Biomedical subjects

Anil Thapa

Publications and source records attributed to Anil Thapa.

6 recordsLinked to original sources

PubMed2005

Esophageal reconstruction with ECM and muscle tissue in a dog model.

An in vivo study was conducted to determine if an extracellular matrix (ECM) scaffold co-localized with autologous muscle tissue could achieve constructive remodeling of esophageal tissue without stricture. ECM derived from the porcine urinary bladder was processed, decellularized, configured into a tube shape, and terminally sterilized for use as a bioscaffold for esophageal reconstruction in a dog model. Twenty-two dogs were divided into four groups, three groups of five and one group of seven. Groups 1 and 2 were repaired with either ECM alone or muscle tissue alone, respectively. Groups 3 and 4 were repaired with ECM plus either a partial (30%) covering with muscle tissue or a complete (100%) covering with muscle tissue, respectively. Animals in groups 1 and 2 were sacrificed within approximately 3 weeks because of the formation of intractable esophageal stricture. Four of five dogs in group 3 and six of seven dogs in group 4 were survived for 26 days to 230 days and showed constructive remodeling of esophageal tissue with the formation of well organized esophageal tissue layers, minimal stricture, esophageal motility, and a normal clinical outcome. Mechanical testing of a subset of the remodeled esophageal tissue from animals in groups 3 and 4 showed progressive remodeling from a relatively stiff, non-compliant ECM tube structure toward a tissue with near normal biomechanical properties. We conclude that ECM bioscaffolds plus autologous muscle tissue, but not ECM scaffolds or muscle tissue alone, can facilitate the in situ reconstitution of structurally and functionally acceptable esophageal tissue.

Animals↗

PubMed2004

Decreased fibroblast cell density on chemically degraded poly-lactic-co-glycolic acid, polyurethane, and polycaprolactone.

Select prolonged functions of fibroblasts leading to extensive fibrous tissue encapsulation can be detrimental to numerous implant applications, including materials designed for the bladder, vasculature, and bone. Specifically, overextended functions of fibroblasts at the tissue-implant interface for orthopedic applications lead to callus formation, fibrous encapsulation events, and ultimately soft (not desirable hard-bony) tissue juxtaposition. Such events result in insufficient regeneration of bone and compromise the overall success of the implant. The objective of the present in vitro study was to determine, for the first time, fibroblast densities on NaOH-treated poly-lactic-co-glycolic acid co-polymers (PLGA), HNO(3)-treated polyurethane (PU), and NaOH-treated polycaprolactone (PCL). Previous studies have demonstrated increased bladder, vascular, and bone cell densities on chemically treated compared to unaltered PLGA, PU, and PCL films. Results of this study provided evidence of decreased fibroblast numbers on chemically treated PLGA, PU, and PCL after time periods of up to 5 days. Examination of these substrates revealed that all chemically modified polymers possessed a high degree of nanometer surface roughness compared to their respective unaltered polymers. In contrast, other material properties (such as chemistry and wettability) were different when comparing chemically treated PLGA, PU, and PCL films. Since fibroblasts are anchorage-dependent cells whose adhesion is a critical prerequisite to the prolonged, extensive formation of a fibrous-tissue containing extracellular matrix, the present in vitro results of decreased fibroblast densities on chemically degraded PLGA, PU, and PCL suggest that these materials may be suitable materials for numerous tissue-engineering applications and, thus, deserve further investigation.

Absorbable Implants↗

PubMed2004

Endothelial and vascular smooth muscle cell function on poly(lactic-co-glycolic acid) with nano-structured surface features.

Biomaterials that successfully integrate into surrounding tissue should match not only the tissue's mechanical properties, but also its topography. The cellular response to a biomaterial may be enhanced in synthetic polymer formulations by mimicking the surface roughness created by the associated nano-structured extra-cellular matrix components of natural tissue. As a first step towards this endeavor, the goal of the present in vitro study was to use these design parameters to develop a synthetic, nano-structured, polymeric biomaterial that promotes cell adhesion and growth for vascular applications. In a novel manner, poly(lactic-co-glycolic acid) (PLGA) (50/50wt% mix) was synthesized to possess a range (from micron to nanometer) of surface features. Reduction of surface features was accomplished by treating conventional PLGA with various concentrations of NaOH for select periods of time. Results from cell experiments indicated that, compared to conventional PLGA, NaOH treated PLGA enhanced vascular smooth muscle cell adhesion and proliferation. However, PLGA prepared by soaking in NaOH decreased endothelial cell adhesion and proliferation compared to conventional PLGA. After further investigation, this finding was determined to be a result of chemical (and not topographical) changes during polymer synthesis. Surface chemistry effects were removed while retaining nano-structured topography by using polymer/elastomer casting methods. Results demonstrated that endothelial and smooth muscle cell densities increased on nano-structured cast PLGA. For these reasons, the present in vitro study provided the first evidence that nano-structured surface features can significantly improve vascular cell densities; such design criteria can be used in the synthesis of the next-generation of more successful tissue-engineered vascular grafts.

Animals↗

PubMed2003

Polymers with nano-dimensional surface features enhance bladder smooth muscle cell adhesion.

Previous studies investigating the design of synthetic bladder wall substitutes have involved polymers with micro dimensional structures. Since the body is made up of nano-structured components (e.g., extracellular matrix proteins), the focus of the present in vitro study was to design nano-structured polymers for use as synthetic bladder constructs that mimic the topography of natural bladder tissue. In order to complete this task, novel nano-structured biodegradable polymeric films of poly-lactic-co-glycolic-acid (PLGA), poly-ether-urethane (PU), and poly-caprolactone (PCL) were fabricated and separately treated with various concentrations of NaOH (for PLGA and PCL) and HNO(3) (for PU) for select time periods. These treatments reduced the polymer surface feature dimensions from conventional micron dimensions to biologically inspired nanometer dimensions. Select cytocompatibility properties of these biomaterials were tested in vitro. Results provide the first evidence that adhesion of bladder smooth muscle cells is enhanced as polymer surface feature dimensions are reduced into the nanometer range. In addition, surface analysis results reveal that the polymer nanometer surface roughness is the primary design parameter that increases bladder smooth muscle cell adhesion. For this reason, the "next generation" of tissue-engineered bladder constructs with increased efficacy should contain surfaces with nanometer (as opposed to micron) surface features.

Animals↗

PubMed2003

Nano-structured polymers enhance bladder smooth muscle cell function.

It is the hypothesis of the present study that a biocompatible material which mimics the nanometer topography of native bladder tissue will enhance cellular responses and lead to better tissue integration in vivo. Previous in vitro studies have verified the ability to successfully reduce the surface feature dimensions of poly(lactic-co-glycolic acid) (PLGA) and poly(ether urethane) (PU) films into the nanometer regime via chemical etching procedures. Results from these studies also provided the first evidence that bladder smooth muscle cell adhesion was enhanced on chemically treated nano-structured polymeric surfaces compared to their conventional counterparts. Although cell adhesion is necessary for a biomaterial's success, subsequent cell functions (such as long-term cell growth and proliferation) are also critical for tissue ingrowth and long-term implant survival. The present in vitro study, therefore, investigated the function of bladder smooth muscle cells on these novel, nano-structured polymers over the expanded periods of 1, 3 and 5 days. Results indicated that cell number was influenced by both surface roughness and surface chemistry changes; the important contributor, however, was increased nanometer surface roughness. This claim is supported by the fact that cell number was enhanced on nano-structured compared to conventional PLGA and PU once chemistry changes were eliminated using casting techniques.

Animals↗

PubMed2002

Nanostructured polymer/nanophase ceramic composites enhance osteoblast and chondrocyte adhesion.

Osteoblast (bone-forming cell) and chondrocyte (cartilage-synthesizing cell) adhesion on novel nanostructured polylactic/glycolic acid (PLGA) and titania composites were investigated in the present in vitro study. Nanostructured polymers were created by chemically treating micron-structured PLGA with select concentrations of NaOH for various periods of time. Dimensions of ceramics were controlled by utilizing either micron or nanometer grain size titania. Compared with surfaces with conventional or micron surface roughness dimensions, results provided the first evidence of increased osteoblast and chondrocyte adhesion on 100 wt% PLGA films with nanometer polymer surface roughness dimensions. Results also confirmed other literature reports of enhanced osteoblast adhesion on 100 wt% nanometer compared with conventional grain size titania compacts; however, the present study provided the first evidence that decreasing titania grain size into the nanometer range did not influence chondrocyte adhesion. Finally, osteoblast and chondrocyte adhesion increased on 70/30 wt% PLGA/titania composites formulated to possess nanosurface rather than conventional surface feature dimensions. The present study, thus, provided evidence that these nanostructured PLGA/titania composites may possess the ability to simulate surface and/or chemical properties of bone and cartilage, respectively, to allow for exciting alternatives in the design of prostheses with greater efficacy.

Cell Adhesion↗