Highly Hydrophobic Electrospun Fiber Mats From Polyisobutylene-based Thermoplastic Elastomers
arborescent; architecture; Biochemistry & Molecular Biology; block-copolymers; Chemistry; coatings; drug-eluting stent; nanofibers; Polymer Science; surfaces
This paper is the first report of electrospinning neat polyisobutylene-based thermoplastic elastomers. Two generations of these materials are investigated: a linear poly(styrene-b-isobutylene-b-styrene) (LSIBS) triblock copolymer and a dendritic poly(isobutylene-b-p-methylstyrene) (DIB-MS), also a candidate for biomedical applications. Cross-polarized optical microscopy shows birefringence, indicating orientation in the electrospun fibers, which undergo large elongation and shear during electrospinning. In contrast to the circular cross section of LSIBS fibers, DIB-MS yields dumbbell-shaped fiber cross sections for the combination of processing conditions, molecular weight, and architecture. Hydrophobic surfaces with a water contact angle as high as 146 +/- 30 degrees were obtained with DIB-MS that had the noncircular fiber cross section and a hierarchical arrangement of nano- to micrometer-sized fibers in the mat. These highly water repellent fiber mats were found to serve as an excellent scaffold for bovine chondrocytes to produce cartilage tissue.
Lim G T; Puskas J E; Reneker D H; Jakli A; Horton W E
Biomacromolecules
2011
2011-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1021/bm200157b" target="_blank" rel="noreferrer noopener">10.1021/bm200157b</a>
Two Generations Of Synthetic Membranes For Biological/medical Applications
amphiphilic membranes; amphiphilic networks; biocompatibility; diffusion; domains; Glucose; immunoisolation; insulin diffusion; isobutylene; living carbocationic polymerization; membranes; polyisobutylene; Polymer Science; polymers; selective permeability; tricomponent
Two generations of amphiphilic membranes synthesized in our laboratories for biologicaUniedical applications are highlighted. Recent results obtained with representative 2nd generation membranes designed specifically for immunoencapsulation of pancreatic islets and cells, are Summarized. The latter tri-component membranes comprise well-defined hydrophilic poly(ethylene glycol) and hydrophobic/oxyphilic polydimethylsiloxane segments crosslinked by oxyphilic polycyclosiloxane domains, which also provide reinforcement. Select membranes are demonstrated to allow the diffusion of glucose and insulin but prevent the permeation of immunoglobulin G. These membranes remain permeable despite long incubation in IgG solution.
Kennedy J P; Rosenthal K S; Kashibhatla B
Designed Monomers and Polymers
2004
2004
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1163/1568555042474112" target="_blank" rel="noreferrer noopener">10.1163/1568555042474112</a>
Synthesis And Characterization Of Tubular Amphiphilic Networks With Controlled Pore Dimensions For Insulin Delivery
drug release; Polymer Science
A convenient laboratory process for the preparation of thin-walled (similar to 0.02 cm) tubular amphiphilic membranes has been developed. The membranes are suitable for implantation and isolation of pancreatic islets from immune responses. The process involves the simultaneous free radical copolymerization/crosslinking of dimethyl acrylamide (DMAAm) and methacrylate ditelechelic polyisobutylene (MA-PIB-MA) in narrow-bore (similar to 4 mm inner diameter) glass tubes horizontally rotating in a thermostated oven. The pore sizes of the membranes can be controlled by the length, i.e. molecular weight, of the hydrophilic poly(dimethyl acrylamide) (PDMAAm) segment (M-c,M-hydrophilic). Pore sizes, M-c,M-hydrophilic's, and molecular weight cut-off (MWCO) ranges of designed amphiphilic membranes were characterized in terms of Stokes (or viscosity) radii (Rs) and the relationships between these parameters were evaluated. Membranes were designed to allow the rapid diffusion of molecules such as insulin (M-n = 5733 g/mol, R-s = 1.34 nm) but to be opaque to serum albumin (M-n > 66 000 g/mol, R-s > 3.62 nm) and larger proteins such as immunoglobulins. The diffusion coefficients (D) and permeabilities (P) of tubular and flat-sheet amphiphilic membranes have been compared and were found to be similar. Membrane pore size dimensions of the tubular devices were determined by the out-diffusion of commercially available protein markers of known molecular weights (M-n = 6500-66 000 g/mol) and dimensions (R-s = 1.50-3.62 nm). It was found that the minimum M-c,M-hydrophilic or R-s that still allows the diffusion of insulin is similar to 800 g/mol or similar to 1.34 nm, respectively, and that the maximum M-c,M-hydrophilic or R-s that prevents the ingress of antibodies is similar to 5000 g/mol or similar to 3.62 nm, respectively. According to diffusion experiments, the presence or absence of lightly crosslinked 1% calcium alginate does not affect the rate of diffusion of glucose and insulin through our tubules. These membranes are being used in vivo for encapsulating islet cells for implantation to correct type 1 diabetes.
Kennedy J P; Fenyvesi G; Na S; Keszler B; Rosenthal K S
Designed Monomers and Polymers
2000
2000
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1163/156855500750198762" target="_blank" rel="noreferrer noopener">10.1163/156855500750198762</a>
Amphiphilic Membranes With Controlled Mesh Dimensions For Insulin Delivery
immunosuppression; islets; networks; Polymer Science; porcine; release; xenotransplantation
A series of amphiphilic networks (membranes), consisting of hydrophilic poly(N,N-dimethylacrylamide) (PDMAAM) main chains crosslinked by hydrophobic telechelic polyisobutylene di- and trimethacrylates (MA-PIB-MA or circle divide (PEB-MA)(3)) have been synthesized and used for the preparation of thin-walled tubules suitable for the immunoisolation of porcine islets. The molecular weight cut-off (MWCO) ranges, insulin and glucose diffusion coefficients and permeabilities of various membranes have been determined. The molecular weight of the PDMAAM moiety between two hydrophobic crosslinking points M-c,M-hydrophilic) controls permeability, which in turn can be controlled by synthesis conditions. The strengths and elongations of water-swollen membranes crosslinked with circle divide (PIB-MA)(3) are superior by a factor of about two to those prepared with MA-PIB-MA. Based on the values from these experiments, a well-defined membrane prepared with circle divide (PEB-MA)(3) was selected and used to encapsulate porcine islet cells. Gratifyingly, the encapsulated islet cells remain functional and viable, and cells within the tubule release insulin upon glucose challenge. These in vitro experiments are sufficiently promising to encourage us to continue our studies to develop a bioartificial pancreas.
Kennedy J P; Fenyvesi G; Levy R P; Rosenthal K S
Macromolecular Symposia
2001
2001-06
Journal Article or Conference Abstract Publication
n/a
Photoresponsive Coumarin Polyesters That Exhibit Cross-linking And Chain Scission Properties
derivatives; dimerization; drug-delivery; hydrogels; light-triggered release; mechanisms; Polymer Science; polymeric nanoparticles; protecting groups; scaffolds; solid-state
Maddipatla Mvsn; Wehrung D; Tang C; Fan W Z; Oyewumi M O; Miyoshi T; Joy A
Macromolecules
2013
2013-07
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1021/ma400584y" target="_blank" rel="noreferrer noopener">10.1021/ma400584y</a>
ECM Production of Primary Human and Bovine Chondrocytes in Hybrid PEG Hydrogels Containing Type I Collagen and Hyaluronic Acid
osteoarthritis; Chemistry; Biochemistry & Molecular Biology; prevalence; stem-cells; matrix; arthritis; articular-cartilage; knee; networks; Polymer Science; chondral defects; microfracture
The development of advanced materials that facilitate hyaline cartilage formation and regeneration in aging populations is imperative. Critical to the success of this endeavor is the optimization of ECM production from clinically relevant cells. However, much of the current literature focuses on the investigation of primary bovine chondrocytes from young calves, which differ significantly than osteoarthritic cells from human sources. This study examines the levels of extracellular matrix (ECM) production using various levels of type I collagen and hyaluronic acid in poly(ethylene glycol) dimethacrylate (PEGDM) hydrogels in total knee arthroplasties, compared with the results from bovine chondrocytes. The addition of type 1 collagen in both the presence and absence of low levels of hyaluronic acid increased ECM production and/or retention in scaffolds containing either bovine or human chondrocytes. These findings are supported consistently with colorimetric quantification, whole mount extracellular matrix staining for both cell types, and histological staining for glycoaminoglycans and collagen of human chondrocyte containing samples. While exhibiting similar trends, the relative ECM productions levels for the primary human chondrocytes are significantly less than the bovine chondrocytes which reinforces the need for additional optimization.
Callahan L A S; Ganios A M; McBurney D L; Dilisio M F; Weiner S D; Horton W E; Becker M L
Biomacromolecules
2012
2012-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1021/bm3003336" target="_blank" rel="noreferrer noopener">10.1021/bm3003336</a>
The role of mineral in the storage of elastic energy in turkey tendons
age; Biochemistry & Molecular Biology; Chemistry; collagen; crosslinks; mechanical properties; Polymer Science; tissue
Mammals elastically store energy in leg and foot tendons during locomotion. In the turkey, much of the force generated by the gastrocnemius muscle is stored as elastic energy during tendon deformation and not within the muscle. During growth, avian tendons mineralize in the portions distal to the muscle and show increased tensile strength and modulus as a result. The purpose of this study was to evaluate the viscoelastic behavior of turkey tendons and self-assembled collagen fiber models to determine the molecular basis for tendon deformation. The stress-strain behavior of tendons and self-assembled collagen fibers was broken into elastic and viscous components. The elastic component was found to be to a first approximation independent of source of the collagen and to depend only on the extent of cross-linking. In the absence of cross-links the elastic component of the stress was found to be negligible for self-assembled type I collagen fibers. In the presence of cross-links the behavior approached that found for mineralized turkey tendons. The elastic constant for turkey tendon was shown to be between 5 and 7.75 GPa while it was about 6.43 Gpa for self-assembled collagen fibers aged for 6 months at 22 degreesC. The viscous component for mineralized turkey tendons was about the same as that of self-assembled collagen fibers aged for 6 months, a result suggesting that addition of mineral does not alter the viscous properties of tendon. It is concluded that elastic energy storage in tendons involves direct stretching of the collagen triple-helix, nonhelical ends, and cross-links between the molecules and is unaffected by mineralization. Furthermore, it is hypothesized that mineralization of turkey tendons is an efficient means of preserving elastic energy storage while providing for increased load-bearing ability required for locomotion of adult birds.
Silver F H; Christiansen D; Snowhill P B; Chen Y; Landis W J
Biomacromolecules
2000
2000
Journal Article
<a href="http://doi.org/10.1021/bm9900139" target="_blank" rel="noreferrer noopener">10.1021/bm9900139</a>
Molecular basis for elastic energy storage in mineralized tendon
Biochemistry & Molecular Biology; bone; Chemistry; collagen fibrils; dentin phosphophoryn; electron-microscopic tomography; in-vivo; matrix; Polymer Science; proteoglycan
Animals store elastic energy in leg and foot tendons during locomotion. In the turkey, much of the locomotive force generated by the gastrocnemius muscle is stored as elastic energy during tendon deformation. Little energy storage occurs within the muscle. During growth of some avians, including the turkey, leg tendons mineralize in the portions distal to the attached muscle and show increased tensile strength and modulus as a result. The put-pose of this study is to test the hypothesis that the degree of elastic energy storage in mineralizing turkey tendon is directly related to the tendon mineral content. To test this hypothesis, the stress-strain behavior of tendons was separated into elastic and viscous components. Both the elastic spring constant and the elastic energy stored, calculated up to a strain of 20%, were found to be proportional to tendon mineral content. It is concluded that mineralization is an efficient means for increasing the amount of elastic energy storage that is required for increased load-bearing ability needed for locomotion of adult birds. Examination of molecular models of the hole region, where mineralization is initiated within the collagen fibril, leads to the hypothesis that elastic energy is stored in the tendon by direct stretching of the flexible regions. Flexible regions within the collagen molecule fall within the positively stained bands of the collagen D period. It is proposed that mineralization increases the stored elastic energy by preventing flexible regions within the positively stained bands from stretching. These observations suggest that mineralization be-ins in the hole region due to the large number of charged amino acid residues found in the d and e bands.
Silver F H; Freeman J W; Horvath I; Landis W J
Biomacromolecules
2001
2001
Journal Article
<a href="http://doi.org/10.1021/bm0100615" target="_blank" rel="noreferrer noopener">10.1021/bm0100615</a>