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At least 91 records · Page 5Linked to original sources
PubMed1996

Tissue engineering of a bioartificial kidney: a universal donor organ.

Cell therapy and tissue engineering may well likely dominate medical therapeutics in the next century. Growing a functional glomerular filter and tubule reabsorber from a combination of cells, biomaterials, and synthetic polymers to replace renal excretory and regulatory functions is a specific example of these evolving technologies. The kidney was the first organ whose function was substituted by an artificial device. The kidney was also the first organ to be successfully transplanted. The ability to replace renal function with these revolutionary technologies in the past was due to the fact that renal excretory function is based on natural physical forces which govern solute and fluid movement from the body compartment to the external environment. The need for coordinated mechanical or electrical activities got renal substitution was not required. Accordingly, the kidney may well be the first organ to be available as a tissue-engineered implantable device as a fully functional replacement part for the human body. The prospects of a "universal donor" bioartificial kidney for the treatment of end-stage renal disease are clearly achievable as we approach the next millennium.

Artificial Organs↗
PubMed2005

Biochemical consequences of alginate encapsulation: a NMR study of insulin-secreting cells.

In this study we explore the biochemical consequences of alginate encapsulation on betaTC3 cells. (13)C NMR spectroscopy and isotopomer analysis were used to investigate the effects of encapsulation on several enzymatic processes associated with the TCA cycle. Our data show statistically significant differences in various enzymatic fluxes related to the TCA cycle and insulin secretion between monolayer and alginate-encapsulated cultures. The principal cause for these effects was the process of trypsinization. Embedding the trypsinized cells in alginate beads did not have a compounded effect on the enzymatic fluxes of entrapped cells. However, an additional small but statistically significant decrease in insulin secretion was measured in encapsulated cells. Finally, differences in either enzymatic fluxes or glucose consumption as a function of bead diameter were not observed. However, differences in T(2), assessed by (1)H NMR microimaging, were observed as a function of bead diameter, suggesting that smaller beads became more organized with time in culture, while larger beads displayed a looser organization.

Alginates↗
PubMed2005

Fabrication of viable tissue-engineered constructs with 3D cell-assembly technique.

We have recently developed an organ manufacturing technique that enables us to form cell/biomaterial complex three-dimensional (3D) architectures in designed patterns. This technique employs a highly accurate 3D micropositioning system with a pressue-controlled syringe to deposit cell/biomaterial structures with a lateral resolution of 10 microm. The pressure-activated micro-syringe is equipped with a fine-bore exit needle using which a wide variety of 3D patterns with different arrays of channels (through-holes) were created. The channels can supply living cells with nutrients and allow removing the cell metabolites. The embedded cells remain viable and perform biological functions as long as the 3D structures are retained. The new technology has the potential for eventual high-throughput production of artificial human tissues and organs.

Animals↗
PubMed2006

Polysurgery of cell sheet grafts overcomes diffusion limits to produce thick, vascularized myocardial tissues.

Recently, the field of tissue engineering has progressed rapidly, but poor vascularization remains a major obstacle in bioengineering cell-dense tissues, limiting the viable size of constructs due to hypoxia, nutrient insufficiency, and waste accumulation. Therefore, new technologies for fabricating functional tissues with a well-organized vasculature are required. In the present study, neonatal rat cardiomyocytes were harvested as intact sheets from temperature-responsive culture dishes and stacked into cell-dense myocardial tissues. However, the thickness limit for layered cell sheets in subcutaneous tissue was approximately 80 microm (3 layers). To overcome this limitation, repeated transplantation of triple-layer grafts was performed at 1, 2, or 3 day intervals. The two overlaid grafts completely synchronized and the whole tissues survived without necrosis in the 1 or 2 day interval cases. Multistep transplantation also created approximately 1 mm thick myocardium with a well-organized microvascular network. Furthermore, functional multilayer grafts fabricated over a surgically connectable artery and vein revealed complete graft perfusion via the vessels and ectopic transplantation of the grafts was successfully performed using direct vessel anastomoses. These cultured cell sheet integration methods overcome long-standing barriers to producing thick, vascularized tissues, revealing a possible solution for the clinical repair of various damaged organs, including the impaired myocardium.

Animals↗
PubMed2004

What's in the pipeline about bladder reconstructive surgery? Some remarks on the state of the art.

The fusion of engineering with cell biology and advances in biomaterials may lead to de novo construction of implantable organs. Engineering of neobladder from autologous urothelial and smooth muscle cells cultured on biocompatible, either synthetic or naturally-derived substrates, is now feasible in preclinical studies and may have clinical applicability in the near future. The development of a bioartificial bladder would warrant the prevention of both the metabolic and neoplastic shortcomings of the intestinal neobladder. Two tissue-engineering techniques for bladder reconstruction have been tested on animals: 1) the in vivo technique involves the use of naturally-derived biomaterials for functional native bladder regeneration 2) the in vitro technique involves the establishment of autologous urothelial and smooth muscle cell culture from the host's urinary tract, after which the cells are seeded on the biodegradable matrix-scaffold to create a composite graft that is implanted into the same host for complete histotectonic regeneration. Waiting for the creation of a complete tissue-engineered bladder with a trigone-shaped base, we suggest, in surgical oncology after radical cystectomy, the realization of conduit or continent pouch using tissue-engineered material.

Animals↗
PubMed2001

Development of a hybrid liver support system.

Hybrid liver systems are being developed as temporary extracorporeal liver support therapy. The overview given here emphasizes the development of both hepatocyte culture models for bioreactors and of systems for clinical therapy. In vitro studies demonstrate long term external metabolic function in isolated primary hepatocytes within bioreactors. These systems are capable of supporting essential liver functions. Animal experiments verify the possibility of upscaling bioreactors for clinical treatment. However, since there is no reliable animal model for investigating the treatment of acute liver failure, the promising results obtained from these studies have limited relevance to human beings. The small number of clinical studies performed thus far are not sufficient to enable any conclusions concerning improvements in the therapy of acute liver failure. Although important progress has been made in the development of these systems, multiple hepatocyte culture models and bioreactor constructions are being discussed in the literature, indicating competition in this field of medical research. For the use of hepatocytes and sinusoidal endothelial cells in coculture, a bioreactor has been designed. The construction is based on capillaries for hepatocyte aggregate immobilization. Four separate capillary membrane systems, each permitting a different function, are woven in order to create a three-dimensional network. Cells are perfused via independent capillary membrane compartments. Decentralized oxygen supply and carbon dioxide removal with low gradients is possible. The parallel use of identical units enables easy upscaling. Initial studies on the use of discarded organs that are unsuitable for transplantation as a source for primary human liver cells seem to be promising.

Bioartificial Organs↗
PubMed2005

Facts and theories of induced organ regeneration.

Induced organ regeneration is de novo synthesis of a physiological, or nearly physiological, organ at the same anatomical site as the organ that is being replaced. Regeneration of skin, peripheral nerves and the conjunctiva, described in this chapter, have been accomplished using biologically active scaffolds (regeneration templates) seeded with epithelial cells; devices for regeneration of the first two organs are in clinical use. There is substantial empirical evidence that templates induce regeneration by blocking contraction, the major mechanism for closure of severe wounds in adults. Templates appear to function by interfering with normal myofibroblast function well as by acting as temporary configurational guides for synthesis of new stroma that resembles that of the organ under replacement. The combined evidence supports a theory which predicts that selective blocking of the adult healing response uncovers the latent fetal response to injury and leads to organ regeneration. An independent theory suggests that loss of regenerative potential during the mammalian fetal-adult transition is associated with simultaneous acquisition of individual immunocompetence.

Adaptation, Physiological↗
PubMed2002

[Intersections of reconstructive surgery in the area of regenerative medicine].

Based on significant progress in biotechnology, "Regenerative Medicine" is evolving as a new discipline that could significantly change current therapeutic approaches. Medicine, stem cell biology, tissue engineering, nanotechnology, genomic research, material sciences, as well as system- and process-engineering come together to answer fundamental problems of human disease, including trauma and aging. The long-term goal is to create a profound knowledge of individualized therapy originating from nonbiological organ replacement, through hybridized systems, to fully biological implants and finally to human regenerative systems in vivo. Two model tissues, including heart valves and liver tissue are discussed in the context of in vivo and in vitro regeneration technologies. Extracellular matrix regulates tissue differentiation in at least three ways, including the biochemical composition of the matrix constituents, the 3-D organization or architecture, and via mechanical forces mediated to the cells by the matrix. The in vivo extracellular matrix constitutes a biopolymer which potentially plays a permissive role for tissue differentiation.

Animals↗
PubMed2001

Current progress and perspectives in cell therapy for diabetes mellitus.

Recent advances of cell transplantation and tissue engineering are remarkable. And also the diabetic treatment using pancreatic beta cells have performed great advances. Even clinical islet transplantation has been considered a common curative treatment for diabetes mellitus in the place of an experimental treatment. Still more the lack of donor's organ as a worst problem of transplantation will be overcome by using the beta cells produced in vitro culture. Therefore diabetes mellitus will be closed to cure in the near future.

Animals↗
PubMed2001

[Application of tissue engineering in medicine].

Tissue engineering is a new field, which is based on engineering and life biology. It studies the structure of creatures and shows a wide prospect of treating the functional obstacle of tissues' and organs' wane. Lots of success has been achieved during the passed years and most of them were used on clinical. According to the origin of germinal layer during embryo development, the applying progress of tissue engineering in medicine is discussed.

Bioartificial Organs↗
PubMed2005

Similarities and differences between induced organ regeneration in adults and early foetal regeneration.

At least three organs (skin, peripheral nerves and the conjunctiva) have been induced to regenerate partially in adults following application of porous, degradable scaffolds with highly specific structure (templates). Templates blocked contraction and scar formation by inducing a reduction in the density of contractile fibroblasts (probably myofibroblasts) and by preventing these cells to organize themselves appropriately in the wound. In contrast, during early foetal healing, myofibroblasts were absent and wounds did not close by contraction but rather by spontaneous regeneration. The adult regenerative process has so far led to imperfect recovery of the physiological anatomy of skin (skin appendages were missing), while early foetal healing has led to apparently complete restoration. Furthermore, the mechanism of the adult regenerative process involves thwarting of myofibroblast function while, during early foetal healing, differentiation of myofibroblasts has not yet occurred. The data suggest that induced organ regeneration in the adult is the result of partial reversion to early foetal healing. If so, the adult may conceal a foetal response that may be subject to activation following application of highly active scaffolds or of other substances or cells.

Adult↗
PubMedDate not supplied

Biomimetic collagen scaffolds for human bone cell growth and differentiation.

Type I collagen provides a structural framework for connective tissues and plays a central role in the temporal cascade of events leading to the formation of new bone from progenitors. The aim of this study was to examine the ability of the cell-binding domain of type I collagen (P-15 peptide) to promote human bone marrow stromal cell adhesion, proliferation, and differentiation on three-dimensional scaffolds. Human bone marrow stromal cells were selected, expanded, and cultured on particulate microporous ABM ("pure" hydroxyapatite) phase adsorbed with or without P-15 under basal or osteogenic conditions. Immobilized P-15 increased alkaline phosphatase activity and bone morphogenetic protein 2 (BMP-2) gene expression after 1 and 5 days as determined by real-time polymerase chain reaction. P-15 promoted human bone marrow stromal cell attachment, spreading, and alignment on ABM as well as alkaline phosphatase-specific activity in basal and osteogenic cultures. The presence of mineralized bone matrix, extensive cell ingrowth, and cellular bridging between three-dimensional matrices adsorbed with P-15 was confirmed by confocal microscopy, scanning electron microscopy, and alizarin red staining. Negligible cell growth was observed on ABM alone. In vivo diffusion chamber studies using MF1-nu/nu mice showed bone matrix formation and organized collagen formation after 6 weeks. These studies indicate the potential of P-15 to generate appropriate biomimetic microenvironments for osteoblasts and demonstrate the potential for the exploitation of extracellular matrix cues for osteogenesis and, ultimately, bone regeneration.

Adsorption↗
PubMed2004

[Acellular matrix for functional reconstruction of the urogenital tract. Special form of "tissue engineering"?].

Organ substitution and reconstruction of the urogenital system still poses a problem regarding an adequate substitute. Usually non-organ-specific materials are used for reconstruction (bowl, buccal mucosa). This nonspecific tissue can cause side effects that result from the origin and the natural function. Different groups have shown that an acellular matrix graft in the urinary bladder and the urethra served as a scaffold for complete regeneration of all organ wall components and that this organ-specific regeneration simultaneously facilitates functional restitution. New approaches will presumably effect better regeneration after seeding the matrix with organ-specific cells (i.e., urothelial cells). Smaller studies on genital reconstructive surgery could show that vaginal substitution with an acellular matrix might be possible or that there could be a possible substitute for the tunica during surgical treatment of Peyronie's disease.

Absorbable Implants↗
PubMed2004

Synthesis of tissues and organs.

Symbolism that describes the synthetic processes for chemical compounds has been used to describe, in qualitative terms, the synthesis of tissues and organs at the correct anatomical site. The synthetic process is summarized in the reaction diagram, a shorthand representation of the reactants, reactor, and products. Analysis of a large number of independent protocols has led to identification of the simplest synthetic pathways for two organs that have been studied extensively: skin and peripheral nerves. These apparently irreducible reaction diagrams for the two organs are not only simple but surprisingly similar, a fact suggesting the existence of general rules for the synthesis of other organs as well. The only two reactants that are required are an active scaffold (a macromolecular network synthesized as a highly porous analogue of the extracellular matrix) and a seeding of epithelial cells of the organ being synthesized. Scaffolds possessed biological (regenerative) activity provided that they were capable of blocking the contraction process that leads to closure of the injured site. Such activity requires that the density of ligands for binding of contractile cells on the scaffold maintains a sufficiently high level over the period of synthesis.

Animals↗
PubMed2007

Engineering skin to study human disease--tissue models for cancer biology and wound repair.

Recent advances in the engineering of three-dimensional tissues known as skin equivalents, that have morphologic and phenotypic properties of human skin, have provided new ways to study human disease processes. This chapter will supply an overview of two such applications--investigations of the incipient development of squamous cell cancer, and studies that have characterized the response of human epithelium during wound repair. Using these novel tools to study cancer biology, it has been shown that cell-cell interactions inherent in three-dimensional tissue architecture can suppress early cancer progression by inducing a state of intraepithelial dormancy. This dormant state can be overcome and cancer progression enabled by altering tissue organization in response to tumor promoters or UV irradiation or by modifying the interaction of tumor cells with extracellular matrix proteins or their adjacent epithelia. By adapting skin equivalent models of human skin to study wound reepithelialization, it has been shown that several key responses, including cell proliferation, migration, differentiation, growth-factor responsiveness and protease expression, will mimic the response seen in human skin. In this light, these engineered models of human skin provide powerful new tools for studying disease processes in these tissues as they occur in humans.

Animals↗
PubMed2006

An overview on the development of a bio-artificial pancreas as a treatment of insulin-dependent diabetes mellitus.

This paper presents the concept and most of the research undertaken all over the world for the development of a bio-artificial pancreas (BAP) device over the last 30 years. The devices studied, meant to mimic the insulin secretion of the natural organ, were diverse and have been reviewed. Allogeneic or xenogeneic cells or cell clusters have been separated from the host's immune system by synthetic biocompatible semipermeable membranes to prevent the need, of the host, for immune-suppressing regimens. The biocompatible polymer used as a barrier and its intrinsic characteristics, the cell immobilization or suspension media, the existence or not of co-immobilized molecules or cells, the number of devices used and the implantation site, were addressed.

Acrylic Resins↗
PubMed2005

The effect of PEGT/PBT scaffold architecture on the composition of tissue engineered cartilage.

A highly interconnecting and accessible pore network has been suggested as one of a number of prerequisites in the design of scaffolds for tissue engineering. In the present study, two processing techniques, compression-molding/particulate-leaching (CM), and 3D fiber deposition (3DF), were used to develop porous scaffolds from biodegradable poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) co-polymers with varying pore architectures. Three-dimensional micro-computed tomography (microCT) was used to characterize scaffold architectures and scaffolds were seeded with articular chondrocytes to evaluate tissue formation. Scaffold porosity ranged between 75% and 80%. Average pore size of tortuous CM scaffolds (182 microm) was lower than those of organized 3DF scaffolds (525 microm). The weight ratio of glycosaminoglycans (GAG)/DNA, as a measure of cartilage-like tissue formation, did not change after 14 days of culture whereas, following subcutaneous implantation, GAG/DNA increased significantly and was significantly higher in 3DF constructs than in CM constructs, whilst collagen type II was present within both constructs. In conclusion, 3DF PEGT/PBT scaffolds create an environment in vivo that enhances cartilaginous matrix deposition and hold particular promise for treatment of articular cartilage defects.

Animals↗
PubMed2001

Emulsion-derived foams (PolyHIPEs) containing poly(epsilon-caprolactone) as matrixes for tissue engineering.

The preparation of PolyHIPE foams containing poly(epsilon-caprolactone) from macromonomers by free radical homo- or copolymerization is described. The macromonomers are synthesized from PCL diols and are polymerized in the continuous phase of high internal phase emulsions (HIPEs). Subsequent drying yields low-density foams with cell diameters of 5-100 microm. Foam morphology, as determined by scanning electron microscopy, depends on the type of diluent (styrene, methyl methacrylate, or toluene) added to the emulsion organic phase and on the PCL content. Increasing the latter increases the continuous phase viscosity to a point where emulsion formation is impeded. Foam swelling in toluene, 2-propanol, and water was investigated by solvent imbibition and increased with increasing solvent hydrophobicity. Furthermore, it was found generally to decrease with increasing PCL content, due to increasing cross-link density. Swelling generally increased when higher molar mass PCL macromonomer was used due to the formation of a less tightly cross-linked network. One type of foam sample was shown to support the growth of human fibroblasts over a period of 2.5 days.

Bioartificial Organs↗