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At least 235 records · Page 13Linked to original sources
PubMed2004

Reconstruction of the ocular surface by transplantation of a serum-free derived cultivated conjunctival epithelial equivalent.

PURPOSE: The purpose of this study was to investigate the use of a serum-free derived cultivated conjunctival epithelial sheet for ocular surface transplantation and reconstruction. METHODS: Seven subjects with various ocular surface disorders were selected for the procedure: one patient had an extensive conjunctival nevus, three patients had pterygium, two patients had persistent leaking trabeculectomy blebs, and one patient had bilateral superior limbic keratoconjunctivitis. Conjunctival epithelial cells were harvested from the forniceal conjunctiva of patients 2 weeks before the definitive surgery. Cultivation of conjunctival epithelial cells on human amniotic membrane (HAM) was carried out under serum-free conditions. At the time of transplantation, the area of diseased conjunctiva was excised and the cultured conjunctival epithelium-HAM composite was transplanted onto the surgical defect. Patients were followed up with serial slit-lamp examinations, fluorescein staining, and photographic documentation. RESULTS: A confluent stratified conjunctival epithelial sheet was formed on the HAM within 12 to 14 days. Transplanted grafts remained well-epithelialized after surgery. A successful outcome, defined as resolution of the disease, maintenance of conjunctival epithelialization, maintenance of graft integrity, and absence of significant complications, was obtained in all seven patients. A good functional and cosmetic result was achieved in all eyes. The mean follow-up period was 11.6 months (range, 6-18 months). CONCLUSIONS: Transplantation of a serum-free derived autologous cultivated conjunctival epithelial sheet on HAM was successfully performed in seven patients with ocular surface disorders. This may provide a novel method for conjunctival replacement in conditions where the normal conjunctiva is damaged or deficient.

Adult↗
PubMed2000

New methods of bladder augmentation.

Gastrointestinal segments are commonly used for bladder replacement or repair. However, when gastrointestinal tissue is in contact with the urinary tract, several complications may ensue. Recent surgical approaches have relied on native urological tissue for reconstruction. These are based on sound surgical principles, allowing for the exclusion of tissue that is not urological. De-epithelialized bowel segments, either alone or over native urothelium, have also been used. An experimental system of progressive dilatation for ureters and bladders has been proposed. This appears promising, although it has yet to be attempted clinically. There has been a resurgence of interest in the use of acellular collagen-based matrices as scaffolds for bladder regeneration; experimental work is currently underway. Recently, functional bladder tissue has been engineered using selective cell transplantation. This technique uses autologous cells, so avoiding rejection. Tissue is obtained from the host, the cells then dissociated and expanded in vitro, re-attached to a matrix and implanted into the same host. Clinical trials are currently being arranged. Even though the use of bowel for bladder tissue replacement was first proposed over 100 years ago, it remains the gold standard, despite its associated problems. It is evident that urothelial-urothelial anastomoses are preferable functionally. Experience is currently being gained with the recent clinical and experimental approaches to augmentation cystoplasty. It is hoped that this will result in more technologies and methods for bladder augmentation.

Animals↗
PubMed2006

Bladder wall replacement by tissue engineering and autologous keratinocytes in minipigs.

OBJECTIVE: To develop a tissue-engineered bladder wall replacement with autologous cells and a biodegradable scaffold, as whenever there is a lack of native urological tissue the bladder is reconstructed with different bowel segments, which has inevitable complications. MATERIAL AND METHODS: Skin biopsies were taken from six minipigs, and primary fibroblast and keratinocyte cell cultures established. A partial resection of the urinary bladder was reconstructed by a cell-seeded scaffold covered with completely differentiated epithelium and supported by a mucosa-free pedicled ileum graft. Each pig was assessed urodynamically and by cystography before operation and every month until explantation; the pigs were killed at 1, 2 and 3 months after augmentation. Control groups (of six pigs each) with bladder augmentation with complete or denuded ileum were used. The bladders were assessed histologically and by distensibility measurements RESULTS: The differentiated keratinocyte epithelium was still present on the reconstructed bladder wall after 3 months. The overall shrinkage rate was 6.5%. The engineered bladder wall had lower distensibility than the native one. The inflammatory reaction present initially had disappeared after 3 months. CONCLUSIONS: The implanted, tissue-engineered substitution of the bladder wall is not only a bridging graft, but also a complete reconstruction. With this model, extended bladder wall substitution seems feasible and should be investigated in further studies.

Animals↗
PubMed2004

Research into the development of a wearable bioartificial kidney with a continuous hemofilter and a bioartificial tubule device using tubular epithelial cells.

Current hemodialysis treatment is insufficient because of intermittent treatment and loss of tubular function. In order to overcome the loss of tubular function, a bioartificial kidney has been developed consisting of continuous hemofiltration (CHF) with 10 L/day of filtrate and a bioartificial tubule device using proximal tubular epithelial cells and hollow fiber membranes. Ten L/day of CHF enabled plasma levels of urea, creatinine, uric acid and, beta2-microglobulin in eight renal failure patients to be maintained at remarkably low levels. The concept was tested with 6 L (4 mL/min) of 10 L/day (7 mL/min) filtrate regenerated by a bioartificial tubule device and 4 L/day (3 mL/min) replaced by food and drinks. Lewis lung cancer-porcine kidney 1 (LLC-PK1) cells with a cell density of 107 cells/mL were seeded inside polysulfone hollow fiber modules four times at 1 h intervals while rotating the module 90 degrees each time, and were cultured for 48 h to form confluent monolayers. The leak rates of urea and creatinine across LLC-PK1 cell-attached polysulfone membrane modules (membrane areas: 56 cm2 and 4000 cm2) were investigated. Via conversion from 56 m2 to 1 m2 hollow fiber modules with LLC-PK1 cells for 24 h, the transport rates of H2O, glucose and Na+ were, respectively, 40, 65 and 35% of the target transported amounts from 6 L/day of filtrate. The rates are expected to approach 100% when 4-5 g/dL of albumin is added to the basal portion of the medium since the results were obtained without the addition of albumin for colloidal osmotic pressure.

Animals↗
PubMed2004

Recent progress of vascular graft engineering in Japan.

The development of a small-diameter vascular graft has long been awaited. This review covers research activities, achievements and progress on vascular engineering in Japan, which was conducted over the last decade. The article includes recently developed experimental scaffolds, biologically active artificial extracellular matrices (ECMs) or non-fouling synthetic coatings, cell sourcing including the autologous vascular cell type, endothelial progenitor cells and genetically-engineered, temporary endothelial-like cells. The discussions were presented from biomechanical, biomaterial, cellular and tissue aspects. Once the mechano-biological and biologically active extracellular milieus are established in a designed vascular graft, the functional, structural and mechanical tissue morphogenesis and adaptation of implanted vascular grafts may proceed with implantation duration, and the spatio-temporal tissue modulations at cytokine, cellular, ECM levels under physiological stress proceed to regenerate vascular tissue architecture. The ultimate solution to a small-diameter vascular graft should be realized by optimal combinations of these factors.

Animals↗
PubMed2004

Bone marrow cells in the repair and modulation of heart and blood vessels: emerging opportunities in native and engineered tissue and biomechanical materials.

Adult bone marrow-derived stem/progenitor cells have traditionally been considered to be tissue-specific cells with limited capacity for differentiation. However, recent discoveries have generated tremendous excitement regarding possible applications of stem cells, particularly bone marrow-derived stem cells, in the treatment of human diseases. The potential ability to regenerate cells of various different lineages has raised the therapeutic possibility of using these bone marrow-derived stem cells as a source of cells for tissue repair and regeneration. Tissue engineering is a rapidly expanding interdisciplinary field aimed at restoring function to tissues through the delivery of constructs which become integrated into the patient. The use of bone marrow-derived stem cells provides a less invasive source for cells applicable to tissue engineering, including cardiovascular tissues such as heart valves, blood vessels, and myocardium. Although these strategies are in the early stages of development, they are conceptually promising and offer important insights into the future treatment of various cardiovascular ailments.

Animals↗
PubMed2006

Fabrication of myomucosal flap using tissue-engineered bioartificial mucosa constructed with oral keratinocytes cultured on amniotic membrane.

The purpose of this study was to fabricate bioartificial mucosa using cultured oral keratinocytes (OKCs) on an amniotic membrane (AM), and to evaluate the possibility of developing a prelaminated myomucosal flap using the fabricated bioartificial mucosa and local muscle flap. Buccal mucosa was harvested from male New Zealand rabbits (n = 40, 2.5-3.0 kg) and primary cultivation was performed. The cultured OKCs were seeded on the AM and a submerged culture was performed. Prelamination of the bioartificial mucosa was performed on the latissimus dorsi (LD) muscle of rabbits. Survival rate, layer of OKCs, and Cinamon's score (CS) based on macroscopic and microscopic examinations were evaluated 7, 10, 14, and 21 days after prelamination (n = 10 per day). The OKCs cultured on AM showed multiple layers (3.85 +/- 1.32) and cells were tightly adhered with desmosomes. Basal layer cells adhered to the AM with hemidesmosomes. In addition, the AM played an excellent role as a substrate for the OKCs and simplified handling during prelamination. A myomucosal flap with OKCs cultured on AM was fabricated within 2 weeks (CS: 11.05 +/- 2.63). The basement component of laminin was observed 2 weeks after prelamination and showed enough strength to adhere to the underlying fascia. A myomucosal flap was successfully developed using prelamination of bioartificial mucosa on the LD muscle between 10 and 14 days.

Amnion↗
PubMed2006

Transplantation of reconstructed corneal layer composed of corneal epithelium and fibroblasts on a lyophilized amniotic membrane to severely alkali-burned cornea.

The purpose of this article was to evaluate the graft efficacy of reconstructed corneal layer, composed of autologous corneal epithelium and fibroblasts on a lyophilized amniotic membrane (LAM), in a severely alkali-burned corneal model. After biopsy specimens were obtained from the left eyes of 24 rabbits, the corneal epithelial cells and fibroblasts were expanded in vitro and the corneal layer was reconstructed on LAM. Thirty-six eyes of rabbits underwent alkali burn (1 N NaOH, 30 s) to create a limbal deficiency and a deeply damaged corneal stroma. Four weeks later, group 1 underwent a graft of the reconstructed corneal layer composed of autologous corneal epithelium and fibroblasts on LAM. Group 2 was transplanted with a graft of the reconstructed autologous corneal epithelium, and group 3 served as a control without surgery. Wound healing and stabilization of the ocular surfaces occurred much faster in group 1 than in groups 2 and 3. The eyes in group 3 revealed typical limbal deficiencies with conjuctivalization and persistent corneal epithelial defects. However, the corneas in group 1 developed only mild peripheral neovascularization. Immunohistochemical staining in group 1 demonstrated that p63, cytokeratin 3, E-cadherin, transforming growth factor (TGF)-beta1, and collagen IV were expressed strongly in the corneal epithelium and basement membrane. On the basis of these results, transplantation of the reconstructed corneal layer, composed of autologous corneal epithelium and fibroblasts on LAM, partially accelerated the recovery of the alkali-injured rabbit ocular surface, and might be useful therapeutically for the treatment of patients with severely damaged cornea.

Amnion↗
PubMedDate not supplied

Tissue engineering of bone: the reconstructive surgeon's point of view.

Bone defects represent a medical and socioeconomic challenge. Different types of biomaterials are applied for reconstructive indications and receive rising interest. However, autologous bone grafts are still considered as the gold standard for reconstruction of extended bone defects. The generation of bioartificial bone tissues may help to overcome the problems related to donor site morbidity and size limitations. Tissue engineering is, according to its historic definition, an "interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function". It is based on the understanding of tissue formation and regeneration and aims to rather grow new functional tissues than to build new spare parts. While reconstruction of small to moderate sized bone defects using engineered bone tissues is technically feasible, and some of the currently developed concepts may represent alternatives to autologous bone grafts for certain clinical conditions, the reconstruction of large-volume defects remains challenging. Therefore vascularization concepts gain on interest and the combination of tissue engineering approaches with flap prefabrication techniques may eventually allow application of bone-tissue substitutes grown in vivo with the advantage of minimal donor site morbidity as compared to conventional vascularized bone grafts. The scope of this review is the introduction of basic principles and different components of engineered bioartificial bone tissues with a strong focus on clinical applications in reconstructive surgery. Concepts for the induction of axial vascularization in engineered bone tissues as well as potential clinical applications are discussed in detail.

Bioartificial Organs↗
PubMed2004

The tissue engineering of blood vessels and the heart.

The engineering of biological substitutes and strategies for the replacement and/or repair of blood vessels and the components of the heart represents an important challenge for tissue engineering. In this review, the progress to date and the barriers remaining are addressed. Even though the progress has been considerable and there are even some approaches that have entered clinical trials, we are still a ways off from having FDA-approved replacements and/or repair strategies.

Animals↗
PubMed2005

Design and assessment of a tissue-engineered model of human phalanges and a small joint.

OBJECTIVES: To develop models of human phalanges and small joints by suturing different cell-polymer constructs that are then implanted in athymic (nude) mice. DESIGN: Models consisted of bovine periosteum, cartilage, and/or tendon cells seeded onto biodegradable polymer scaffolds of either polyglycolic acid (PGA) or copolymers of PGA and poly-L-lactic acid (PLLA) or poly-epsilon-caprolactone (PCL) and PLLA. Constructs were fabricated to produce a distal phalanx, middle phalanx, or distal interphalangeal joint. SETTING AND SAMPLE POPULATION: Studies of more than 250 harvested implants were conducted at the Northeastern Ohio Universities College of Medicine. EXPERIMENTAL VARIABLE: Polymer scaffold, cell type, and implantation time were examined. OUTCOME MEASURE: Tissue-engineered specimens were characterized by histology, transmission electron microscopy, in situ hybridization, laser capture microdissection and qualitative and quantitative polymerase chain reaction analysis, magnetic resonance microscopy, and X-ray microtomography. RESULTS: Over periods to 60 weeks of implantation, constructs developed through vascularity from host mice; formed new cartilage, bone, and/or tendon; expressed characteristic genes of bovine origin, including type I, II and X collagen, osteopontin, aggrecan, biglycan, and bone sialoprotein; secreted corresponding proteins; responded to applied mechanical stimuli; and maintained shapes of human phalanges with small joints. CONCLUSION: Results give insight into construct processes of tissue regeneration and development and suggest more complete tissue-engineered cartilage, bone, and tendon models. These should have significant future scientific and clinical applications in medicine, including their use in plastic surgery, orthopaedics, craniofacial reconstruction, and teratology.

Animals↗
PubMed2001

Non-Invasive monitoring of a bioartificial pancreas in vitro and in vivo.

Monitoring biochemical processes relevant to the function, survival, and longevity of tissue-engineered pancreatic constructs is important for the development of an optimum construct design as well as patient care management after implantation. In this report we demonstrate the ability of nuclear magnetic resonance (NMR) techniques to monitor aspects of intracellular metabolism, overall morphology, and distribution of a microencapsulation based bioartificial pancreas in vitro and in vivo.

Animals↗
PubMed2001

An overview of the immune system with specific reference to membrane encapsulation and islet transplantation.

The concept of immunoisolation by use of a bioartificial membrane is discussed, concentrating on the immunological mechanisms that are likely to be operative in the light of recent information on the workings of the immune system. Special attention is given to the use of encapsulation for the purpose of treating autoimmune diabetes by implantation of xenogeneic islet tissue. It is argued that the term immunoisolation is misleading because the immune system is always activated by the indirect pathway of antigen presentation and that the term immunomodulation would be more appropriate.

Animals↗
PubMed2001

Cellular support systems for alginate microcapsules containing islets, as composite bioartificial pancreas.

To improve the functional performance of microencapsulated islets, we examined the effects of putative cellular support systems, consisting of rat purified Sertoli cells (SC) and astrocytes (AA), on coenveloped allogeneic islets. Coincubation of islets with SC but not AA, resulted in significant stimulation of beta cell mitogenesis, coupled with a significant increase in in vitro glucose-stimulated insulin release. Preliminarily, the xenotransplantation of coencapsulated rat islets and homologous SC significantly prolonged remission of hyperglycemia in diabetic mice.

Alginates↗
PubMed2001

Preclinical development of the Islet Sheet.

The Islet Sheet is a thin planar bioartificial endocrine pancreas fabricated by gelling highly purified alginate and islets of Langerhans. Acellular alginate layers form a uniform immunoprotective barrier to host rejection of the encapsulated cells, with the tissue nourished by passive diffusion from adjacent host tissue. The overall thickness of the Islet Sheet, 250 microm, is chosen to maximize nutrient diffusion. In this paper we describe the early development of the Islet Sheet, including purification and fractionation of the alginates used, difficulties in maintaining sheet planarity, and preliminary metabolic studies in pancreatectomized dogs. In a key experiment, approximately 75,000 allogeneic islet equivalents in six Islet Sheets were sutured to the omentum of a 7-kg female beagle dog at the time of pancreatectomy. Fasting euglycemia was maintained for 84 days. Fed blood sugars were usually below 150 mg/dL. A single injection of 2 U insulin was administered on day 9, and antibiotics were administered for two weeks. No other drugs were used. IVGTT post implant was not normal, but seemed to improve between 30 and 60 days. Upon omentectomy and sheet removal the metabolic parameters deteriorated to a frankly diabetic state within seven days. The sheets did not remain flat, but fragments were recovered within hard, mostly acellular capsules. Dithizone staining showed islets within alginate sheets recovered from the interior of these capsules, suggesting that allogeneic islet tissue survived 84 days and was responsible for maintaining fasting euglycemia.

Animals↗
PubMed2001

In vitro test of new biomaterials for the development of a bioartificial pancreas.

The implantation of macroencapsulated islets has the potential to restore endogenous insulin secretion in type 1 diabetics, with no need for lifetime immunosuppression. To match the physiological fluctuations of blood glucose concentrations with appropriate insulin release, the macroencapsulation material must combine immunoprotection with optimal diffusion properties for glucose and insulin. The impact of chemical modifications of polysulphone (PSU) capillary polymers with a cutoff of 50 kD on glucose-induced insulin secretion of macroencapsulated rat islets was studied in perifusion experiments. The insulin release of free-floating islets showed the typical rapid response to glucose stimulation. Total insulin release (AUC between minute 30 and 120 of perifusion) reached 117+/-22 ng/ml. Blending PSU with polyvinylpyrrolidone or sodium-dodecyl-sulfate was not suitable for islet macroencapsulation, since glucose-induced insulin release was absent or disturbed. Hydroxy-methylation (CH2OH) of PSU improved the secretory behavior of macroencapsulated islets depending on the degree of PSU substitution (DS 0.8, AUC 62+/-15 ng/ml; DS 1.8, 111+/-24 ng/ml). In highly substituted PSU-capillaries the kinetics of glucose-induced insulin release was very similar to that observed in free-floating islets. Two consecutive glucose stimulations potentiated insulin release of free-floating islets during the second period of stimulation. Furthermore, freshly isolated macroencapsulated islets responded with more efficient insulin secretion after the initial priming. In conclusion, in vitro membrane screening identified highly substituted hydroxy-methylated PSU as the material of choice for islet encapsulation in a bioartificial pancreas.

Animals↗