Publications by authors named "Treena Livingston Arinzeh"

23 Publications

  • Page 1 of 1

The Effect of Physical Cues of Biomaterial Scaffolds on Stem Cell Behavior.

Adv Healthc Mater 2021 02 4;10(3):e2001244. Epub 2020 Dec 4.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA.

Stem cells have been sought as a promising cell source in the tissue engineering field due to their proliferative capacity as well as differentiation potential. Biomaterials have been utilized to facilitate the delivery of stem cells in order to improve their engraftment and long-term viability upon implantation. Biomaterials also have been developed as scaffolds to promote stem cell induced tissue regeneration. This review focuses on the latter where the biomaterial scaffold is designed to provide physical cues to stem cells in order to promote their behavior for tissue formation. Recent work that explores the effect of scaffold physical properties, topography, mechanical properties and electrical properties, is discussed. Although still being elucidated, the biological mechanisms, including cell shape, focal adhesion distribution, and nuclear shape, are presented. This review also discusses emerging areas and challenges in clinical translation.
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http://dx.doi.org/10.1002/adhm.202001244DOI Listing
February 2021

Biodegradable zinc oxide composite scaffolds promote osteochondral differentiation of mesenchymal stem cells.

Biotechnol Bioeng 2020 01 6;117(1):194-209. Epub 2019 Oct 6.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey.

Osteoarthritis (OA) involves the degeneration of articular cartilage and subchondral bone. The capacity of articular cartilage to repair and regenerate is limited. A biodegradable, fibrous scaffold containing zinc oxide (ZnO) was fabricated and evaluated for osteochondral tissue engineering applications. ZnO has shown promise for a variety of biomedical applications but has had limited use in tissue engineering. Composite scaffolds consisted of ZnO nanoparticles embedded in slow degrading, polycaprolactone to allow for dissolution of zinc ions over time. Zinc has well-known insulin-mimetic properties and can be beneficial for cartilage and bone regeneration. Fibrous ZnO composite scaffolds, having varying concentrations of 1-10 wt.% ZnO, were fabricated using the electrospinning technique and evaluated for human mesenchymal stem cell (MSC) differentiation along chondrocyte and osteoblast lineages. Slow release of the zinc was observed for all ZnO composite scaffolds. MSC chondrogenic differentiation was promoted on low percentage ZnO composite scaffolds as indicated by the highest collagen type II production and expression of cartilage-specific genes, while osteogenic differentiation was promoted on high percentage ZnO composite scaffolds as indicated by the highest alkaline phosphatase activity, collagen production, and expression of bone-specific genes. This study demonstrates the feasibility of ZnO-containing composites as a potential scaffold for osteochondral tissue engineering.
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http://dx.doi.org/10.1002/bit.27173DOI Listing
January 2020

Aligned fibrous PVDF-TrFE scaffolds with Schwann cells support neurite extension and myelination in vitro.

J Neural Eng 2018 10 24;15(5):056010. Epub 2018 May 24.

Materials Science and Engineering Program, New Jersey Institute of Technology, Newark, NJ 07102, United States of America.

Objective: Polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE), which is a piezoelectric, biocompatible polymer, holds promise as a scaffold in combination with Schwann cells (SCs) for spinal cord repair. Piezoelectric materials can generate electrical activity in response to mechanical deformation, which could potentially stimulate spinal cord axon regeneration. Our goal in this study was to investigate PVDF-TrFE scaffolds consisting of aligned fibers in supporting SC growth and SC-supported neurite extension and myelination in vitro.

Approach: Aligned fibers of PVDF-TrFE were fabricated using the electrospinning technique. SCs and dorsal root ganglion (DRG) explants were co-cultured to evaluate SC-supported neurite extension and myelination on PVDF-TrFE scaffolds.

Main Results: PVDF-TrFE scaffolds supported SC growth and neurite extension, which was further enhanced by coating the scaffolds with Matrigel. SCs were oriented and neurites extended along the length of the aligned fibers. SCs in co-culture with DRGs on PVDF-TrFE scaffolds promoted longer neurite extension as compared to scaffolds without SCs. In addition to promoting neurite extension, SCs also formed myelin around DRG neurites on PVDF-TrFE scaffolds.

Significance: This study demonstrated PVDF-TrFE scaffolds containing aligned fibers supported SC-neurite extension and myelination. The combination of SCs and PVDF-TrFE scaffolds may be a promising tissue engineering strategy for spinal cord repair.
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http://dx.doi.org/10.1088/1741-2552/aac77fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125183PMC
October 2018

Transplantation of Schwann Cells Inside PVDF-TrFE Conduits to Bridge Transected Rat Spinal Cord Stumps to Promote Axon Regeneration Across the Gap.

J Vis Exp 2017 11 3(129). Epub 2017 Nov 3.

The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine; Department of Cell Biology, University of Miami Miller School of Medicine; Department of Neurological Surgery, University of Miami Miller School of Medicine;

Among various models for spinal cord injury in rats, the contusion model is the most often used because it is the most common type of human spinal cord injury. The complete transection model, although not as clinically relevant as the contusion model, is the most rigorous method to evaluate axon regeneration. In the contusion model, it is difficult to distinguish regenerated from sprouted or spared axons due to the presence of remaining tissue post injury. In the complete transection model, a bridging method is necessary to fill the gap and create continuity from the rostral to the caudal stumps in order to evaluate the effectiveness of the treatments. A reliable bridging surgery is essential to test outcome measures by reducing the variability due to the surgical method. The protocols described here are used to prepare Schwann cells (SCs) and conduits prior to transplantation, complete transection of the spinal cord at thoracic level 8 (T8), insert the conduit, and transplant SCs into the conduit. This approach also uses in situ gelling of an injectable basement membrane matrix with SC transplantation that allows improved axon growth across the rostral and caudal interfaces with the host tissue.
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http://dx.doi.org/10.3791/56077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755304PMC
November 2017

Three-dimensional piezoelectric fibrous scaffolds selectively promote mesenchymal stem cell differentiation.

Biomaterials 2017 Dec 19;149:51-62. Epub 2017 Sep 19.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102-1982, USA. Electronic address:

The discovery of electric fields in biological tissues has led to efforts in developing technologies utilizing electrical stimulation for therapeutic applications. Native tissues, such as cartilage and bone, exhibit piezoelectric behavior, wherein electrical activity can be generated due to mechanical deformation. Yet, the use of piezoelectric materials have largely been unexplored as a potential strategy in tissue engineering, wherein a piezoelectric biomaterial acts as a scaffold to promote cell behavior and the formation of large tissues. Here we show, for the first time, that piezoelectric materials can be fabricated into flexible, three-dimensional fibrous scaffolds and can be used to stimulate human mesenchymal stem cell differentiation and corresponding extracellular matrix/tissue formation in physiological loading conditions. Piezoelectric scaffolds that exhibit low voltage output, or streaming potential, promoted chondrogenic differentiation and piezoelectric scaffolds with a high voltage output promoted osteogenic differentiation. Electromechanical stimulus promoted greater differentiation than mechanical loading alone. Results demonstrate the additive effect of electromechanical stimulus on stem cell differentiation, which is an important design consideration for tissue engineering scaffolds. Piezoelectric, smart materials are attractive as scaffolds for regenerative medicine strategies due to their inherent electrical properties without the need for external power sources for electrical stimulation.
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http://dx.doi.org/10.1016/j.biomaterials.2017.09.024DOI Listing
December 2017

Controlled Release of Vanadium from a Composite Scaffold Stimulates Mesenchymal Stem Cell Osteochondrogenesis.

AAPS J 2017 07 22;19(4):1017-1028. Epub 2017 Mar 22.

Department of Biomedical Engineering, New Jersey Institute of Technology, University Heights, Newark, New Jersey, 07102, USA.

Large bone defects often require the use of autograft, allograft, or synthetic bone graft augmentation; however, these treatments can result in delayed osseous integration. A tissue engineering strategy would be the use of a scaffold that could promote the normal fracture healing process of endochondral ossification, where an intermediate cartilage phase is later transformed to bone. This study investigated vanadyl acetylacetonate (VAC), an insulin mimetic, combined with a fibrous composite scaffold, consisting of polycaprolactone with nanoparticles of hydroxyapatite and beta-tricalcium phosphate, as a potential bone tissue engineering scaffold. The differentiation of human mesenchymal stem cells (MSCs) was evaluated on 0.05 and 0.025 wt% VAC containing composite scaffolds (VAC composites) in vitro using three different induction media: osteogenic (OS), chondrogenic (CCM), and chondrogenic/osteogenic (C/O) media, which mimics endochondral ossification. The controlled release of VAC was achieved over 28 days for the VAC composites, where approximately 30% of the VAC was released over this period. MSCs cultured on the VAC composites in C/O media had increased alkaline phosphatase activity, osteocalcin production, and collagen synthesis over the composite scaffold without VAC. In addition, gene expressions for chondrogenesis (Sox9) and hypertrophic markers (VEGF, MMP-13, and collagen X) were the highest on VAC composites. Almost a 1000-fold increase in VEGF gene expression and VEGF formation, as indicated by immunostaining, was achieved for cells cultured on VAC composites in C/O media, suggesting VAC will promote angiogenesis in vivo. These results demonstrate the potential of VAC composite scaffolds in supporting endochondral ossification as a bone tissue engineering strategy.
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http://dx.doi.org/10.1208/s12248-017-0073-9DOI Listing
July 2017

Gelatin Scaffolds Containing Partially Sulfated Cellulose Promote Mesenchymal Stem Cell Chondrogenesis.

Tissue Eng Part A 2017 09 25;23(17-18):1011-1021. Epub 2017 May 25.

Department of Biomedical Engineering, New Jersey Institute of Technology , Newark, New Jersey.

Articular cartilage has a limited capacity to heal after damage from injury or degenerative disease. Tissue engineering constructs that more closely mimic the native cartilage microenvironment can be utilized to promote repair. Glycosaminoglycans (GAGs), a major component of the cartilage extracellular matrix, have the ability to sequester growth factors due to their level and spatial distribution of sulfate groups. This study evaluated the use of a GAG mimetic, cellulose sulfate, as a scaffolding material for cartilage tissue engineering. Cellulose sulfate can be synthesized to have a similar level and spatial distribution of sulfates as chondroitin sulfate C (CSC), the naturally occurring GAG. This partially sulfated cellulose (pSC) was incorporated into a fibrous gelatin construct by the electrospinning process. Scaffolds were characterized for fiber morphology and overall stability over time in an aqueous environment, growth factor interaction, and for supporting mesenchymal stem cell (MSC) chondrogenesis in vitro. All scaffold groups had micron-sized fibers and maintained overall stability in aqueous environments. Increasing concentrations of the transforming growth factor-beta 3 (TGF-β3) were detected on scaffolds with increasing pSC. MSC chondrogenesis was enhanced on the scaffold with the highest pSC concentration as seen with the highest collagen type II production, collagen type II immunostaining, expression of cartilage-specific genes, and ratio of collagen type II to collagen type I production. These studies demonstrated the potential of pSC sulfate as a scaffolding material for cartilage tissue engineering.
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http://dx.doi.org/10.1089/ten.TEA.2016.0461DOI Listing
September 2017

The Biology of Bone and Ligament Healing.

Foot Ankle Clin 2016 Dec;21(4):739-761

Department of Orthopaedics, Rutgers-New Jersey Medical School, Medical Sciences Building, Room E-659, 185 South Orange Avenue, Newark, NJ 07103, USA.

This review describes the normal healing process for bone, ligaments, and tendons, including primary and secondary healing as well as bone-to-bone fusion. It depicts the important mediators and cell types involved in the inflammatory, reparative, and remodeling stages of each healing process. It also describes the main challenges for clinicians when trying to repair bone, ligaments, and tendons with a specific emphasis on Charcot neuropathy, fifth metatarsal fractures, arthrodesis, and tendon sheath and adhesions. Current treatment options and research areas are also reviewed.
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http://dx.doi.org/10.1016/j.fcl.2016.07.017DOI Listing
December 2016

Investigating cellulose derived glycosaminoglycan mimetic scaffolds for cartilage tissue engineering applications.

J Tissue Eng Regen Med 2018 01 28;12(1):e592-e603. Epub 2017 Mar 28.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.

Articular cartilage has a limited capacity to heal and, currently, no treatment exists that can restore normal hyaline cartilage. Creating tissue engineering scaffolds that more closely mimic the native extracellular matrix may be an attractive approach. Glycosaminoglycans, which are present in native cartilage tissue, provide signalling and structural cues to cells. This study evaluated the use of a glycosaminoglycan mimetic, derived from cellulose, as a potential scaffold for cartilage repair applications. Fully sulfated sodium cellulose sulfate (NaCS) was initially evaluated in soluble form as an additive to cell culture media. Human mesenchymal stem cell (MSC) chondrogenesis in pellet culture was enhanced with 0.01% NaCS added to induction media as demonstrated by significantly higher gene expression for type II collagen and aggrecan. NaCS was combined with gelatine to form fibrous scaffolds using the electrospinning technique. Scaffolds were characterized for fibre morphology, overall hydrolytic stability, protein/growth factor interaction and for supporting MSC chondrogenesis in vitro. Scaffolds immersed in phosphate buffered saline for up to 56 days had no changes in swelling and no dissolution of NaCS as compared to day 0. Increasing concentrations of the model protein lysozyme and transforming growth factor-β3 were detected on scaffolds with increasing concentrations of NaCS (p < 0.05). MSC chondrogenesis was enhanced on the scaffold with the lowest NaCS concentration as seen with the highest collagen type II production, collagen type II immunostaining, and expression of cartilage-specific genes. These studies demonstrate the feasibility of cellulose sulfate as a scaffolding material for cartilage tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/term.2331DOI Listing
January 2018

Enhanced noradrenergic axon regeneration into schwann cell-filled PVDF-TrFE conduits after complete spinal cord transection.

Biotechnol Bioeng 2017 02 26;114(2):444-456. Epub 2016 Sep 26.

The Miami Project to Cure Paralysis, Lois Pope LIFE Center, University of Miami Miller School of Medicine, P.O. Box 016960, Mail locator R-48, Miami, Florida 33101.

Schwann cell (SC) transplantation has been utilized for spinal cord repair and demonstrated to be a promising therapeutic strategy. In this study, we investigated the feasibility of combining SC transplantation with novel conduits to bridge the completely transected adult rat spinal cord. This is the first and initial study to evaluate the potential of using a fibrous piezoelectric polyvinylidene fluoride trifluoroethylene (PVDF-TrFE) conduit with SCs for spinal cord repair. PVDF-TrFE has been shown to enhance neurite growth in vitro and peripheral nerve repair in vivo. In this study, SCs adhered and proliferated when seeded onto PVDF-TrFE scaffolds in vitro. SCs and PVDF-TrFE conduits, consisting of random or aligned fibrous inner walls, were transplanted into transected rat spinal cords for 3 weeks to examine early repair. Glial fibrillary acidic protein (GFAP) astrocyte processes and GFP (green fluorescent protein)-SCs were interdigitated at both rostral and caudal spinal cord/SC transplant interfaces in both types of conduits, indicative of permissivity to axon growth. More noradrenergic/DβH (dopamine-beta-hydroxylase) brainstem axons regenerated across the transplant when greater numbers of GFAP astrocyte processes were present. Aligned conduits promoted extension of DβH axons and GFAP processes farther into the transplant than random conduits. Sensory CGRP (calcitonin gene-related peptide) axons were present at the caudal interface. Blood vessels formed throughout the transplant in both conduits. This study demonstrates that PVDF-TrFE conduits harboring SCs are promising for spinal cord repair and deserve further investigation. Biotechnol. Bioeng. 2017;114: 444-456. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/bit.26088DOI Listing
February 2017

Piezoelectric materials for tissue regeneration: A review.

Acta Biomater 2015 Sep 7;24:12-23. Epub 2015 Jul 7.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102-1982, USA. Electronic address:

Unlabelled: The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues raised the question whether or not electric fields play an important role in cell function. It has kindled research and the development of technologies in emulating biological electricity for tissue regeneration. Promising effects of electrical stimulation on cell growth and differentiation and tissue growth has led to interest in using piezoelectric scaffolds for tissue repair. Piezoelectric materials can generate electrical activity when deformed. Hence, an external source to apply electrical stimulation or implantation of electrodes is not needed. Various piezoelectric materials have been employed for different tissue repair applications, particularly in bone repair, where charges induced by mechanical stress can enhance bone formation; and in neural tissue engineering, in which electric pulses can stimulate neurite directional outgrowth to fill gaps in nervous tissue injuries. In this review, a summary of piezoelectricity in different biological tissues, mechanisms through which electrical stimulation may affect cellular response, and recent advances in the fabrication and application of piezoelectric scaffolds will be discussed.

Statement Of Significance: The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues has kindled research and the development of technologies using electrical stimulation for tissue regeneration. Piezoelectric materials generate electrical activity in response to deformations and allow for the delivery of an electrical stimulus without the need for an external power source. As a scaffold for tissue engineering, growing interest exists due to its potential of providing electrical stimulation to cells to promote tissue formation. In this review, we cover the discovery of piezoelectricity in biological tissues, its connection to streaming potentials, biological response to electrical stimulation and commonly used piezoelectric materials for tissue regeneration. This review summarizes their potential as a promising scaffold in the tissue engineering field.
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http://dx.doi.org/10.1016/j.actbio.2015.07.010DOI Listing
September 2015

Evaluating protein incorporation and release in electrospun composite scaffolds for bone tissue engineering applications.

J Biomed Mater Res A 2015 Oct 16;103(10):3117-27. Epub 2015 Mar 16.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, 07102.

Electrospun polymer/ceramic composites have gained interest for use as scaffolds for bone tissue engineering applications. In this study, we investigated methods to incorporate Platelet Derived Growth Factor-BB (PDGF-BB) in electrospun polycaprolactone (PCL) or PCL prepared with polyethylene oxide (PEO), where both contained varying levels (up to 30 wt %) of ceramic composed of biphasic calcium phosphates, hydroxyapatite (HA)/β-tricalcium phosphate (TCP). Using a model protein, lysozyme, we compared two methods of protein incorporation, adsorption and emulsion electrospinning. Adsorption of lysozyme on scaffolds with ceramic resulted in minimal release of lysozyme over time. Using emulsion electrospinning, lysozyme released from scaffolds containing a high concentration of ceramic where the majority of the release occurred at later time points. We investigated the effect of reducing the electrostatic interaction between the protein and the ceramic on protein release with the addition of the cationic surfactant, cetyl trimethylammonium bromide (CTAB). In vitro release studies demonstrated that electrospun scaffolds prepared with CTAB released more lysozyme or PDGF-BB compared with scaffolds without the cationic surfactant. Human mesenchymal stem cells (MSCs) on composite scaffolds containing PDGF-BB incorporated through emulsion electrospinning expressed higher levels of osteogenic markers compared to scaffolds without PDGF-BB, indicating that the bioactivity of the growth factor was maintained. This study revealed methods for incorporating growth factors in polymer/ceramic scaffolds to promote osteoinduction and thereby facilitate bone regeneration.
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http://dx.doi.org/10.1002/jbm.a.35444DOI Listing
October 2015

An investigation of common crosslinking agents on the stability of electrospun collagen scaffolds.

J Biomed Mater Res A 2015 Feb 28;103(2):762-71. Epub 2014 May 28.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, 07102-1982.

Electrospinning is a widely used processing method to form fibrous tissue engineering scaffolds that mimic the structural features of the native extracellular matrix. Electrospun fibers made of collagen have been sought because it is a natural structural protein that supports cell attachment and growth. Yet, conventional solvents used to electrospin collagen can result in the loss of hydrolytic stability and fiber morphology of the scaffold. This study evaluated the effect of commonly used synthetic and natural crosslinking agents, genipin, glutaraldehyde, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), and EDC with N-hydroxysulfosuccinimide (EDC-NHS), on electrospun collagen. Crosslinked collagen scaffolds were assessed for structural integrity in an in vitro immersion study for up to 3 months. Their cytocompatibility was evaluated by human mesenchymal stem cell morphology and proliferation. Our results showed that dimensional stability and cytocompatibility of crosslinked electrospun collagen scaffolds are dependent on the type of crosslinking agent used. Collagen scaffolds treated with EDC and EDC-NHS were structurally stable and retained fiber structure for up to 3 months and were cytocompatible. Therefore, EDC and EDC-NHS are favorable crosslinking agents for electrospun collagen that can be utilized in tissue engineering applications.
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http://dx.doi.org/10.1002/jbm.a.35222DOI Listing
February 2015

Evaluating apatite formation and osteogenic activity of electrospun composites for bone tissue engineering.

Biotechnol Bioeng 2014 May 22;111(5):1000-17. Epub 2013 Nov 22.

Department of Biomedical Engineering, New Jersey Institute of Technology, University Heights, 614 Fenster Hall, Newark, New Jersey, 07102-1982.

Significant interest has been in examining calcium phosphate ceramics, specifically β-tricalcium phosphate (β-TCP) (Ca3 (PO4)2 ) and synthetic hydroxyapatite (HA) (Ca10 (PO4)6 (OH)2 ), in composites and more recently, in fibrous composites formed using the electrospinning technique for bone tissue engineering applications. Calcium phosphate ceramics are sought because they can be bone bioactive, which means an apatite forms on their surface that facilitates bonding to bone tissue, and are osteoconductive. However, studies examining the bioactivity of electrospun composites containing calcium phosphates and their corresponding osteogenic activity have been limited. In this study, electrospun composites consisting of (20/80) HA/TCP nanoceramics and poly (ϵ-caprolactone) (PCL) were fabricated. Solvent and solvent combinations were evaluated to form scaffolds with a maximum concentration and dispersion of ceramic and pore sizes large enough for cell infiltration and tissue growth. PCL was dissolved in either methylene chloride (Composite-MC) or a combination of methylene chloride (80%) and dimethylformamide (20%; Composite-MC + DMF). Composites were evaluated in vitro for degradation, apatite formation, and osteogenic differentiation of human mesenchymal stem cells (MSCs) with an emphasis on temporal gene expression of osteogenic markers and the pluripotent gene Sox-2. Apatite formation and the osteogenic differentiation was the greatest for Composite-MC as determined by gene expression, protein production and biochemical markers, even without the presence of osteoinductive factors in the media, in comparison to Composite-MC + DMF and unfilled PCL mats. Sox-2 levels also reduced over time. The results of this study demonstrate that the solvent or solvent combination used in preparing the electrospun composite mats plays a critical role in determining their bioactivity which may, in turn, affect cell behavior.
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http://dx.doi.org/10.1002/bit.25146DOI Listing
May 2014

Structural changes in PVDF fibers due to electrospinning and its effect on biological function.

Biomed Mater 2013 Aug 17;8(4):045007. Epub 2013 Jun 17.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102-1982, USA.

Polyvinylidine fluoride (PVDF) is being investigated as a potential scaffold for bone tissue engineering because of its proven biocompatibility and piezoelectric property, wherein it can generate electrical activity when mechanically deformed. In this study, PVDF scaffolds were prepared by electrospinning using different voltages (12-30 kV), evaluated for the presence of the piezoelectric β-crystal phase and its effect on biological function. Electrospun PVDF was compared with unprocessed/raw PVDF, films and melt-spun fibers for the presence of the piezoelectric β-phase using differential scanning calorimetry, Fourier transform infrared spectroscopy and x-ray diffraction. The osteogenic differentiation of human mesenchymal stem cells (MSCs) was evaluated on scaffolds electrospun at 12 and 25 kV (PVDF-12 kV and PVDF-25 kV, respectively) and compared to tissue culture polystyrene (TCP). Electrospinning PVDF resulted in the formation of the piezoelectric β-phase with the highest β-phase fraction of 72% for electrospun PVDF at 25 kV. MSCs cultured on both the scaffolds were well attached as indicated by a spread morphology. Cells on PVDF-25 kV scaffolds had the greatest alkaline phosphatase activity and early mineralization by day 10 as compared to TCP and PVDF-12 kV. The results demonstrate the potential for the use of PVDF scaffolds for bone tissue engineering applications.
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http://dx.doi.org/10.1088/1748-6041/8/4/045007DOI Listing
August 2013

Examining the formulation of emulsion electrospinning for improving the release of bioactive proteins from electrospun fibers.

J Biomed Mater Res A 2014 Mar 30;102(3):674-84. Epub 2013 May 30.

Department of Biomedical Engineering, New Jersey Institute of Technology, University Heights, 614 Fenster Hall, Newark, New Jersey, 07102.

Emulsion electrospinning has been sought as a method to prepare fibrous materials/scaffolds for growth factor delivery. Emulsion conditions, specifically sonication and the addition of a surfactant, were evaluated to determine their effect on the release and bioactivity of proteins from electrospun scaffolds. Polycaprolactone (PCL) and poly(ethylene oxide) (PEO/PCL) blends were evaluated where PEO, a hydrophilic polymer, was shown to enhance the incorporation of proteins. Electrospun scaffolds prepared with the addition of the nonionic surfactant Span® 80 at a concentration greater than the critical micelle concentration followed by mild sonication (10% amplitude) released lysozyme, the model protein, with a higher level of bioactivity as compared with other surfactant and sonication conditions. These conditions were then used to prepare emulsions of platelet-derived growth factor-BB (PDGF-BB) in PEO/PCL blends. Electrospun mats prepared by emulsions consisting of PDGF-BB incorporated with Span® 80 and sonicated at 10% amplitude exhibited a controlled release of PDGF-BB over 96 h as compared with a more rapid release from solutions that were not emulsified (Direct Addition) or emulsions that did not receive Span® 80 or sonication. Bioactive PDGF-BB incorporated in electrospun scaffolds enhanced the osteogenic differentiation of human mesenchymal stem cells as evidenced by increased alkaline phosphatase activity, improved cell attachment and reorganized cytoskeletal filaments. The findings in this study provide improved methods for achieving controlled release of bioactive proteins from electrospun materials.
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http://dx.doi.org/10.1002/jbm.a.34730DOI Listing
March 2014

The influence of piezoelectric scaffolds on neural differentiation of human neural stem/progenitor cells.

Tissue Eng Part A 2012 Oct 9;18(19-20):2063-72. Epub 2012 Jul 9.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102-1982, USA.

Human neural stem/progenitor cells (hNSCs/NPCs) are a promising cell source for neural tissue engineering because of their ability to differentiate into various neural lineages. In this study, hNSC/NPC differentiation was evaluated on piezoelectric, fibrous scaffolds. These smart materials have an intrinsic material property where transient electric potential can be generated in the material upon minute mechanical deformation. hNSCs/NPCs cultured on the scaffolds and films differentiated into β-III tubulin-positive cells, a neuronal cell marker, with or without the presence of inductive factors. In contrast, hNSCs/NPCs cultured on laminin-coated plates were predominantly nestin positive, a NSC marker, in the control medium. Gene expression results suggest that the scaffolds may have promoted the formation of mature neural cells exhibiting neuron-like characteristics. hNSCs/NPCs differentiated mostly into β-III tubulin-positive cells and had the greatest average neurite length on micron-sized, annealed (more piezoelectric), aligned scaffolds, demonstrating their potential for neural tissue-engineering applications.
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http://dx.doi.org/10.1089/ten.TEA.2011.0540DOI Listing
October 2012

Neurite extension of primary neurons on electrospun piezoelectric scaffolds.

Acta Biomater 2011 Nov 14;7(11):3877-86. Epub 2011 Jul 14.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102-1982, USA.

Neural tissue engineering may be a promising option for neural repair treatment, for which a well-designed scaffold is essential. Smart materials that can stimulate neurite extension and outgrowth have been investigated as potential scaffolding materials. A piezoelectric polymer polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE) was used to fabricate electrospun aligned and random scaffolds having nano- or micron-sized fiber dimensions. The advantage of using a piezoelectric polymer is its intrinsic electrical properties. The piezoelectric characteristics of PVDF-TrFE scaffolds were shown to be enhanced by annealing. Dorsal root ganglion (DRG) neurons attached to all fibrous scaffolds. Neurites extended radially on random scaffolds, whereas aligned scaffolds directed neurite outgrowth for all fiber dimensions. Neurite extension was greatest on aligned, annealed PVDF-TrFE having micron-sized fiber dimensions in comparison with annealed and as-spun random PVDF-TrFE scaffolds. DRG on micron-sized aligned, as-spun and annealed PVDF-TrFE also had the lowest aspect ratio amongst all scaffolds, including non-piezoelectric PVDF and collagen-coated substrates. Findings from this study demonstrate the potential use of a piezoelectric fibrous scaffold for neural repair applications.
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http://dx.doi.org/10.1016/j.actbio.2011.07.013DOI Listing
November 2011

Microscale versus nanoscale scaffold architecture for mesenchymal stem cell chondrogenesis.

Tissue Eng Part A 2011 Mar 14;17(5-6):831-40. Epub 2010 Dec 14.

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.

Nanofiber scaffolds, produced by the electrospinning technique, have gained widespread attention in tissue engineering due to their morphological similarities to the native extracellular matrix. For cartilage repair, studies have examined their feasibility; however these studies have been limited, excluding the influence of other scaffold design features. This study evaluated the effect of scaffold design, specifically examining a range of nano to micron-sized fibers and resulting pore size and mechanical properties, on human mesenchymal stem cells (MSCs) derived from the adult bone marrow during chondrogenesis. MSC differentiation was examined on these scaffolds with an emphasis on temporal gene expression of chondrogenic markers and the pluripotent gene, Sox2, which has yet to be explored for MSCs during chondrogenesis and in combination with tissue engineering scaffolds. Chondrogenic markers of aggrecan, chondroadherin, sox9, and collagen type II were highest for cells on micron-sized fibers (5 and 9 μm) with pore sizes of 27 and 29 μm, respectively, in comparison to cells on nano-sized fibers (300 nm and 600 to 1400 nm) having pore sizes of 2 and 3 μm, respectively. Undifferentiated MSCs expressed high levels of the Sox2 gene but displayed negligible levels on all scaffolds with or without the presence of inductive factors, suggesting that the physical features of the scaffold play an important role in differentiation. Micron-sized fibers with large pore structures and mechanical properties comparable to the cartilage ECM enhanced chondrogenesis, demonstrating architectural features as well as mechanical properties of electrospun fibrous scaffolds enhance differentiation.
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http://dx.doi.org/10.1089/ten.TEA.2010.0409DOI Listing
March 2011

Mesenchymal stem cells accelerate bone allograft incorporation in the presence of diabetes mellitus.

J Orthop Res 2010 Jul;28(7):942-9

Department of Orthopaedics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School and Graduate School of Biomedical Sciences, , Newark, New Jersey 07102, USA.

Allograft (Allo) incorporation in the presence of a systemic disease like diabetes mellitus (DM) is becoming a major issue in the orthopedic community. Mesenchymal stem cells (MSC) are multipotent stem cells that may be derived from adult, whole bone marrow and have been shown to induce bone formation in segmental defects when combined with the appropriate carrier/scaffold. The objectives of this study were to analyze the effect of DM upon Allo incorporation in a segmental rat femoral defect and to also investigate MSC augmentation of Allo incorporation. Segmental (5 mm) femoral defects were created in non-DM and DM rats and treated with Allo containing demineralized bone matrix (DBM) or DBM with MSC augmentation. Histological scoring at 4 weeks demonstrated less mature bone in the DM/DBM group compared to its non-DM counterpart (p < 0.001). However, there was significantly more mature bone in the DM/MSC group when compared to the DM/DBM group at both 4 and 8 weeks (p < 0.001 and p = 0.004). Furthermore, significantly more bone formation was observed in the DM/MSC group compared to the DM/DBM group at the 4-week time point (p < 0.001). The results of this study suggest that MSC are a potential adjunct for bone regeneration when implanted in an orthotopic site in the presence of DM.
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http://dx.doi.org/10.1002/jor.21065DOI Listing
July 2010

Osteogenic differentiation of human mesenchymal stem cells on poly(ethylene glycol)-variant biomaterials.

J Biomed Mater Res A 2009 Dec;91(4):975-84

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102.

This study evaluated the osteogenic differentiation of human mesenchymal stem cells (MSCs), on tyrosine-derived polycarbonates copolymerized with poly(ethylene glycol) (PEG) to determine their potential as a scaffold for bone tissue engineering applications. The addition of PEG in the backbone of polycarbonates has been shown to alter mechanical properties, degradation rates, degree of protein adsorption, and subsequent cell adhesion and motility in mature cell phenotypes. Its effect on MSC behavior is unknown. MSC morphology, motility, proliferation, and osteogenic differentiation were evaluated on polycarbonates containing 0-5% PEG over a 14 day culture. MSCs on polycarbonates containing 0% or 3% PEG content upregulated the expression of osteogenic markers as demonstrated by alkaline phosphatase activity and osteocalcin expression although at different stages in the 14 day culture. Cells on polycarbonates containing no PEG were characterized as having early onset of cell spreading and osteogenic differentiation. Cells on 3% PEG surfaces were delayed in cell spreading and osteogenic differentiation, but had the highest motility as compared with cells on substrates containing no PEG and substrates containing 5% PEG at early time points. Throughout the culture, cells on polycarbonates containing 5% PEG had the lowest levels of osteogenic markers, displayed poor cell-substrate adhesion, and established cell-cell aggregates. Thus, designing substrates with minute variations in PEG may serve as a tool to guide MSC adhesion and motility accompanying osteogenic differentiation, and may be beneficial for abundant bone tissue formation in vivo.
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http://dx.doi.org/10.1002/jbm.a.32310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783514PMC
December 2009

Mesenchymal stem cells for bone repair: preclinical studies and potential orthopedic applications.

Foot Ankle Clin 2005 Dec;10(4):651-65, viii

New Jersey Institute of Technology Biomedical Engineering, 614 East Building, University Heights, Newark, NJ 07102, USA.

Mesenchymal stem cells (MSCs), derived from adult bone marrow, are multi-potent stem cells capable of differentiating along several lineage pathways. From a small bone marrow aspirate, MSCs can be readily isolated and easily expanded. Therefore, MSCs are thought to be a readily available source of cells for many tissue engineering and regenerative medicine applications. This review covers preclinical models that evaluate the efficacy of MSC-loaded scaffolds in large bone defects as a potential substitute for autologous and allogeneic bone grafts. This review also covers new approaches to clinical use of MSC technology.
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http://dx.doi.org/10.1016/j.fcl.2005.06.004DOI Listing
December 2005

Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect.

J Bone Joint Surg Am 2003 Oct;85(10):1927-35

Osiris Therapeutics, Baltimore, Maryland, USA.

Background: Mesenchymal stem cells from adult bone marrow are multipotent cells capable of forming bone, cartilage, and other connective tissues. In a previous study, we demonstrated that autologous mesenchymal stem cells could repair a critical-sized bone defect in the dog. The objective of this study was to determine whether the use of allogeneic mesenchymal stem cells could heal a critical-sized bone defect in the femoral diaphysis in dogs without the use of immunosuppressive therapy.

Methods: A critical-sized segmental bone defect, 21 mm in length, was created in the mid-portion of the femoral diaphysis of twelve adult dogs that weighed between 22 and 25 kg. Each defect was treated with allogeneic mesenchymal stem cells loaded onto a hollow ceramic cylinder consisting of hydroxyapatite-tricalcium phosphate. A complete mismatch between donor stem cells and recipient dogs was identified by dog leukocyte antigen typing prior to implantation. The healing response was evaluated histologically and radiographically at four, eight, and sixteen weeks after implantation. The radiographic and histological results at sixteen weeks were compared with the historical data for the control defects, which included defects that had been treated with a cylinder loaded with autologous mesenchymal stem cells, defects treated with a cylinder without mesenchymal stem cells, and defects that had been left untreated (empty). The systemic immune response was evaluated by the analysis of recipient serum for production of antibodies against allogeneic cells.

Results: For defects treated with allogeneic mesenchymal stem cell implants, no adverse host response could be detected at any time-point. Histologically, no lymphocytic infiltration occurred and no antibodies against allogeneic cells were detected. Histologically, by eight weeks, a callus spanned the length of the defect, and lamellar bone filled the pores of the implant at the host bone-implant interface. Fluorescently labeled allogeneic cells were also detected. At sixteen weeks, new bone had formed throughout the implant. These results were consistent with those seen in implants loaded with autologous cells. Implants loaded with allogeneic or autologous stem cells had significantly greater amounts of bone within the available pore space than did cell-free implants at sixteen weeks (p < 0.05).

Conclusions: The results of this study demonstrated that allogeneic mesenchymal stem cells loaded on hydroxyapatite-tricalcium phosphate implants enhanced the repair of a critical-sized segmental defect in the canine femur without the use of immunosuppressive therapy. No adverse immune response was detected in this model.
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http://dx.doi.org/10.2106/00004623-200310000-00010DOI Listing
October 2003