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Biomedical subjects

Stephen F Badylak

Publications and source records attributed to Stephen F Badylak.

33 records · Page 2Linked to original sources
PubMed2005

Analytically derived material properties of multilaminated extracellular matrix devices using the ball-burst test.

Xenogeneic extracellular matrices (ECMs) have been shown to be effective as naturally occurring scaffolds for soft-tissue repair. As acellular tissue substitutes at the time of surgical implantation, ECMs are subjected to the mechanical forces and micro-environmental conditions representative of the anatomical location in which they are placed. Ideally such natural scaffolds would possess mechanical properties that allow for normal tissue function in and around the implant site. The ball-burst test was used to simulate biaxial forces and to determine the strength of the ECM scaffold under a relevant physiological loading condition. The ball-burst test, in itself, does not quantify intrinsic mechanical properties and therefore a methodology was developed to determine the maximum stress resultant tangent modulus (MSRTM) or the maximum stress tangent modulus (MSTM), stress to failure (sigma(f)), failure stress resultant (N(f)), ball-burst pressure (P), and maximum elongation (lambda(max)) from the raw ball-burst data obtained at a constant-rate of transverse. The analytical methodology was compared to finite element simulations and showed good correlation with the analytical solution presented. The proposed approximations were used to compute biaxial failure properties for a variety of multilaminate ECM devices with varying number of layers, disinfection and sterilization, and organ origin.

Animals↗
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

Biaxial strength of multilaminated extracellular matrix scaffolds.

Xenogeneic extracellular matrix (ECM) can be harvested and configured to function as a bioscaffold for tissue and organ reconstruction. The mechanical properties of the ECM vary depending upon the tissue from which it is harvested. Likewise, the manufacturing steps required to develop ECMs into medical grade devices will affect the surface morphology and the mechanical properties of the bioscaffold; important properties for constructive tissue remodeling. The present study compared the ball-burst strength of five different ECM scaffolds before and after treatment with peracetic acid (PAA): porcine small intestinal submucosa (SIS), porcine urinary bladder submucosa (UBS), porcine urinary bladder matrix (UBM), a composite of UBS + UBM, and canine stomach submucosa (SS). This study also compared the mechanical properties of 2- and 4-layer ECM scaffolds. Results showed 2-layer SS devices had the highest ball-burst value of all 2-layer ECM devices. Moreover, all 4-layer ECM devices had similar ball-burst strength except for 4-layer UBM devices which was the weakest. PAA-treatment decreased the ball-burst strength of SS and increased the ball-burst strength of UBS 2-layer devices. This study showed the material properties of the ECM scaffolds could be engineered to mimic those of native soft tissues (i.e. vascular, musculotendinous, etc) by varying the number of layers and modifying the disinfection/sterilization treatments used for manufacturing.

Absorbable Implants↗
PubMed2004

Xenogeneic extracellular matrix as a scaffold for tissue reconstruction.

Bioscaffolds derived from xenogeneic extracellular matrix (ECM) have been used in numerous tissue engineering applications. The safety and efficacy of such scaffolds when used for the repair and reconstruction of numerous body tissues including musculoskeletal, cardiovascular, urogenital and integumentary structures has been shown in both preclinical animal studies and in human clinical studies. More than 200,000 human patients have been implanted with xenogeneic ECM scaffolds. These ECM scaffolds are typically prepared from porcine organs such as small intestine or urinary bladder, which are subjected to decellularization and terminal sterilization without significant loss of the biologic effects of the ECM. The composition of these bioscaffolds includes the structural and functional proteins that are part of native mammalian extracellular matrix. The three-dimensional organization of these molecules distinguishes ECM scaffolds from synthetic scaffold materials and is associated with constructive tissue remodeling instead of scar tissue. The biologic response to these xenogeneic bioscaffolds, including the immune response, is discussed herein.

Animals↗
PubMed2004

The use of porcine small intestinal submucosa to enhance the healing of the medial collateral ligament--a functional tissue engineering study in rabbits.

INTRODUCTION: Small intestinal submucosa (SIS) from porcine has been successfully used as a collagen scaffold for the repair of various tissues, including those of the human vascular, urogenital, and musculoskeletal systems. The objective of this study was to evaluate whether SIS can be used to enhance the healing process of a medial collateral ligament (MCL) with a gap injury in a rabbit model. METHODS: A 6 mm wide gap was surgically created in the right MCL of 20 skeletally mature, female New Zealand White rabbits. In 10 rabbits, a strip of SIS was sutured onto the two ends of the MCL, while for the other 10 animals their injured MCL remained untreated and served as a non-treated group. The left MCL of all animals was exposed and undermined serving as the sham-operated side. At 12 weeks post-healing, eight hind limbs from each group were used for mechanical testing. The cross-sectional areas (CSA) of the MCLs were measured. The femur-MCL-tibia complex (FMTC) was tensile tested to failure. The load-elongation curves representing the structural properties of the FMTC and the stress-strain curves representing the mechanical properties of the healing MCL were obtained. The remaining two animals from each group were prepared for histological evaluation. RESULTS: The CSA between the SIS-treated and non-treated groups were not significantly different (p>0.05). Both treatment groups appeared to increase by nearly 40% compared to the sham-operated side, although statistical significance was not found for the non-treated group (p>0.05). The stiffness of the FMTC from the SIS-treated group was 56% higher than the non-treated group (45.7+/-13.3 N/mm vs. 29.2+/-9.2 N/mm, respectively, p<0.05) and the ultimate load also nearly doubled (117.434.5 N vs. 66.4+/-31.4 N, respectively, p<0.05). These values were lower compared to the sham-operated side (89.7+/-15.3 N/mm and 332.0+/-50.8 N, respectively). The tangent modulus of the healing MCL (279.7+/-132.1 MPa vs. 149.0+/-76.5 MPa, respectively) and stress at failure (15.7+/-4.1 MPa vs. 10.2+/-3.9 MPa, respectively) both increased by more than 50% with SIS treatment (p<0.05). Yet, each remained lower compared to the sham-operated side (936.3+/-283.6 MPa and 75.6+/-14.2 MPa, respectively). Blinded histological comparisons between the SIS-treated MCL and the non-treated control demonstrated qualitatively that the SIS treated group had increased cellularity, greater collagen density, and improved collagen fiber alignment. CONCLUSION: Healing of a gap MCL injury was significantly enhanced with SIS. The improved mechanical properties and histological appearance of the MCL suggest that SIS treatment improves the quality of tissue and renders the possibility for future studies investigating functional tissue engineering of healing ligaments.

Animals↗
PubMed2004

A comparison of suture retention strengths for three biomaterials.

BACKGROUND: The suture holding capacity, suture retention strength, and burst strength of three biomaterials (Marlex), SIS, and PeriGuard) were evaluated to compare their performance characteristics in an ex vivo setting representing the immediate postoperative period. MATERIAL/METHODS: A circular defect was created in the fascial tissue of the abdominal aponeurosis collected from normal dogs. Defects were repaired with either Marlex (polypropylene mesh), Periguard (bovine pericardium) or small intestinal submucosa (SIS) using 2-0 prolene and a 1.0-cm suture bite. The force required to induce failure at the repair site was recorded as the suture-holding capacity. Suture retention strength was calculated as the load distribution over the specimen cross-section in contact with the suture at the time of rupture. Burst strength of the raw materials was also measured. RESULTS: The suture-holding capacity was 370.9+/-56.2 N for Marlex; 214.3+/-36.1 N for Periguard, and 287.9+/-34.3 N for SIS. The suture retention strengths were: Marlex, 413.4+/-59.7 N/mm2; Periguard, 97.0+/-20.1 N/mm2; and SIS, 106.9+/-12.7 N/mm2. The burst strength of Marlex, Periguard and SIS were 476.7+/-50.8 N, 432.12+/-82.1 N, and 433.6+/-79.5 N respectively. CONCLUSIONS: All three materials provide adequate strength and suture-holding capacities to be of use in the repair of soft tissue defects.

Animals↗
PubMed2003

Host protection against deliberate bacterial contamination of an extracellular matrix bioscaffold versus Dacron mesh in a dog model of orthopedic soft tissue repair.

The resistance of two biomaterials, one synthetic and one biologic in origin, to deliberate bacterial infection was compared in a dog model of orthopedic soft tissue reconstruction. Twenty-four adult female dogs were randomly divided into two equal groups and a 2.0-cm-round full-thickness defect was created on the lateral surface of the stifle joint, leaving only the synovium and skin intact. The defect was surgically repaired with either Dacron trade mark mesh or a porcine derived extracellular matrix (ECM) scaffold material. The repair site was inoculated with 1 x 10(8) Staphylococcus aureus at the time of surgery and the dogs were survived for 28 days. Results showed a chronic pyogranulomatous inflammatory response at the Dacron trade mark implant sites versus a constructive tissue-remodeling response without residual inflammation at the ECM implant site. Three dogs in the group receiving the Dacron trade mark mesh were treated with Keflex trade mark (500 mg bid x 7 days) for signs of septicemia. A quantitative bacterial count of the implant sites at the time of sacrifice showed 6.52 x 10(5) +/- 1.2 x 10(6) and 6.5 x 10(2) +/- 1.8 x 10(3) bacteria per gram of tissue for the Dacron trade mark and ECM scaffold sites, respectively (P <.03). The ECM implant material was more resistant than the synthetic implant material to persistent infection following deliberate bacterial contamination and the ECM scaffold supported constructive tissue remodeling.

Animals↗
PubMed2002

Natural anti-galactose alpha1,3 galactose antibodies delay, but do not prevent the acceptance of extracellular matrix xenografts.

Naturally occurring antibodies to the galactose alpha1,3 galactose (alpha gal) epitope expressed on xenogeneic grafts are a major barrier to organ transplantation in humans. Porcine small intestinal submucosa (SIS) expresses the alpha gal epitope and is currently being used as a bioscaffold for tissue remodeling. To examine in detail the potential role of the alpha gal epitope in immune recognition of this acellular, avascular biomaterial, we have used mice which have a genetic disruption in the alpha1,3 galactosyltransferase gene (alpha gal(-/-)mice) and thus express natural anti-alpha gal antibodies in a manner similar to humans. It was found that alpha gal(-/-)mice produced IgM anti-alpha gal antibodies in addition to IgG1 SIS-specific antibodies, which did not bind to the alpha gal epitope. Histological examination of implant sites demonstrated an early inflammatory response that consisted predominantly of neutrophils in both alpha gal(+/+) and alpha gal(-/-)mice. However, while alpha gal(+/+)mice completely remodeled SIS implants by day 25, alpha gal(-/-)mice still exhibited some visible SIS together with inflammatory cellular infiltrates at this time point. Nevertheless, by day 35, the implant site in alpha gal(-/-)mice appeared to be entirely remodeled although a few acute inflammatory cells were still present. Immunization of alpha gal(-/-)mice with sheep erythrocytes to enhance anti-alpha gal antibody levels led to a more robust early inflammatory response following implantation but did not change the ultimate fate of the graft. We conclude that, in contrast to xenotransplantation of whole organs, naturally-occurring anti-alpha gal antibodies do not influence the ability of xenogeneic extracellular matrices to serve as bioscaffolds for tissue remodeling.

Animals↗
PubMed2002

The extracellular matrix as a scaffold for tissue reconstruction.

The extracellular matrix (ECM) consists of a complex mixture of structural and functional proteins and serves an important role in tissue and organ morphogenesis, maintenance of cell and tissue structure and function, and in the host response to injury. Xenogeneic and allogeneic ECM has been used as a bioscaffold for the reconstruction of many different tissue types in both pre-clinical and human clinical studies. Common features of ECM-associated tissue remodeling include extensive angiogenesis, recruitment of circulating progenitor cells, rapid scaffold degradation and constructive remodeling of damaged or missing tissues. The ECM-induced remodeling response is a distinctly different phenomenon from that of scar tissue formation.

Animals↗
PubMed2002

The Th2-restricted immune response to xenogeneic small intestinal submucosa does not influence systemic protective immunity to viral and bacterial pathogens.

Implantation of mice with xenogeneic extracellular matrix (ECM) not only results in tissue remodeling but also elicits a strong Th2 immune response. It is possible that the Th2 cytokines induced by ECM act systemically and result in immune suppression to unrelated antigens. In this case, the recipient would be predisposed to immune dysfunction and have increased susceptibility to various pathogens. The purpose of this study was to determine if ECM implantation does, in fact, influence the immune response to other antigens. Four models were examined to determine the effects of ECM implantation on systemic immunity. In the first model, mice were subcutaneously implanted with porcine small intestinal submucosa (SIS) and immunized with a T-dependent subunit vaccine against influenza virus. The antibody response and protection against lethal infection were then measured. The second model consisted of similar experiments performed using a T-independent polysaccharide vaccine against S. pneumoniae. In the third model, mice were implanted and the cell-mediated response to dinitrofluorobenzene (DNFB) challenge was determined. The fourth model involved examining the influence of SIS implantation on rejection of xenogeneic skin grafts. We found that antibody levels of mice vaccinated against influenza virus or S. pneumoniae were not affected by SIS implantation and these mice did not exhibit increased or decreased susceptibility to either infectious agent. Similarly, mice implanted with ECM showed no cell-mediated immune dysfunction upon challenge with DNFB or xenogeneic skin grafts. The results of this study demonstrate that the Th2-restricted response induced by xenogeneic ECM implantation does not cause generalized immune suppression. Therefore, SIS implantation does not increase susceptibility to viral or bacterial pathogenic agents.

Animals↗
PubMed2002

Retention of endothelial cell adherence to porcine-derived extracellular matrix after disinfection and sterilization.

Extracellular matrices (ECM) derived from porcine tissue are associated with rapid and extensive repopulation with host cells when used as scaffolds for in vivo tissue repair. Cell adhesion to substrates used for tissue engineering has been studied extensively but the factors that mediate this phenomenon in ECM scaffolds following treatment with oxidants and sterilants have not been examined. Cell adhesion assays were used to examine human microvascular endothelial cell (HMEC) attachment to ECM graft materials harvested from small intestinal submucosa (SIS) and urinary bladder matrix (UBM) following decellularization and sterilization procedures designed to render the ECM safe for clinical use. HMECs were able to attach directly to these ECM scaffolds via several attachment proteins present within the ECM, including type I collagen, type IV collagen, and fibronectin. The ability of the SIS ECM and UBM ECM to support the growth and proliferation of HMEC was also examined. HMEC were able to grow to single-layer confluence on both surfaces of SIS and UBM sheets. The endothelial cells were also able to penetrate the SIS and UBM at later time points if they were seeded on the abluminal side of the ECM sheets. The ability of the processed ECM to support HMEC attachment and proliferation is similar to that reported for unprocessed ECM and may therefore play a role in the rapid remodeling response observed when these matrices are implanted in vivo as scaffolds for wound repair.

Animals↗
PubMed2002

Body mass index and disability in adulthood: a 20-year panel study.

OBJECTIVES: This study examined whether body mass index (BMI) or change in BMI raises the risk of disability in adulthood. METHODS: The relation between BMI and upper- and lower-body disability was examined among adult subjects from a national longitudinal survey (n = 6833). Tobit regression models were used to examine the effect of BMI on disability 10 and 20 years later. RESULTS: Obesity (BMI > or = 30) at baseline or becoming obese during the study was associated with higher levels of upper- and, especially, lower-body disability. In persons who began the study with a BMI of 30 or more and became normal weight, disability was not reduced. Underweight persons (BMI < 18.5) also manifested higher disability in most instances. CONCLUSIONS: Disability risk was higher for obese persons, but overweight was not consistently associated with higher disability.

Activities of Daily Living↗
PubMedDate not supplied

Assessing porcine liver-derived biomatrix for hepatic tissue engineering.

Acellular, biologically derived matrices such as small intestinal submucosa have been extensively utilized to induce tissue regeneration and remodeling of connective tissue, vascular grafts, and urinary bladder; however, decellularized scaffolds have not been explored for their potential utility in hepatic tissue engineering. In the case of both extracorporeal hepatocyte-based devices and implantable hepatocyte-scaffold tissue-engineered constructs, maintenance of hepatocellular function is of prime importance. In this study, we specifically explored decellularized, porcine, liver-derived biomatrix (LBM) as a bioresorbable scaffold for primary hepatocytes. Primary rat hepatocytes were cultured on LBM and compared with well-characterized hepatocyte culture models--double-gel cultures that promote maintenance of liver-specific functions for many weeks, and adsorbed collagen monolayers that lead to the rapid decline of hepatocellular function and viability. Hepatocytes were maintained for up to 45 days on LBM and liver-specific functions such as albumin synthesis, urea production, and P-450 IA1 activity were found to be significantly improved over adsorbed collagen cultures. Our data indicate that LBM may be a favorable alternative to existing scaffolds for tissue engineering in that it is bioresorbable, can be easily manipulated, and supports long-term hepatocellular functions in vitro.

Animals↗