The composite scaffolds had 50–85% porosities with interlinked porous networks. Moreover, investigation of the cell proliferation, adhesion, and viability using MTT test, and mouse preosteoblast cell proved the cytocompatibile nature of the composite scaffolds with improved cell attachment and proliferation. All these results essentially illustrated that this composite could be a potential for bone tissue engineering applications.

Wound healing is a dynamic and well-orchestrated process that can be promoted by creating an optimal environment with wound dressing. An ideal wound dressing material should possess a suitable matrix, structure and bioactive components, functioning synergistically to accelerate wound healing. Wound dressings that allow reproducibility and customizability are highly desirable in clinical practice. In this study, using chitosan (CS) as the matrix and bioglass (BG) as the biological component, a spatially designed dressing scaffold was fabricated from a home-made cryogenic printing system. The micro- and macro-structures of the scaffold were highly controllable and reproducible. The printed scaffold exhibited interconnected and hierarchical pore structures, as well as good flexibility and water absorption capacity, and these properties were not affected by the content of BG. Nevertheless, when the content of BGs exceeded 20% that of CS, the tension strength and elongation rate reduced, but in vitro antibacterial, cell proliferation and migration performance were enhanced. In vivo examinations revealed that the composite scaffold significantly promoted wound healing process, with the group having 30% bioglass showing better wound closure, neovascularization and collagen deposition than other groups. These results indicate that the 3D printed CS/BG composite scaffold is a promising dressing material that accelerates wound healing.

In this study, an antibacterial degummed silk fiber (ADSF)/nano-hydroxyapatite/polylactic acid (ADSF/nHA/PLA) porous scaffold with antibacterial properties was prepared by using degummed silk fiber (DSF) loaded with silver nano-particles (Ag NPs) as a reinforcing material. In the experiment, ADSF and nHA were used as the main variables to investigate the effect of the change of the composition ratio on the performance of the composite scaffold, and a composite scaffold with excellent performance was obtained. Firstly, the DSFs were treated with dopamine (DA) and the silver ions were reduced to Ag NPs using the strong reducibility of polydopamine (PDA) to prepare ADSF loaded with Ag NPs. Finally, ADSF/nHA/PLA composite scaffolds with antibacterial properties were prepared using ADSF as a reinforcing material. In addition, samples were found to have good mineralization capacity in in vitro mineralization experiments. At the same time, in cell culture and antibacterial experiments, ADSF/nHA/PLA scaffolds were found to have good bioactivity, biocompatibility and antibacterial properties. All the results showed that the Ag NPs loaded DSF improved the performance of the nHA/PLA composite scaffold, while the ADSF/nHA/PLA had good bioactivity and antibacterial properties, making the antibacterial ADSF/nHA/PLA composite scaffold has a great potential for bone tissue engineering.

Şahin, Yeşim Müge (Arel Author), 3D bioprinting provides an innovative strategy to fabricate a new composite scaffold material consisted in a porous and rough structure with using polycaprolactone (PCL), beta-tricalcium phosphate (?-TCP), and collagen as a building block for tissue engineering. We investigated the optimization of the scaffold properties based on the ?-TCP concentration using 3D bioprinting method. Computer-aided drawing was applied in order to digitally design the scaffolds while instead of solid filaments, materials were prepared as a blend solution and controlled evaporation of the solvent during the bioprinting was enabled the proper solidification of the scaffolds, and they were successfully produced with well-defined porous structure. This work demonstrated the feasibility of complex PCL/?-TCP/collagen scaffolds as an alternative in the 3D bioprinting engineering to the fabrication of porous scaffolds for tissue engineering. © 2019, Australian Ceramic Society., This study has been founded by BAPKO, Marmara University, grant no. FEN-C-YLP-090217-0066.

Diabetic wound is a major problem that often needs amputation of the concerned organ in patients suffering from diabetes. In diabetes, the prolonged phase of inflammation obstructs the further phases of healing which, in turn, lead to improper healing of the wounds in diabetes. Pioglitazone (Pio) hydrochloride is an antidiabetic drug with reported anti-inflammatory properties. The aim of this study was to develop a Pio-nanostructured lipid carrier (Pio-NLC)-loaded collagen/chitosan (COL-CS) scaffold and evaluate its healing ability in diabetic wounds. The results of characterization of composite scaffolds reveal that cross-linked scaffolds possess optimum porosity, low matrix degradation, and sustained drug release compared with noncross-linked scaffolds. The in vitro studies reveal that the Pio-NLC-COL-CS scaffold was biocompatible and enhanced cell growth compared with control and NLC-COL-CS. Using the streptozotocin-induced diabetic wound model, significantly (p