Showing papers on "Tissue engineering published in 1999"

DNA delivery from polymer matrices for tissue engineering.

Abstract: We have proposed engineering tissues by the incorporation and sustained release of plasmids encoding tissue-inductive proteins from polymer matrices. Matrices of poly(lactide-co-glycolide) (PLG) were loaded with plasmid, which was subsequently released over a period ranging from days to a month in vitro. Sustained delivery of plasmid DNA from matrices led to the transfection of large numbers of cells. Furthermore, in vivo delivery of a plasmid encoding platelet-derived growth factor enhanced matrix deposition and blood vessel formation in the developing tissue. This contrasts with direct injection of the plasmid, which did not significantly affect tissue formation. This method of DNA delivery may find utility in tissue engineering and gene therapy applications.

Stem cell technology and bioceramics: From cell to gene engineering

Abstract: Mesenchymal stem cells reside in bone marrow and, when these cells are incorporated into porous ceramics, the composites exhibit osteo-chondrogenic phenotypic expression in ectopic (subcutaneous and intramuscular) or orthotopic sites. The expressional cascade is dependent upon the material properties of the delivery vehicle. Bioactive ceramics provide a suitable substrate for the attachment of the cells. This is followed by osteogenic differentiation directly on the surface of the ceramic, which results in bone bonding. Nonbioactive materials show neither surface-dependent cell differentiation nor bone bonding. The number of mesenchymal stem cells in fresh adult bone marrow is small, about one per one-hundred-thousand nucleated cells, and decreases with donor age. In vitro cell culture technology can be used to mitotically expand these cells without the loss of their developmental potency regardless of donor age. The implanted composite of porous ceramic and culture-expanded mesenchymal stem cells exhibits in vivo osteo-chondrogenic differentiation. In certain culture conditions, these stem cells differentiate into osteoblasts, which make bone matrix on the ceramic surface. Such in vitro prefabricated bone within the ceramic provides immediate new bone-forming capability after in vivo implantation. Prior to loading of the cultured, marrow-derived mesenchymal stem cells into the porous ceramics, exogenous genes can be introduced into these cells in culture. Combining in vitro manipulated mesenchymal stem cells with porous ceramics can be expected to effect sufficient new bone-forming capability, which can thereby provide tissue engineering approaches to patients with skeletal defects in order to regenerate skeletal tissues.

Cardiac tissue engineering: cell seeding, cultivation parameters, and tissue construct characterization.

Abstract: Cardiac tissue engineering has been motivated by the need to create functional tissue equivalents for scientific studies and cardiac tissue repair. We previously demonstrated that contractile cardiac cell-polymer constructs can be cultivated using isolated cells, 3-dimensional scaffolds, and bioreactors. In the present work, we examined the effects of (1) cell source (neonatal rat or embryonic chick), (2) initial cell seeding density, (3) cell seeding vessel, and (4) tissue culture vessel on the structure and composition of engineered cardiac muscle. Constructs seeded under well-mixed conditions with rat heart cells at a high initial density ((6-8) x 10(6) cells/polymer scaffold) maintained structural integrity and contained macroscopic contractile areas (approximately 20 mm(2)). Seeding in rotating vessels (laminar flow) rather than mixed flasks (turbulent flow) resulted in 23% higher seeding efficiency and 20% less cell damage as assessed by medium lactate dehydrogenase levels (p < 0.05). Advantages of culturing constructs under mixed rather than static conditions included the maintenance of metabolic parameters in physiological ranges, 2-4 times higher construct cellularity (p &le 0.0001), more aerobic cell metabolism, and a more physiological, elongated cell shape. Cultivations in rotating bioreactors, in which flow patterns are laminar and dynamic, yielded constructs with a more active, aerobic metabolism as compared to constructs cultured in mixed or static flasks. After 1-2 weeks of cultivation, tissue constructs expressed cardiac specific proteins and ultrastructural features and had approximately 2-6 times lower cellularity (p < 0.05) but similar metabolic activity per unit cell when compared to native cardiac tissue.

Autologous chondrocyte transplantation.

Abstract: The intrinsic capacity of cartilage to repair chondral injuries is poor. Different techniques to induce cartilage repair with the use of extrinsic chondrogeneic cell sources have been explored in experimental models. Cells can be harvested autologously or as allografts from a healthy part of the donor tissue, isolated, expanded in vitro, and finally implanted into the defect in high densities. Pure chondrocytes, epiphyseal or mature, allogeneic or autologous, and other types of mesenchymal cells have been used. The composition and structure of the extracellular cartilage matrix are maintained through a balance of anabolic and catabolic activities controlled by the unique chondrocytes. They keep the cartilage alive; they alone maintain it and regulate it. It therefore seems important to use true committed chondrocytes to repair a local cartilaginous defect. The rational basis for the use of committed autologous chondrocytes in combination with a covering periosteal membrane in the treatment of deep cartilage defects is presented.

Decrease in culture temperature releases monolayer endothelial cell sheets together with deposited fibronectin matrix from temperature‐responsive culture surfaces

Abstract: Bovine aortic endothelial cells were cultured on surfaces grafted with a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm), in the presence of serum Cells adhered, spread, proliferated, and reached confluency as observed on ungrafted tissue culture polystyrene dishes A decrease in culture temperature released cells only from the grafted surfaces without enzymatic or ethylenediaminetetraacetic acid treatment Upon lowering temperature, the culture surfaces changed from hydrophobic to hydrophilic owing to the hydration of grafted PIPAAm and thus weakened the cell attachment to the dishes Released cells maintained cell-cell junctions composing monolayer cell sheets Immunoblotting and immunofluorescence microscopy revealed that fibronectin (FN) was deposited and accumulated on the grafted surfaces during the culture Furthermore, the deposited FN matrix adhering to cell sheets was also recovered from temperature-responsive surfaces by low-temperature treatment, while trypsin treatment destroyed the matrix The recovery of FN by low-temperature treatment was as high as by physical scraping with a rubber blade Temperature-responsive surfaces can provide a novel method to use cultured confluent cell sheets for tissue engineering, and also to elucidate structure and function of deposited extracellular matrix during cell culture

In vitro analysis of biodegradable polymer blend/hydroxyapatite composites for bone tissue engineering.

Abstract: Blends of biodegradable polymers, poly(caprolactone) and poly(D, L-lactic-co-glycolic acid), have been examined as scaffolds for applications in bone tissue engineering. Hydroxyapatite granules have been incorporated into the blends and porous discs were prepared. Mechanical properties and degradation rates in vitro of the composites were determined. The discs were seeded with rabbit bone marrow or cultured bone marrow stromal cells and incubated under physiological conditions. Polymer/ceramic scaffolds supported cell growth throughout the scaffold for 8 weeks. Scanning and transmission electron microscopy, and histological analyses were used to characterize the seeded composites. This study suggests the feasibility of using novel polymer/ceramic composites as scaffold in bone tissue engineering applications.

Three‐dimensional nano‐HAp/collagen matrix loading with osteogenic cells in organ culture

Abstract: Transplantation of osteogenic cells with a suitable matrix is one strategy for engineering bone tissue. Three-dimensional distribution and growth of cells within the porous scaffold are of clinical significance for the repair of large bony defects. A nano-HAp/collagen (nHAC) composite that mimics the natural bone both in composition and microstructure to some extent was employed as a matrix for the tissue engineering of bone. A porous nHAC composite was produced in sheet form and convolved to be a three-dimensional scaffold. Using organ culture techniques and the convolving method, we have developed three-dimensional osteogenic cells/nHAC constructs in vitro. Scanning electron microscopic and histological examination has demonstrated the development of the cells/material complex. Spindle-shaped cells migrating out of bone fragments continuously proliferated and migrated throughout the network of the coil. The porous nHAC scaffold provided a microenvironment resembling that seen in vivo, and cells within the composite eventually acquired a tridimensional polygonal shape. In addition, new bone matrix was synthesized at the interface of bone fragments and the composite.

Tissue engineering of bone. Cell based strategies.

Abstract: Skeletal tissue regeneration requires the interaction of three basic biologic elements: cells, growth and differentiation factors, and extracellular matrix scaffolds. Therapeutic approaches for tissue engineered repair of bone defects have attempted to mimic the natural process of bone repair by delivering a source of cells capable of differentiating into osteoblasts, inductive growth and differentiation factors, or bioresorbable scaffolding matrices to support cellular attachment, migration, and proliferation. Sophisticated designs even have tried to combine two or more of these elements. The development of cell based approaches has advanced dramatically in recent years as an understanding of musculoskeletal cell biology improves. Cell based approaches do not depend on the presence of local osteoprogenitors for the synthesis of new bone and, as a result, they particularly are attractive for patients who have a diminished pool of these progenitors, or in whom the host tissue bed has been compromised. This review highlights the development of cell based approaches for the tissue engineering of bone, and offers perspectives on the optimal elements for success. Although logistical and regulatory issues remain to be solved, cell based therapies for the repair of clinically significant bone defects rapidly are approaching clinical feasibility.

Tissue engineering of ligament and tendon healing.

Abstract: Ligaments and tendons are bands of dense connective tissue that mediate normal joint movement and stability. Injury to these structures may result in significant joint dysfunction because they either heal by production of inferior matrix or do not heal at all. The process of ligament and tendon healing is complex and the roles of cellular and biochemical mediators continue to be elucidated. The expression of growth factors and growth factor receptors is modulated after injury, and cells from healing tissues are responsive to growth factors. Tissue engineering offers the potential to improve the quality of ligaments and tendons during the healing process. The concept is based on the manipulation of cellular and biochemical mediators to affect protein synthesis and improve tissue remodeling. Recently, novel techniques such as application of growth factors, gene transfer techniques, and cell therapy have shown promise and may become effective biologic therapies in the future. Many groups have been successful in introducing marker and therapeutic genes into ligaments and tendons. Cell therapy involves the introduction of mesenchymal progenitor cells as a pluripotent cell source into the healing environment. The combination of cell therapy with growth factor application via gene transfer offers new avenues to improve ligament and tendon healing.

Design of biomimetic habitats for tissue engineering with P-15, a synthetic peptide analogue of collagen.

Abstract: In tissues, collagen forms the scaffold for cell attachment and migration, and it modulates cell differentiation and morphogenesis by mediating the flux of chemical and mechanical stimuli. We are constructing biomimetic environments by immobilizing a collagen-derived high-affinity cell-binding peptide P-15 in three-dimensional (3-D) templates. The cell-binding peptide can be expected to transduce mechanical forces. In their physiological environment, periodontal ligament fibroblasts (PDLF) are subject to significant mechanical forces. We have examined the behavior of human PDLF in culture on particulate bovine anorganic bone mineral (ABM) coated with P-15 (ABM-P-15). Greater numbers of cells associated with ABM-P-15 compared to ABM alone. Higher levels of incorporation of radiolabeled precursors in DNA and protein were consistent with the presence of larger numbers of cells on ABM-P-15 compared to ABM cultures. Scanning electron microscopic examination showed that cultures on ABM-P-15 generated highly oriented 3-D colonies of elongated cells and formed copious amounts of fibrous as well as membranous matrix reminiscent of ligamentous structures. PDLF cultured on ABM formed sparse monolayers with little order and a meager matrix. Alizarin Red stained the matrix of particle associated cells and inter-particle cellular bridges in P-15-associated cultures, indicating mineralization. 3-D colony formation and ordering of cells along with increased mineralization suggests that the coupling of cells to the ABM matrix through P-15 may provide a biomimetic environment permissive for cell differentiation and morphogenesis. Our studies suggest that ABM-P-15 templates may be effective as endosseous grafts, and, when seeded with PDLF, these matrices may serve as tissue engineered substitutes for autologous bone grafts.

Articular cartilage regeneration using periosteum.

Abstract: Periosteum has chondrogenic potential that makes it possible to repair or regenerate cartilage in damaged joints. Whole periosteal explants also can be cultured in vitro for the purpose of studying chondrogenesis. This chondrogenic potential arises because the cambium layer of periosteum contains chondrocyte precursor cells that form cartilage during limb development and growth in utero, and does so once again during fracture healing. The advantages of whole tissue periosteal transplants for cartilage repair include the fact that this tissue meets the three primary requirements for tissue engineering: a source of cells, a scaffold for delivering and retaining them, and a source of local growth factors. Data from in vivo studies show that periosteum transplanted into osteochondral articular defects produce cartilage that can restore the articular cartilage and be replaced by bone in the subchondral region. This capacity is determined by surgical factors such as the orientation of the cambium layer, postoperative factors such as the use of continuous passive motion, and the age and maturity of the experimental animal. In vitro studies have shown that the chondrogenic potential of periosteal explants is determined by culture, donor conditions, and technical factors. Chondrogenesis is optimized by suspension of the explants in agarose under aerobic conditions, with supplementation of the media using fetal calf serum and growth factors, particularly transforming growth factor-beta 1. The role of physical factors currently is being investigated, but studies show that the mechanical environment is important. Donor factors that are important include the harvest site, the size of the periosteal explant, and most importantly the age of the donor. Periosteal chondrogenesis follows a specific time course of events, with proliferation preceding differentiation. The current challenge is to clarify the process of periosteal chondrogenesis and its regulation at the cellular and molecular levels, so that it can be controlled intelligently and optimized for the purpose of cartilage repair and regeneration.

Skeletal muscle tissue engineering using isolated myoblasts on synthetic biodegradable polymers: preliminary studies.

Abstract: Skeletal muscle is responsible for the control of voluntary movement and the maintenance of structural contours of the body. Muscle loss or deficiency is encountered in various pathological states, and attempts to correct them have been employed with limited success. The aim of the present study was to tissue engineer three-dimensional vascularized skeletal muscle using isolated myoblasts attached to synthetic biodegradable polymer for tissue replacement in the enhancement of muscle regeneration. Myoblasts derived from neonatal rats (3-5-day-old), Fisher CDF-F344, were seeded onto polyglycolic acid meshes and implanted into the omentum of syngeneic adult Fisher CDF-F344 rats. Rats were sacrificed on day 30 and day 45 after the transplantation, and the cell-polymer constructs were harvested for morphological analysis. Histological analysis of the constructs were performed by hematoxylin and eosin, and immunohistochemical staining was positive for alpha sarcomeric actin and desmin skeletal muscle marker. Viable myoblasts organized between strands of degrading polymer mesh formed the new tissue, and vascularization of the entire construct was observed. Organization of neomuscle strands surrounded by vascularized tissue composed of degrading polymer and fusing myoblasts demonstrated the ability of myoblast constructs to survive, reorganize and regenerate tissue-like structures. Since myoblast transplantation to date has been limited to the cellular level of replacement, myoblast-polyglycolic acid constructs may be useful in defining the application of tissue engineering for future skeletal muscle transplantations.

Chondrocyte aggregation and reorganization into three-dimensional scaffolds.

Abstract: Articular cartilage has a very limited self-repairing capacity; thus, chondral lesions normally result in chronic degeneration and, eventually, osteoarthritis development. Currently, tissue engineering offers a new tool for the clinical treatment of osteochondral defects. The present investigation aimed to develop an in vitro engineered cartilage using a new class of semisynthetic scaffolds. Two nonwoven meshes of hyaluronan esters (Hyaff(R) derivatives) were seeded with sternal chick embryo chondrocytes cultured for up to 21 days, after which time they were assessed for both the cellular growth profile and histological features. Avian chondrocytes easily adhered and proliferated onto hyaluronan-based scaffolds, demonstrating a significant preference for the fully esterified benzylic form. Histochemical staining revealed the presence of a neosynthesized glycosaminoglycan-rich extracellular matrix, and immunohistochemistry confirmed the deposition of collagen type II. Moreover, ultrastructural observations supported evidence that chondrocytes grown onto a hyaluronan-derived three-dimensional scaffold maintained their unique phenotype and organization in a cartilage-like extracellular matrix. These findings support the further pursuit of a transplantable engineered cartilage using human chondrocytes for the regeneration of chondral lesions.

Cardiac organogenesis in vitro: reestablishment of three-dimensional tissue architecture by dissociated neonatal rat ventricular cells.

Abstract: The mammalian heart does not regenerate in vivo. The heart is, therefore, an excellent candidate for tissue engineering approaches and for the use of biosynthetic devices in the replacement or augmentation of defective tissue. Unfortunately, little is known about the capacity of isolated heart cells to re-establish tissue architectures in vitro. In this study, we examined the possibility that cardiac cells possess a latent organizational potential that is unrealized within the mechanically active tissue but that can be accessed in quiescent environments in culture. In the series of experiments presented here, total cell populations were isolated from neonatal rat ventricles and recombined in rotating bioreactors containing a serum-free medium and surfaces for cell attachment. The extent to which tissue-like structure and contractile function were established was assessed using a combination of morphological, physiological, and biochemical techniques. We found that mixed populations of ventricular cells formed extensive three-dimensional aggregates that were spontaneously and rhythmically contractile and that large aggregates of structurally-organized cells contracted in unison. The cells were differentially distributed in these aggregates and formed architectures that were indistinguishable from those of intact tissue. These architectures arose in the absence of three-dimensional cues from the matrix, and the formation of organotypic structures was apparently driven by the cells themselves. Our observations suggest that cardiac cells possess an innate capacity to re-establish complex, three-dimensional, cardiac organization in vitro. Understanding the basis of this capacity, and harnessing the organizational potential of heart cells, will be critical in the development of tissue homologues for use in basic research and in the engineering of biosynthetic implants for the treatment of cardiac disease.

Evaluation of biodegradable, three-dimensional matrices for tissue engineering of heart valves.

Abstract: A crucial factor in tissue engineering of heart valves is the type of scaffold material. In the following study, we tested three different biodegradable scaffold materials, polyglycolic acid (PGA), polyhydroxyalkanoate (PHA), and poly-4-hydroxybutyrate (P4HB), as scaffolds for tissue engineering of heart valves. We modified PHA and P4HB by a salt leaching technique to create a porous matrix. We constructed trileaflet heart valve scaffolds from each polymer and tested them in a pulsatile flow bioreactor. In addition, we evaluated the cell attachment to our polymers by creating four tubes of each material (length equals 4 cm; inner diameter, 0.5 cm), seeding each sample with 8,000,000 ovine vascular cells, and incubating the cell-polymer construct for 8 days (37 degrees C and 5% CO2). The seeded vascular constructs were exposed to continuous flow for 1 hour. Analysis of samples included DNA assay before and after flow exposure, 4-hydroxyproline assay, and environmental scanning electron microscopy (ESEM). We fabricated trileaflet heart valve scaffolds from porous PHA and porous P4HB, which opened and closed synchronously in a pulsatile bioreactor. It was not possible to create a functional trileaflet heart valve scaffold from PGA. After seeding and incubating the PGA-, PHA-, and P4HB-tubes, there were significantly (p < 0.001) more cells on PGA compared with PHA and P4HB. There were no significant differences among the materials after flow exposure, but there was a significantly higher collagen content (p < 0.017) on the PGA samples compared with P4HB and PHA. Cell attachment and collagen content was significantly higher on PGA samples compared with PHA and P4HB. However, PHA and P4HB also demonstrate a considerable amount of cell attachment and collagen development and share the major advantage that both materials are thermoplastic, making it possible to mold them into the shape of a functional scaffold for tissue engineering of heart valves.

Principles of tissue engineering applied to programmable osteogenesis

Abstract: This article presents a strategy for design, engineering, and fabrication of a bioresorbable, manufactured bone graft substitute (BGS) device. The approach is based on established precepts of osteogenesis, molecular biology of hyaluronic acid and osteoinductive proteins, and theoretical preformance criteria for such a device collated from the literature of 1991 to 1996. Application of this design and engineering strategy results in a composite device consisting of a D,D-L,L-polylactic acid macrostructure optimized to the architecture of cancellous bone, a microstructure composed of a filamentous velour of hyaluronan and a recombinant human bone morphogenetic protein 2 (rhBMP-2). The performance of this construct was tested in vivo in the dog, intertransverse process, spinal fusion model and in a critical sized defect of the rabbit radius. Data from these studies are used to illustrate principle points of the design and engineering concept.

Frontiers in tissue engineering: in vitro modulation of chondrogenesis

Abstract: Cartilage tissue engineering can provide functional cartilaginous constructs that can be used for controlled in vitro studies of chondrogenesis and potentially for in vivo articular cartilage repair. Ideally, engineered cartilage should be indistinguishable from native articular cartilage with respect to zonal organization, biochemical composition, and mechanical properties. In the model system presented here, chondrogenic cells are expanded in vitro as required, seeded onto three-dimensional polymeric scaffolds, and cultured in bioreactor vessels. During the course of in vitro cultivation, construct cellularity plateaus at a physiologic level, fractions of glycosaminoglycan and Type II collagen increase progressively, and the scaffold biodegrades. Construct structure (composition, morphology) and function (biosynthetic activity, mechanical properties) depend on cultivation conditions. This paper reviews recent studies of in vitro modulation of chondrogenesis by: (1) cell seeding density and source; (2) the tissue regeneration template; (3) biochemical regulatory signals; (4) mixing, mass transport and hydrodynamic forces; and (5) cultivation time. Key requirements and some of the critical research needs for successful cartilage tissue engineering are discussed.

Cartilage tissue engineering: Current limitations and solutions

Abstract: Articular cartilage repair remains one of the most intensely studied orthopaedic topics. To date the field of tissue engineering has ushered in new methodologies for the treatment of cartilage defects. The authors' 10-year experience using principles of tissue engineering applied to resurfacing of cartilage defects is reported. Which cell type to use, chondrocytes versus chondroprogenitor cells, and their inherent advantages and disadvantages are discussed. Chondrocytes initially were used as the preferred cell type but were shown to have long term disadvantages in models used by the authors. Mesenchymal stem cells can be used effectively to overcome the limitations experienced with the use of differentiated chondrocytes. The use of mesenchymal stem cells as platforms for retroviral transduction of genes useful in cartilage repair introduces the concept of gene modified tissue engineering. The fundamental conditions for promoting and conducting a viable cartilage repair tissue, regardless of which cell type is used, also were studied. Placement of a synthetic porous biodegradable polymer scaffold was found to be a requirement for achieving an organized repair capable of functionally resurfacing a cartilage defect. A new modular device for intraarticular fixation of various graft composites has been developed. This new cartilage repair device is composed of bioabsorbable polymers and is capable of being delivered by the arthroscope.

Repair of human articular cartilage after implantation of autologous chondrocytes

Abstract: Tissue engineering is an increasingly popular method of addressing pathological disorders of cartilage. Recent studies have demonstrated its clinical efficacy, but there is little information on the structural organisation and biochemical composition of the repair tissue and its relation to the adjacent normal tissue. We therefore analysed by polarised light microscopy and immunohistochemistry biopsies of repair tissue which had been taken 12 months after implantation of autologous chondrocytes in two patients with defects of articular cartilage. Our findings showed zonal heterogeneity throughout the repair tissue. The deeper zone resembled hyaline-like articular cartilage whereas the upper zone was more fibrocartilaginous. The results indicate that within 12 months autologous chondrocyte implantation successfully produces replacement cartilage tissue, a major part of which resembles normal hyaline cartilage.

Repair of human articular cartilage after implantation of autologous chondrocytes

Abstract: Tissue engineering is an increasingly popular method of addressing pathological disorders of cartilage. Recent studies have demonstrated its clinical efficacy, but there is little information on the structural organisation and biochemical composition of the repair tissue and its relation to the adjacent normal tissue. We therefore analysed by polarised light microscopy and immunohistochemistry biopsies of repair tissue which had been taken 12 months after implantation of autologous chondrocytes in two patients with defects of articular cartilage. Our findings showed zonal heterogeneity throughout the repair tissue. The deeper zone resembled hyaline-like articular cartilage whereas the upper zone was more fibrocartilaginous. The results indicate that within 12 months autologous chondrocyte implantation successfully produces replacement cartilage tissue, a major part of which resembles normal hyaline cartilage.

Ligament tissue engineering using synthetic biodegradable fiber scaffolds.

Abstract: Tissue engineering offers the possibility of replacing damaged human ligaments with engineered ligament tissues. Hence, we attempted to culture in vitro ligament tissues by seeding human anterior cruciate ligament (ACL) and medial collateral ligament (MCL) cells onto synthetic biodegradable polymer fiber scaffolds. The ACL and MCL cells readily attached to the scaffold fibers. These cells and their secreted matrix soon surrounded the scaffold fibers and bridged the gaps in between. Beginning at 2 weeks, portions of the scaffolds were completely filled with tissue matrix. By 5 weeks, the scaffolds became single bundles of tissue. Thus the cell/fiber system appears to be a viable system for culturing ligament tissues. Additionally, cell proliferation under mechanical and biochemical stimuli was studied for up to 4 days. Whereas mechanical stimulus and transforming growth factor enhanced proliferation, inflammatory agents (lipopolysaccharide and complement C5a) had a negative effect. This work can thus contr...

Building a meniscus. Biologic considerations.

Abstract: Creating a tissue engineered meniscus requires that specific biologic considerations such as cell type, matrix scaffold, bioreactor design (in vitro, in vivo, or both), and environmental conditions (media, cytokines, physical stimuli) be addressed. Meniscal cells, fibroblasts, and mesenchymal stem cells have been proposed as potential cell sources and have been grown (either in vivo or in vitro) on various cell matrices including collagen based scaffolds, biodegradable polymers, and small intestine submucosa. In addition, various environmental factors (nutrients, growth factors) have been used to optimize cell proliferation in vitro. Although these tissue engineering paradigms have produced a meniscuslike construct, the long term functional capabilities of this engineered tissue have yet to be proven. The concept of tissue engineering holds great promise for the generation of tissues or organs unable to repair or regenerate themselves. In terms of the meniscal tissue, however, the principles of tissue engineering may be best used to enhance and optimize the natural regeneration of the meniscus.