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Objective: To determine the effect of common beverages and accelerated aging on the colour stability of filled resins, which could potentially be used for fabrication of 3D‐printed orthodontic brackets. Materials and Methods: GR‐17.1 (shades A1, A2, and A3), and GR‐10 Guide resins (pro3dure medical, Eden Prairie, MN) were printed on an Asiga MAX UV printer into discs 2 mm thick, with a diameter of 10 mm, and then post‐print processed as per manufacturer's instructions. Discs were immersed in 5 mL of coffee, tea, red wine, or distilled water for 7 days. Another group was subjected to accelerated aging in accordance with ISO Standard 4892‐2. Ten samples were produced per resin, per treatment condition. Colour measurements were taken on the discs before and after treatment using a spectrophotometer against white and black reference tiles to assess colour and translucency differences with the CIEDE2000 colour difference formula. Results: While initial colour of the printed resin discs was acceptable, all resin groups underwent significant colour change during the experiment. Red wine and coffee produced the greatest colour and translucency change, followed by tea, with accelerated aging producing the least change in colour and translucency. Conclusion: The 3D‐printed resins tested underwent significant changes in colour and translucency following exposure to endogenous and exogenous sources of staining, which may affect their acceptability for fabrication of aesthetic orthodontic brackets. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of printing material and air abrasion of bracket pads on the shear bond strength of 3D‐printed plastic orthodontic brackets when bonded to the enamel of extracted human teeth. Materials and Methods: Premolar brackets were 3D‐printed using the design of a commercially available plastic bracket in two biocompatible resins: Dental LT Resin and Dental SG Resin (n = 40/material). 3D‐printed brackets and commercially manufactured plastic brackets were divided into two groups (n = 20/group), one of which was air abraded. All brackets were bonded to extracted human premolars, and shear bond strength tests were performed. The failure types of each sample were classified using a 5‐category modified adhesive remnant index (ARI) scoring system. Results: Bracket material and bracket pad surface treatment presented statistically significant effects for shear bond strengths, and a significant interaction effect between bracket material and bracket pad surface treatment was observed. The non‐air abraded (NAA) SG group (8.87 ± 0.64 MPa) had a statistically significantly lower shear bond strength than the air abraded (AA) SG group (12.09 ± 1.23 MPa). In the manufactured brackets and LT Resin groups, the NAA and AA groups were not statistically significantly different within each resin. A significant effect of bracket material and bracket pad surface treatment on ARI score was observed, but no significant interaction effect between bracket material and pad treatment was found. Conclusion: 3D‐printed orthodontic brackets presented clinically sufficient shear bond strengths both with and without AA prior to bonding. The effect of bracket pad AA on shear bond strength depends on the bracket material. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the wear resistance of a recently developed three‐dimensional (3D) printed denture teeth resin compared to three commercially available prefabricated denture teeth. Materials and Methods: A total of 88 maxillary first molar denture teeth were evaluated: C (Classic; Dentsply Sirona, York, PA), DCL (SR Postaris DCL; Ivoclar Vivadent, Schaan, Liechtenstein), IPN (Portrait IPN; Dentsply Sirona, York, PA), and F (Denture Teeth A2 Resin 1 L; Formlabs, Somerville, MA). The 3D printed denture tooth specimens were fabricated from a methacrylate‐based photopolymerizing resin using stereolithography (SLA). Denture teeth were subjected to a three‐body wear test with a poly(methylmethacrylate) (PMMA) abrasive slurry. A Leinfelder‐style four station wear apparatus with custom bullet‐shaped milled zirconia styli was utilized with a load force of 36–40 N at 1.7 Hz for 200,000 cycles. Maximum depth of wear was measured using a lab grade scanner and analyzing software program. Data were analyzed using a one‐way ANOVA followed by the Tukey's Multiple Comparisons post hoc test (α = 0.05). Results: A statistically significant difference in depth of wear was found between denture tooth materials (p < 0.001). The mean vertical depth of wear for the 3D printed denture teeth (0.016 ± 0.010 mm) was statistically significantly less than the prefabricated denture teeth. The highly cross‐linked denture teeth, DCL (0.036 ± 0.011 mm) and IPN (0.035 ± 0.014 mm), exhibited statistically significantly less wear than the conventional acrylic denture teeth. The conventional acrylic denture teeth demonstrated the greatest wear (0.058 ± 0.014 mm). No significant difference in depth of wear was found between DCL and IPN (p > 0.001). Conclusions: Denture tooth material significantly influences the depth of wear. The 3D printed denture teeth demonstrated superior wear resistance compared to the commercially available prefabricated denture teeth when opposed to zirconia. Denture teeth fabricated with SLA technology may have a promising future in prosthetic dentistry. [ABSTRACT FROM AUTHOR]

Key points: This is the first long‐term human clinical trial to report on effects of nicotinamide riboside (NR) on skeletal muscle mitochondrial function, content and morphology.NR supplementation decreases nicotinamide phosphoribosyltransferase (NAMPT) protein abundance in skeletal muscle.NR supplementation does not affect NAD metabolite concentrations in skeletal muscle.Respiration, distribution and quantity of muscle mitochondria are unaffected by NR.NAMPT in skeletal muscle correlates positively with oxidative phosphorylation Complex I, sirtuin 3 and succinate dehydrogenase. Preclinical evidence suggests that the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide riboside (NR) boosts NAD+ levels and improves diseases associated with mitochondrial dysfunction. We aimed to determine if dietary NR supplementation in middle‐aged, obese, insulin‐resistant men affects mitochondrial respiration, content and morphology in skeletal muscle. In a randomized, placebo‐controlled clinical trial, 40 participants received 1000 mg NR or placebo twice daily for 12 weeks. Skeletal muscle biopsies were collected before and after the intervention. Mitochondrial respiratory capacity was determined by high‐resolution respirometry on single muscle fibres. Protein abundance and mRNA expression were measured by Western blot and quantitative PCR analyses, respectively, and in a subset of the participants (placebo n = 8; NR n = 8) we quantified mitochondrial fractional area and mitochondrial morphology by laser scanning confocal microscopy. Protein levels of nicotinamide phosphoribosyltransferase (NAMPT), an essential NAD+ biosynthetic enzyme in skeletal muscle, decreased by 14% with NR. However, steady‐state NAD+ levels as well as gene expression and protein abundance of other NAD+ biosynthetic enzymes remained unchanged. Neither respiratory capacity of skeletal muscle mitochondria nor abundance of mitochondrial associated proteins were affected by NR. Moreover, no changes in mitochondrial fractional area or network morphology were observed. Our data do not support the hypothesis that dietary NR supplementation has significant impact on skeletal muscle mitochondria in obese and insulin‐resistant men. Future studies on the effects of NR on human skeletal muscle may include both sexes and potentially provide comparisons between young and older people. Key points: This is the first long‐term human clinical trial to report on effects of nicotinamide riboside (NR) on skeletal muscle mitochondrial function, content and morphology.NR supplementation decreases nicotinamide phosphoribosyltransferase (NAMPT) protein abundance in skeletal muscle.NR supplementation does not affect NAD metabolite concentrations in skeletal muscle.Respiration, distribution and quantity of muscle mitochondria are unaffected by NR.NAMPT in skeletal muscle correlates positively with oxidative phosphorylation Complex I, sirtuin 3 and succinate dehydrogenase. [ABSTRACT FROM AUTHOR]

The use of anaesthetics severely influences substrate metabolism. This poses challenges for patients in clinical settings and for the use of animals in diabetes research. Sevoflurane can affect regulation of glucose homoeostasis at several steps, but the tissue‐specific response remains to be determined. The aim of the study was to investigate the pharmacological effect of sevoflurane anaesthesia on glucose homoeostasis during hyperinsulinaemic clamp conditions, the gold standard method for assessment of whole‐body insulin sensitivity. Conscious mice (n = 6) and mice under sevoflurane anaesthesia (n = 8) underwent a hyperinsulinaemic clamp where constant infusion of insulin and donor blood was administered during variable glucose infusion to maintain isoglycaemia. 2‐[1‐14C]‐deoxy‐D‐glucose was infused to determine tissue‐specific uptake of glucose in adipose tissue, heart, brain and skeletal muscle. Sevoflurane anaesthesia severely impaired insulin‐stimulated whole‐body glucose uptake demonstrated by a 50% lower glucose infusion rate (GIR). This was associated with decreased glucose uptake in brain, soleus, triceps and gastrocnemius muscles in sevoflurane‐anaesthetized mice compared to conscious mice. Plasma‐free fatty acids (FFA), a potent inducer of insulin resistance, increased by 42% in mice during sevoflurane anaesthesia. In addition, insulin secretion from pancreatic β‐cell was lower in fasted, anaesthetized mice. Sevoflurane anaesthesia impairs insulin secretion, induces insulin resistance in mice and reduces glucose uptake in non‐insulin‐sensitive tissue like the brain. The underlying mechanisms may involve sevoflurane‐induced mobilization of FFA. [ABSTRACT FROM AUTHOR]

This study investigated the use of injectable poly(propylene fumarate) (PPF) formulations for mandibular fracture stabilization applications. A full factorial design with main effects analysis was employed to evaluate the effects of the PPF: N-vinyl pyrrolidone (NVP, crosslinking agent) ratio and dimethyl toluidine (DMT, accelerator) concentration on key physicochemical properties including setting time, maximum temperature, mechanical properties, sol fraction, and swelling ratio. Additionally, the effects of formulation crosslinking time on the mechanical and swelling properties were investigated. The results showed that increasing the PPF:NVP ratio from 3:1 to 4:1 or decreasing the DMT concentration from 0.05 to 0.01 v/w % significantly decreased all mechanical properties as well as significantly increased the sol fraction and swelling ratio. Also, increasing the crosslinking time at 37°C from 1 to 7 days significantly increased all mechanical properties and decreased both the sol fraction and swelling ratio. This study further showed that the flexural stiffness of ex vivo stabilized rabbit mandibles increased from 1.7 ± 0.3 N/mm with a traditional mini-plate fixator to 14.5 ± 4.1 N/mm for the 4:1 (0.05 v/w % DMT) PPF formulation at day 1. Overall, the formulations tested in this study were found to have properties suitable for potential further consideration in mandibular fracture fixation applications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 529-538, 2015. [ABSTRACT FROM AUTHOR]

Space maintainers (SMs) used for craniofacial reconstruction function to preserve the void space created upon bone loss and promote soft tissue healing over the defect. Polymethylmethacrylate-based SMs present several drawbacks including implant exposure, secondary removal surgeries, and potential bacterial contamination during implantation. To address these issues, a novel composite material comprising poly(propylene fumarate) (PPF) with N-vinyl pyrrolidone (NVP) as the crosslinking agent, carboxymethylcellulose (CMC) hydrogel as a porogen, and antibiotic loaded poly(lactic- co-glycolic acid) (PLGA) microparticles as antibiotic carriers and porogen was fabricated. CMC was incorporated at 40 wt % to impart rapid porosity while PLGA microparticles were incorporated at 30 or 40 wt % to release either clindamycin or colistin. This study was designed to examine the effects of PPF:NVP ratio, PLGA wt %, and the drug dose on the mass loss, temporal porosity change and drug release kinetics of the composite construct. Mass loss decreased significantly in constructs containing 3:2 PPF:NVP ratio with 30 wt % PLGA (63.2 ± 0.8%) compared to the 2:3 PPF:NVP ratio (80.3 ± 1.0% and 85.3 ± 1.3% for 30 and 40 wt % PLGA content, respectively) at 8 weeks. In formulations with 3:2 PPF:NVP ratio, incorporation of 40 versus 30 wt % PLGA significantly increased the porosity at 8 weeks under accelerated degradation conditions. Constructs released clindamycin or colistin at concentrations above the minimum inhibitory concentration for target pathogens for 45 and 77 days, respectively. This study demonstrates that the composition of PPF/CMC/PLGA constructs can be modulated to achieve properties suitable for craniofacial degradable space maintenance applications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1485-1497, 2015. [ABSTRACT FROM AUTHOR]

In this study, a full factorial approach was used to investigate the effects of poly(ethylene glycol) (PEG) molecular weight (MW; 10,000 vs. 35,000 nominal MW), crosslinker-to-macromer carbon-carbon double bond ratio (DBR; 40 vs. 60), crosslinker type (PEG-diacrylate (PEGDA) vs. N, N′-methylene bisacrylamide (MB)), crosslinking extent of incorporated gelatin microparticles (low vs. high), and incubation medium composition (with or without collagenase) on the swelling and degradation characteristics of oligo[(poly(ethylene glycol) fumarate)] (OPF) hydrogel composites as indicated by the swelling ratio and the percentage of mass remaining, respectively. Each factor consisted of two levels, which were selected based on previous in vitro and in vivo studies utilizing these hydrogels for various tissue engineering applications. Fractional factorial analyses of the main effects indicated that the mean swelling ratio and the mean percentage of mass remaining of OPF composite hydrogels were significantly affected by every factor. In particular, increasing the PEG chain MW of OPF macromers significantly increased the mean swelling ratio and decreased the mean percentage of mass remaining by 5.7 ± 0.3 and 17.2 ± 0.6%, respectively. However, changing the crosslinker from MB to PEGDA reduced the mean swelling ratio and increased the mean percentage of mass remaining of OPF composite hydrogels by 4.9 ± 0.2 and 9.4 ± 0.9%, respectively. Additionally, it was found that the swelling characteristics of hydrogels fabricated with higher PEG chain MW or with MB were more sensitive to increases in DBR. Collectively, the main and cross effects observed between factors enables informed tuning of the swelling and degradation properties of OPF-based hydrogels for various tissue engineering applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3477-3487, 2014. [ABSTRACT FROM AUTHOR]

The objective of the present study was to develop a preclinical animal model for evaluating bone augmentation and to examine the level of bone augmentation induced by hydrogel composites. Design criteria outlined for the development of the animal model included rigid immobilization of bilateral implants apposed to the parietal bone of the rat, while avoiding the calvarial sutures. The animal model was evaluated through the implantation of hydrogel composites of oligo(poly(ethylene glycol) fumarate) (OPF) and gelatin microparticles releasing bone morphogenetic protein-2 (BMP-2). The BMP-2 release profile was varied and compared to the implantation of a material control without BMP-2. Each hydrogel composite was implanted within a polypropylene cassette, which was immobilized to the calvarial bone using screws, and empty cassettes were implanted as a control. The design criteria for the animal model were realized; however, the level of bone augmentation did not vary between any of the groups after 4 weeks. Osteoclastic bone resorption occurred to a higher extent in groups releasing BMP-2, but the cause could not be elucidated. In conclusion, a promising bone augmentation model was established in the rat; however, refinement of the hydrogel composites was suggested to optimize the constructs for bone augmentation applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2079-2088, 2014. [ABSTRACT FROM AUTHOR]

In this work, we investigated the viability and osteogenic differentiation of mesenchymal stem cells encapsulated with gelatin microparticles (GMPs) in an injectable, chemically and thermally gelling hydrogel system combining poly( N-isopropylacrylamide)-based thermogelling macromers containing pendant epoxy rings with polyamidoamine-based hydrophilic and degradable diamine crosslinking macromers. Specifically, we studied how the parameters of GMP size and loading ratio affected the viability and differentiation of cells encapsulated within the hydrogel. We also examined the effects of cell and GMP co-encapsulation on hydrogel mineralization. Cells demonstrated long-term viability within the hydrogels, which was shown to depend on GMP size and loading ratio. In particular, increased interaction of cells and GMPs through greater available GMP surface area, use of an epoxy-based chemical gelation mechanism, and the tunable high water content of the thermogelled hydrogels led to favorable long-term cell viability. Compared with cellular hydrogels without GMPs, hydrogels co-encapsulating cells and GMPs demonstrated greater production of alkaline phosphatase by cells at all time-points and a transient early enhancement of hydrogel mineralization for larger GMPs at higher loading ratios. Such injectable, in situ forming hydrogels capable of delivering and maintaining populations of encapsulated mesenchymal stem cells and promoting mineralization in vitro offer promise as novel therapies for applications in tissue engineering and regenerative medicine. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1222-1230, 2014. [ABSTRACT FROM AUTHOR]

Bone regenerative medicine, based on the combined use of cells and scaffolds, represents a promising strategy in bone regeneration. Hydrogels have attracted huge interests for application as a scaffold for minimally invasive surgery. Collagen and oligo(poly(ethylene glycol)fumarate) (OPF) hydrogels are the representatives of two main categories of hydrogels, that is, natural- and synthetic-based hydrogels. With these the optimal cell-loading (i.e., cell distribution inside the hydrogels) method was assessed. The cell behavior of both bone marrow- and adipose tissue-derived mesenchymal stem cells (BM- and AT-MSCs) in three loading methods, which are dispersed (i.e., homogeneous cell encapsulation, D), sandwich (i.e., cells located in between two hydrogel layers, S), and spheroid (i.e., cell pellets encapsulation, Sp) loading in two hydrogel systems (i.e., collagen and OPF), was compared. The results suggested that the cell behavior was influenced by the hydrogel type, meaning cells cultured in collagen hydrogels had higher proliferation and osteogenic differentiation capacity than in OPF hydrogels. In addition, AT-MSCs exhibited higher proliferation and osteogenic properties compared to BM-MSCs. However, no difference was observed for mineralization among the three loading methods, which did not approve the hypothesis that S and Sp loading would increase osteogenic capacity compared to D loading. In conclusion, D and Sp loading represents two promising cell loading methods for injectable bone substitute materials that allow application of minimally invasive surgery for cell-based regenerative treatment. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 935-946, 2014. [ABSTRACT FROM AUTHOR]

Drug delivery through tissue-engineered scaffolds provides a composite approach to address the regenerative limitations of simple material implantation, providing expanded avenues for therapeutic tissue-repair strategies in the clinic. Both nano- and microfibrous scaffolds generated by a variety of techniques have been investigated for their potential in drug-delivery applications. While nanofibers mimic the structure and organization of natural extracellular matrix, microfibers provide more sustained release of drugs, larger pores to facilitate cell infiltration, and improved mechanical support. Various methods exist to embed drugs within the fiber matrix to modulate the release kinetics specific to the tissue-engineering application. The current article reviews the established and emerging fabrication methods for drug-loaded fiber-based scaffolds and addresses how further combination into composite scaffolds can enhance drug delivery and tissue regeneration. [ABSTRACT FROM AUTHOR]

The combination of reduced oxygen tension and flow perfusion bioreactor culture is investigated for its effect on the proliferation, glycosaminoglycan production, and chondrogenic gene expression of bovine articular chondrocytes on porous polymer scaffolds. It was hypothesized that the combination of such factors would more closely replicate the in situ environment of these cells, leading to improvements in the cell phenotype. Chondrocytes were seeded onto electrospun poly(ε-caprolactone) scaffolds and cultured in static or perfusion culture in either normoxic or hypoxic conditions for 6days. Results demonstrated that the combination of hypoxic and perfusion culture led to an increase in chondrocyte proliferation and glycosaminoglycan production, as well as an improvement in the ratio of collagen II/I gene expression over perfusion culture alone. The results demonstrate the need to combine multiple signals in vitro, in order to improve tissue growth by more closely replicating the native environment of cells. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3158-3166, 2013 [ABSTRACT FROM AUTHOR]

Porous polymethylmethacrylate (PMMA) has been used as an alloplastic bone substitute in the craniofacial complex, showing integration with the surrounding soft and hard tissue. This study investigated the physicochemical properties of curing and cured mixtures of a PMMA-based bone cement and a carboxymethylcellulose (CMC) gel porogen. Four formulations yielding porous PMMA of varied porosity were examined; specifically, two groups containing 30% (w/w) CMC gel in the mixture using a 7% (w/v) or 9% (w/v) stock CMC gel (30-7 and 30-9, respectively) and two groups containing 40% (w/w) CMC gel (40-7 and 40-9). An additional group comprising solid PMMA without CMC was investigated. The incorporation of the CMC gel into the PMMA bone cement during polymerization decreased the setting time from 608 ± 12 s for the solid PMMA to 427 ± 10 s for the 40-9 group, and decreased the maximum temperature from 81 ± 4°C for the solid PMMA to 38 ± 2°C for the 40-9 group. The porous PMMA groups exhibited reduced compressive strength and bending modulus and strength relative to the solid PMMA. All the porous PMMA formulations released more unconverted methylmethacrylate (MMA) monomer and N,N-dimethyl-p-toluidine (DMT) from cured specimens and less MMA and DMT from curing specimens than the solid PMMA. The data suggest that the physicochemical properties of the porous PMMA formulations are appropriate for their application in craniofacial space maintenance. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013. [ABSTRACT FROM AUTHOR]

Devitalization and demineralization processing of biodegradable polymer and extracellular matrix (ECM) hybrid constructs was explored for the effect on the retention of ECM components and construct osteogenicity. Hybrid constructs were generated by seeding osteogenically predifferentiated rat mesenchymal stem cells (MSCs) onto electrospun poly(ε-caprolactone) fiber meshes and culturing in osteogenic medium for 12 or 16 days within a flow perfusion bioreactor to create an ECM coating. The resulting constructs were then either devitalized (using a freeze-thaw or a detergent technique), devitalized and demineralized, or left untreated, and subsequently characterized for DNA, glycosaminoglycan, collagen, and calcium content. The osteogenicity of each construct was investigated by culturing MSCs on the hybrid constructs within a flow perfusion bioreactor for 4, 8, and 12 days in osteogenic medium. Histological staining demonstrated that devitalization via the freeze-thaw method retained the thickest coating of ECM components within the constructs. Demineralization and devitalization processing of ECM coated constructs resulted in a decrease in their osteogenicity. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013. [ABSTRACT FROM AUTHOR]

This study investigated the formulation of a two-component biodegradable bone cement comprising the unsaturated linear polyester macromer poly(propylene fumarate) (PPF) and crosslinked PPF microparticles for use in craniofacial bone repair applications. A full factorial design was employed to evaluate the effects of formulation parameters such as particle weight percentage, particle size, and accelerator concentration on the setting and mechanical properties of crosslinked composites. It was found that the addition of crosslinked microparticles to PPF macromer significantly reduced the temperature rise upon crosslinking from 100.3°C ± 21.6°C to 102.7°C ± 49.3°C for formulations without microparticles to 28.0°C ± 2.0°C to 65.3°C ± 17.5°C for formulations with microparticles. The main effects of increasing the particle weight percentage from 25 to 50% were to significantly increase the compressive modulus by 37.7 ± 16.3 MPa, increase the compressive strength by 2.2 ± 0.5 MPa, decrease the maximum temperature by 9.5°C ± 3.7°C, and increase the setting time by 0.7 ± 0.3 min. Additionally, the main effects of increasing the particle size range from 0-150 μm to 150-300 μm were to significantly increase the compressive modulus by 31.2 ± 16.3 MPa and the compressive strength by 1.3 ± 0.5 MPa. However, the particle size range did not have a significant effect on the maximum temperature and setting time. Overall, the composites tested in this study were found to have properties suitable for further consideration in craniofacial bone repair applications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2252-2259, 2012. [ABSTRACT FROM AUTHOR]

In this study, an injectable, biodegradable hydrogel composite of oligo[poly(ethylene glycol) fumarate] (OPF) was investigated as a carrier of mouse embryonic stem cells (mESCs) for the treatment of myocardial infarction (MI). The OPF hydrogels were used to encapsulate mESCs. The cell differentiation in vitro over 14 days was determined via immunohistochemical examination. Then, mESCs encapsulated in OPF hydrogels were injected into the LV wall of a rat MI model. Detailed histological analysis and echocardiography were used to determine the structural and functional consequences after 4 weeks of transplantation. With ascorbic acid induction, mESCs could differentiate into cardiomyocytes and other cell types in all three lineages in the OPF hydrogel. After transplantation, both the 24-hr cell retention and 4-week graft size were significantly greater in the OPF + ESC group than that of the PBS + ESC group ( P < 0.01). Four weeks after transplantation, OPF hydrogel alone significantly reduced the infarct size and collagen deposition and improved the cardiac function. The heart function and revascularization improved significantly, while the infarct size and fibrotic area decreased significantly in the OPF + ESC group compared with that of the PBS + ESC, OPF and PBS groups ( P < 0.01). All treatments had significantly reduced MMP2 and MMP9 protein levels compared to the PBS control group, and the OPF + ESC group decreased most by Western blotting. Transplanted mESCs expressed cardiovascular markers. This study suggests the potential of a method for heart regeneration involving OPF hydrogels for stem cell encapsulation and transplantation. [ABSTRACT FROM AUTHOR]

Reconstruction of composite defects involving bone and soft tissue presents a significant clinical challenge. In the craniofacial complex, reconstruction of the soft and hard tissues is critical for both functional and aesthetic outcomes. Constructs for space maintenance provide a template for soft tissue regeneration, priming the wound bed for a definitive repair of the bone tissue with greater success. However, materials used clinically for space maintenance are subject to poor soft tissue integration, which can result in wound dehiscence. Porous materials in space maintenance applications have been previously shown to support soft tissue integration and to allow for drug release from the implant to further prepare the wound bed for definitive repair. This study evaluated solid and low porosity (16.9% ± 4.1%) polymethylmethacrylate space maintainers fabricated intraoperatively and implanted in a composite rabbit mandibular defect model for 12 weeks. The data analyses showed no difference in the solid and porous groups both histologically, evaluating the inflammatory response at the interface and within the pores of the implants, and grossly, observing the healing of the soft tissue defect over the implant. These results demonstrate the potential of porous polymethylmethacrylate implants formed in situ for space maintenance in the craniofacial complex, which may have implications in the potential delivery of therapeutic drugs to prime the wound site for a definitive bone repair. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012. [ABSTRACT FROM AUTHOR]

This study used a rat subcutaneous implantation model to investigate gradual in situ pore formation in a self-regulating degradable chitosan-based material, which comprises lysozyme incorporated into biomimetic calcium phosphate (CaP) coatings at the surface to control the scaffold degradation and subsequent pore formation. Specifically, the in vivo degradation of the scaffolds, the in situ pore formation, and the tissue response were investigated. Chitosan or chitosan/starch scaffolds were studied with and without a CaP coating in the presence or absence of lysozyme for a total of six experimental groups. Twenty-four scaffolds per group were implanted, and eight scaffolds were retrieved at each of three time points (3, 6, and 12 weeks). Harvested samples were analyzed for weight loss, microcomputed tomography, and histological analysis. All scaffolds showed pronounced weight loss and pore formation as a function of time. The highest weight loss was 29.8% ± 1.5%, obtained at week 12 for CaP chitosan/starch scaffolds with lysozyme incorporated. Moreover, all experimental groups showed a significant increase in porosity after 12 weeks. At all time points no adverse tissue reaction was observed, and as degradation increased, histological analysis showed cellular ingrowth throughout the implants. Using this innovative methodology, the ability to gradually generate pores in situ was clearly demonstrated in vivo. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012. [ABSTRACT FROM AUTHOR]

Significant progress has been made in understanding the hematopoietic supportive capacity of both mesenchymal stem cells (MSCs) and osteogenic cells in maintaining hematopoietic stem and progenitor cells (HSPCs) in vitro. However the role of HSPCs in regulating their bone marrow niche environment through influencing the function of neighboring cell populations to complete this reciprocal relationship is not well understood. In this study, we investigated the influence of HSPCs on the osteogenic differentiation of MSCs in vitro, using a highly enriched population of hematopoietic cells with the phenotype c-Kit+Sca-1+Lineage− (KSL) and bone marrow derived mesenchymal stromal cells in direct contact co-culture in medium with or without the addition of the osteogenic supplement dexamethasone. The data suggest that a low dose of HSPCs in co-culture with MSCs in combination with dexamethasone treatment accelerates the osteogenic progression of MSCs, as evidenced in the earlier peak in alkaline phosphatase activity and enhanced calcium deposition compared to cultures of MSCs alone. We observed a longer persistence of functional primitive hematopoietic stem and progenitor cells in the population treated with dexamethasone, and this observation was positively correlated with enhanced osteogenic differentiation of MSCs. Therefore, our findings further support the concept that HSPCs are actively involved in regulating the development and maintenance of the stem cell niche environment in which they reside. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1544-1553, 2011 [ABSTRACT FROM AUTHOR]

In the present work, neonatal human dermal fibroblasts (nHDFs) were evaluated as a potential cell source for intervertebral disc repair. Chondrogenic differentiation of nHDFs was studied in the presence or absence of hydrostatic compression under normal and hypoxic conditions. In addition, the potentially synergistic effects of mechanical stimulation and bone morphogenetic protein (BMP)-2 on the chondrogenic differentiation of nHDFs were assessed. Mechanical stimulation was applied to the cells encapsulated in alginate beads using a custom-built bioreactor system for either a 1- or 3-week period at a frequency of 1 Hz for 4 h/day. In general, after 21 days of culture, high cell viability was observed for all the groups, with the exception of the groups exposed to intermittent mechanical stimulation for 3 weeks. Long-term intermittent application of mechanical stimulation under low O2 conditions resulted in elevated collagen biosynthesis rate from day 0. Inclusion of BMP-2 for this group improved the chondrogenic differentiation of nHDFs, as indicated by elevated aggrecan gene expression and an increased collagen production rate compared to the day 0 group. Thus, the combination of hypoxia, BMP-2 supplementation, and long-term intermittent application of dynamic hydrostatic pressure was found to be a potent promoter of the chondrogenic differentiation of nHDFs. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2011. [ABSTRACT FROM AUTHOR]

This research investigates the release of plasmid DNA from novel hydrogel composites of oligo(poly(ethylene glycol) fumarate) (OPF) and cationized gelatin microspheres (CGMS), as well as the swelling and degradation of these materials in vitro. The release of total DNA and of double‐stranded DNA was measured fluorescently, and the swelling properties and polymer mass loss of the hydrogels were assessed. Further, the structural integrity of the released DNA was determined through electrophoresis. It was found that plasmid DNA can be released in a sustained fashion over the course of up to 49–140 days in vitro from hydrogels of OPF synthesized from poly(ethylene glycol) of nominal molecular weights of 10 kDa and 3 kDa, respectively, with the release kinetics depending upon the material composition and the method of DNA loading. Released DNA was predominately double‐stranded DNA (dsDNA) in structure and of the open‐circular conformation. The results suggest that DNA release from hydrogel composites of OPF and CGMS is dominated by the degradation of the OPF component of the gels. Electrophoresis results indicate that the released DNA retains suitable conformation for potential bioactivity over the course of at least 63 days of release. Thus, these studies demonstrate the potential of composites of OPF and CGMS in controlled gene delivery applications. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006 [ABSTRACT FROM AUTHOR]

1. In a previous study it was demonstrated that a decrease in liver blood flow produced a decrease in clearance of recombinant human tissue-type plasminogen activator (rt-PA). 2. The purpose of this randomized, double-blind, placebo-controlled, three-way, cross-over investigation was to determine the effect of nifedipine (20 mg orally), a compound that increases liver blood flow, on plasma concentrations of steady state endogenous and recombinant tissue-type plasminogen activator (t-PA and rt-PA) (35 mg of rt-PA over 2 h) in nine healthy male volunteers. 3. Nifedipine increased liver blood flow by 95% (42-167%) (mean (95% confidence interval)) as assessed by indocyanine green (ICG, 0.5 mg kg-1 i.v. bolus injection) clearance. 4. Nifedipine did not influence the plasma concentrations of total rt-PA antigen and activity as evaluated by the areas under the rt-PA curves from 30 min (time at which nifedipine was ingested) to 90 min during the rt-PA infusion (P > 0.05) and by analysis of a possible treatment x time interaction (P > 0.05). In addition, the plasma concentrations of endogenous t-PA remained unchanged when nifedipine was given alone. 5. In conclusion, by using nifedipine as a model compound it was demonstrated that the combination of rt-PA and a compound which increases liver blood flow probably does not lead to substantial changes in plasma concentrations of rt-PA.