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Applying informatics in tissue engineering.

OBJECTIVE: To facilitate tissue engineering strategies determination with informatics tools. METHODS: Firstly, tissue engineering experimental data were standardized and integrated into a centralized database; secondly, we used data mining tools (e.g. artificial neural networks and decision trees) to predict the outcomes of tissue engineering strategies; thirdly, a strategy design algorithm was developed, and its efficacy was validated with animal experiments; lastly, we constructed an online database and a decision support system for tissue engineering. RESULTS: The artificial neural networks and the decision trees respectively predicted the outcomes of tissue engineering strategies with the predictive accuracy of 95.14% and 85.26%. Following the strategies generated by computer, we cured 18 of the 20 experimental animals with a significantly lower cost than usual. CONCLUSION: Informatics is beneficial for realizing safe, effective and economical tissue engineering.

Artificial Intelligence↗

Bone and cartilage reconstruction with tissue engineering approaches.

Tissues can be engineered to create new cartilage, bone, or bone-cartilage composites using synthetic polymer scaffolding as cell anchorage sites on which cells are transplanted. Topics discussed in this article include cell culture, material sciences, cell transplantation, tissue engineering, and clinical applications.

Animals↗

Adipose tissue engineering based on mesenchymal stem cells and basic fibroblast growth factor in vitro.

Despite the clinical need for reconstructive and plastic surgery, the supply of engineered adipose tissue equivalents still remains a challenge. As yet, only preadipocytes have been applied as a cell material for the in vitro tissue engineering of fat. Herein, we report the establishment of a three-dimensional (3-D) long-term cell culture, using bone marrow-derived mesenchymal stem cells (MSCs) as an alternative cell source and custom-made poly(lactic-co-glycolic acid) (PLGA) scaffolds as a cell carrier. Cell-polymer constructs were cultivated for 4 weeks in both the absence and presence of basic fibroblast growth factor (bFGF), which was previously shown to strongly enhance the adipogenesis of MSCs in conventional 2-D short-term culture. A striking enhancement of the adipogenic differentiation of MSCs and tissue development caused by bFGF in the 3-D culture was observed by osmium tetroxide histology and scanning electron microscopy. At the molecular level, reflecting the increased accumulation of lipids, bFGF increased the enzymatic activity of glycerol-3-phosphate dehydrogenase, a late marker of adipogenesis, and the expression of adipocyte-specific genes peroxisome proliferator activated receptor-gamma2 (PPARgamma2) and glucose transporter-4 (GLUT4), as assessed by reverse transcription-polymerase chain reaction. This study demonstrates that the use of bone marrow-derived MSCs, especially in combination with bFGF, may represent a promising approach to adipose tissue engineering.

Adipogenesis↗

[Tissue engineering in urology].

Tissue engineering refers to the techniques that are aimed at regeneration of human tissues and organs. Two elements are necessary for these techniques: matrix and cells. Matrix is the scaffold where tissues may organise. Cells are either autologous cells stimulated to regenerate in vivo, aided by implantation of matrix ("guided tissue regeneration"), or autologous cells cultured outside the body (in vitro) and later returned as auto-transplants. All types of conventional tissue reconstructive surgery need tissue engineering. These techniques have been introduced recently into the clinical practice. One of the main limitations of reconstructive surgery in genitourinary tract is the lack of autologous tissue. Two autotransplants could be distinguished: coherent tissue structure or cell suspensions. The great number of studies published in this area emphasizes the importance of the future clinical implication in urology.

Animals↗

[Supervision, administration and standard research related to tissue engineered medical products].

Tissue engineering advance in supplying the reparative and reconstructive medicine with promising tissue engineered medical products(TEMPs) and the new therapy alternative. The related supervision and administration of TEMPs is being developed and the standard research of TEMPs is also in progress. The Food and Drug Administration(FDA) of the United States has treated TEMPs as combined products and supervised them according to the level of risk to patients. Lately, FDA has determined that the Center for Devices and Radiological Health (CDRH) should take charge of examination and approval of TEMPs, with the cooperation of the Center for Biological Evaluations and Research(CBER). The regulatory controls have been established respectively in European Union and Japan. In China, TEMPs are identified as medical devices combined with cells. The Department of Medical Device of the State Food and Drug Administration (SFDA) is responsible for the examination and approval of TEMPs, and National Institute for the Control of Pharmaceutical & Biological Products(NICPBP) is responsible for evaluation tests. The standards of TEMPs are formulated mainly by the American Society of Testing Materials(ASTM) and International Standardization Organization(ISO).

Biological Products↗

The Pittsburgh Tissue Engineering Initiative.

The Pittsburgh Tissue Engineering Initiative (PTEI) is the prime catalyst for tissue-engineering research and the development of a viable for-profit tissue-engineering industry in southwestern Pennsylvania. PTEI operates targeted programs that support commercializable research; provide professional and community education; and facilitate interactions between academic medical centers, regional government, and industry to support the development of a vibrant tissue-engineering industry. This article discusses the types of research and education programs provided by PTEI and provides a brief summary of some of the tissue-engineering-related research in the region.

Biotechnology↗

Skeletal homeostasis in tissue-engineered bone.

Tissue-engineering strategies to stimulate bone regeneration may offer an alternative approach to conventional orthopaedic and maxillofacial surgical therapies. Over the last decade, significant advances have been accomplished in developing biomimetic matrices, growth factors, cell transplantation and gene delivery therapeutics to support new bone growth. However, it is not known if tissue-engineered bone recapitulates the biology of normal skeletal tissue in response to physiologic cues. Here, we report that bone formed by the differentiation of transplanted murine bone marrow stromal cells (BMSCs) responds to a systemically delivered calciotropic hormone. Ectopic ossicles in mice exposed to catabolic doses of parathyroid hormone (PTH) had increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts as compared to control mice. In contrast, treatment with anabolic doses of PTH promoted a marked increase in trabecular bone mass as analyzed by microcomputed tomography and histomorphometry. Our findings demonstrate that bone formed from transplanted BMSCs is responsive to normal physiologic signals, and can be augmented by the addition of a systemic anabolic agent. Because multiple and distinct ossicles can be generated in a single animal, this versatile system may be used to: (a) elucidate cellular/molecular mechanisms in bone regeneration; (b) study cell-to-cell interactions in the bone marrow microenvironment in health and disease; and (c) evaluate the efficacy of osteotropic agents that modulate bone turnover in vivo.

Acid Phosphatase↗

Gene-enhanced tissue engineering for dental hard tissue regeneration: (1) overview and practical considerations.

Gene-based therapies for tissue regeneration involve delivering a specific gene to a target tissue with the goal of changing the phenotype or protein expression profile of the recipient cell; the ultimate goal being to form specific tissues required for regeneration. One of the principal advantages of this approach is that it provides for a sustained delivery of physiologic levels of the growth factor of interest.This manuscript will review the principals of gene-enhanced tissue engineering and the techniques of introducing DNA into cells. Part 2 will review recent advances in gene-based therapies for dental hard tissue regeneration, specifically as it pertains to dentin regeneration/pulp capping and periodontal regeneration.

Journal Article↗

Analysis of cell growth and diffusion in a scaffold for cartilage tissue engineering.

Developments in tissue engineering over the past decade have offered promising future for the repair and reconstruction of damaged tissues. To regenerate three dimensional and weight-bearing implants, advances in biomaterials and manufacturing technologies prompted cell cultivations with natural or artificial scaffolds, in which cells are allowed to proliferate, migrate, and differentiate in vitro. In this article, we develop a mathematical model for cell growth in a porous scaffold. By treating the cell-scaffold construct as a porous medium, a continuum model is set up based on basic principles of mass conservation. In addition to cell growth kinetics, we incorporate cell diffusion in the model to describe the effects of cell random walks. Computational results are compared to experimental data found in the literature. With this model, we are able to investigate cell motility, heterogeneous cell distributions, and non-uniform seeding for tissue engineering applications. Results show that random walks tend to enhance uniform cell spreads in space, which in turn increases the probabilities for cells to acquire nutrients; therefore random walks are likely to be a positive contribution to the overall cell growth on scaffolds.

Animals↗

[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↗

Decellularized placental matrices for adipose tissue engineering.

A tissue-engineered adipose substitute would be invaluable to plastic surgeons for reconstructive, corrective, and cosmetic procedures. This work involves the design of a scaffold for soft tissue augmentation incorporating the decellularized extracellular matrix (ECM) of human placenta. We have developed a protocol to decellularize an intact, large segment (8 cm by 8 cm) of the human placenta. To facilitate the complete decellularization of the dense matrix, a system was designed to perfuse the required chemicals into the placenta via the existing vasculature. Following processing, the original architecture of the placental ECM was preserved, including an intact vascular network. Histological, immunohistochemical, and scanning electron microscopic analyses confirmed the removal of the cells and cellular debris and characterized the composition and structure of the matrix. In vitro cell culture experimentation showed that the placental decellular matrix (PDM) could facilitate the adhesion of primary human adipose precursor cells at early time points. The PDM has great potential for use as a scaffold for adipose tissue engineering, as the placenta is a rich source of human ECM components that can be readily harvested without harm to the donor.

Adipose Tissue↗

Tissue engineering with chondrocytes.

Tissue engineering of cartilage, using chondrocytes based on the use of synthetic biodegradable polymer cell delivery vehicles (scaffolds), is an alternate treatment modality for replacing missing cartilage. Cartilage tissue engineering has an important role to play in the generation of graft material for head and neck reconstruction. It is an approach to fabricate cartilage constructs in vitro, which could be used in reconstructive surgery. Methods involve (1) harvesting septal cartilage during septoplasty, (2) isolating chondrocytes through enzymatic digestion of the septal cartilage, (3) expanding the cell number in a two-dimensional monolayer culture, using serum-free media, (4) seeding the cells onto a biodegradable polymer scaffold, and (5) cultivating the seeded scaffolds in a rotating bioreactor. In this article we briefly outline the methodology and clinical applications of cartilage grown ex vivo.

Absorbable Implants↗

Animal models of spinal cord injury for evaluation of tissue engineering treatment strategies.

Tissue engineering approaches to spinal cord injury (SCI) treatment are attractive because they allow for manipulation of native regeneration processes involved in restoration of the integrity and function of damaged tissue. A clinically relevant spinal cord regeneration animal model requires that the model mimics specific pathologic processes that occur in human SCI. This manuscript discusses issues related to preclinical testing of tissue engineering spinal cord regeneration strategies from a number of perspectives. This discussion includes diverse causes, pathology and functional consequences of human SCI, general and species related considerations, technical and animal care considerations, and data analysis methods.

Animals↗

Tissue engineering, morphogenesis, and regeneration of the periodontal tissues by bone morphogenetic proteins.

Tissue engineering is the emerging field of science developing techniques for fabrication of new tissues for replacement based on principles of cell and developmental biology and biomaterials. Morphogenesis is the cascade of pattern formation and the attainment of form of the various organs and the organism as a whole. The periodontium consist of the periodontal ligament, cementum, and alveolar bone. Bone has considerable potential for regeneration and therefore is a prototypic model for tissue engineering. The three main ingredients for tissue engineering are regulatory signals, responding stem cells, and extracellular matrix. Recent advances in molecular biology of the bone morphogenetic proteins (BMPs) have set the stage for tissue engineering of bone and related tissues, including the periodontium. Bone-derived BMPs, with a collagenous matrix as carrier, induced cementum and alveolar bone regeneration in surgically created furcation defects in the primate. It is noteworthy that there was morphogenesis of periodontal ligament and a faithful insertion of Sharpey's fibers into cementum. In the same furcation model, recombinant human osteogenic protein-1 (rhOP-1, also known as BMP-7), in conjunction with the collagenous carrier, induced extensive cementogenesis with insertion of Sharpey's fibers into the newly formed cementum. The observation that BMPs induce cementogenesis and periodontal ligament formation indicates that these proteins may have multiple functions in vivo not limited to cartilage and bone induction. The rapid advances in the molecular biology of BMPs and their receptors bode well for novel strategies to engineer the regeneration of the periodontal tissues.

Alveolar Process↗

From lab bench to market: critical issues in tissue engineering.

Revolutionary advances in tissue engineering are redefining approaches to tissue repair and transplantation through the creation of replacement tissues that remain biointeractive after implantation, imparting physiologic functions as well as structure to the tissue or organ damaged by disease or trauma.(1,2) Over the last decade this field has moved from "science fiction" to "science fact" with the research-oriented acceptance of its potential to regulatory approvals allowing commercial products to be available for use in many countries. The maintenance of tissue integrity, functionality, and viability from cell seeding through product manufacture, shipping, and end-use has been accomplished through innovations in design and scale-up of both tissue growth and preservation processes. These unique systems have enabled the delivery of tissue-engineered products that are uniform inter- and intra-lot, readily available as off-the-shelf products, easy to use, and efficacious. Skin replacement products are the most advanced, with several tissue-engineered wound care materials on the market in the U.S. and in several international communities.(3-5) The potential impact of this field is far broader, offering novel solutions to the medical field for drug screening and development, genetic engineering, and total tissue and organ replacement.

Animals↗

Advances in skeletal tissue engineering with hydrogels.

OBJECTIVES: Tissue engineering has the potential to make a significant impact on improving tissue repair in the craniofacial system. The general strategy for tissue engineering includes seeding cells on a biomaterial scaffold. The number of scaffold and cell choices for tissue engineering systems is continually increasing and will be reviewed. DESIGN: Multilayered hydrogel systems were developed to coculture different cell types and develop osteochondral tissues for applications including the temporomandibular joint. EXPERIMENTAL VARIABLE: Hydrogels are one form of scaffold that can be applied to cartilage and bone repair using fully differentiated cells, adult and embryonic stem cells. OUTCOME MEASURE: Case studies represent an overview of our laboratory's investigations. RESULTS: Bilayered scaffolds to promote tissue development and the formation of more complex osteochondral tissues were developed and proved to be effective. CONCLUSION: Tissue engineering provides a venue to investigate tissue development of mutant or diseased cells and potential therapeutics.

Animals↗

Tissue engineering: the current status of this futuristic modality in head neck reconstruction.

PURPOSE OF REVIEW: To define tissue engineering and describe the components that are involved in engineering tissue. To provide examples of the most recent developments in tissue engineering as they apply to the otolaryngologist. To provide a general overview of selected exciting advances outside the field of general otolaryngology but of general interest to the reconstructive community. RECENT FINDINGS: Tissue engineering is a rapidly evolving field that can be defined as the regeneration of new tissues through the use of biologic mediators and matricis. The three components required are scaffolds, signaling molecules, and cells. A significant amount of work has been done to generate bone, cartilage, cornea, and vascular grafts. Tissue engineered bone is the only tissue type that has been evaluated in Phase III clinical trials and is in routine clinical use. Engineered bone from BMP-2 and BMP-7 is used in orthopedics for lumbar fusions and long bone nonunions. Clinical application of bone tissue engineering in the head and neck is limited to case reports. There has been success in tissue engineering with cartilage for the nose and ear in immune incompetent animal models but there has been difficulty with generating scaffolds that do not incite an immune reaction in an immune competent model. The most advanced organ engineered is a bladder that has been successful in a canine model. SUMMARY: Tissue engineering holds the promise of "off the shelf" parts for reconstruction of tissues and organs. The widest clinical application is with bone in orthopedics. Applications in the head and neck are limited, at present, due to the immunogenicity of the scaffolds and the challenging wounds encountered in both cancer and cosmetic patients.

Animals↗