Porous Composite Scaffolds Research Articles

Anti-infective efficacy, cytocompatibility and biocompatibility of a 3D-printed osteoconductive composite scaffold functionalized with quaternized chitosan.

Although plenty of conductive scaffold biomaterials have been exploited to improve bone regeneration under infection, potential tissue toxicity under high concentration and antibiotic-resistance are their main deficiencies. This study indicated that HACC-grafted PLGA/HA composite scaffold prepared using an innovative 3D-printing technique and covalent grafting strategy showed significantly enhanced antibacterial activities, especially against the antibiotic-resistant strains, together with good osteogenic activity and biocompatibility. Therefore, it provides an effective porous composite scaffold to combat the infected bone defect in clinic with decreased risks of bacterial resistance and open a feasible strategy for the modification of scaffold interfaces involved in the bone regeneration and anti-infection.

Morphological examination of highly porous polylactic acid/Bioglass® scaffolds produced via nonsolvent induced phase separation.

In this study, we produce highly porous (up to ∼91%) composite scaffolds of polylactic acid (PLA) containing 2 wt % sol-gel-derived 45S5 Bioglass® particles via nonsolvent induced phase separation at -23°C with no sacrificial phases involved. Before the incorporation of the bioglass with PLA, the particles are surface modified with a silane coupling agent which effectively diminishes agglomeration between them leading to a better dispersion of bioactive particles throughout the scaffold. Interestingly, the incorporation route (via solvent dichloromethane or nonsolvent hexane) of the surface modified particles in the foaming process has the greatest impact on porosity, crystallinity, and morphology of the scaffolds. The composite scaffolds with a morphology consisting of both mesopores and large macropores, which is potentially beneficial for bone regeneration applications, are examined further. SEM images show that the surface modified bioglass particles take-up a unique configuration within the mesoporous structure of these scaffolds ensuring that the particles are well interlocked but not completely covered by PLA such that they can be in contact with physiological fluids. The results of preliminary in vitro tests confirm that this PLA/bioglass configuration promotes the interaction of the bioactive phase with physiological fluids. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2433-2442, 2017.

High-Pressure Compression-Molded Porous Resorbable Polymer/Hydroxyapatite Composite Scaffold for Cranial Bone Regeneration

Fabricating porous scaffolds with sufficient mechanical properties is a challenge for healing bone defects. High-pressure compression-molded (HPCM) porous composite scaffold comprising poly(l-lactide) (PLLA), poly(lactide-co-glycolide) (PLGA), and hydroxyapatite (HA) was prepared and showed upregulated mechanical properties due to a solid network structure and a highly ordered crystalline architecture. The compressive yield strength and modulus of the HPCM scaffold molded at 1000 MPa and 180 °C were 0.91 and 6.84 MPa, respectively. The HPCM scaffold also exhibited an interconnected porous architecture with porosity greater than 80%, an appropriate degradation rate, and enhanced cell proliferation. Moreover, the HPCM scaffold supported the healing of a rat calvarial defect in vivo.

Design and fabrication of novel chitin hydrogel/chitosan/nano diopside composite scaffolds for tissue engineering

In this research, novel porous composite scaffolds consisting of chitin, chitosan and nano diopside powder were prepared using the freeze-drying method. The prepared nanocomposite scaffolds were characterized by SEM, XRD, BET, TGA and FT-IR techniques. In addition, swelling, degradation and biomineralization capability, cell viability and cell attachment of the composite scaffolds were evaluated. The results indicated better swelling and degradation properties of such scaffolds their ability to become bioactive. Cytocompatibility of the scaffolds were assessed by MTT assay and cell attachment studies using Human Gingival Fibroblast cells. Cell viability studies demonstrated no sign of toxicity and cells were found to be attached to the pore walls within the scaffolds. These results suggested that the developed composite scaffolds could be a potential candidate for tissue engineering.

Effect of Hydroxyapatite: Fibroin Ratio on Hydroxyapatite/Fibroin/Chitosan Porous Scaffold Characteristics

Autografting is a bone replacement technique used in orthopedic surgery. Bone tissue engineering is a new technique that offers promise, and could help alleviate this risk. Bioceramics, biopolymers or composite can be fabricated for artificial bone scaffold and used for bone regeneration. This study used three types of biomaterials – hydroxyapatite (HA), fibroin, and chitosan – to form porous scaffold. HA and fibroin were prepared from natural materials. HA was synthesized from mollusk shell by wet chemical precipitation method, while silk fibroin was extracted from silk worm’s cocoons. The HA and fibroin were mixed in a variety of ratios along with a fixed amount of chitosan before fabricating composite porous scaffolds by freeze-drying. The resulting scaffolds were evaluated for biodegradability, biocompatibility, porosity pore morphology and mechanical property. The fabricated scaffolds had an interconnected porous structure with a pore size of 200-400 μm and porosity in a range of 93-95%. The average degradation rate of the scaffold in lysozyme was between 7-17% at 7 days. A biocompatibility test showed that the scaffold was non-cytotoxic, making it a good candidate for future bone tissue engineering applications.

Preparation and performance control of poly(lactic acid) fiber/polyurethane composite porous biomimetic-aligned scaffolds

Because of important potential and application prospect of aligned scaffolds in tissue engineering, it is necessary to prepare aligned scaffolds different from previous methods. We have prepared poly(lactic acid) fiber/polyurethane adhesive composite-aligned scaffolds by 1000 poly(lactic acid) melt parallel arrangement fibers and different polyurethane contents at 5, 10, 20, 25, and 30% separately. It can be found that polyurethane contents have great influence on bonding effect between fiber and adhesive, surface and cross-sectional morphology, thickness, weight, contact angle, stress and strain, pore diameter, porosity, pore interconnectivity, water absorption, and gelatin impregnation. The maximum of pore diameter and porosity of aligned scaffolds can be achieved to 64.24 µm and 66.67% by controlling poly(lactic acid) fiber parallel arrangement and polyurethane adhesive content. Moreover, the ultimate stresses of aligned scaffolds are 3.47 MPa along length direction and 1.02 MPa in width direction. Each composite-aligned scaffold has better fiber parallel arrangement, pore structure, and stress.

Modification and cytocompatibility of biocomposited porous PLLA/HA-microspheres scaffolds

Poly(L-lactic acid) and hydroxyapatie (PLLA/HA) composite scaffolds have good properties and suit to use as bone tissue engineering. In this work, hollow HA microspheres (HAM) with poor crystallinity were fabricated by a flame-drying method. The HAM has the potential to be used to release drugs or proteins in addition to improve osteoconductivity. Different ratios of PLLA/HAM were used to prepare porous composite scaffolds using the thermally induced phase separation technique. The HAMs were randomly incorporated into the PLLA porous scaffolds. As the HAMs ratio was increased, the porous composite scaffolds changed from ladder-like into isotropic structure. In addition, the compressive strength of PLLA/HAMs composite scaffolds improved first and declined with the increasing of HAMs ratio in the scaffolds. In vitro experiment showed that PLLA/HAMs composite scaffolds improved the attachment, migration, and differentiation of osteoblastic cells. These results demonstrated that the PLLA/HAMs composite scaffolds were superior to plain PLLA scaffold for bone tissue engineering.

Collagen/chitosan porous bone tissue engineering composite scaffold incorporated with Ginseng compound K

In this study, suitable scaffold materials for bone tissue engineering were successfully prepared using fish scale collagen, hydroxyapatite, chitosan, and beta-tricalcium phosphate. Porous composite scaffolds were prepared by freeze drying method. The Korean traditional medicinal ginseng compound K, a therapeutic agent for the treatment of osteoporosis that reduces inflammation and enhances production of bone morphogenetic protein-2, was incorporated into the composite scaffold. The scaffold was characterized for pore size, swelling, density, degradation, mineralization, cell viability and attachment, and its morphological features were examined using scanning electron microscopy. This characterization and in vitro analysis showed that the prepared scaffold was biocompatible and supported the growth of MG-63 cells, and therefore has potential as an alternative approach for bone regeneration.

Strontium doped poly-ε-caprolactone composite scaffolds made by reactive foaming

In the reconstruction and regeneration of bone tissue, a primary goal is to initiate bone growth and to stabilize the surrounding bone. In this regard, a potentially useful component in biomaterials for bone tissue engineering is strontium, which acts as cationic active agent, triggering certain intracellular pathways and acting as so called dual action bone agent which inhibits bone resorption while stimulating bone regeneration. In this study we established a novel processing for the foaming of a polymer (poly-ε-caprolactone) and simultaneous chemical reaction of a mixture of calcium and strontium hydroxides to the respective carbonates using supercritical carbon dioxide. The resultant porous composite scaffold was optimized in composition and strontium content and was characterized via different spectroscopic (infrared and Raman spectroscopy, energy dispersive X-ray spectroscopy), imaging (SEM, μCT), mechanical testing and in vitro methods (fluorescence vital staining, MTT-assay). As a result, the composite scaffold showed good in vitro biocompatibility with partly open pore structure and the expected chemistry. First mechanical testing results indicate sufficient mechanical stability to support future in vivo applications.

Hydroxyapatite-Poly(Vinyl Alcohol)-Sodium Alginate Porous Hydrogels with Poly(Vinyl Alcohol) Surface Layer Used for Articular Cartilage Repair

The double-layered PVA/nanohydroxyapatite (nHA)-poly (vinyl alcohol)(PVA)-sodium alginate (SA) porous composite scaffolds used as synthetic articular cartilage were prepared by the freeze-thawing method, gas foaming method and crosslink method of Ca2+ ion, i.e., upper PVA layer for the cartilage substitute and underlying SA30 porous hydrogels for bone bonding. The microstructure and morphology of composite hydrogels were characterized using scanning electronic microscopy (SEM).It had high porosity and uniform pores. The content of HA in SA30 matrix were tested by Energy-dispersive X-ray spectroscopy (EDS). The biological properties of the composite hydrogels had been evaluated by co-culture and MTT. All results indicate that the PVA/SA30 hydrogels has good potential for repairing or replacing articular cartilage.

Effects of γ-Ray Irradiation on the Properties of Nano-Hydroxyapatite/Polyurethane Composite Porous Scaffolds

To well understand the influence of the sterilization on the properties of biomaterials prior to application is pivotal. The effect of γ-ray irradiation on the mechanical and thermal properties of nanohydroxyapatite/polyurethane (n-HA/PU) porous scaffold for bone tissue engineering was studied in this paper. The mechanical testing, fourier transform infrared spectroscopy and thermal analysis were employed to determine the structure and properties change of these composite scaffolds after γ-ray irradiation with different doses.The results show that thermal stability, and mechanical properties of the composite scaffolds increase after γ-ray irradiation with doses of15 kGy to 25 kGy, especially the irradiation dose of 15kGy which imposed a remarkable effect on these properties. However, a reverse trend is found when the 50kGy irradiation dose was applied.In general, it can be concluded that sterilization using γ-ray irradiation with proper dose has no adverse effect on the properties of n-HA/PU composite scaffolds.

Hydroxyapatite/chitosan-based porous three-dimensional scaffolds with complex geometries

Porous scaffolds based on nano-hydroxyapatite (nHAp) and chitosan (CS), are among the composite materials that hold great potential in tissue engineering applications. The aim of this work was to develop porous chitosan-based scaffolds with high nHAp content (75% w/w) having increased mechanical properties that can be successfully machined into complex three-dimensional shapes. The scaffolds were prepared and characterized using ATR-FTIR spectroscopy, X-ray diffraction, optical microscopy, scanning electron microscopy, and μCT imaging. nHAp was prepared utilizing a biomimetic procedure employing hyperbranched poly(ethyleneimine), PEI, that affords stable nanoparticle dispersions in water, which were used in combination with CS, or N‐acetylated CS, for the development of composite porous 3D scaffolds. For comparison, scaffolds using commercially available micron-sized hydroxyapatite particles (mHAp) were also prepared. Morphological analysis of scaffolds revealed an open interconnected highly porous structure with pores dimensions ranging from ∼200μm to 700μm, volume fractions of 79–83%, and surface/volume ratios of 25–30mm−1. In scaffolds consisting of commercial HAp, agglomerated particles are clearly observed, while when nHAp nanoparticles were used excellent dispersion is attained. The mechanical properties of the scaffolds (Young modulus under compression and compressive strength) are markedly improved by the use of nHAp and, even more, by the use of N‐acetylated CS. The enhancement in mechanical strength is attributed to the nanoparticles’ excellent dispersion, and furthermore for the N-acetylated CS based scaffolds to its ability to form an extended hydrogen bonding network between adjacent polymer chains. The mechanical properties were proved sufficient enough for the production of 3D bio-implants of complex geometry employing a computer numerical control precision milling machine.

A novel method to fabricate porous tricalcium phosphate composite scaffolds for bone tissue engineering applications

This study reports a novel approach for the fabrication of three-dimensional scaffolds using tricalcium phosphate, carboxymethyl cellulose composite with alginate. Microporous (<20 μm) scaffold fibres were made by incorporating gas bubbles within fibres, stabilizing it with surfactants and subsequently removing the gas by vacuum treatment. The morphology of the scaffold was characterized using scanning electron microscopy (SEM). Further, for quantitative determination of pore size, the porosity distribution of the scaffold fibre was determined using mercury intrusion porosimetry (MIP). The volume porosity of these scaffolds was determined by liquid displacement method. Compressive strength, rigidity constant and stiffness index of the constructs were also determined. The in vitro bioactivity studies of these scaffolds were carried out in simulated body fluid (SBF) for 2/4 weeks. This study showed that the scaffold provides a favourable substrate conditions to form a bone-like mineral phase, which might play a significant role in osteointegration.

Effects of sintering temperature on the compressive mechanical properties of collagen/hydroxyapatite composite scaffolds for bone tissue engineering

Hydroxyapatite (HA) porous scaffolds were prepared by a template method and fabricated using either collagen (COL) or COL/HA particles. The sintering temperature was varied to discover the sintering effects on the mechanical properties of the scaffold. It was found that fabrication of pure HA scaffolds with COL or COL/HA particles introduced a distinct layer or phase, causing the fabricated scaffolds to be strengthened and their mechanical properties to be improved. Moreover, it was found that higher sintering temperatures also enhanced the mechanical properties of fabricated HA porous composite scaffolds by reducing porosity.

Nanoengineered bioactive 3D composite scaffold: A unique combination of graphene oxide and nanotopography for tissue engineering applications

A tissue engineering composite scaffold serves as a temporary skeleton to accommodate and stimulate new tissue growth. Here we report the development of a biodegradable porous composite scaffold made from the bioactive chitosan (CHN) and hyaluronic acid (HYA) with graphene oxide (GO). The CHN–HYA–GO composite scaffold was successfully prepared and compared with CHN-HYA composite scaffold and found that CHN–HYA–GO significantly improved mechanical and biological properties. Moreover, the CHN–HYA–GO composite scaffold possessed an adequate porosity, swelling behavior and degradation rate to mimic the extracellular matrix (ECM) with a favorable cell attachment and proliferation. The cells in contact with CHN–HYA–GO composite scaffolds remained viable and exhibited a high growth potential. Therefore the uniquely fabricated CHN–HYA–GO composite scaffolds possess great potential for various tissue engineering applications.

Fabrication of silk fibroin/cellulose whiskers–chitosan composite porous scaffolds by layer-by-layer assembly for application in bone tissue engineering

Bone tissue engineering necessitates a three-dimensional porous scaffold design to closely mimic the in vivo physiological biomimetic microenvironment with good mechanical properties to support the adhesion and proliferation of osteoblasts. In this study, a silk fibroin/cellulose nanowhiskers–chitosan (SF/CNW–CS) composite scaffold with excellent mechanical properties and biological compatibility was prepared by layer-by-layer assembly of CNW and CS onto a porous SF scaffold fabricated by freeze-drying. The morphology, assembly construct, and mechanical properties of the SF/CNW–CS composite scaffold were characterized using different technical methods. The hierarchical lamellar structure was formed by assembly of CNW and CS onto the SF lamella. Increasing the number of CNW and CS assembly layers to 108 slightly decreased the porosity from 86 to 78 % and simultaneously changed the compressive stress–strain curves from soft to hard tissue-like properties with an increase in compressive modulus from 2.5 to 12.5 MPa. Human MG-63 osteosarcoma cells were further cultured on the SF/CNW–CS scaffold to evaluate their suitability for bone tissue engineering. The results indicated that the SF/CNW–CS composite scaffold supported cell proliferation and promoted the levels of biomineralization-relevant alkaline phosphatase activity and osteocalcin expression over those for a porous SF scaffold. Taken together, our results indicate that the porous SF/CNW–CS composite material will be a promising tissue engineering scaffold for bone generation and implantation.

A mechanical evaluation of micro-HA/CS composite scaffolds with interconnected spherical macropores.

BackgroundIn the process of bone defective reparation and engineered bone tissue construction, osteoblasts are adhered to the surface of the scaffold materials and impart the external mechanical load to the osteoblasts. So, the dynamic mechanical property of the scaffolds play an important role in the bone tissue repair and it is valuable to research. Material type and the architectural design of scaffolds are also important to facilitate cell and tissue growth. The aim of this study was to prepare a kind of material with good pore connectivity and analyze its dynamic mechanical property.MethodsFabrication and characterization of micro-hydroxyapatite(m-HA)/chitosan(CS) polymer composite scaffolds with well interconnected spherical pore architectures were reports. Micro-HA was prepared by being calcined and ball milled. Paraffin spheres in the range of 160–330 µm were fabricated with a dispersion method and used as the porogen in the fabrication of the scaffolds. Polymer scaffolds were fabricated by the technique of compression molding and particulate leaching method. The effects of the porogen content on the properties of the scaffolds were studied.ResultsWith the increase of porogen, the pore of the scaffolds increased and became interconnected. Cyclic loading of three scaffolds were tested with 10 % strain under four levels of loading frequency, 0.1, 0.5, 1 and 1.5 Hz. The porous composite scaffolds exhibited a viscosity-elastic behaviour with a maximum stress of 3–4 kPa. At each frequency, modulus value is decreased with the paraffin microspheres content, but there was no significance difference in the peak stress of the three samples. All the samples tested displayed clear hysteresis loops. There was no significance difference in the peak hysteresis of the three samples, and the hysteresis difference values between the sixth compression cycle and the initial cycle for three samples was similar, with no statistically significant differences.ConclusionsMicro-HA/CS composite scaffolds with interconnected spherical macropores were fabricated using pherical paraffin as porogen. The porous composite scaffolds exhibited a viscosity-elastic behaviour with good repeatability. It is benefit to study the influence of the mechanical load on the cell of the scaffold.

In vitro release of osteopromotive molecule icariin from porous composite scaffolds for bone defect repair

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Preparation of Calcium Phosphate/Polyurethane Composite Porous Scaffolds for Bone Repair by in situ Self-foaming Method

One of the main technical problems in preparation of calcium phosphate/polyurethane (CaP/PU) compos- ite scaffold for bone repair is to obtain a porous structure with uniformly distributed pores. The reason for this is due to the heterogeneous dispersion of the added foaming agents within the composite resulting in the increasing viscosity of polymer precursor during the composite fabrication process. To solve this problem, we report a novel method through incorporation of calcium hydrogen phosphate (DCPD) with polymer phase to achieve a composite system in early period of the synthesis process of CaP/PU composite. The uniformly distributed crystal water from DCPD can be released when temperature reaches above 75 ℃ and serve as foaming agents to react with isocyanate group in the PU and generate CO2 gas. The generation of gas leads to a self-foaming process and consequently in- duces CaP/PU composite to form a porous scaffold. Scanning electron microscopy (SEM) observations show that CaP/PU composite scaffolds with uniform porous structure, high porosity and interconnectivity were obtained at 90 ℃. The mechanical strength can be doubled by re-curing treatment for the scaffold at 110 ℃ for 24 h. The re- sulting CaP/PU composite scaffolds with uniformly porous structure, high porosity and interconnectivity have shown potential applications in bone tissue engineering. Moreover, this simple and efficient method may provide new approaches for the preparation of polyurethane- based porous scaffolds.

Processing and characterization of chitosan/PVA and methylcellulose porous scaffolds for tissue engineering

Biomimetic porous scaffold chitosan/poly(vinyl alcohol) CS/PVA containing various amounts of methylcellulose (MC) (25%, 50% and 75%) incorporated in CS/PVA blend was successfully produced by a freeze drying method in the present study. The composite porous scaffold membranes were characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), swelling degree, porosity, degradation of films in Hank's solution and the mechanical properties. Besides these characterizations, the antibacterial activity of the prepared scaffolds was tested, toward the bacterial species Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). FTIR, XRD and DSC demonstrated that there was strong intermolecular hydrogen bonding between the molecules of CS/PVA and MC. The crystalline microstructure of the scaffold membranes was not well developed. SEM images showed that the morphology and diameter of the scaffolds were mainly affected by the weight ratio of MC. By increasing the MC content in the hybrid scaffolds, their swelling capacity and porosity increased.The mechanical properties of these scaffolds in dry and swollen state were greatly improved with high swelling ratio. The elasticity of films was also significantly improved by the incorporation of MC, and the scaffolds could also bear a relative high tensile strength. These findings suggested that the developed scaffold possess the prerequisites and can be used as a scaffold for tissue engineering.