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Biomedical subjects

Stephen Badylak

Publications and source records attributed to Stephen Badylak.

6 recordsLinked to original sources

Towards the development of a pediatric ventricular assist device.

The very limited options available to treat ventricular failure in children with congenital and acquired heart diseases have motivated the development of a pediatric ventricular assist device at the University of Pittsburgh (UoP) and University of Pittsburgh Medical Center (UPMC). Our effort involves a consortium consisting of UoP, Children's Hospital of Pittsburgh (CHP), Carnegie Mellon University, World Heart Corporation, and LaunchPoint Technologies, Inc. The overall aim of our program is to develop a highly reliable, biocompatible ventricular assist device (VAD) for chronic support (6 months) of the unique and high-risk population of children between 3 and 15 kg (patients from birth to 2 years of age). The innovative pediatric ventricular assist device we are developing is based on a miniature mixed flow turbodynamic pump featuring magnetic levitation, to assure minimal blood trauma and risk of thrombosis. This review article discusses the limitations of current pediatric cardiac assist treatment options and the work to date by our consortium toward the development of a pediatric VAD.

Biocompatible Materials↗

Extracellular matrix as a scaffold for laryngeal reconstruction.

Porcine-derived xenogeneic extracellular matrix (ECM) has been successfully used as a scaffold for tissue repair and reconstruction in numerous preclinical animal studies and human applications. These scaffolds are completely and rapidly degraded and replaced by host-derived tissues that frequently mimic the original tissue composition and architecture. The purpose of the present study was to examine the morphology of ECM scaffolds after their use for laryngeal reconstruction. Thirty adult female dogs were subjected to a partial hemilaryngectomy. The right thyroid cartilage and vocal fold were replaced with ECM scaffold, and the dogs were painlessly sacrificed from 1 week to 12 months after surgery. Histologic examination of the reconstructed tissue showed the presence of a simple squamous epithelial lining, organized glandular structures within the submucosa, reconstructed thyroid cartilage, and bundles of skeletal muscle by 3 months after surgery. We conclude that ECM scaffolds are promising templates for constructive remodeling of laryngeal tissue.

Animals↗

Extracellular matrix for myocardial repair.

OBJECTIVE: To evaluate the remodeling characteristics of an extracellular matrix (ECM) scaffold when used as a template for myocardial repair. BACKGROUND: Xenogeneic ECM has been shown to be an effective scaffold for the repair and reconstitution of several tissues, including lower urinary tract structures, dura mater, the esophagus, musculotendinous tissues, and blood vessels. These ECM scaffolds are completely degraded in vivo and induce a host cellular response that supports. Constructive remodeling rather than scar tissue formation. METHODS: Full-thickness circular defects measuring approximately 2.5 cm in diameter were created in the right ventricular anterior walls of 6 adult Yucatán pigs and 4 adult mongrel dogs. The defects were repaired with an ECM sheet 80 m thick that was derived from either the porcine small intestinal submucosa or the porcine urinary bladder matrix. The animals lived for periods of 6 to 24 weeks before sacrifice. RESULTS: There was a complete replacement of the acellular scaffolds by a mixture of tissue types, including well-vascularized fibrous connective tissue, cartilage, adipose connective tissue, and myocardial tissue. The remodeled scaffold tissue showed spontaneous contractility and peak contractile force equivalent to 70% of the contractile force of the adjacent native myocardium. CONCLUSIONS: We conclude that porcine ECM scaffolds alter the typical scar tissue healing response in myocardial tissue and instead support vascularization and the local development of multiple tissue types, including contractile myocardium.

Animals↗

Morphologic study of small intestinal submucosa as a body wall repair device.

BACKGROUND: The extracellular matrix (ECM) derived from porcine small intestinal submucosa (SIS) has been used as a constructive scaffold for tissue repair in both preclinical animal studies and human clinical trials. Quantitative characterization of the host tissue response to this xenogeneic scaffold material has been lacking. MATERIALS AND METHODS: The morphologic response to a multilaminate form of the SIS-ECM was evaluated in a chronic, 2-year study of body wall repair in two separate species: the dog and the rat. Morphologic response to the SIS-ECM was compared to that for three other commonly used bioscaffold materials including Marlex mesh, Dexon, and Perigard. Quantitative measurements were made of tissue consistency, polymorphonuclear cell response, mononuclear cell response, tissue organization, and vascularity at five time points after surgical implantation: 1 week, 1, 3, and 6 months, and 2 years. RESULTS: All bioscaffold materials functioned well as a repair device for large ventral abdominal wall defects created in these two animal models. The SIS-ECM bioscaffold showed a greater number of polymorphonuclear leukocytes at the 1-week time point and a greater degree of graft site tissue organization after 3 months compared to the other three scaffold materials. There was no evidence for local infection or other detrimental local pathology to any of the graft materials at any time point. CONCLUSIONS: Like Marlex, Dexon, and Perigard, the SIS-ECM is an effective bioscaffold for long-term repair of body wall defects. Unlike the other scaffold materials, the resorbable SIS-ECM scaffold was replaced by well-organized host tissues including differentiated skeletal muscle.

Abdominal Muscles↗

Fibronectin peptides mediate HMEC adhesion to porcine-derived extracellular matrix.

Extracellular matrices (ECM) derived from porcine tissues have been shown to support the successful repair and remodeling of injured tissues when evaluated in animal models. Cell-matrix interactions, including ligand-integrin associations that facilitate endothelial cell adhesion, are clearly important in the tissue remodeling process. The goal of the present study was to identify the peptide sequences within the ubiquitous protein fibronectin (FN) that may be important in the initial interactions between the host endothelial cells and the ECM scaffold. Human microvascular endothelial cells (HMEC) were seeded upon porcine ECM after having been subjected to pretreatment with peptide ligands derived from tissue FN and were allowed to attach for 20 min. Non-adherent cells were removed and the remaining, tritium-labeled cells attached to the ECM were counted. Results showed that cyclo-RGD and REDV, but not LDV or PHSRN, play a role in mediating the attachment of HMEC to porcine ECM.

Animals↗

Antimicrobial activity associated with extracellular matrices.

Materials derived from extracellular matrices (ECMs) are being evaluated as scaffolds for surgical reconstruction of damaged or missing tissues. It is important to understand the susceptibility of these biological materials to bacterial infections. ECMs derived from porcine small intestinal submucosa (SIS) and urinary bladder submucosa (UBS) were found to possess antimicrobial activity. ECM extracts, obtained by digesting these acellular matrices in acetic acid, demonstrated antibacterial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Antimicrobial activity was determined using a minimal inhibitory concentration assay. Bacteriostatic activity was detected at protein concentrations of ECM extracts equivalent to 0.77-1.60 mg/mL. ECM extracts were found to inhibit bacterial growth for up to at least 13 h. The resulting extracts consisted of water-soluble peptides and proteins with molecular weights ranging from <4 to >100 kDa and lower molecular weight compounds, as determined by size exclusion liquid chromatography.

Animals↗