Institute for Regenerative Engineering
Institute for Regenerative Engineering
Dorcemus D.L.,University of Connecticut |
Dorcemus D.L.,Institute for Regenerative Engineering |
George E.O.,Institute for Regenerative Engineering |
Dealy C.N.,UCONN Health |
And 3 more authors.
Tissue Engineering - Part A | Year: 2017
Over the last decade, engineered structures have been developed for osteochondral (OC) tissue regeneration. While the optimal structure design is yet to be determined, these scaffolds require in vitro evaluation before clinical use. However, the means by which complex scaffolds, such as OC scaffolds, can be tested are limited. Taking advantage of a mesenchymal stem cell's (MSC's) ability to respond to its surrounding we harness external cues, such as the cell's mechanical environment and delivered factors, to create an in vitro culture system for OC tissue engineering with a single cell source on a gradient yet integrated scaffold system. To do this, the effect of hydrogel stiffness on the expression of human MSCs (hMSCs) chondrogenic differentiation was studied using histological analysis. Additionally, hMSCs were also cultured in different combinations of chondrogenic and osteogenic media to develop a co-differentiation media suitable for OC lineage differentiation. A uniquely graded (density-gradient matrix) OC scaffold with a distal cartilage hydrogel phase specifically tailored to support chondrogenic differentiation was cultured using a newly developed simulated in vivo culture method. The scaffold's culture in co-differentiation media models hMSC infiltration into the scaffold and subsequent differentiation into the distal cartilage and proximal bone layers. Cartilage and bone marker staining along with specific matrix depositions reveal the effect of external cues on the hMSC differentiation. As a result of these studies a model system was developed to study and culture OC scaffolds in vitro. © Copyright 2017, Mary Ann Liebert, Inc. 2017.
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.
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
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.
News Article | February 17, 2017
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.
Gohil S.V.,UConn Health |
Gohil S.V.,Institute for Regenerative Engineering |
Brittain S.B.,University of Connecticut |
Kan H.-M.,UConn Health |
And 6 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.
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.
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.
PubMed | UConn Health, Stevens Institute of Technology, Institute for Regenerative Engineering and University of Connecticut
Type: Journal Article | Journal: Critical reviews in biomedical engineering | Year: 2016
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.