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Biomedical subjects

S F Badylak

Publications and source records attributed to S F Badylak.

At least 37 records · Page 2Linked to original sources

Characterization of small intestinal submucosa regenerated canine detrusor: assessment of reinnervation, in vitro compliance and contractility.

PURPOSE: We characterized small intestinal submucosa regenerated canine bladder. MATERIALS AND METHODS: We subjected 15-month small intestinal submucosa regenerated canine bladder strips to in vitro muscle bath compliance, contractility testing and immunohistochemical staining. RESULTS: Compliance studies demonstrated no significant difference between small intestinal submucosa regenerated and control bladders, which were 30-fold more compliant than native small intestinal submucosal graft material. Contractility studies demonstrated contractile responses and innervation similar to those of normal canine bladder. Afferent nerves were demonstrated through immunohistochemical techniques. CONCLUSIONS: These characteristics further support the regenerative capacity of small intestinal submucosa and its potential use as a bladder augmentation material.

Animals↗

Clusters of lymphoma in ferrets.

Cluster outbreaks of lymphoma and leukemia have been associated with viral infections in many species including humans, cattle, and cats. This study describes epidemiological, clinical, and pathological features of cluster outbreaks of lymphoma in multiferret households and examines and compares the Aleutian disease virus (ADV) and feline leukemia virus (FeLV) status of cases, ferrets at risk, and controls. Three ferret groups with 21 cases of histologically diagnosed lymphoma (12.6% cumulative incidence) and their cohabitants (n = 35) were examined and compared with three control groups (n = 52) of cohabitating ferrets without lymphoma. A familial distribution was observed in one group but most cases were not consanguinous. Ferrets greater than 3 years of age developed chronic disease in two of the groups and 2-year-old adults had acute disease in the remaining group. Lymphocytosis, splenomegaly, and lymphadenopathy were prominent features. Histologically, predominantly small noncleaved cell and polymorphous lymphoid lesions were observed. All of the ferrets with lymphoma that were tested for ADV and FeLV using serology or PCR were negative. The rate of ADV antibody among cases or ferrets at risk was not significantly different from controls. None of the cluster ferrets were seropositive for FeLV p27 antigen using a monoclonal ELISA. Infection with a novel ferret virus is suspected, but an etiological agent has not yet been identified.

Aleutian Mink Disease Virus↗

Detrusor regeneration in the rat using porcine small intestinal submucosal grafts: functional innervation and receptor expression.

PURPOSE: To evaluate functional characteristics of regenerated bladder induced by small intestinal submucosa (SIS). MATERIALS AND METHODS: Strips from bladder regenerated from SIS and normal rat bladder were evaluated by in vitro muscle bath contractility studies. RESULTS: The present results indicate that SIS-regenerated bladder 1) demonstrates contractile activity; 2) expresses muscarinic, purinergic and beta adrenergic receptors; and 3) exhibits functional cholinergic and purinergic innervation that is similar to the normal rat urinary bladder muscle. CONCLUSIONS: These functional characteristics of SIS-regenerated tissue demonstrated in the present study further support use of SIS material as a bladder augmentation material.

Animals↗

Mechanical properties of xenogeneic small-intestinal submucosa when used as an aortic graft in the dog.

Small-intestinal submucosa (SIS) has been shown to induce tissue remodelling in vivo when used as a vascular graft. The present study investigated in physical and mechanical properties of remodeled aortic grafts derived from xenogeneic SIS material. Eight infrarenal aortic grafts were implanted in mongrel dogs. The grafts were explanted at 1 or 2 months and tested for compliance and hoop mechanical properties. The morphologic changes within the grafts were also characterized. The remodeling process produced graft structures which were significantly stronger than both the normal artery (P = .012) and the original SIS graft (P = .0001), and the compliance of these structures was one third that of normal artery and similar to the original SIS grafts. The remodeled grafts were > 10 times the thickness of the implanted SIS. Immunohistochemical analysis of remodeled tissues suggest that the SIS material was degraded and resorbed over time. The remodeling process transformed a material which was physically and mechanically quite different from normal aorta into a blood conduit which had the physical and mechanical properties needed to function in this mammalian arterial system.

Animals↗

The use of xenogeneic small intestinal submucosa as a biomaterial for Achilles tendon repair in a dog model.

A study was conducted to evaluate the tissue response to a xenogeneic biomaterial when this material was used to repair an experimentally induced Achilles tendon defect in the dog. Twenty dogs had a 1.5 cm segmental defect of the Achilles tendon created surgically which was then repaired with acellular connective tissue derived from porcine small intestinal submucosa (SIS). The animals were sacrificed at 1, 2, 4, 8, 12, 16, 24, and 48 weeks and the neotendons examined for uniaxial longitudinal tensile strength, morphologic appearance, hydroxyproline (collagen) content, and disappearance of the originally implanted SIS material over time. The contralateral normal Achilles tendons served as controls as did four additional dogs that had a 1.5 cm segmental Achilles tendon defect created surgically without subsequent surgical repair with SIS. Results showed the SIS remodeled neotendons to be stronger than the musculotendinous origin or the boney insertion (> 1000 N) by 12 weeks after surgery and to consist of organized collagen-rich connective tissue similar to the contralateral normal tendons. The four dogs in which no SIS was implanted showed inferior strength at the comparable time points of 4, 8, 12, and 16 weeks. Immunohistochemical studies suggest that the SIS biomaterial becomes degraded within the first eight weeks and serves as a temporary scaffold around which the body deposits appropriate and organized connective tissue. SIS is a promising biomaterial worthy of further investigation for orthopedic soft tissue applications.

Achilles Tendon↗

Healing comparison of small intestine submucosa and ePTFE grafts in the canine carotid artery.

Continuing investigation of small-diameter vascular graft materials suggests that unacceptable graft complications continue and that the ideal material has not yet been found. We compared healing of xenogeneic small diameter grafts (3.5 to 5.0 mm diameter) made from porcine small intestine submucosa (SIS) implanted in the carotid artery to expanded polytetrafluorethylene (ePTFE) in the contralateral carotid in 8 dogs. Two dogs were sacrificed for graft evaluation at 7, 28, 90, and 180 days after surgery. Only one SIS graft was occluded at 28 days and the other 7 were patent. Six of 8 ePTFE grafts were occluded with thrombi. One was patent at 7 and one at 90 days. At 7 days post-implant, the luminal surface of the SIS graft was covered by a thick (30 microns), compact fibrin meshwork. By 28 days endothelial cells were seen completely covering the fibrin meshwork which stained for FVIII-related antigen. Smooth muscle cells were observed in the neo-intima. Most ePTFE grafts had fibrin on the luminal surface which formed fibrin thrombi with platelets and numerous red blood cells. Complete endothelial coverage of the ePTFE grafts was not observed by 180 days. There was not a pronounced neointima seen on the luminal surface of the graft. The vasa vasorum was present in the fibrous capsule surrounding the ePTFE graft, but it did not penetrate into the graft as seen in the SIS graft. At 90 days the SIS vascular graft had the histological appearance similar to a normal artery. The SIS graft potency and healing characteristics were superior to the synthetic ePTFE graft and warrant further investigation.

Animals↗

Experimental assessment of small intestinal submucosa as a bladder wall substitute.

OBJECTIVES: This study determined the feasibility of promoting urinary bladder regeneration with porcine-derived small intestinal submucosa (SIS). METHODS: Twenty-two Sprague-Dawley rats underwent partial cystectomy with immediate bladder augmentation with SIS. Bladders were harvested for histologic evaluation at 2, 4, 8, 12, 24, and 48 weeks. RESULTS: Histologically at 2 weeks, there was infiltration of the graft material with viable host cells consisting of fibroblasts, macrophages, and blood vessels covered by complete mucosal urothelium comprised of transitional cells. During the next 10 weeks, collagen formation and maturation were noted, and by the end of 12 weeks, the SIS graft was comprised of a mature collagen matrix admixed with thinly scattered disorganized smooth muscle bundles and covered by normal urothelium. At 48 weeks, all three layers of the normal bladder (urothelium, smooth muscle, and serosa) were present and were grossly and microscopically indistinguishable from the normal rat urinary bladder. CONCLUSIONS: This study further supports the concept of bladder regeneration and suggests that SIS may be a viable material for bladder augmentations.

Animals↗

Infective endocarditis in a collegiate wrestler.

A 21-year-old collegiate wrestler was admitted to the hospital suffering from acute left lower quadrant abdominal pain. Blood cultures taken at the time of admission showed Staphylococcus aureus. The results of a computed tomography scan and a two-dimensional echocardiogram were consistent with a diagnosis of infective endocarditis. Therapy consisted of a 14-day hospitalization, a 28-day course of parenteral antibiotics, and subsequent follow-up visits. He returned to full participation in wrestling after 15 weeks.

Journal Article↗

Small intestinal submucosa: utilization for repair of rodent abdominal wall defects.

Prosthetic graft material is often used for the repair of abdominal wall defects that result from trauma, infection, neoplastic, or congenital deformities. A new material, porcine small intestinal submucosa, has been successfully used as an arterial and venous graft material in both canine and primate animal models with graft patency and infection rates equal to autologous vein. On the basis of these studies, small intestinal submucosa was used as a graft material for the repair of a 2 x 2-cm full-thickness defect of the muscle and fascia in the rodent abdominal wall (N = 11). Two animals were euthanized at 1 week, 2 weeks, 4 weeks, 2 months, and 3 months. At the time of euthanization, no abdominal hernias were noted and only minimal intra-abdominal adhesions were observed. One animal died on postoperative day 5 as a result of a wound dehiscence. Histological analysis of the excised abdominal wall hernia repairs revealed moderate initial inflammation but with incorporation of small intestinal submucosa with minimal inflammation at 2 months. No evidence of graft-versus-host rejection was noted with hematoxylin and eosin stains and light microscopy. Porcine small intestinal submucosa merits further study as a graft material for abdominal wall replacement.

Abdominal Muscles↗

Small intestinal submucosa: utilization as a wound dressing in full-thickness rodent wounds.

Wound dressings are used as a temporary wound covering to promote wound healing, control wound exudate, and decrease wound contamination as well as evaporative water loss. A new material, porcine small intestinal submucosa, has been used successfully as an arterial and venous graft in both canine and primate animal models with graft patency and infection rates equal to autologous vein. Based on these studies, small intestinal submucosa was used as a biological wound dressing in 20 x 20 mm full-thickness wounds made on Sprague-Dawley rats. In the controls (group I, n = 12), an acrylic frame (20 x 20 mm) was sutured to the wound edges, followed by placement of a thin polyurethane film. In the small intestinal submucosa-treated animals (group II, n = 12), the wound was covered with small intestinal submucosa and then with the acrylic frame and polyurethane film. The wounds were examined both visually and histologically at postapplication days 3, 7, 14, 28, 42 and 56. In addition, the wound contraction rate of 6 animals in both groups were recorded at postapplication day 0 and then at 1 week, 1 month, 2 months, and 3 months. Histological analysis (hematoxylin-eosin and periodic acid-Schiff stains) of the small intestinal submucosa-treated wounds revealed no host-versus-graft rejection and a rate of epithelialization equal to that of the control group. The wound contraction rate was statistically significant (higher; p < .05) in the control group compared to the small intestinal submucosa-treated group. Porcine small intestinal submucosa merits further study as both a biological wound dressing and as a substrate for cultured cells.

Animals↗

Experimental evaluation of small intestinal submucosa as a microvascular graft material.

The evaluation of porcine small intestine submucosa (SIS) in a microsurgical model was conducted using an interpositional graft in the rat femoral artery. The SIS grafts were fabricated from processed porcine material that was wrapped around a glass tube and oversewn longitudinally to produce a tubular structure. Of the 42 animals studied, 7 received grafts of untreated SIS (group I), 7 of the grafts were presoaked (PSH) in heparin (Group II), 7 animals were treated with systemic heparin prior to implantation of PSH-SIS (group III), 7 animals received SIS grafts crosslinked to heparin (group IV), 7 animals received SIS grafts crosslinked to urokinase (group V), and 7 animals received untreated autologous epigastric vein grafts (group VI). Patency was assessed postoperatively and selected grafts were evaluated by histology. All SIS grafts failed to maintain patency beyond the first postoperative hour. Histologic examination of the thrombosed graft surfaces revealed a smooth luminal surface with a thick layer of attached fibrin and platelets with a central occluding thrombus. The thickness of the induced fibrin layer appears to narrow intraluminal space significantly at the microvascular level. While having excellent success at vessel diameters greater than 3 mm, and in a variety of nonporcine animal models without xenographic rejection, SIS in this model was thrombogenic despite a favorable surface morphology as demonstrated by SEM. Even with use of heparin and urokinase SIS graft thrombosis occurred.

Animals↗

Comparison of the resistance to infection of intestinal submucosa arterial autografts versus polytetrafluoroethylene arterial prostheses in a dog model.

PURPOSE: Prosthetic graft infection represents a most challenging complication to the vascular surgeon. Although expanded polytetrafluoroethylene (ePTFE) grafts have an acceptable patency rate, especially in the large-diameter arterial location, bacterial contamination of this material usually requires surgical removal of the graft. METHODS: We compared the resistance of large-diameter ePTFE grafts and grafts constructed of small intestinal submucosa (SIS) to deliberate infection with Staphylococcus aureus. Eighteen dogs were divided into two equal groups, and the infrarenal aorta was replaced with either ePTFE or SIS graft material. One hundred million S. aureus organisms were deposited directly on the graft at the time of surgery, and the dogs were observed for 30 days. RESULTS: One dog with an ePTFE graft died of hemorrhage from anastomosis site at 21 days. Of the remaining eight dogs with ePTFE grafts, four had positive culture results from the removed graft material, and all had histologic evidence for persistent infection. These dogs also had chronic fever, and the average white blood cell count at day 30 was 15,600/mm3. All nine dogs with SIS grafts had patent grafts, were afebrile after the first week, had an average white blood cell count of 11,500/mm3 at 30 days (p value = NS), had negative culture results, and had the histologic appearance of graft remodeling with collagen that was free of active inflammation. CONCLUSIONS: We conclude that large-diameter arterial SIS grafts are more resistant to persistent infection with S. aureus than ePTFE grafts in this dog model of deliberate bacterial inoculation.

Anastomosis, Surgical↗

Biocompatibility of small-intestinal submucosa in urinary tract as augmentation cystoplasty graft and injectable suspension.

We explored the biocompatibility of fluidized canine small-intestinal submucosa (SIS) for periureteral injection and as a patch graft for bladder augmentation in pigs. Gross evaluation 8 weeks after submucosal injection showed persistence of the nodule. Histologic examination showed thickened submucosa with spindle cells embedded in poorly organized fibrous material. There was no evidence of inflammatory reaction or granuloma formation. Subserosal nodules likewise persisted and demonstrated capillary ingrowth. Grafts of SIS became epithelialized within 3 weeks with maintenance of bladder capacity. Ingrowth of capillaries and smooth muscle could be seen in later specimens. Although further studies with longer follow-up are needed, SIS appears to be a promising graft material in the urinary tract.

Animals↗

Stroke volume with dynamic cardiomyoplasty during ventricular fibrillation in the acute dog.

The objective of this study was to determine the pumping capability of dynamic cardiomyoplasty during induced ventricular fibrillation. In this acute study of 6 dogs, the pumping capability of the unconditioned left latissimus dorsi (LD) muscle (141 to 292 gm), wrapped around both ventricles, was investigated during induced ventricular fibrillation. Left-ventricular and femoral artery pressure, the ECG and aortic root flow velocity were monitored. Prior to inducing ventricular fibrillation, the ability of the unconditioned LD muscle to augment stroke volume (SV), was quantified as the area under the aortic flow-velocity record. The ventricles were then fibrillated and, after 10 sec, rhythmic 250 msec trains (1/sec) of stimuli (40/sec) were delivered to the thoracodorsal nerve to contract the LD muscle tetanically. In no case could dynamic cardiomyoplasty produce the same SV as when the ventricles were beating normally. In one animal, the SV attained two percent of the normal SV by 5 contractions; in another, the SV reached one percent by 25 contractions. In the remaining animals, the SV varied around 20% of the prefibrillation SV. By 90 contractions, the stroke volume was 10% of the prefibrillation value. The progressive decrease in SV was likely a consequence of LD muscle ischemia and fatigue, since the latissimus dorsi muscle provided low blood flow during the period of fibrillation.

Animals↗

Differential expression of muscle regulatory factor genes in normal and denervated adult rat hindlimb muscles.

Skeletal muscle represents an excellent model system in which to examine regulatory mechanisms that modulate gene expression in the mature adult organism. Individual muscle fibers can be categorized as fast- or slow-twitch based upon several physiological and molecular criteria, including metabolic enzyme activity and contractile protein isoforms. Each property can be influenced by a variety of factors such as changes in motor neuron activity or alterations in hormone levels, although the molecular pathways by which environmental factors affect gene expression remain largely unknown. As a first step in identifying potential regulators of fiber-type diversity, the expression patterns of four basic/helix-loop-helix muscle regulatory factors (MRFs), referred to as MyoD, myogenin, Myf-5, and MRF4, were examined in normal adult rat muscles which differed in their phenotypic properties. As expected, all four MRFs were expressed at detectable levels in the muscles studied. However, different muscles accumulated different proportions and combinations of MRF transcripts. For example, myogenin expression was maximally detected in slow-twitch muscles whereas MyoD transcripts were found predominantly in muscles exhibiting a fast-twitch phenotype. Induced phenotypic changes in two fast-twitch muscles via denervation lead to a large and rapid increase in transcript levels of all four MRFs as early as 24 hr following denervation, with myogenin transcripts approaching 150-200-fold higher levels than innervated contralateral muscles within 7 days. These results suggest that myogenin, as well as the other three MRFs, may be involved in both the initial establishment as well as maintenance of fiber-type diversity in the developing organism.

Animals↗

Porosity of porcine small-intestinal submucosa for use as a vascular graft.

The porosity of a vascular graft material has been suggested as a major factor affecting the rate and degree of neovascularization of newly implanted grafts, with higher porosities generally associated with better performance. The objective of this study was to determine the water porosity of a new vascular graft material, small-intestinal submucosa (SIS), and to compare the values to those reported for other common vascular graft materials. In addition, the porosity of SIS was investigated with respect to applied pressure and applied uniaxial tension. Both rectangular, flat specimens and tubular specimens of SIS were subjected to static water pressure, and water was collected as it passed through the SIS material. SIS has a typical porosity of 0.52 mL/min.cm-2 at an applied pressure of 120 mm Hg. Although porosity appeared to be unaffected by uniaxial tension, it increased in proportion to applied pressure at a rate of 4.8 x 10(-3) mL/min.cm-2/mm Hg. These low porosity values and the past success of SIS as a vascular graft material suggest that high-porosity materials are not required for implant success.

Animals↗