Poly(ε‐caprolactone) composite scaffolds loaded with gentamicin‐containing β‐tricalcium phosphate/gelatin microspheres for bone tissue engineering applications

In this study, novel poly(ε‐caprolactone) (PCL) composite scaffolds were prepared for bone tissue engineering applications, where gentamicin‐loaded β‐tricalcium phosphate (β‐TCP)/gelatin microspheres were added to PCL. The effects of the amount of β‐TCP/gelatin microspheres added to the PCL scaffold on various properties, such as the gentamicin release rate, biodegradability, morphology, mechanical strength, and pore size distribution, were investigated. A higher amount of filler caused a reduction in the mechanical properties and an increase in the pore size and led to a faster release of gentamicin. Human osteosarcoma cells (Saos‐2) were seeded on the prepared composite scaffolds, and the viability of cells having alkaline phosphatase (ALP) activity was observed for all of the scaffolds after 3 weeks of incubation. Cell proliferation and differentiation enhanced the mechanical strength of the scaffolds. Promising results were obtained for the development of bone cells on the prepared biocompatible, biodegradable, and antimicrobial composite scaffolds. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40110.     

Fabrication and characterization of poly(ε-caprolactone)/gelatin nanofibrous scaffolds for retinal tissue engineering

Different ratios of poly(ε-caprolactone) (PCL) and gelatinwere used to fabricate scaffolds for regeneration of retinal pigment epithelium (RPE) layer. Physical and chemical characterizations were performed and the behavior of human RPE cells on the scaffolds was evaluated subsequently. An increase in gelatin content in the scaffold enhanced hydrophilicity, RPE cell attachment, proliferation, and spreading over PCL scaffolds. Granular and cytoplasmic expressions of RPE65 and Cytokeratin 8/18 markers confirmed the presence of RPE cells. It was believed that PCL/gelatin scaffolds could be used as substrates to replace RPE extracellular matrix to facilitate regeneration of RPE layer in retinal diseases.     

Effect of protein adsorption on cell uptake and blood clearance of methoxy poly(ethylene glycol)‐poly(caprolactone) nanoparticles

The interactions between nanoparticles and cells or tissues are frequently mediated by different biomolecules adsorbed onto the surface of nanoparticles. In this study, several methoxy poly(ethylene glycol)‐poly(ε‐caprolactone) (mPEG‐PCL) copolymers with various mPEG/PCL ratios were synthesized and used to produce three types of mPEG‐PCL nanoparticles. The protein‐adsorption behavior of nanoparticles was assessed using fetal‐bovine‐serum (FBS) as a model protein. The cell uptake of nanoparticles at different nanoparticle doses as well as various culture periods was examined by measuring their endocytosis rate related to Hela cells cultured in FBS‐free and FBS‐contained media. The blood clearance of nanoparticles was evaluated using Kunming mice to see the differences in circulation durations of nanoparticles. Results suggest that that FBS is able to significantly regulate the cell uptake of nanoparticles in vitro, and on the other hand, the size and mPEG/PCL molar ratio of mPEG/PCL nanoparticles are closely correlated to their blood clearance. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42884.     

Fabrication of LaCl3‐containing nanofiber scaffolds and their application in skin wound healing

Poly(?‐caprolactone) (PCL)/gelatin (GE) nanofiber scaffolds with varying concentrations of lanthanum chloride (LaCl₃, from 0 to 25 mM) were fabricated by electrospinning. The scaffolds were characterized by scanning electron microscopy, contact angle and porosity measurements, mechanical strength tests, and in vitro degradation studies. In vitro cytotoxicity and cell adhesion and proliferation studies were performed to assess the biocompatibility of the scaffolds, and in vivo wound healing studies were conducted to assess scaffold applications in the clinic. All prepared scaffolds were noncytotoxic, and the growth of adipose tissue–derived stem cells on LaCl₃‐containing scaffolds was better than on the pure PCL/GE scaffold. Cell proliferation studies showed the greatest cell growth in the PCL/GE/LaCl₃ scaffolds. Further, in vivo studies proved that the PCL/GE/LaCl₃ scaffolds can promote wound healing. The results suggest that nanofiber scaffolds containing LaCl₃ promote cell proliferation and have good biocompatibility, and thus potential for application in the treatment of skin wounds. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46672.     

Materials selection and residual solvent retention in biodegradable electrospun fibers

Electrospun tissue engineering scaffolds provide mechanical support to seeded cells that populate the structure while depositing specific extracellular matrix components. The potent sterilizing agent 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) is often used in electrospinning investigations involving biologically‐derived polymers. Surprisingly, there has been no study of solvent retention versus composition even though materials selection should influence organic solvent content. We developed a method quantifying HFIP retention following electrospinning of gelatin, polycaprolactone (PCL), and PCL‐gelatin blends using electro‐spray mass spectroscopy. The acetone content of acetone‐spun PCL was also established. Pure gelatin fiber contained as much as 1600 ppm of HFIP. In contrast, little acetone or HFIP was detected in 100% PCL. Gelatin clearly has a greater affinity for HFIP than PCL and materials selection has a strong influence on the amount of retained solvent. Vacuum + heat treatment at 37 and 45ºC reduced [HFIP] to 10 and 5.6 ppm, respectively, levels having no demonstrated effects on mammalian cell viability. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Fabrication and Evaluation of Polycaprolactone–Poly(hydroxybutyrate) or Poly(3‐Hydroxybutyrate‐co‐3‐Hydroxyvalerate) Dual‐Leached Porous Scaffolds for Bone Tissue Engineering Applications

Polycaprolactone (PCL) blend with poly(hydroxybutyrate) (PHB) or poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) dual‐leached scaffolds are prepared by using the solvent casting and salt–polymer‐leaching technique. The blending of the PHB and PHBV in PCL scaffolds results in decreased porosities of the scaffolds, and the water absorption capacities of the scaffolds also decrease. The compressive modulus of the PCL–PHB and PCL–PHBV dual‐leached scaffolds is greatly increased by the blending of PHB or PHBV matrix. An indirect cytotoxicity evaluation of all scaffolds with mouse fibroblastic cells (L929) and mouse calvaria‐derived preosteoblastic cell (MC3T3‐E1) indicates that all dual‐leached scaffolds are posed as nontoxic to cells. Both PCL–PHB and PCL–PHBV dual‐leached scaffolds are supported by the attachment of MC3T3‐E1 at significantly higher levels to tissue culture polystyrene plate (TCPS) and are able to support the proliferation of MC3T3‐E1 at higher levels to that cells on TCPS and PCL scaffolds. For mineralization, cells cultured on surfaces of PCL–PHB and PCL–PHBV dual‐leached scaffolds show higher mineral deposition than on TCPS and PCL scaffold.

     

Assessment of cell proliferation in knitting scaffolds with respect to pore‐size heterogeneity,surface wettability,and surface roughness

In this study, various types of poly(ε‐caprolactone) (PCL) knitting scaffolds were fabricated and analyzed to assess the cell‐culturing characteristics of knitting scaffolds with respect to pore‐size heterogeneity, surface wettability, and surface roughness. First, control knitting scaffolds were fabricated using 150‐µm‐diameter PCL monofilaments. Using chloroform and NaOH, PCL knitting scaffolds with varying roughness, pore‐size heterogeneity, and surface wettability were fabricated. Cell‐culture assessments were performed on these six types of PCL knitting scaffolds. Saos‐2 cells were used for cell assessments and cultured for 14 days on each scaffold. Consequently, heterogeneous pore‐size distribution and high surface wettability were found to enhance cell proliferation in knitting scaffolds. In addition, for highly hydrophobic knitting scaffolds exhibiting water contact angles greater than 110 degrees, smaller surface roughness was found to enhance cell proliferation. According to this study, in the case of knitting scaffold, NaOH‐treated knitting scaffold, without any control for the pore‐size homogenization, could be a candidate as the optimal knitting scaffold. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42566.     

Herbally derived polymeric nanofibrous scaffolds for bone tissue regeneration

Hydroxyapatite (HA), the bone mineral and Cissus quadrangularis (CQ), a medicinal plant with osteogenic activity, are attaining increasing interest as a potential therapeutic agent for enhanced bone tissue regeneration. In the present study a synergistic effect of these two agents were analyzed by fabricating PCL‐CQ‐HA nanofibrous scaffolds by electrospinning and compared with PCL‐CQ and PCL (control) nanofibrous scaffolds. Morphology, composition, hydrophilicity, and mechanical properties of the electrospun PCL, PCL‐CQ, PCL‐CQ‐HA nanofibrous scaffolds were examined by Field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), Contact angle and Tensile tests, respectively. The response of human foetal osteoblast cells on these scaffolds were evaluated using MTS assay, alkaline phosphatase activity, alizarin red staining, and osteocalcin expression for bone tissue regeneration. While the observed cellular response to both groups of scaffolds was better than for the control PCL scaffold, the PCL‐CQ‐HA nanofibrous scaffolds provided the most favorable substrate for cell proliferation and mineralization. The results showed that PCL‐CQ‐HA nanofibrous scaffolds had appropriate surface roughness for the osteoblast adhesion, proliferation, and mineralization comparing with other scaffolds. The observed investigation of physicochemical and biological properties suggests that the CQ‐HA loaded PCL nanofibrous scaffolds serve as a potential biocomposite material for bone tissue engineering. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39835.     

The odontogenic differentiation of human dental pulp stem cells on hydroxyapatite-coated biodegradable nanofibrous scaffolds

The authors aimed to design nanofibrous (NF) scaffolds that facilitate odontogenic and osteogenic differentiation of human dental pulp-derived mesenchymal stem cells (DPSCs) in vitro. For this purpose, hydroxyapatite (HA)–loaded poly (L-lactic acid)/poly (?-caprolactone) (PLLA:PCL 2;1) blend NFs were prepared using the electrospinning method. Alizarin red activity and cell viability were evaluated by MTT assay, and SEM revealed the proliferation properties of NF scaffolds. QRT-PCR results demonstrated that HA-loaded PLLA/PCL can lead to osteoblast/odontoblast differentiation in DPSCs through the up-regulation of related genes, thus indicating that electrospun biodegradable PCL/PLA/HA has remarkable prospects as scaffolds for bone and tooth tissue engineering.     

Coating of polyelectrolyte multilayer thin films on nanofibrous scaffolds to improve cell adhesion

The adhesion of L929 cells to poly(?‐caprolactone) (PCL) nanofibers was successfully improved via coating with polyelectrolyte multilayer thin films (PEMs), which enhanced the potential of this material as a scaffold in tissue engineering applications. With the electrostatic self‐assembly technique, poly(diallyldimethylammonium chloride) (PDADMAC) and poly(sodium 4‐styrene sulfonate) (PSS) were formed as four‐bilayer PEMs on electrospun PCL nanofiber mats. Because PDADMAC and PSS are strong polyelectrolytes, they provided stable films with good adhesion on the fibers within a wide pH range suitable for the subsequent processes and conditions. PDADMAC and gelatin were also constructed as four‐bilayer PEMs on top of the PDADMAC‐ and PSS‐coated nanofibers with the expectation that the gelatin would improve the cell adhesion. L929 cells from mouse fibroblasts were then seeded on both uncoated and coated scaffolds to study the cytocompatibility and in vitro cell behavior. It was revealed by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay that both the uncoated and coated nanofiber mats were nontoxic as the cell viability was comparable to that of those cultured in the serum‐free medium that was used as a control. The MTT assay also demonstrated that cells proliferated more efficiently on the coated nanofibers than those on the uncoated ones during the 48‐h culture period. As observed by scanning electron microscopy, the cells spread well on the coated nanofibers, especially when gelatin was incorporated. The surface modification of PCL nanofiber mats described in this research is therefore an effective technique for improving cell adhesion. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Embryonic Stem Cell Differentiation to Cardiomyocytes on Nanostructured Scaffolds for Myocardial Tissue Regeneration

With recent advances in developmental and stem cell biology, the application of stem cells in tissue engineering has received great attention and designing of suitable scaffolds to support cell growth, differentiation, and functional tissue organization are advancing toward effective tissue regeneration. Regeneration of the infarct myocardium after myocardial infarction (MI), which is caused by the abrupt occlusion of one or more of the coronary arteries in the heart is one of the most demanding aspects in tissue engineering. Embryonic stem cells (ESCs) can differentiate into many cell types and has been considered as a cell source for cardiac regeneration. In this regard, nanofibrous scaffolds received great attention in tissue engineering field due to their similarity in morphology to native extracellular matrix (ECM) and various scaffolds have been studied as cardiac patches over the previous years. In this study poly (ε-caprolactone) (PCL)/gelatin nanofibrous scaffolds were fabricated by electrospinning and embroyonic bodies (EBs) were formed using ESCs seeded on the nanofibrous scaffolds. SEM images revealed cell outgrowth from EBs and the spreading of cells over the nanofibrous scaffolds were observed. Immunocytochemistry results showed the cellular expression of cardiac proteins, namely α-actinin and connexin 43 on the nanofibrous scaffolds indicating the differentiation of EBs to cardiomyocytes. Results of our study showed that PCL/gelatin nanofibrous scaffolds can act as a promising substrate for differentiation of EBs to cardiomyocytes and could be applied for cardiac tissue engineering.     

Three​-dimensional porous poly(ε-caprolactone)/beta-tricalcium phosphate microsphere-aggregated scaffold for bone tissue engineering

In this study, porous scaffolds made of polycaprolactone (PCL)/β-tricalcium phosphate (BTCP) biocomposite were fabricated for bone tissue engineering (BTE) applications. The microsphere-aggregated scaffolds were prepared with various BTCP concentrations (10wt%, 20wt%, 50wt%) by the freeze-drying method. The porosity of obtained microsphere-aggregated scaffolds with various pore sizes was 80–85%, where this value was about 70% for the PCL/BTCP (50) sample with no microsphere formation. The results indicated that adding BTCP has enhanced mechanical strength, and the mineralization of PCL/BTCP composite scaffolds has been increased compared to the pure PCL scaffolds in simulated body fluid (SBF). The adhesion and proliferation of mouse bone marrow mesenchymal stem cells (mMSCs) seeded onto PCL/BTCP scaffolds were enhanced compared to the PCL. In addition, in terms of differentiation, the incorporation of BTCP led to increasing the mineral deposition and alkaline phosphatase activity of mMSCs. The synergistic effect of using microsphere-aggregated scaffolds along with BTCP as a reinforcing agent in PCL biocomposite showed that these porous biocomposite scaffolds have the potential application in BTE.     

Ternary blend nanofibres of poly(lactic acid), polycaprolactone and cellulose acetate butyrate for skin tissue scaffolds: influence of blend ratio and polycaprolactone molecular mass on miscibility,morphology, crystallinity and thermal properties

Ternary blends of poly(lactic acid) (PLA), polycaprolactone (PCL) and cellulose acetate butyrate (CAB) were fabricated into the form of electrospun nanofibres targeted for skin tissue scaffolds. The effects of blend ratio and molecular mass of PCL (PCL1 and PCL2) on morphology, miscibility, crystallinity, thermal properties, surface hydrophilicity and cell culture of the nanofibres were investigated. Blends with high PLA loading (80/10/10 PLA/PCL/CAB) gave fibres with a smooth surface, owing to the enhanced miscibility between the polymer chains from the presence of CAB, which acts as compatibilizer. In contrast, blends with high PCL loading were immiscible, which led to beads during the electrospinning process. The increased molecular mass of PCL2 produced smoother fibres than low‐molecular‐mass PCL1. The XRD patterns of blends of PLA/PCL1/CAB and PLA/PCL2/CAB were similar to one another, in which the high‐crystallinity peaks of PCL seen for 20/70/10 blends were very small for 50/40/10 blends and much less prevalent for 80/10/10 blends. Better fibre formation (80/10/10 > 50/40/10 > 20/70/10) with less crystallinity occurs in well‐formed fibres. Selected blends of PLA/PCL/CAB promoted growth of NIH/3T3 fibroblast cells, demonstrating that our novel biocompatible ternary blend nanofibrous scaffolds have potential in skin tissue repair applications. In addition, this work helps in the design and understanding of the factors that control the properties of nanofibrous PLA/PCL/CAB scaffolds. © 2017 Society of Chemical Industry     

Assessment of cell proliferation in salt‐leaching using powder (SLUP) scaffolds with penetrated macro‐pores

In this study, a salt‐leaching using powder (SLUP) scaffold with penetrated macropores was proposed to enhance cell proliferation. A SLUP scaffold is a salt‐leaching scaffold with an arbitrary pore configuration. Although SLUP scaffolds have several advantage over traditional salt‐leaching scaffolds, the cell ingrowth might be poor compared with solid freeform fabrication scaffolds, which have well‐interconnected pores. We therefore proposed SLUP scaffolds with penetrated macropores to assist the cell ingrowth. First, polycaprolactone (PCL) powders with a grain size of 63–100 μm and NaCl powders with a grain size of 100–180 μm were prepared. Next, a uniformly perforated mold was fabricated using an rapid prototyping (RP) system. Then, 500‐, 820‐, or 1200‐μm‐diameter needles were inserted into the holes of the RP mold. Subsequently, the mold was filled with a mixed powder of PCL/NaCl (30 : 70 vol %). The mold was then heated in the oven at 100°C for 30 min, and both the needles and the mold were removed from the PCL/NaCl mixture. Then, the PCL/NaCl mixture was soaked in DI water for 24 h to leach out NaCl particles and dried in a vacuum desiccator for 24 h. The porosity of fabricated scaffolds was calculated using a simple equation, and the compressive stiffness was measured using a universal testing machine. Moreover, each scaffold (10 × 10 × 10 mm³) was seeded with 100,000 Saos‐2 cells and cultured for 14 days. The cell proliferation characteristics were assessed using a CCK‐8 assay at 1, 7, and 14 days for comparison with the control scaffolds, that is, the SLUP scaffolds with no penetrated macropores. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40240.     

Synthesis and characterization of conductive neural tissue engineering scaffolds based on urethane-polycaprolactone

Polymeric biomaterials play a key role in enhancement of lengthy nerve regeneration and various types of scaffolds were used to pave the way for nerve regeneration. Electrospun fibrous scaffolds have special potential applicability in controlling the cell behaviors such as adhesion, growth, proliferation and function. This study attempted to design a conductive and porous fibrous scaffold containing polycaprolactone (PCL) and polyaniline (PANI) with controllable degradation rate by adding urethane groups in scaffold structures. FTIR and NMR analysis was used to characterize the chemical bonds. Morphology, porosity, conductivity and degradation rate of scaffolds were also evaluated. To assess the cell–scaffold interaction, PC-12 cell line was cultured on the scaffolds. Results showed that the degradation rate of composite samples significantly increased in 50 time period. It seems that these results suggest that the composite fibrous scaffolds having proportions of UPCL/PCL/PANI45:20:35 exhibit the most balanced properties that meet all of the required specifications for neural cells and possess a potential application in neural tissue engineering.     

Biomimetic Polycaprolactone-Graphene Oxide Composites for 3D Printing Bone Scaffolds

Bone shows a radial gradient architecture with the exterior densified cortical bone and the interior porous cancellous bone. However, previous studies presented uniform designs for bone scaffolds that do not mimic natural bone's gradient structure. Hence, mimicking native bone structures is still challenging in bone tissue engineering. In this study, a novel biomimetic bone scaffold with Haversian channels is designed, which approximates mimicking the native bone structure. Also, the influence of adding graphene oxide (GO) to polycaprolactone (PCL)-based scaffolds are investigated by preparing PCL/GO composite ink containing 0.25% and 0.75% GO and then 3D printing scaffolds by an extrusion-based machine. Scanning electron microscopy (SEM) is used for morphological analysis. SEM reveals good printability and interconnected pore structure. The contact angle test shows that wettability reinforces with the increase of GO content. The mechanical behavior of the scaffolds under compression is examined numerically and experimentally. The results indicate that incorporation of GO can affect bone scaffolds' Young's modulus and von Mises stress distribution. Moreover, the biodegradation rates accelerate in the PCL/GO scaffolds. Biological characterizations, such as cell growth, viability, and attachment, are performed utilizing osteoblast cells. Compared to pure PCL, an enhancement is observed in cell viability in the PCL/GO scaffolds.     

One‐Pot Fabrication of Poly(ε‐Caprolactone)‐Incorporated Bovine Serum Albumin/Calcium Alginate/Hydroxyapatite Nanocomposite Scaffolds by High Internal Phase Emulsion Templates

In this work, the authors report an effective one‐pot method to prepare poly(ε‐caprolactone) (PCL)‐incorporated bovine serum albumin (BSA)/calcium alginate/hydroxyapatite (HAp) nanocomposite (NC) scaffolds by templating oil‐in‐water high internal phase emulsion (HIPE), which includes alginate, BSA, and HAp in water phase and PCL in oil phase. The water phase of HIPEs is solidified to form hydrogels containing emulsion droplets via gelation of alginate induced by Ca²⁺ ions released from HAp. And the prepared hydrogels are freeze‐dried to obtain PCL‐incorporated porous scaffolds. The obtained scaffolds possess interconnected pore structures. Increasing PCL concentration clearly enhances the compressive property and BSA stability, decreases the swelling ratio of scaffolds, which assists in improving the scaffold stability. The anti‐inflammatory drug ibuprofen can be highly efficiently loaded into scaffolds and released in a sustained rate. Furthermore, mouse bone mesenchymal stem cells can successfully proliferate on the scaffolds, proving the biocompatibility of scaffolds. All results show that the PCL‐incorporated NC scaffolds possess promising potentials in tissue engineering application.

     

Surface‐engineered hydroxyapatite nanocrystal/ poly(ε‐caprolactone) hybrid scaffolds for bone tissue engineering

To achieve novel polymer/bioceramic composite scaffolds for use in materials for bone tissue engineering, we prepared organic/inorganic hybrid scaffolds composed of biodegradable poly(ε‐caprolactone) (PCL) and hydroxyapatite (HA), which has excellent biocompatibility with hard tissues and high osteoconductivity and bioactivity. To improve the interactions between the scaffolds and osteoblasts, we focused on surface‐engineered, porous HA/PCL scaffolds that had HA molecules on their surfaces and within them because of the biochemical affinity between the biotin and avidin molecules. The surface modification of HA nanocrystals was performed with two different methods. Using Fourier transform infrared, X‐ray diffraction, and thermogravimetric analysis measurements, we found that surface‐modified HA nanocrystals prepared with an ethylene glycol mediated coupling method showed a higher degree of coupling (%) than those prepared via a direct coupling method. HA/PCL hybrid scaffolds with a well‐controlled porous architecture were fabricated with a gas‐blowing/particle‐leaching process. All HA/PCL scaffold samples exhibited approximately 80–85% porosity. As the HA concentration within the HA/PCL scaffolds increased, the porosity of the HA/PCL scaffolds gradually decreased. The homogeneous immobilization of biotin‐conjugated HA nanocrystals on a three‐dimensional, porous scaffold was observed with confocal microscopy. According to an in vitro cytotoxicity study, all scaffold samples exhibited greater than 80% cell viability, regardless of the HA/PCL composition or preparation method. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Pore Size Distribution and Blend Composition Affect In Vitro Prevascularized Bone Matrix Formation on Poly(Vinyl Alcohol)/Gelatin Sponges

This study aims at identifying compositional and architectural (pore size and distribution) parameters of biocompatible scaffolds, which can be best suitable for both osteoblasts and endothelial cells to produce optimized 3D cocultured constructs. Spongy scaffolds are prepared using poly(vinyl alcohol) (PVA) and gelatin (G) at different weight compositions (PVA/G range: 100/0–50/50, w/w) via emulsion and freeze‐drying. The higher the gelatin content, the larger is the volume occupied by higher size pores. Human umbilical vein endothelial cells and human mesenchymal stromal cells are independently differentiated on the scaffolds to select the best candidate for the coculture. The results of metabolic activity and histology on single platforms show both cell‐ and material‐type dependent outcomes. PVA/G 80/20 scaffolds are finally selected and allow the formation of mineralized matrix containing organized endothelial‐like structures. This study highlights the need for systematic investigations on multifactorial parameters of scaffolds to improve vascularized bone substitutes.     

Evaluation of the chondrogenic differentiation of mesenchymal stem cells on hybrid biomimetic scaffolds

Hybrid materials are widely and promisingly used as scaffolds in cartilage tissue remodeling. In this study, hybrid scaffolds consist of polycaprolactone (PCL), poly(vinyl alcohol) (PVA) with/without gelatin (GEL) to mimic natural cartilage extracellular matrix (ECM) were investigated. Scaffolds were prepared by freeze drying and characterized by scanning electron microscopy and compressive mechanical testing. Biological assays of mesenchymal stem cell (MSC) cultures, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, and dimethyl methylene blue were performed, and real‐time polymerization chain reaction analysis of the cartilage‐specific ECM gene marker expression was done. The results show an open interconnected porous structure with a compression modulus of 1.27 ± 0.04 MPa. The surface of the scaffolds showed an excellent efficiency in the adhesion and proliferation of MSCs. A significant increase in the proteoglycan content from 3.70 ± 0.96 to 5.4 ± 1.13 μg/mL was observed after 14 days in the PCL–PVA–GEL scaffolds. The expression amount of the sex‐determining region Y–Box 9 (SOX9) and collagen II (COL2) mRNA levels of the MSCs showed significant increases in SOX9 and COL2, respectively in comparison with PCL–PVA scaffold. The study revealed that the aforementioned scaffold as a blend of natural and synthetic polymers may be a promising substrate in tissue engineering for cartilage repair with MSC transplantation. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40635.