-
[show abstract]
[hide abstract]
ABSTRACT: Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed "PolyMorphine", was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopies, and infrared spectroscopy. The weight-average molecular weight and the thermal properties were determined. The hydrolytic degradation pathway of the polymer was determined by in vitro studies, showing that free morphine is released. In vitro cytocompatibility studies demonstrated that PolyMorphine is non-cytotoxic towards fibroblasts. In vivo studies using mice showed that PolyMorphine provides analgesia for 3days, 20 times the analgesic window of free morphine. The animals retained full responsiveness to morphine after being subjected to an acute morphine challenge.
Journal of Controlled Release 08/2012; 162(3):538-44. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Continuous biomaterial advances and the regenerating potential of the adult human peripheral nervous system offer great promise for restoring full function to innervated tissue following traumatic injury via synthetic nerve guidance conduits (NGCs). To most effectively facilitate nerve regeneration, a tissue engineering scaffold within a conduit must be similar to the linear microenvironment of the healthy nerve. To mimic the native nerve structure, aligned poly(lactic-co-glycolic acid)/bioactive polyanhydride fibrous substrates were fabricated through optimized electrospinning parameters with diameters of 600 ± 200 nm. Scanning electron microscopy images show fibers with a high degree of alignment. Schwann cells and dissociated rat dorsal root ganglia demonstrated elongated and healthy proliferation in a direction parallel to orientated electrospun fibers with significantly longer Schwann cell process length and neurite outgrowth when compared to randomly orientated fibers. Results suggest that an aligned polyanhydride fiber mat holds tremendous promise as a supplement scaffold for the interior of a degradable polymer NGC. Bioactive salicylic acid-based polyanhydride fibers are not limited to nerve regeneration and offer exciting promise for a wide variety of biomedical applications.
Journal of Biomedical Materials Research Part A 03/2011; 97(3):230-42. · 2.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Microscale plasma-initiated patterning (μPIP) is a novel micropatterning technique used to create biomolecular micropatterns on polymer surfaces. The patterning method uses a polydimethylsiloxane (PDMS) stamp to selectively protect regions of an underlying substrate from oxygen plasma treatment resulting in hydrophobic and hydrophilic regions. Preferential adsorption of the biomolecules onto either the plasma-exposed (hydrophilic) or plasma-protected (hydrophobic) regions leads to the biomolecular micropatterns. In the current work, laminin-1 was applied to an electrospun polyamide nanofibrillar matrix following plasma treatment. Radial glial clones (neural precursors) selectively adhered to these patterned matrices following the contours of proteins on the surface. This work demonstrates that textured surfaces, such as nanofibrillar scaffolds, can be micropatterned to provide external chemical cues for cellular organization.
Colloids and surfaces. B, Biointerfaces 01/2011; 84(2):591-6. · 2.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Scanning probe recognition microscopy (SPRM) with auto-tracking of individual nanofibres is used for investigation of the key nanoscale properties of polyamide a nanofibrillar matrix that promotes more in vivo-like forms and functions for cultured cells. Both unmodified and fibroblast growth factor-2-modified nanofibres are considered. The contributions of nanofibrillar matrix elasticity and surface roughness to cellular behaviour are examined. East Lansing, Michigan. Her research interests include neurobiology and nanotechnology, with a special emphasis on astrocyte/neuron interactions and regulation of neuronal regeneration by naturally occurring and synthetic extracellular matrix. Ijaz Ahmed received his Masters in Biological Sciences from the University of Saskatchewan, Canada and his PhD in Biomedical Sciences from the University of Central Lancashire, England. His research interests include neurobiology of glial cells. Roberto Delgado-Rivera is a fourth year graduate student at Rutgers University in the Department of Chemistry and Chemical Biology. He received his BS in Industrial Biotechnology at the University of Puerto Rico, Mayagüez. His research focuses in the area of surface modification and characterisation of polymeric materials for tissue engineering applications. He has been able to perform research under a highly cross-disciplinary research program involving the areas of cellular and molecular biology, nanobiotechnoloy, polymer engineering and biointerfacial characterisation.
Int. J. Nanomanufacturing. 01/2010; 63:279-290.
-
[show abstract]
[hide abstract]
ABSTRACT: Implantable biodegradable nerve guidance conduits (NGCs) have the potential to align and support regenerating cells, as well as prevent scar formation. In this study in vitro bioassays and in vivo material evaluations were performed using a nerve guidance conduit material made from a novel polyanhydride blend. In vitro cytotoxicity studies with both fibroblasts and primary chick neurons demonstrated that the proposed polyanhydride blend was non-cytotoxic. Subcutaneous implantation for 7days in rats resulted in an initial fibrin matrix, minimal macrophage presence and angiogenesis in the surrounding tissues. Nerve guidance conduits fabricated from the proposed polyanhydride blend material may serve as favorable biocompatible tissue engineering devices.
Acta biomaterialia 11/2009; 6(6):1917-24. · 3.98 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An electrospun nonwoven matrix of polyamide nanofibers was employed as a new model for the capillary basement membrane at the blood-brain barrier (BBB). The basement membrane separates astrocytes from endothelial cells and is associated with growth factors, such as fibroblast growth factor-2 (FGF-2). FGF-2 is produced by astrocytes and induces specialized functions in endothelial cells, but also has actions on astrocytes. To investigate potential autocrine actions of FGF-2 at the BBB, astrocytes were cultured on unmodified nanofibers or nanofibers covalently modified with FGF-2. The former assumed an in vivo-like stellate morphology that was enhanced in the presence of cross-linked FGF-2. Furthermore, astrocyte monolayers established on unmodified nanofibers were more permissive for neurite outgrowth when cultured with an overlay of neurons than similar monolayers established on standard tissue culture surfaces, while astrocytes cultured on FGF-2-modifed nanofibers were yet more permissive. The observed differences were due in part to progressively increasing amounts of FGF-2 secreted by the astrocytes into the medium; hence FGF-2 increases its own expression in astrocytes to modulate astrocyte-neuron interactions. Soluble FGF-2 was unable to replicate the effects of cross-linked FGF-2. Nanofibers alone up-regulated FGF-2, albeit to a lesser extent than nanofibers covalently modified with FGF-2. These results underscore the importance of both surface topography and growth factor presentation on cellular function. Moreover, these results indicate that FGF-2-modified nanofibrillar scaffolds may demonstrate utility in tissue engineering applications for replacement and regeneration of lost tissue following central nervous system (CNS) injury or disease.
Matrix biology: journal of the International Society for Matrix Biology 03/2009; 28(3):137-47. · 3.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent research indicates that nanophysical properties as well as biochemical cues can influence cellular re-colonization of a tissue scaffold. It has also been shown nanoscale elasticity can strongly influence cellular responses. In the present work, quantitative investigations of the elasticity of a nanofibrillar matrix scaffold that has demonstrated promise for spinal cord injury repair are compared with complementary transmission electron microscopy investigations, performed to assess nanofiber internal structures. Interpretive model improvements are identified and discussed.
MRS Proceedings. 12/2008; 1240.
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The design of implants comprised of biodegradable electrospun nanofibers for the purpose of bridging injuries in damaged spinal cord is discussed. Electrospun nanofibers structurally mimic the extracellular matrix on which neurons and other cell types grow in vivo. This property has created great interest for their use in tissue engineering applications. However, their employment as biomimetic surfaces for such in vivo applications is still in its infancy.RESULTS: A nonwoven fabric comprised of electrospun polyamide nanofibers supported modest axonal regeneration in injured adult rat spinal cord. Covalent modification of the nanofibers with a bioactive peptide derived from the neuroregulatory extracellular matrix molecule tenascin-C enhanced the ability of the nanofibers to facilitate axonal regrowth. However, the random orientation of the nanofibrillar fabric folds was an impediment to the forward movement of axons.CONCLUSIONS: Polyamide nanofibers covalently modified with neuroactive molecules provide a promising material for grafts to promote spinal cord regeneration. However, for the proper guidance of regrowing axons, attention must be paid to the engineering of ordered nanofibrillar structures. Copyright © 2007 Society of Chemical Industry
Polymer International 10/2007; 56(11):1340 - 1348. · 1.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The design of implants comprised of biodegradable electrospun nanofibers for the purpose of bridging injuries in damaged spinal cord is discussed. Electrospun nanofibers structurally mimic the extracellular matrix on which neurons and other cell types grow in vivo. This property has created great interest for their use in tissue engineering applications. However, their employment as biomimetic surfaces for such in vivo applications is still in its infancy. RESULTS: A nonwoven fabric comprised of electrospun polyamide nanofibers supported modest axonal regeneration in injured adult rat spinal cord. Covalent modification of the nanofibers with a bioactive peptide derived from the neuroregulatory extracellular matrix molecule tenascin-C enhanced the ability of the nanofibers to facilitate axonal regrowth. However, the random orientation of the nanofibrillar fabric folds was an impediment to the forward movement of axons.
Polym Int. 01/2007; 56:1340-1348.
