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Biomedical subjects

A Atala

Publications and source records attributed to A Atala.

At least 19 recordsLinked to original sources
PubMed2001

In vitro biocompatibility assessment of naturally derived and synthetic biomaterials using normal human urothelial cells.

The reconstruction of urinary tissues often employs various types of biomaterials, and adequate material biocompatibility is essential for the successful reconstruction of urinary tissues. In this study we utilized a primary normal human urothelial cell culture system to evaluate the in vitro biocompatibility of a number of naturally derived biomaterials [i.e., bladder submucosa, small intestinal submucosa, collagen, and alginate] and polymeric biomaterials [i.e., poly(glycolic acid), poly(L-lactic acid), poly(lactic-co-glycolic acid), and silicone] that are either experimentally or clinically used in urinary reconstructive surgery. To determine the cytotoxic and bioactive effects of these biomaterials, the cell viability, metabolic activity, apoptotic properties, and DNA-synthesis activity were measured with four types of assays [Neutral Red, 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl tetrazolium bromide, apoptotic activity, and tritiated thymidine incorporation assays] using extract and direct contact methods. Most of the biomaterials tested did not induce significant cytotoxic effects and exhibited normal metabolic function and cell growth in vitro. This normal primary human urothelial cell culture model is suitable for in vitro biocompatibility assessments and is able to provide information on the cell-biomaterial interactions and the ability of biomaterials to support bioactive cell functions.

Apoptosis↗
PubMed2001

Vascular endothelial growth factor-mediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype.

Vascular endothelial growth factor (VEGF), which is often produced at high levels by tumor cells, is a well-known mediator of tumor angiogenesis. VEGF receptor tyrosine kinases, KDR/Flk-1 and Flt-1, have been thought to be expressed exclusively by endothelial cells. In this study, we have used a prostate tumor progression series comprised of a differentiated rat prostate epithelial cell line, NbE-1, and its highly motile clonal derivative, FB2. Injection of NbE-1 cells into the inferior vena cava of syngeneic rats indicated that these cells are nontumorigenic. Using the same model, FB2 cells generated rapidly growing and well-vascularized tumors in the lungs. NbE-1 expressed marginal levels of VEGF, whereas high levels of VEGF protein were detected in FB2-conditioned medium and in FB2 tumors in vivo. Analysis of (125)I-VEGF(165) binding to NbE-1 and FB2 cells indicated that only motile FB2 cells expressed the VEGF receptor Flt-1. Consistent with this finding, physiological concentrations of VEGF induced chemotactic migration in FB2 but not in NbE-1 cells. This is the first documentation of a functional Flt-1 receptor in prostate tumor cells. Our results suggest two roles for VEGF in tumor progression: a paracrine role as an angiogenic factor and a previously undescribed role as an autocrine mediator of tumor cell motility.

Animals↗
PubMed2001

Continuous release of endostatin from microencapsulated engineered cells for tumor therapy.

Research studies suggest that tumor-related angiogenesis contributes to the phenotype of malignant gliomas. We assessed the effect of local delivery of the angiogenesis inhibitor endostatin on human glioma cell line (U-87MG) xenografts. Baby hamster kidney (BHK) cells were stably transfected with a human endostatin (hES) expression vector and were encapsulated in alginate-poly L-lysine (PLL) microcapsules for long-term delivery of hES. The release of biologically active endostatin was confirmed using assays of bovine capillary endothelial (BCE) proliferation and of tube formation. Human endostatin released from the microcapsules brought about a 67. 2% inhibition of BCE proliferation. Furthermore, secreted hES was able to inhibit tube formation in KDR/PAE cells (porcine aortic endothelial cells stably transfected with KDR, a tyrosine kinase) treated with conditioned U-87MG medium. A single local injection of encapsulated endostatin-secreting cells in a nude mouse model resulted in a 72.3% reduction in subcutaneous U87 xenografts' weight 21 days post treatment. This inhibition was achieved by only 150.8 ng/ml human endostatin secreted from 2 x 10(5) encapsulated cells. Encapsulated endostatin-secreting cells are effective for the treatment of human glioblastoma xenografts. Continuous local delivery of endostatin may offer an effective therapeutic approach to the treatment of a variety of tumor types.

Alginates↗
PubMed2001

Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo.

Arterial conduits are increasingly preferred for surgical bypass because of inherent functional properties conferred by arterial endothelial cells, especially nitric oxide production in response to physiologic stimuli. Here we tested whether endothelial progenitor cells (EPCs) can replace arterial endothelial cells and promote patency in tissue-engineered small-diameter blood vessels (4 mm). We isolated EPCs from peripheral blood of sheep, expanded them ex vivo and then seeded them on decellularized porcine iliac vessels. EPC-seeded grafts remained patent for 130 days as a carotid interposition graft in sheep, whereas non-seeded grafts occluded within 15 days. The EPC-explanted grafts exhibited contractile activity and nitric-oxide-mediated vascular relaxation that were similar to native carotid arteries. These results indicate that EPCs can function similarly to arterial endothelial cells and thereby confer longer vascular-graft survival. Due to their unique properties, EPCs might have other general applications for tissue-engineered structures and in treating vascular diseases.

Animals↗
PubMed2001

A noninvasive test for vesico-ureteric reflux in children.

OBJECTIVE: To report the development and testing of a device for the noninvasive diagnosis of vesico-ureteric reflux (VUR) which avoids the need for urethral catheterization (currently required to reliably determine the presence of VUR), and which thus avoids the anxiety of parents and patients that causes many families to refuse such evaluation. PATIENTS AND METHODS: Fifty-four children (49 girls and five boys, mean age 7.2 years, range 4-14) previously evaluated as having VUR volunteered to participate; no child was symptomatic at the time of the study. Refluxing units were known to be present by voiding cysto-urethrography (within 1 year, mean 7 months) in 45 and absent in 16. The device developed acquires electronically processed acoustic signals from the child during an observed urination. The signals are then analysed 'off-line' to determine the presence or absence of VUR. The initial preparation for the test included: (i) a full bladder [at least 0.80 x ((2 + age) x 30 mL)] measured by ultrasonography; and (ii) localization of the pelvi-ureteric junction by ultrasonography to accurately place the device's sensors on the child's back. The children were then positioned at a commode after placing the sensors; the recording was started and continued until voiding occurred. The children were tested with the recording and analysis team unaware of the presence and/or degree of VUR. The first 47 studies were single-kidney examinations and the remaining seven included simultaneous monitoring of both kidneys. RESULTS: Sixty-one renal units were assessed and interpretable signals were obtained from 54 (89%). There were seven episodes of 'system failure' when no interpretable data were obtained. One unit with no VUR had a 'reflux' signal; in four kidneys, spontaneous (two) and postsurgical (two) resolution of reflux was predicted by the testing and subsequently verified by cyclic radionuclide cystography. CONCLUSIONS: This noninvasive diagnostic technique detected VUR in 35 of 37 refluxing units and verified no reflux in 16 of 17 units without VUR. Further refinements may allow this technology to be used in all children with suspected VUR.

Adolescent↗
PubMed2001

Editorial

Explore the source record for details and available documents.

Journal Article↗
PubMed2001

Tubularized incised plate urethroplasty: expanded use in primary and repeat surgery for hypospadias.

PURPOSE: We evaluated the impact of tubularized incised plate urethroplasty on primary and repeat hypospadias repair. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all boys who underwent hypospadias repair at our institution during a recent 3-year period. The level of the hypospadias defect, technique of repair, primary repair versus reoperation, age at surgery and complications were recorded. RESULTS: A total of 520 hypospadias repairs were done from May 1996 through June 1999. We began to perform tubularized incised plate urethroplasty in November 1996. During the ensuing consecutive 32 months 181 primary and 25 repeat hypospadias repairs were done using this technique. Mean patient age at surgery was 22 months (range 3 months to 30 years). During the 6 months immediately before we began to use this method the Mathieu flip-flap procedure was the most commonly performed technique, accounting for 38% of all hypospadias repairs. In contrast, during the last 6 months reviewed tubularized incised plate urethroplasty accounted for 63% of all repairs, including 41 of 65 primary operations (63%) and 4 of 6 reoperations (67%), while no Mathieu procedures were performed. Postoperative followup was 6 to 38 months for tubularized incised plate repair. Overall meatal stenosis and a urethrocutaneous fistula developed in 1 and 14 boys, respectively (7% complication rate). CONCLUSIONS: Tubularized incised plate urethroplasty has become the preferred technique of primary and repeat hypospadias repair at our institution. The technique has few complications as well as proved success and versatility that continues to expand its applicability and popularity.

Adolescent↗
PubMed2001

Tissue engineered stents created from chondrocytes.

PURPOSE: Trauma, operations or instrumentation of the urethra or ureter may lead to stricture disease. The use of a natural urethral stent made of autologous tissue would be advantageous due to its biocompatibility. In this study we investigated the feasibility of engineering cartilage stents in vitro and in vivo. MATERIALS AND METHODS: We fabricated 40 cylinders 10 mm. long with an inner and outer diameter of 5 and 9 mm., respectively, from polyglycolic acid mesh coated with 50:50 polylactic-co-glycolic acid. Chondrocytes isolated from bovine shoulders were seeded onto the tubular polymer scaffolds at a seeding density of 60 x 106 cells per ml. Scanning electron microscopy was performed to determine the even distribution of chondrocytes throughout the polymer scaffolds. We implanted 20 cylinders under the skin of nude mice and 20 were cultured in stirred bio-reactors. Cytological characteristics, collagen content and mechanical durability were evaluated 4 and 10 weeks after cell seeding. RESULTS: Gross examination of the engineered stents showed the solid, glistening appearance of cartilaginous tissue. Cytological analyses with hematoxylin and eosin, trichrome, alcian blue and safranin O confirmed cartilage, and the deposition of collagen and glycosaminoglycan in each group. Increased deposition of collagen and glycosaminoglycan was observed in the stents created in vivo. Biomechanical testing demonstrated that the cartilaginous cylinders in each group were readily elastic and withstood high degrees of pressure. CONCLUSIONS: This study demonstrates the feasibility of creating cartilaginous stents in vitro and in vivo using chondrocyte seeded polymer matrices. This technology may be useful clinically for stricture disease in the genitourinary tract.

Animals↗
PubMed2000

Systems for therapeutic angiogenesis in tissue engineering.

The goals in tissue engineering include the replacement of damaged, injured, or missing body tissues with biologically compatible substitutes. To overcome initial tissue-mass loss, improved vascularization of the regenerated tissue is essential. Two pathways of tissue neovascularization are known: vasculogenesis, the in situ assembly of capillaries from undifferentiated endothelial cells (EC), and angiogenesis, the sprouting of capillaries from preexisting blood vessels. Recent advances in our understanding of the process of bloodvessel growth have provided significant tools for the neovascularization of bioengineered tissues. Several growth factors serve as stimuli for EC proliferation and migration as well as the formation of new blood vessels. They convey their effects via specific receptors expressed on the surface of EC. Vascular epithelial growth factor (VEGF) is a major regulator of neovascularization. VEGF plays a major role in the early development of blood-cell progenitors. Basic fibroblast growth factor (bFGF) was identified as the first angiogenic factor. It is a potent inducer of EC proliferation and blood-vessel growth in vitro and in vivo. VEGF and bFGF have been injected into undervascularized ischemic tissues, resulting in new blood-vessel formation and tissue perfusion. Gene-therapy approaches using VEGF cDNA injection into ischemic tissues have augmented the formation of collateral vessels. Angiogenic factors such as VEGF and bFGF have also been incorporated into bioengineered tissues and have facilitated blood-vessel growth. Other approaches such as prevascularization of the matrix prior to cell seeding and incorporation of EC into the bioengineered tissues have produced encouraging results. This article reviews the process of blood-vessel growth and tissue vascularization, placing emphasis on strategies that can be employed for efficient vascularization of engineered tissues in vitro and in vivo.

Angiogenesis Inducing Agents↗
PubMed2000

Bladder augmentation techniques in women.

Augmentation cystoplasty is performed in women for a variety of indications, including neurogenic bladder dysfunction, inflammatory diseases, small fibrosed bladders, idiopathic urge incontinence and enuresis. The preoperative evaluation, surgical techniques and postoperative management are reviewed. Complications of stone formation, urinary tract infections, mucus production, metabolic disturbances, hematuria and dysuria syndrome, tumors and perforations are addressed. In addition, alternative techniques such as ureterocystoplasty, autoaugmentation, seromuscular cystoplasty and the future of augmentation of the bladder utilizing techniques of tissue engineering are discussed. The management of pregnancy in women who have previously undergone augmentation cystoplasty is also reviewed.

Cecum↗
PubMed2000

Biomaterials for tissue engineering.

Biomaterials play a critical role in the engineering of new functional genitourinary tissues for the replacement of lost or malfunctioning tissues. They provide a temporary scaffolding to guide new tissue growth and organization and may provide bioactive signals (e.g., cell-adhesion peptides and growth factors) required for the retention of tissue-specific gene expression. A variety of biomaterials, which can be classified into three types--naturally derived materials (e.g., collagen and alginate), acellular tissue matrices (e.g., bladder submucosa and small-intestinal submucosa), and synthetic polymers [e.g., polyglycolic acid, polylactic acid, and poly(lactic-co-glycolic acid)]--have proved to be useful in the reconstruction of a number of genitourinary tissues in animal models. Some of these materials are currently being used clinically for genitourinary applications. Ultimately, the development or selection of appropriate biomaterials may allow the engineering of multiple types of functional genitourinary tissues.

Biocompatible Materials↗
PubMed2000

Tissue engineering of the bladder.

When gastrointestinal tissue is used for bladder augmentation or replacement, multiple complications may ensue, such as infection, metabolic disturbances, urolithiasis, perforation, increased mucous production, and malignancy. Therefore, alternative methods are being sought for cystoplasty. There has been a resurgence of interest in the use of acellular collagen-based matrices as scaffolds for bladder regeneration. Experimental work involving several collagen matrices, such as allogenic bladder and intestinal tissues, is currently being conducted in several academic centers. Recently, functional bladder tissue has been engineered using selective cell transplantation. The approach that has been followed for bioengineering of bladder tissue involves the use of autologous cells, thus avoiding rejection, whereby a biopsy of tissue is obtained from the host, after which the cells are dissociated and expanded in vitro, reattached to a matrix, and implanted into the same host.

Biocompatible Materials↗
PubMed2000

Tissue-engineering applications for phallic reconstruction.

Pathologic penile conditions often require reconstructive surgery. Due to the limited amount of autologous tissues available for reconstruction, other tissue substitutes have been used. Phallic reconstruction using engineered autologous genital tissue, i.e., tissue derived from the patient's own cells, may be preferable. In this article we describe tissue-engineering approaches that may be applicable to genital reconstruction.

Biocompatible Materials↗
PubMed2000

Experimental and clinical experience using tissue regeneration for urethral reconstruction.

Various urethral conditions often require additional tissue for reconstruction. Although several innovative tissues have been proposed for possible use as free grafts for urethral repair, all have specific advantages and disadvantages. The use of these tissues may be associated with additional procedures for graft retrieval, prolonged hospitalization, and donor-site morbidity. For these reasons, alternate materials have been sought for urethral repair. Our laboratory has developed an acellular collagen matrix that has shown adequate urothelial-cell epithelialization and urethral-tissue regeneration both experimentally and clinically. After a 3-year follow-up period, all patients who have had their urethras reconstructed with the acellular matrix are doing well, showing no clinical change from their immediate postoperative results. Other acellular materials may soon be tried clinically. Long-term studies need to be conducted before any of these materials can be accepted for routine use in urethral reconstructive procedures.

Animals↗
PubMed2000

Renal therapy using tissue-engineered constructs and gene delivery.

Currently available renal replacement therapies are not optimal for most patients. In addition to the inherent shortage of transplant organs, significant complications are associated with renal transplantation and immunosuppressive therapy. Dialysis neglects the resorptive, homeostatic, metabolic, and endocrinologic functions of the kidney and only partially replaces its filtration properties, resulting in morbidity and mortality. Application of tissue-engineering techniques may improve many aspects of renal function replacement. Identification of the growth factors capable of directing tissue development and of the technique to be used for their delivery would aid in the engineering of human tissue. The combination of tissue-engineering strategies with gene therapy might allow the transfection of diseased tissues with designated cDNA to eliminate inherent or acquired defects. Devices that have been targeted at replacing a single aspect of renal function, in addition to three-dimensional renal units that are capable of excreting urine-like solutes, have been used experimentally. Combination of these strategies may allow the formation of tissue-engineered kidneys in the future.

Biocompatible Materials↗