Raymond and Beverly Sackler Center for Biomedical

Anderson, United States

Raymond and Beverly Sackler Center for Biomedical

Anderson, United States
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Peach M.S.,University of Connecticut Health Center | Peach M.S.,Raymond and Beverly Sackler Center for Biomedical | Ramos D.M.,University of Connecticut Health Center | Ramos D.M.,Raymond and Beverly Sackler Center for Biomedical | And 13 more authors.
PLoS ONE | Year: 2017

Rotator cuff (RC) tears represent a large proportion of musculoskeletal injuries attended to at the clinic and thereby make RC repair surgeries one of the most widely performed musculoskeletal procedures. Despite the high incidence rate of RC tears, operative treatments have provided minimal functional gains and suffer from high re-tear rates. The hypocellular nature of tendon tissue poses a limited capacity for regeneration. In recent years, great strides have been made in the area of tendonogenesis and differentiation towards tendon cells due to a greater understanding of the tendon stem cell niche, development of advanced materials, improved scaffold fabrication techniques, and delineation of the phenotype development process. Though in vitro models for tendonogenesis have shown promising results, in vivo models have been less successful. The present work investigates structured matrices mimicking the tendon microenvironment as cell delivery vehicles in a rat RC tear model. RC injuries augmented with a matrix delivering rat mesenchymal stem cells (rMSCs) showed enhanced regeneration over suture repair alone or repair with augmentation, at 6 and 12-weeks postsurgery. The local delivery of rMSCs led to increased mechanical properties and improved tissue morphology. We hypothesize that the mesenchymal stem cells function to modulate the local immune and bioactivity environment through autocrine/paracrine and/or cell homing mechanisms. This study provides evidence for improved tendon healing with biomimetic matrices and delivered MSCs with the potential for translation to larger, clinical animal models. The enhanced regenerative healing response with stem cell delivering biomimetic matrices may represent a new treatment paradigm for massive RC tendon tears. © 2017 Peach et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Nada A.A.,University of Connecticut Health Center | Nada A.A.,Raymond and Beverly Sackler Center for Biomedical | Nada A.A.,National Research Center of Egypt | James R.,University of Connecticut Health Center | And 11 more authors.
Polymers for Advanced Technologies | Year: 2014

The electrospinning of chitosan remains challenging due to its rigid crystalline structure, insufficient viscosity, and limited solubility in common organic solvents. This work presents a "smart" chitosan modification that allows electrospinning irrespective of molecular weight or deacetylation value and without blending with synthetic polymers. A novel derivative, namely 2-nitrobenzyl-chitosan (NB), at various molar compositions of chitosan:2-nitrobenzaldehyde (1:1 (NB-1), 1:0.5 (NB-2), 1:0.25 (NB-3)) was synthesized by the reaction between amino groups of chitosan and aldehyde groups of 2-nitrobenzaldehyde. In this Schiff base, 2-nitrobenzaldehyde protects the amine functionalities of chitosan and improves its solubility in trifluoroacetic acid. 2-nitrobenzaldehyde is a photoactivatable-caged compound that cleaves off from iminochitosan on ultraviolet exposure yielding neat chitosan. Derivatives showed improved solubility in trifluoroacetic acid and dynamic viscosities in the range of 1.34±0.7 to 12±0.5Pa·s based on the degree of substitution and concentration. Electrospinning conditions were optimized to produce bead free nanofibers in the range of 100-600nm, and concentrations beyond 12% (wt/v) for NB-1 and NB-2, and 15% (wt/v) for NB-3 were suitable. Photolysis did not alter fiber morphology; however, regenerated chitosan matrices were soluble in culture media presumably due to the presence of 2-nitrosobenzoic acid in trace amounts. Human skin fibroblasts exhibited excellent (>90%) cytocompatibility on treatment with polymer extractions from cross-linked regenerated chitosan matrices prepared to the ISO standard. Newly synthesized iminochitosan derivatives were very effective against microorganisms including bacteria (Gram-positive and Gram-negative), fungi, and yeast. These fiber matrices may serve as scaffolds for a variety of tissue healing and factor delivery applications. © 2014 John Wiley & Sons, Ltd.

Jaiswal D.,University of Connecticut | Jaiswal D.,Raymond and Beverly Sackler Center for Biomedical | James R.,University of Connecticut | James R.,Raymond and Beverly Sackler Center for Biomedical | And 10 more authors.
Journal of Biomedical Nanotechnology | Year: 2015

Electrospinning of water-soluble polymers and retaining their mechanical strength and bioactivity remain challenging. Volatile organic solvent soluble polymers and their derivatives are preferred for fabricating electrospun nanofibers. We report the synthesis and characterization of 2-nitrobenzyl-gelatin (N-Gelatin)-a novel gelatin Schiff base derivative-and the resulting electrospun nanofiber matrices. The 2-nitrobenzyl group is a photoactivatable-caged compound and can be cleaved from the gelatin nanofiber matrices following UV exposure. Such hydrophobic modification allowed the fabrication of gelatin and blend nanofibers with poly(caprolactone) (PCL) having significantly improved tensile properties. Neat gelatin and their PCL blend nanofiber matrices showed a modulus of 9.08±1.5 MPa and 27.61±4.3 MPa, respectively while the modified gelatin and their blends showed 15.63±2.8 MPa and 24.47±8.7 MPa, respectively. The characteristic infrared spectroscopy band for gelatin Schiff base derivative at 1560 cm-1 disappeared following exposure to UV light indicating the regeneration of free NH2 group and gelatin. These nanofiber matrices supported cell attachment and proliferation with a well spread morphology as evidenced through cell proliferation assay and microscopic techniques. Modified gelatin fiber matrices showed a 73% enhanced cell attachment and proliferation rate compared to pure gelatin. This polymer modification methodology may offer a promising way to fabricate electrospun nanofiber matrices using a variety of proteins and peptides without loss of bioactivity and mechanical strength. © 2015 American Scientific Publishers All rights reserved.

Guadalupe E.,University of Connecticut | Ramos D.,University of Connecticut | Ramos D.,Raymond and Beverly Sackler Center for Biomedical | Ramos D.,University of Connecticut | And 8 more authors.
Journal of Applied Polymer Science | Year: 2015

Electrospun nanofiber matrices have attracted a great deal of attention as matrices for skin repair and regeneration. The current manuscript reports the fabrication and characterization of a bioactive polycaprolactone (PCL) fiber matrix for its ability to deliver multiple factors. Bioactive PCL matrices were created by incorporating a model angiogenic factor and a model antibiotic drug. Chitosan coating on the fiber matrices significantly improved the ability to hold moisture and contributed to antibiotic activity. These fiber matrices have a modulus of 5.8 ± 1.3 MPa and matrices subjected to degradation over 4 weeks did not lose their tensile properties due to slow degradation rate. Chitosan coating avoided the initial burst release commonly associated with fiber matrices and only 60% of the encapsulated drug was released over a period of 15 days. Control PCL-chitosan matrices were able to reduce Staphylococcus aureus (S. aureus ) growth both in static and dynamic condition as compared to formulations with 50 mg gentamicin. In general, all the fiber matrices were able to support fibroblast growth and maintained normal cell morphology. Such bioactive bandages may serve as versatile and less expensive alternatives for the treatment of complex wounds. © 2015 Wiley Periodicals, Inc.

Bagshaw K.R.,University of Connecticut | Hanenbaum C.L.,University of Connecticut | Carbone E.J.,Institute for Regenerative Engineering | Carbone E.J.,Raymond and Beverly Sackler Center for Biomedical | And 12 more authors.
Therapeutic Delivery | Year: 2015

Acute and chronic pain control is a significant clinical challenge that has been largely unmet. Local anesthetics are widely used for the control of post-operative pain and in the therapy of acute and chronic pain. While a variety of approaches are currently used to prolong the duration of action of local anesthetics, an optimal strategy to achieve neural blockage for several hours to days with minimal toxicity has yet to be identified. Several drug delivery systems such as liposomes, microparticles and nanoparticles have been investigated as local anesthetic delivery vehicles to achieve prolonged anesthesia. Recently, injectable responsive hydrogels raise significant interest for the localized delivery of anesthetic molecules. This paper discusses the potential of injectable hydrogels to prolong the action of local anesthetics. © 2015 Future Science Ltd

Mikael P.E.,University of Connecticut Health Center | Mikael P.E.,University of Connecticut | Mikael P.E.,Raymond and Beverly Sackler Center for Biomedical | Amini A.R.,University of Connecticut Health Center | And 11 more authors.
Biomedical Materials (Bristol) | Year: 2014

Designing biodegradable scaffolds with bone-compatible mechanical properties has been a significant challenge in the field of bone tissue engineering and regenerative engineering. The objective of this work is to improve the polymeric scaffold's mechanical strength by compositing it with mechanically superior carbon nanotubes. Poly(lactide-co-glycolide) (PLGA) microsphere scaffolds exhibit mechanical properties in the range of human cancellous bone. On the other hand, carbon nanotubes have outstanding mechanical properties. The aim of this study is to improve further the mechanical strength of PLGA scaffolds such that they may be applicable for a wide range of load-bearing repair and regeneration applications. We have formed composite microspheres of PLGA containing pristine and modified (with hydroxyl (OH), carboxylic acid (COOH)) multi-walled carbon nanotubes (MWCNTs), and fabricated them into three-dimensional porous scaffolds. Results show that by adding only 3% MWCNTs, the compressive strength and modulus was significantly increased (35 MPa, 510.99 MPa) compared to pure PLGA scaffolds (19 MPa and 166.38 MPa). Scanning electron microscopy images showed excellent cell adhesion and proliferation. In vitro studies exhibited good cell viability, proliferation and mineralization. The in vivo study, however, indicated differences in inflammatory response throughout the 12 weeks of implantation, with OH-modified MWCNTs having the least response, followed by unmodified and COOH-modified exhibiting a more pronounced response. Overall, our results show that PLGA scaffolds containing water-dispersible MWCNTs are mechanically stronger and display good cellular and tissue compatibility, and hence are potential candidates for load-bearing bone tissue engineering. © 2014 IOP Publishing Ltd.

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.

Vivekanandan J.,Bannari Amman Institute of Technology | Mahudeswaran A.,Bannari Amman Institute of Technology | Tang X.-Y.,University of Connecticut Health Center | Kumbar S.G.,University of Connecticut Health Center | And 2 more authors.
Chemical Papers | Year: 2015

Novel copolymers of poly(aniline-co-m-chloroaniline)-doped dodecylbenzenesulphonic acid (DBSA) with embedded silver nanoparticles were synthesised using the in situ chemical oxidative method. The structural properties of the copolymers were characterised using the UV-VIS and FTIR spectroscopic methods. The crystalline nature of the copolymer was demonstrated by way of the X-ray diffraction (XRD) pattern. Scanning electron microscopy (SEM) revealed the presence of particle agglomerates measuring 50 nm to 100 nm on the surface of the nanocomposites. The electrical conductivity of the copolymer was dependent on the monomer composition and was found to be in the range of 10-2 S cm-1 to 10-6 S cm-1 with an increasing chloroaniline content and exhibiting improved solubility. © 2015 Institute of Chemistry, Slovak Academy of Sciences 2015.

News Article | February 17, 2017
Site: www.eurekalert.org

The University of Connecticut has joined the Advanced Regenerative Manufacturing Institute as a partner for the purpose of sharing its revolutionary human tissue and limb regeneration technologies. The institute, which is headquartered in New Hampshire, aims to speed the growth and use of engineered human tissues and organs to meet the increasing health needs of the nation and its citizens, especially soldiers. "We need to develop 21st-century tools for engineered tissue manufacturing that will allow these innovations to be widely available, similar to how a 15th-century tool - the printing press - allowed knowledge to spread widely during the Renaissance," said the chairman of ARMI, inventor Dean Kamen. ARMI is the 12th Manufacturing USA Institute, a national network of public-private partnerships intended to nurture manufacturing innovation and accelerate commercialization. With public-private investment funding approaching nearly $300 million, ARMI brings together a consortium of nearly 100 partner organizations from across industry, government, academia, and the non-profit sector to develop next-generation manufacturing processes and technologies for cells, tissues, and organs. "We are excited to collaborate with ARMI to lend our expertise to our country and push our regenerative engineering discoveries and breakthroughs closer to the bedsides of soldiers and Americans in need of vital medical care," said Dr. Cato T. Laurencin, an internationally acclaimed surgeon-scientist who is chief executive officer of the Connecticut Institute for Clinical and Translational Science (CICATS) at UConn, and director of the Institute for Regenerative Engineering and The Raymond and Beverly Sackler Center for Biomedical, Biological, Physical, and Engineering Sciences at UConn Health. UConn is currently working toward regenerating a human knee within six years and an entire limb by 2030. Laurencin's brainchild is the HEAL Project - Hartford Engineering A Limb - which was launched in November 2015 and is the first international effort for knee and limb engineering. Laurencin, whose laboratory research successes include the growth of bone and knee ligaments, is known as a pioneer in the field of regenerative engineering and material sciences. At UConn, collaborators making the partnership with ARMI possible include innovative regenerative engineering scientist Lakshmi S. Nair, known for her research advances in growing musculoskeletal tissue at the Institute for Regenerative Engineering at UConn Health. The new ARMI initiative at UConn benefits from strong support by Dr. Bruce T. Liang, dean of the UConn School of Medicine, Kazem Kazerounian, dean of the UConn School of Engineering, and Jeff Seemann, UConn's vice president for research. "In joining ARMI, UConn will contribute to the program's mission to bring together the country's most talented researchers to accelerate the advancement of tissue bioengineering and regeneration discoveries, while helping bring these promising, much needed breakthroughs to patients in their clinical care," said Seemann.

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