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Farmington, CT, United States

Brittain S.B.,UCONN Health | Gohil S.V.,UCONN Health | Nair L.S.,UCONN Health | Nair L.S.,Institute for Regenerative Engineering | Nair L.S.,University of Connecticut
Current Medicinal Chemistry | Year: 2014

Statins are currently used as an effective cholesterol-lowering medication through inhibition of the mevalonate pathway, but recent studies show their potential for bone repair. The bone anabolic effects of statins have been largely attributed to their ability to enhance BMP-2 expression in osteoblast cells. In vitro studies have demonstrated that statins can increase the expression of osteogenic and angiogenic markers such as alkaline phosphatase, vascular endothelial growth factor, and osteocalcin in cells. In vivo, statins have been shown to promote significant new bone growth when injected systemically or locally in combination with a scaffold. The potential anabolic effects of statins on bone make them attractive candidates to support bone regeneration. Since the molecular pathways by which statins induce osteoblast differentiation are still unclear, further investigations are required to elucidate the detailed cellular signaling mechanisms involved to determine the type of statin, optimal dose and mode of delivery to effectively utilize their anabolic effect. This also warrants the development of novel vehicles to locally deliver statins for the desired time periods to support optimal tissue regeneration in vivo. © 2014 Bentham Science Publishers. Source

Anderson M.,UCONN Health | Anderson M.,Institute for Regenerative Engineering | Anderson M.,Raymond and Beverly Sackler Center for Biomedical Biological Physical and Engineering science | Shelke N.B.,UCONN Health | And 9 more authors.
Critical Reviews in Biomedical Engineering | Year: 2015

Treatment of large peripheral nerve damages ranges from the use of an autologous nerve graft to a synthetic nerve growth conduit. Biological grafts, in spite of many merits, show several limitations in terms of availability and donor site morbidity, and outcomes are suboptimal due to fascicle mismatch, scarring, and fibrosis. Tissue engineered nerve graft substitutes utilize polymeric conduits in conjunction with cues both chemical and physical, cells alone and or in combination. The chemical and physical cues delivered through polymeric conduits play an important role and drive tissue regeneration. Electrical stimulation (ES) has been applied toward the repair and regeneration of various tissues such as muscle, tendon, nerve, and articular tissue both in laboratory and clinical settings. The underlying mechanisms that regulate cellular activities such as cell adhesion, proliferation, cell migration, protein production, and tissue regeneration following ES is not fully understood. Polymeric constructs that can carry the electrical stimulation along the length of the scaffold have been developed and characterized for possible nerve regeneration applications. We discuss the use of electrically conductive polymers and associated cell interaction, biocompatibility, tissue regeneration, and recent basic research for nerve regeneration. In conclusion, a multifunctional combinatorial device comprised of biomaterial, structural, functional, cellular, and molecular aspects may be the best way forward for effective peripheral nerve regeneration. © 2015 Begell House, Inc. Source

Shelke N.B.,UCONN Health | Shelke N.B.,Institute for Regenerative Engineering | Shelke N.B.,Raymond and Beverly Sackler Center for Biomedical | Lee P.,Stevens Institute of Technology | And 11 more authors.
Polymers for Advanced Technologies | Year: 2016

Scaffolds used for soft tissue regeneration are designed to mimic the native extracellular matrix (ECM) structurally and provide adequate mechanical strength and degradation properties. Scaffold architecture, porosity, stiffness and presence of soluble factors have been shown to influence human mesenchymal stem cells (hMSCs) differentiation along neuronal lineage. The present manuscript evaluated the performance of a composite scaffold comprised of electrospun polycaprolactone (PCL) nanofiber lattice coated with sodium alginate (SA) for neural tissue engineering. The nanofiber lattice was included in the scaffold to provide tensile strength and retain suture thread on the nerve graft. Sodium alginate was used to control matrix hydrophilicity, material stiffness and controlled release of biological molecules. The effect of SA molecular weight on the composite scaffold tensile properties, hMSCs adhesion, proliferation and neurogenic differentiation was evaluated. Both random and aligned composite scaffolds showed significantly higher tensile properties as compared to PCL fiber matrix alone indicating the reinforcement of SA hydrogel into fiber lattice. Low molecular weight SA coating because of its low viscosity resulted in uniform penetration into the fiber lattice and resulted in significantly higher tensile strength as compared to high molecular weight SA. Both composite scaffolds showed a controlled SA erosion rate and lost >95% of the SA coating over a period of 10days under in vitro conditions. Composite scaffolds showed progressive hMSCs growth over 14days and resulted in significantly higher amount of DNA content (almost double on day 7 and 14) as compared to control PCL fiber matrices. Immunostaining experiments showed higher and uniform expression of the neurotropic protein S-100 on composite scaffolds containing low molecular weight SA. These composite scaffolds may be suitable for peripheral nerve regeneration. © 2016 John Wiley & Sons, Ltd. Source

Gohil S.V.,UCONN Health | Gohil S.V.,Institute for Regenerative Engineering | Brittain S.B.,University of Connecticut | Kan H.-M.,UCONN Health | And 5 more authors.
Journal of Materials Chemistry B | Year: 2015

Enzymatically cross-linkable phenol-conjugated glycol chitosan was prepared by reacting glycol chitosan with 3-(4-hydroxyphenyl)propionic acid (HPP). The chemical modification was confirmed by FTIR, 1H-NMR and UV spectroscopy. Glycol chitosan hydrogels (HPP-GC) with or without rhBMP-2 were prepared by the oxidative coupling of the substituted phenol groups in the presence of hydrogen peroxide and horse radish peroxidase. Rheological characterization demonstrated the feasibility of developing hydrogels with varying storage moduli by changing the polymer concentration. The gel presented a microporous structure with pore sizes ranging from 50-350 μm. The good viability of encapsulated 7F2 osteoblasts indicated non-toxicity of the gelation conditions. In vitro release of rhBMP-2 in phosphate buffer solution showed ∼11% release in 360 h. The ability of the hydrogel to maintain the in vivo bioactivity of rhBMP-2 was evaluated in a bilateral critical size calvarial bone defect model in Col3.6 transgenic fluorescent reporter mice. The presence of fluorescent green osteoblast cells with overlying red alizarin complexone and yellow stain indicating osteoclast TRAP activity confirmed active cell-mediated mineralization and remodelling process at the implantation site. The complete closure of the defect site at 4 and 8 weeks post implantation demonstrated the potent osteoinductivity of the rhBMP-2 containing gel. This journal is © The Royal Society of Chemistry. Source

Lee P.,Stevens Institute of Technology | Tran K.,Stevens Institute of Technology | Chang W.,Stevens Institute of Technology | Fang Y.-L.,Stevens Institute of Technology | And 10 more authors.
Polymers for Advanced Technologies | Year: 2015

The goal of this study was to determine the efficacy of the bioactive scaffold system to initiate bone marrow stromal cell (BMSC) differentiation into osteogenic and chondrogenic lineages in various culture media compositions. In the biphasic polymeric scaffolds, the chondrogenic layer contained aligned polycaprolactone nanofibers embedded with chondroitin sulfate and hyaluronic acid, while osteogenic layer carried nano-hydroxyapatite. Many studies for in vitro testing of osteochondral scaffolds incorporate the use of complicated bioreactors or growth factors for the formation of cartilage and bone tissue, thus true efficacy of the scaffold system cannot be determined. The present study compared the effect of several media compositions consisting of osteogenic, chondrogenic components, and control basal media. Scaffolds seeded with BMSCs following 28days in vitro culture in different induction and basal media were evaluated for osteogenic and chondrogenic markers such as aggrecan, collagen type II, bone sialoprotein, alkaline phosphatase (ALP), and runt-related transcription factor 2 (Runx-2). Cartilage scaffold layer of the biphasic scaffold resulted in the expression of chondrogenic markers such as aggrecan and collagen type II by BMSCs in control and induction media compositions. The bone scaffold layer supported the expression of osteogenic markers such as ALP and Runx-2 by BMSCs in control and induction media compositions. The cartilage scaffold layer under the osteogenic induction media encouraged the growth of hypertrophic cartilage as marked by the positive expression of Runx-2. Expression of collagen type II and aggrecan on the cartilage layer in basal media was confirmed by immunostaining. These studies suggest that the bioactive scaffolds were able to support the osteogenic and chondrogenic phenotype development in the absence of growth factors and induction media. © 2015 John Wiley & Sons, Ltd. Source

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