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The development of an engineered adipose tissue substitute, capable of supporting reliable, predictable, and complete fat tissue formation, would be of significant value in the fields of plastic and reconstructive surgery. Towards the goal of engineering an optimized microenvironment for adipogenesis, a decellularization strategy was developed for adipose tissue, which yielded 3-D scaffolds with preserved extracellular matrix architecture. A significant volume of scaffolding material could be obtained from a human tissue source that is commonly discarded. Histology, immunohistochemistry, and scanning electron microscopy confirmed the efficacy and reproducibility of the approach, and also indicated that the basement membrane was conserved in the processed matrix, including laminin and collagen type IV. Seeding experiments with human adipose-derived stem cells indicated that the decellularized adipose tissue (DAT) provided an inductive microenvironment for adipogenesis, supporting the expression of the master regulators PPARγ and CEBPα, without the need for exogenous differentiation factors. High levels of adipogenic gene expression and glycerol-3-phosphate dehydrogenase activity were observed in the induced DAT scaffolds, as compared to cells grown in monolayer or cell aggregate culture. The protein data emphasized the importance of the cell donor source in the development of tissue-engineering strategies for large-volume soft tissue regeneration. © 2010 Elsevier Ltd. Source

Babasola I.O.,Queens University | Bianco J.,Human Mobility Research Center | Amsden B.G.,Human Mobility Research Center

Low molecular weight poly(5-ethylene ketal ε-caprolactone-co-d,l- lactide) (PEKCDLLA) is being considered as a viscous liquid, injectable depot for localized drug delivery. This polymer degrades in vitro via surface erosion, which is potentially advantageous for the proposed application. However, the in vivo degradation rate and mechanism, and tissue response, to polymers based on 5-ethylene ketal ε-caprolactone have not yet been reported. The purpose of this study was to measure the in vivo weight loss and change in polymer properties and assess the tissue response to PEKCDLLA after subcutaneous injection in rats. The tissue response was assessed histologically using Masson's trichrome staining and immunohistochemically by staining for CD68 positive cells. The polymer lost weight with time in a nearly linear fashion but did not exhibit significant changes in number average molecular weight, polydispersity index, and glass transition temperature or monomer ratio, consistent with a surface erosion process. The tissue response to the polymer was moderate and comparable to that reported in the literature for other degradable polymers used in clinical applications. These findings indicate that PEKCDLLA is a promising candidate for injectable drug delivery (Figure Presented). © 2012 American Chemical Society. Source

Babasola O.I.,Queens University | Babasola O.I.,Human Mobility Research Center | Amsden B.G.,Queens University | Amsden B.G.,Human Mobility Research Center

Liquid, injectable hydrophobic polymers are potentially useful as depot systems for localized drug delivery. Low molecular weight polymers of 5-ethylene ketal ε-caprolactone and copolymers of this monomer with d,l-lactide were prepared and their properties assessed with respect to their suitability for this purpose. The polymers were amorphous and of low viscosity, and the viscosity was adjustable by choice of initiator and/or by copolymerizing with d,l-lactide. Lower viscosity polymers were attained by using 350 Da methoxy poly(ethylene glycol) as an initiator in comparison to octan-1-ol, while copolymerization with d,l-lactide increased viscosity. The initiator used had no significant effect on the rate of mass loss in vitro, and copolymers with d,l-lactide (DLLA) degraded faster than 5-ethylene ketal ε-caprolactone (EKC) homopolymers. For the EKC-based polymers, a nearly constant degradation rate was observed. This finding was attributed to the hydrolytic susceptibility of the EKC-EKC ester linkage, which was comparable to that of DLLA-DLLA, coupled with a higher molecular weight of the water-soluble degradation product and the low initial molecular weight of the EKC-based polymers. Cytotoxicity of the hydrolyzed EKC monomer to 3T3 fibroblast cells was comparable to that of ε-caprolactone, suggesting that polymers prepared from EKC may be well tolerated upon in vivo implantation. © 2011 American Chemical Society. Source

Russo V.,Queens University | Russo V.,Human Mobility Research Center | Young S.,Queens University | Young S.,Human Mobility Research Center | And 5 more authors.

Myocardial infarction (MI) is one of the leading causes of mortality worldwide and is associated with irreversible cardiomyocyte death and pathological remodeling of cardiac tissue. In the past 15 years, several animal models have been developed for pre-clinical testing to assess the potential of stem cells for functional tissue regeneration and the attenuation of left ventricular remodeling. The promising results obtained in terms of improved cardiac function, neo-angiogenesis and reduction in infarct size have motivated the initiation of clinical trials in humans. Despite the potential, the results of these studies have highlighted that the effective delivery and retention of viable cells within the heart remain significant challenges that have limited the therapeutic efficacy of cell-based therapies for treating the ischemic myocardium. In this review, we discuss key elements for designing clinically translatable cell-delivery approaches to promote myocardial regeneration. Key topics addressed include cell selection, with a focus on mesenchymal stem cells derived from the bone marrow (bMSCs) and adipose tissue (ASCs), including a discussion of their potential mechanisms of action. Natural and synthetic biomaterials that have been investigated as injectable cell delivery vehicles for cardiac applications are critically reviewed, including an analysis of the role of the biomaterials themselves in the therapeutic scheme. © 2014 Elsevier Ltd. Source

Fan J.C.Y.,Queens University | Fan J.C.Y.,Human Mobility Research Center | Waldman S.D.,Queens University | Waldman S.D.,Human Mobility Research Center
Annals of Biomedical Engineering

Mechanical stimulation of engineered cartilage constructs is a commonly applied method used to accelerate tissue formation and improve the mechanical properties of the developed tissue. While the effects of compression and shear have been widely studied, the effect of tension has received relatively little attention. As articular cartilage in vivo is subjected to a degree of static tension (pre-tension) even in the absence of externally applied loads, the purpose of this study was to investigate the effect of intermittent static biaxial tensile strains (BTS) on chondrocyte metabolism and resultant tissue formation. Using a custom-design loading fixture to apply BTS, the optimal conditions for stimulating extracellular matrix synthesis were under average magnitudes of 3.8% radial and 2.1% circumferential tensile strains for 30 min. Tissue constructs subjected to tensile strain stimulation 3 times/week for a period of 4 weeks displayed increased thickness (35 ± 18%) and proteoglycan content (22 ± 7%) without an associated change in mechanical properties. In contrast, constructs stimulated daily over the same time period exhibited negligible effects in terms of ECM accumulation suggesting that the frequency of stimulation needs to be precisely controlled. The results of this study demonstrate that while tension can be used as potential biomechanical stimulus to improve tissue formation, further optimization of this process needs to be conducted to improve ECM accumulation and tissue mechanical properties after long-term exposure to tensile stimuli. © 2010 Biomedical Engineering Society. Source

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