LOCAL-IGF-1 and GH application IMPROVES germ cell histology, spermatogenesis and fertility after experimental testicular torsion and detorsion.

OBJECTIVE: To evaluate the impact of insulin like growth factor-1(IGF-1) and growth hormone (GH) on testis histology, spermatogenesis, and fertility in prepubertal rats exposed to 6 h of testicular torsion (TT) and detorsion. MATERIAL-METHOD: Forty-eight male Wistar-albino rats weighing 30-70g and at 3-week age were allocated into six groups involving eight rats in each group as follows: Group 1:Sham, Group 2:Control, Group 3:Gelatin, Group 4:Local-IGF-1, 5: Local-GH, Group 6: Systemic-GH. Right testis was only exposed and sutured in the sham group, and right testes were rotated clockwise, 720°, fixed, and 6 h later, detorsion on the testis was done in groups 2-6. Unloaded gelatin, 5 µg local-IGF-1 loaded, and 2IU rhGH loaded gelatin were sutured to the right testis after detorsion in groups 3-5. In Group 6, 0.3IU/100gr/d rhGH was given for seven days via subcuticular route after detorsion. Each of the rats cohabited with two female rats five weeks later. Afterward, both right and left testes were removed. Mean diameter of seminiferous tubules (STD), mean biopsy score count of the testis (TBSC), mean percentage of haploid cells (HCP) were assessed, and fertility parameters were evaluated. RESULTS: STD and TBSC of the ipsilateral testes were significantly reduced in control and gelatin groups when compared to sham, local-IGF-1, and local-GH groups. STD and TBSC of the ipsilateral testes of the systemic-GH group were decreased compared to the sham group. HCP of the ipsilateral testes of control, gelatin, and systemic-GH groups were significantly lower than the sham, local-IGF-1, and local-GH groups. STD, TBSC, and HCP of the contralateral testes were significantly reduced in control and gelatin groups when compared separately to sham, local-IGF-1, systemic- GH, and local-GH groups. The difference between groups regarding potency, fertility, fecundity indexes, and mean fetus numbers were not significant. CONCLUSION: Even though there was significant and permanent histologic germ cell damage and reduced HCP in both ipsilateral and contralateral testes, experimental 6 h TT and detorsion in prepubertal rats did not have a negative impact on future fertility. Local-IGF-1and rhGH treatment improved germ cell histology and spermatogenesis in both ipsilateral and contralateral testes of prepubertal rats, subjected to 6 h of TT and detorsion.

Potential of pectin for biomedical applications: a comprehensive review.

Pectin is a polysaccharide extracted from various plants, such as apples, oranges, lemons, and it possesses some beneficial effects on human health, including being hypoglycemic and hypocholesterolemic. Therefore, pectin is used in various pharmaceutical and biomedical applications. Meanwhile, its low mechanical strength and fast degradation rate limit its usage as drug delivery devices and tissue engineering scaffolds. To enhance these properties, it can be modified or combined with other organic molecules or polymers and/or inorganic compounds. These materials can be prepared as nano sized drug carriers in the form of spheres, capsules, hydrogels, self assamled micelles, etc., for treatment purposes (mostly cancer). Different composites or blends of pectin can also be produced as membranes, sponges, hydrogels, or 3D printed matrices for tissue regeneration applications. This review is concentrated on the properties of pectin based materials and focus especially on the utilization of these materials as drug carriers and tissue engineering scaffolds, including 3D printed and 3D bioprinted systems covering the studies in the last decade and especially in the last 5 years.

Lithocholic acid conjugated mPEG-b-PCL micelles for pH responsive delivery to breast cancer cells.

In this study, micelles composed of methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) copolymer (mPEG-b-PCL), which has ionically conjugated lithocholic acid (LCA) and providing pH sensitive release of LCA in acidic media, were prepared as drug carrier devices for cancer therapy. Micelles were produced by co-solvent evaporation method at two different temperatures (60 °C and 25 °C) and coded as LCA60**M and LCA25**M, respectively). Hydrodynamic diameters were 86.9 nm and 228.2 nm, and zeta potentials were -7.54 mV and -18.83 mV for LCA60**M and LCA25**M, respectively. For all micelles, release of LCA was higher in acidic media (pH 5.0) compared to physiological media (pH 7.4). Micelles loaded with a fluorescent dye, coumarin 6, demonstrated effective internalization into triple negative MDA-MB-231 breast cancer cells in 4 h. LCA60**M (41.7 ± 1.5%) and LCA25**M (44.5 ± 2.2%) had higher inhibitory effect on the cell migration compared to free LCA (64.7 ± 1.3%). Both LCA conjugated micelles decreased lipogenic activity and increased expressions of Bax (1.3 fold) and p53 (1.2 fold) apoptotic genes. Annexin V-FITC results exhibited high apoptotic cell number after the treatment of MDA-MB-231 cells with micelles. Free LCA and LCA conjugated LCA60**M and LCA25**M micelles decreased mitochondrial transmembrane potential of the cells by 41.8 ± 3.0%, 30.4 ± 0.9%, and 57.1 ± 0.5, respectively. Micelles also caused an effective decrease in angiogenesis ability of HUVECs. The novelty of this study is the prepared micelles, which have ionic conjugation of LCA to mPEG-b-PCL, and pH responsive release of LCA demonstrating effective apoptosis on breast cancer cells. These micelles may have great potential for cancer treatment. However, further in vivo studies are needed before clinical translation.

Corrosion Resistance and Cytocompatibility of Magnesium-Calcium Alloys Modified with Zinc- or Gallium-Doped Calcium Phosphate Coatings.

In orthopedic surgery, metals are preferred to support or treat damaged bones due to their high mechanical strength. However, the necessity for a second surgery for implant removal after healing creates problems. Therefore, biodegradable metals, especially magnesium (Mg), gained importance, although their extreme susceptibility to galvanic corrosion limits their applications. The focus of this study was to control the corrosion of Mg and enhance its biocompatibility. For this purpose, surfaces of magnesium-calcium (MgCa1) alloys were modified with calcium phosphate (CaP) or CaP doped with zinc (Zn) or gallium (Ga) via microarc oxidation. The effects of surface modifications on physical, chemical, and mechanical properties and corrosion resistance of the alloys were studied using surface profilometry, goniometry, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), nanoindentation, and electrochemical impedance spectroscopy (EIS). The coating thickness was about 5-8 µm, with grain sizes of 43.1 nm for CaP coating and 28.2 and 58.1 nm for Zn- and Ga-doped coatings, respectively. According to EIS measurements, the capacitive response (Yc) decreased from 11.29 to 8.72 and 0.15 Ω-1 cm-2 sn upon doping with Zn and Ga, respectively. The Ecorr value, which was -1933 mV for CaP-coated samples, was found significantly electropositive at -275 mV for Ga-doped ones. All samples were cytocompatible according to indirect tests. In vitro culture with Saos-2 cells led to changes in the surface compositions of the alloys. The numbers of cells attached to the Zn-doped (2.6 × 104 cells/cm2) and Ga-doped (6.3 × 104 cells/cm2) coatings were higher than that on the surface of the undoped coating (1.0 × 103 cells/cm2). Decreased corrosivity and enhanced cell affinity of the modified MgCa alloys (CaP coated and Zn and Ga doped, with Ga-doped ones having the greatest positive effect) make them novel and promising candidates as biodegradable metallic implant materials for the treatment of bone damages and other orthopedic applications.

A two-compartment bone tumor model to investigate interactions between healthy and tumor cells.

We produced a novel three-dimensional (3D) bone tumor model (BTM) to study the interactions between healthy and tumor cells in a tumor microenvironment, the migration tendency of the tumor cells, and the efficacy of an anticancer drug, Doxorubicin, on the cancer cells. The model consisted of two compartments: (a) a healthy bone tissue mimic, made of poly(lactic acid-co-glycolic acid) (PLGA)/beta-tricalcium phosphate (ß-TCP) sponge seeded with human fetal osteoblastic cells (hFOB) and human umbilical vein endothelial cells (HUVECs), and (b) a tumor mimic, made of lyophilized collagen sponge seeded with human osteosarcoma cells (Saos-2). The tumor mimic component was placed into a central cavity created in the healthy bone mimic and together they constituted the complete 3D bone tumor model (3D-BTM). The porosities of both sponges were higher than 85% and the diameters of the pores were 199 ± 52 µm for the PLGA/TCP and 50-150 µm for the collagen scaffolds. The compression Young's modulus of the PLGA/TCP and the collagen sponges were determined to be 4.76 MPa and 140 kPa, respectively. Cell proliferation, morphology, calcium phosphate forming capacity and alkaline phosphatase production were studied separately on both the healthy and tumor mimics. All cells demonstrated cellular extensions and spread well in porous scaffolds indicating good cell-material interactions. Confocal microscopy analysis showed direct contact between the cells present in different parts of the 3D-BTM. Migration of HUVECs from the healthy bone mimic to the tumor compartment was confirmed by the increase in the levels of angiogenic factors vascular endothelial growth factor, basic fibroblast growth factor, and interleukin 8 in the tumor component. Doxorubicin (2.7 µg.ml-1) administered to the 3D-BTM caused a seven-fold decrease in the cell number after 24 h of interaction with the anticancer drug. Caspase-3 enzyme activity assay results demonstrated apoptosis of the osteosarcoma cells. This novel 3D-BTM has a high potential for use in studying the metastatic capabilities of cancer cells, and in determining the effective drug types and combinations for personalized treatments.

Biomechanical analysis of a modified suture technique for septal extension grafts: Transloop suture.

BACKGROUND: A successful rhinoplasty procedure requires a well-defined and properly projected nasal tip; however, surgical control of the nasal tip is difficult. The aim of this investigation was to assess the efficacy and safety of a modified suture technique, which can be used to fix the caudal septal extension graft during primary rhinoplasty of the Asian population and revision septorhinoplasties of the Caucasian population, and to compare it with those of other commonly used techniques. METHODS: After peeling of perichondrium of scapular cartilages, cartilage pieces of 3 × 1 cm in size and 2 mm in thickness were divided into two from the midline. These pieces were repaired end-to-end using three different repair techniques: two simple interrupted in Group A (n = 40), vertical figure-of-eight in Group B (n = 40) and modified vertical figure-of-eight (transloop) in Group C (n = 40). All repaired cartilage specimens were subjected to a biomechanical analysis, in which four different forces were applied: tension, lateral bending, shearing and buckling. RESULTS: According to the tensile test, Group C had statistically significantly higher strength than Group A at 2 mm range. The lateral bending test similarly revealed that Group C had statistically significantly higher strength at 1.5 mm and 2 mm range than Group A. However, there was no statistically significant difference between the three groups in the assessment of shearing and buckling forces. CONCLUSION: The modified transloop suture technique provides a more stable repair, and we consider that it can be used as an alternative suture repair method.

Square prism micropillars on poly(methyl methacrylate) surfaces modulate the morphology and differentiation of human dental pulp mesenchymal stem cells.

Use of soluble factors is the most common strategy to induce osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro, but it may raise potential side effects in vivo. The topographies of the substrate surfaces affect cell behavior, and this could be a promising approach to guide stem cell differentiation. Micropillars have been reported to modulate cellular and subcellular shape, and it is particularly interesting to investigate whether these changes in cell morphology can modulate gene expression and lineage commitment without chemical induction. In this study, poly(methyl methacrylate) (PMMA) films were decorated with square prism micropillars with different lateral dimensions (4, 8 and 16 µm), and the surface wettability of the substrates was altered by oxygen plasma treatment. Both, pattern dimensions and hydrophilicity, were found to affect the attachment, proliferation, and most importantly, gene expression of human dental pulp mesenchymal stem cells (DPSCs). Decreasing the pillar width and interpillar spacing of the square prism pillars enhanced cell attachment, cell elongation, and deformation of nuclei, but reduced early proliferation rate. Surfaces with 4 or 8 µm wide pillars/gaps upregulated the expression of early bone-marker genes and mineralization over 28 days of culture. Exposure to oxygen plasma increased wettability and promoted cell attachment and proliferation but delayed osteogenesis. Our findings showed that surface topography and chemistry are very useful tools in controlling cell behavior on substrates and they can also help create better implants. The most important finding is that hydrophobic micropillars on polymeric substrate surfaces can be exploited in inducing osteogenic differentiation of MSCs without any differentiation supplements.

An estradiol releasing, proangiogenic hydrogel as a candidate material for use in soft tissue interposition.

INTRODUCTION AND OBJECTIVES: Soft tissue interposition (STI) using local and/or regional flaps is often necessary in urogenital reconstruction to stimulate wound healing and prevent recurrence. Harvesting STI flaps can cause donor site morbidity and may not be available in some patients. In this study, we designed estradiol (E2) releasing hydrogel that could be used as an alternative to a STI flap and to investigate its ability to stimulate tissue production and angiogenesis. MATERIALS AND METHODS: A hydrogel was constructed by crosslinking a solution of estradiol, methacrylated gelatin (15%, w/v), and methacrylated hyaluronic acid (1%, w/v). The release of estradiol was measured using a UV-spectrophotometer (λmax = 220 nm). Angiogenesis was evaluated by an ex ovo chicken embryo chorioallantoic membrane (CAM) assay. RESULTS: Estradiol was gradually released from the hydrogel over 21 days. The hydrogels could be easily manipulated with surgical forceps without any deformation. The hydrogels significantly increased collagen production of human dermal fibroblasts (HDFs). Scanning electron microscopic examination demonstrated that HDFs produced significantly more extracellular matrix (ECM) on estradiol releasing hydrogels compared with the controls. Estradiol releasing hydrogels doubled the number of blood vessels growing toward the hydrogel compared with the controls (vasculogenic index, 59.6 [±6.4] and 25.6 [±4.0], respectively; [P < 0.05]). CONCLUSION: We present a proangiogenic, degradable hydrogel that can be used as an off-the-shelf available substitute to traditional STI flaps. This is achieved by using estradiol as a potent stimulator of new tissue production and new blood vessel formation.

A bilayer scaffold prepared from collagen and carboxymethyl cellulose for skin tissue engineering applications.

Treatment of chronic skin wound such as diabetic ulcers, burns, pressure wounds are challenging problems in the medical area. The aim of this study was to design a bilayer skin equivalent mimicking the natural one to be used as a tissue engineered skin graft for use in the treatments of problematic wounds, and also as a model to be used in research related to skin, such as determination of the efficacy of transdermal bioactive agents on skin cells and treatment of acute skin damages that require immediate response. In this study, the top two layers of the skin were mimicked by producing a multilayer construct combining two different porous polymeric scaffolds: as the dermis layer a sodium carboxymethyl cellulose (NaCMC) hydrogel on which fibroblasts were added, and as the epidermis layer collagen (Coll) or chondroitin sulfate-incorporated collagen (CollCS) on which keratinocytes were added. The bilayer construct was designed to allow cross-talk between the two cell populations in the subsequent layers and achieves paracrine signalling. It had interconnected porosity, high water content, appropriate stability and elastic moduli. Expression of vascular endothelial growth factor (VEGF), basic-fibroblast growth factor (bFGF) and Interleukin 8 (IL-8), and the production of collagen I, collagen III, laminin and transglutaminase supported the attachment and proliferation of cells on both layers of the construct. Attachment and proliferation of fibroblasts on NaCMC were lower compared to performance of keratinocyte on collagen where keratinocytes created a dense and a stratified layer similar to epidermis. The resulting constructs succesfully mimicked in vitro the natural skin tissue. They are promising as grafts for use in the treatment of deep wounds and also as models for the study of the efficacy of bioactive agents on the skin.

Nuclear targeting peptide-modified, DOX-loaded, PHBV nanoparticles enhance drug efficacy by targeting to Saos-2 cell nuclear membranes.

The aim of this study was to target nano sized (266 ± 25 nm diameter) poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) particles carrying Doxorubicin (DOX), an anticancer agent, to human osteosarcoma cells (Saos-2). A nuclear targeting molecule (Nuclear Localization Signal, NLS), a 17 a.a. peptide, was attached onto the doxorubicin loaded nanoparticles. NLS conjugated nanoparticles surrounded the cell nuclei, but did not penetrate them. Free doxorubicin and doxorubicin loaded nanoparticles entered the cytoplasm and were evenly distributed within the cytoplasm. The localization of the NLS-targeted particles around the nuclear membrane caused a significantly higher decrease in the cancer cell numbers due to apoptosis or necrosis than the untargeted and free doxorubicin formulations showing the importance of targeting the nanoparticles to the nuclear membrane in the treatment of cancer.

PCL-TCP wet spun scaffolds carrying antibiotic-loaded microspheres for bone tissue engineering.

Scaffolds produced for tissue engineering applications are proven to be promising alternatives to be used in healing and regeneration of injured tissues and organs. In this study, porous and fibrous poly(ε-caprolactone) (PCL) scaffolds were prepared by wet spinning technique and modified by addition of tricalcium phosphate (TCP) and by immobilizing gelatin onto fibers. Meanwhile, gelatin microspheres carrying Ceftriaxone sodium (CS), a model antibiotic, were added onto the scaffolds and antimicrobial activity of CS was investigated against Escherichia coli (E. coli), a model gram-negative bacterium. TCP and gelatin were added to enhance mechanical properties while directing the scaffold towards osteogenic infrastructure and to increase hydrophilicity by activating cell attachment via protein molecules, respectively. Modifications with TCP and gelatin enhanced the compression modulus by about 70%, and attachment of Saos-2 cells by 60%, respectively. Release of the antibiotic demonstrated effective antimicrobial activity against E. coli. The bioactive scaffolds were shown to be good candidates for bone tissue engineering applications.

3D printed poly(ε-caprolactone) scaffolds modified with hydroxyapatite and poly(propylene fumarate) and their effects on the healing of rabbit femur defects.

A large variety of approaches have been used to treat large and irregular shaped bone defects with less than optimal success due to material or design issues. In recent years patient specific constructs prepared by additive manufacturing provided a solution to the need for shaping implants to fit irregular defects in the surgery theater. In this study, cylindrical disks of poly(ε-caprolactone) (PCL) were printed by fused deposition modeling and modified with nanohydroxyapatite (HAp) and poly(propylene fumarate) (PPF) to create a mechanically strong implant with well-defined pore size and porosity, controllable surface hydrophilicity (with PPF) and osteoconductivity (with HAp). Cytotoxicity, irritation and inflammation tests demonstrated that the scaffolds were biocompatible. PCL/HAp and PCL/HAp/PPF scaffolds were implanted in the femurs of rabbits with and without seeding with rabbit Bone Marrow Stem Cells (BMSC) and examined after 4 and 8 weeks with micro-CT, mechanically and histologically. BMSC seeded PCL/HAp/PPF scaffolds showed improved tissue regeneration as determined by bone mineral density and micro-CT. Compressive and tension stiffness values (394 and 463 N mm-1) were significantly higher than those of the healthy rabbit femur (316 and 392 N mm-1, respectively) after 8 weeks of implantation. These 3D implants have great potential for patient-specific bone defect treatments.

Quantification of Type, Timing, and Extent of Cell Body and Nucleus Deformations Caused by the Dimensions and Hydrophilicity of Square Prism Micropillars.

Novel digital analysis strategies are developed for the quantification of changes in the cytoskeletal and nuclear morphologies of mesenchymal stem cells cultured on micropillars. Severe deformations of nucleus and distinct conformational changes of cell body ranging from extensive elongation to branching are visualized and quantified. These deformations are caused mainly by the dimensions and hydrophilicity of the micropillars.

The Effects of Local and Systemic Growth Hormone Treatment on Germ Cell Population and Fertility in an Experimental Unilateral Testicular Torsion and Orchiectomy Model.

PURPOSE: We evaluated the effects of local and systemic growth hormone on the germ cell population of the contralateral testes of pubertal rats subjected to unilateral testicular torsion and orchiectomy 24 hours later. MATERIALS AND METHODS: A total of 40 male Wistar-Albino rats at age 3 weeks were divided into 5 groups. In the sham operated group the right testis was sutured and orchiectomy was performed 24 hours later. In groups 2 to 5 orchiectomy was performed 24 hours later following testicular torsion. In groups 3 and 4 unloaded and growth hormone loaded gelatin films, respectively, were sutured on the contralateral testes. In group 5 systemic growth hormone was administered for 7 days. Five weeks later each rat was cohabited with 2 female rats and the left testes were removed for evaluation. Mean seminiferous tubular diameter, mean testicular biopsy score and the mean haploid cell percentage were calculated. Mating studies were performed and fertility parameters were assayed. RESULTS: Mean seminiferous tubular diameter, mean testicular biopsy score and the mean haploid cell percentage of the contralateral testes were significantly decreased in the control and gelatin groups compared with the other groups. There was no difference between the local and systemic growth hormone groups regarding the haploid cell percentage. There were no differences between the groups in mean fetus numbers, mating or fertility and fecundity indexes except in the gelatin group, in which the mean fetus number was significantly lower. CONCLUSIONS: Fertility is not affected in rats after 24 hours of testicular torsion and orchiectomy, although there is germ cell injury and a decrease in the percent of haploid cells. Growth hormone administration resulted in the restoration of germ cell histology and an increase in the haploid cell percentage of the contralateral testes. Growth hormone may improve fertility after unilateral testicular torsion and orchiectomy.

pH-responsive nano carriers for doxorubicin delivery.

PURPOSE: The aim of this study was to design stimuli-responsive nanocarriers for anti-cancer drug delivery. For this purpose, doxorubicin (DOX)-loaded, polysebacic anhydride (PSA) based nanocapsules (NC) were combined with pH-sensitive poly (L-histidine) (PLH). METHOD: PSA nano-carriers were first loaded with DOX and were coated with poly L-histidine to introduce pH sensitivity. The PLH-coated NCs were then covered with polyethylene glycol (PEG) to reduce macrophage uptake. The drug release profile from this system was examined in two different buffer solutions prepared as acidic (pH5) and physiological (pH 7.4) media. The physical and chemical properties of the nanocapsules were characterized by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), ultraviolet and visible absorption spectroscopy (UV-VIS), and scanning electron microscopy (SEM). In vitro studies of the prepared nanocapsules were conducted in MDA-MB-231 breast cancer cells. RESULTS: The results obtained by SEM and DLS revealed that nanocapsules have spherical morphology with an average size of 230 nm. Prepared pH sensitive nanocapsules exhibited pH-dependent drug release profile and promising intracellular release of drug. PEGylation of nanoparticles significantly prevented macrophage uptake compared to non-PEGylated particles.

Poly(sebacic anhydride) nanocapsules as carriers: effects of preparation parameters on properties and release of doxorubicin.

Poly(sebacic anhydride) (PSA) is a promising polymer for the production of drug delivery vehicles. The aim of this work is to study the effect of preparation parameters on the quality of the nanoparticles. In this study, doxorubicin (DOX)-loaded PSA nanocapsules were prepared by an emulsion method. Effects of factors such as type of organic solvent, co-solute (surfactant) and its concentration on drug-loading efficiency, particle size and size distribution, morphology and release profile were examined to gain insight in the preparation and stability of nanostructures. Particles with sizes in the range of 218-1198 nm were prepared. The smallest particles with a narrow size distribution were prepared by using polyvinyl alcohol as a co-solute and dichloromethane as a solvent. Efficiency and intracellular release of doxorubicin from the formulated particles were studied on MDA-MB-231 cells. It was observed that DOX-loaded PSA particles can diffuse into the cells and intracellular antitumour activity is directly related to the released amount of drug from the PSA nanocapsules.

Poly(ester-urethane) scaffolds: effect of structure on properties and osteogenic activity of stem cells.

The present study aimed to investigate the effect of structure (design and porosity) on the matrix stiffness and osteogenic activity of stem cells cultured on poly(ester-urethane) (PEU) scaffolds. Different three-dimensional (3D) forms of scaffold were prepared from lysine-based PEU using traditional salt-leaching and advanced bioplotting techniques. The resulting scaffolds were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), mercury porosimetry and mechanical testing. The scaffolds had various pore sizes with different designs, and all were thermally stable up to 300 °C. In vitro tests, carried out using rat bone marrow stem cells (BMSCs) for bone tissue engineering, demonstrated better viability and higher cell proliferation on bioplotted scaffolds compared to salt-leached ones, most probably due to their larger and interconnected pores and stiffer nature, as shown by higher compressive moduli, which were measured by compression testing. Similarly, SEM, von Kossa staining and EDX analyses indicated higher amounts of calcium deposition on bioplotted scaffolds during cell culture. It was concluded that the design with larger interconnected porosity and stiffness has an effect on the osteogenic activity of the stem cells.

Synthesis and surface modification of polyurethanes with chitosan for antibacterial properties.

Surface modification and providing antibacterial properties to the materials or devices are getting great attention especially in the last decades. In this study, polyurethane (PU) films were prepared by synthesizing them in medical purity from toluene diisocyanate and polypropylene ethylene glycol without using any other ingredients and then the film surfaces were modified by covalent immobilization of chitosan (CH) which has antibacterial activity. CH immobilized PU films (PU-CH) were found to be more hydrophilic than control PU films. Electron Spectroscopy for Chemical Analysis (ESCA) and Atomic Force Microscopy (AFM) analyses showed higher nitrogen contents and rougher surface topography for PU-CH compared to PU films. Modification with CH significantly increased antibacterial activity against Gram positive (Staphylococcus aureus) and Gram negative (Pseudomonas aeruginosa) bacteria. It was observed that the number of bacteria colonies were less about 10(2)-10(5) CFU/mL and number of attached viable bacteria decreased significantly after CH modification of PU films.

A biomimetic growth factor delivery strategy for enhanced regeneration of iliac crest defects.

The importance of provision of growth factors in the engineering of tissues has long been shown to control the behavior of the cells within the construct and several approaches were applied toward this end. In nature, more than one type of growth factor is known to be effective during the healing of tissue defects and their peak concentrations are not always simultaneous. One of the most recent strategies includes the delivery of a combination of growth factors with the dose and timing to mimic the natural regeneration cascade. The sequential delivery of bone morphogenetic proteins BMP-2 and BMP-7 which are early and late appearing factors during bone regeneration, respectively, was shown in vitro to enhance osteoblastic differentiation of bone marrow derived mesenchymal stem cells. In the present study, the aim was to study the effectiveness of this delivery strategy in a rabbit iliac crest model. 3D plotted poly(ε-caprolactone) scaffolds were loaded with BMP carrying nanoparticles to achieve: (a) single BMP-2 or BMP-7 delivery, and (b) their combined delivery in a simultaneous or (c) sequential (biomimetic) fashion. After eight weeks of implantation, computed tomography and biomechanical tests showed better mineralized matrix formation and bone-implant union strength at the defect site in the case of sequential delivery compared to single or simultaneous delivery modes. Bone mineral density (BMD) and push-out stress were: 33.65±2.25 g cm(-3) and 14.5±2.28 MPa, respectively, and almost 2.5 fold higher in comparison to those without growth factors (BMD: 14.14±1.21 g cm(-3); PS: 6.59±0.65 MPa). This study, therefore, supports those obtained in vitro and emphasizes the importance of mimicking the natural timing of bioavailability of osteogenic factors in improving the regeneration of critical-sized bone defects.

Semi-IPN chitosan/polyvinylpyrrolidone microspheres and films: sustained release and property optimisation.

A set of chitosan-polyvinylpyrrolidone (CH-PVP) microspheres were prepared as semi-inter penetrating networks (semi-IPN) and loaded with 5-fluorouracil. In vitro release studies showed faster release for semi-IPN microspheres compared to pure CH samples, and the total release was achieved in about 20-30 days, depending on the composition. In vitro cell studies were achieved against human breast adenocarcinoma cell line cells where adsorption of cells on microspheres with a significant decrease in their number was obtained. Meanwhile, the CH-PVP films, which were prepared with the same compositions as in the microspheres, demonstrated an increase in strength from 66 to 118 MPa as the PVP content was decreased. It can be concluded that the prepared CH-PVP semi-IPN microspheres are novel promising carriers compared to pure CH microspheres since it becomes possible to adjust stability and hydrophilicity of the microspheres as well as the release rates of the drugs from the microspheres by changing the ratio of CH/PVP composition.