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PubMed2006

Heidegger's resonance with engineering: the primacy of practice.

This paper describes how some aspects of Martin Heidegger's philosophy resonate strongly with an engineering outlook. He argued that practice was more "primordial"" than theory, though preserving an important role for theoretical understanding as well, thus speaking to the gap between engineering education (highly theoretical) and engineering practice (mostly empirical). He also underlined the reality of "average" practices into which we are socialized, though affirming the potential for original work and action too, thus providing the grounds for self-actualization whether within the routine or in transcending it. His notion of "thrownness" emphasizes the importance of context, with which engineers are constantly engaged. While all this relates to the idea of our "being", Heidegger also dealt with the influence of time on our practices. Future death could be seen as spurring innovation, cultural history as a source for critiquing current practice and the present "situation" as the immediate context for corrective action. His major book is appropriately called "Being and Time".

Adaptation, Psychological↗
PubMed1996

Engineering the C-terminus of firefly luciferase as an indicator of covalent modification of proteins.

Protein kinase recognition sequences and proteinase sites were engineered into the cDNA encoding firefly luciferase from Photinus pyralis in order to establish whether these modified proteins could be developed as bioluminescent indicators of covalent modification of proteins. Two key domains of the luciferase were modified in order to identify regions of the protein in which peptide sequences may be engineered whilst retaining bioluminescent activity; one between amino acids 209 and 227 and the other at the C-terminus, between amino acids 537 and 550. Mutation of amino acids between residues 209 and 227 reduced bioluminescent activity to less than 1% of wild-type recombinant. In contrast engineering peptide sequences at the C-terminus resulted in specific activities ranging from 0.06-120% of the wild-type recombinant. Addition of cyclic AMP dependent protein kinase catalytic subunit, to a variant luciferase incorporating the kinase recognition sequence, LRRASLG, with a serine at amino-acid position 543 resulted in a 30% reduction in activity. Alkaline phosphatase treatment restored activity. The bioluminescent activity of a variant luciferase containing a thrombin recognition sequence, LVPRES, with the cleavage site positioned between amino acid 542 and 543, decreased by 50% when incubated in the presence of thrombin. The results indicate regions within luciferase where peptide sequences may be engineered while retaining bioluminescent activity and have shown changes in bioluminescent activity when these sites are subjected to covalent modification. Changes in secondary structure, charge and length at the C-terminus of luciferase disrupt the microenvironment of the active site, leading to alterations in light emission. This has important implications both in understanding the evolution of beetle bioluminescence and also in development of bioluminescent indicators of the covalent modification of proteins.

Amino Acid Sequence↗
PubMed1993

V79 Chinese hamster cells genetically engineered for cytochrome P450 and their use in mutagenicity and metabolism studies.

V79 Chinese hamster cells are being genetically engineered for stable expression of cytochromes P450 using a SV40 early promoter containing plasmid as the eukaryotic expression vector. V79 cells lack endogenous cytochrome P450 activity. Therefore, genetically engineered V79 cell lines are defined for the cytochrome P450 isoform acquired upon cDNA mediated gene transfer. V79 cells have a longstanding tradition as indicator cells for various biological endpoints, e.g. mutation, chromosomal aberration, cytotoxicity. The genetically engineered V79 cells combine these useful biological endpoints with metabolic competence. In this sense, V79 cell lines genetically engineered for stable expression of cytochromes P450 present newly developed tools for studying and understanding metabolism related problems in toxicology and pharmacology.

Animals↗
PubMed2006

Natural polymers for gene delivery and tissue engineering.

Although the field of gene delivery is dominated by viral vectors and synthetic polymeric or lipid gene carriers, natural polymers offer distinct advantages and may help advance the field of non-viral gene therapy. Natural polymers, such as chitosan, have been successful in oral and nasal delivery due to their mucoadhesive properties. Collagen has broad utility as gene activated matrices, capable of delivering large quantities of DNA in a direct, localized manner. Most natural polymers contain reactive sites amenable for ligand conjugation, cross-linking, and other modifications that can render the polymer tailored for a range of clinical applications. Natural polymers also often possess good cytocompatibility, making them popular choices for tissue engineering scaffolding applications. The marriage of gene therapy and tissue engineering exploits the power of genetic cell engineering to provide the biochemical signals to influence proliferation or differentiation of cells. Natural polymers with their ability to serve as gene carriers and tissue engineering scaffolds are poised to play an important role in the field of regenerative medicine. This review highlights the past and present research on various applications of natural polymers as particulate and matrix delivery vehicles for gene delivery.

Animals↗
PubMed2006

Tissue engineering by modulated gene delivery.

Tissue engineering is a newly emerging biomedical form to create a local environment which enables cells to promote the proliferation and differentiation for regeneration induction. The cell-induced regeneration of tissues and organs is achieved by making use of the tissue engineering technology or methodology. Several genetic approaches with virus and non-viral vectors or genetically engineered cells have been attempted to enhance tissue regeneration. The basic idea is to promote the cell proliferation and differentiation as well as the secretion of biological signal molecules for tissue regeneration from cells by gene transfection. For successful gene transfection and expression, it is important to develop drug delivery system (DDS) which allows a therapeutic gene to be delivered specifically to the target cell at an appropriate timing for a certain time period. This paper overviews the recent development of gene-modified tissue engineering, briefly explaining delivery technologies necessary to modulate the efficiency of gene transfection.

Animals↗
PubMed2006

Gene delivery strategies for cartilage tissue engineering.

Tissue engineering is a multifaceted technology developed with a purpose of regenerating complex tissues and organs. Cartilage regeneration continues to challenge engineers and a new wave of efforts focus on developing strategies that provide sustained stimulation to cells by growth factors and other biological molecules to promote their differentiation into chondrocytes. Though significant research is dedicated to developing controlled release systems that deliver growth factors directly, a simpler approach to resolving this dilemma involves converting cells into protein producing factories. This is done through gene delivery. Gene Therapy studies published for articular diseases such as rheumatoid and osteoarthritis provide valuable information regarding different types of cells, gene delivery vectors and genes that can potentially be used to regenerate cartilage. Tissue engineering approaches provide the opportunity to combine two or more strategies used for Gene Therapy thus far and create a cohesive system that addresses both cartilage degeneration and synthesis simultaneously. Adopting gene transfer techniques for tissue engineering is a relatively novel approach, as non-viral gene delivery vectors are continually optimized for therapeutic purposes, and reservations about viral vectors have increasingly dampened their appeal. However, every element involved in gene transfection (i.e., the cell, vector and gene) is a variable which decides the physiological and biomechanical properties of the cartilage produced, and significant work still needs to be done in understanding the contribution of each of these factors to cartilage regeneration.

Animals↗
PubMed2004

Umbilical cord blood derived endothelial progenitor cells for tissue engineering of vascular grafts.

BACKGROUND: A substantial limitation regarding present pediatric cardiac surgery is the lack of appropriate materials for the repair of congenital defects. To address this shortcoming, tissue engineering is a scientific field that aims at in vitro fabrication of living autologous grafts with the capacity of growth, repair, and regeneration. Here we focused on tissue engineered vascular grafts using human umbilical cord blood derived endothelial progenitor cells (EPCs), as a noninvasive cell source for pediatric applications. METHODS: EPCs were isolated from 20 ml fresh human umbilical cord blood by Ficoll gradient centrifugation and cultured in endothelial basal medium containing growth factors. After proliferation and differentiation cells were analyzed by immunohistochemistry and seeded onto three-dimensional (3D) biodegradable vascular scaffolds (porosity > 95%, n = 22). Twenty-four hours after seeding the vascular grafts were positioned into a pulse-duplicator-in vitro system and grown for 48 hours under biomimetic conditions. A second group was grown 6 days statically and an additional 6 days biomimetically. Controls were cultured statically. Analysis of the grafts included immunohistochemistry, histology, and scanning electron microscopy. RESULTS: Preseeding differentiated EPCs indicated constant endothelial phenotypes including acetylated low-density lipoprotein, cluster of differentiation 31, von Willebrand factor, and endothelial nitric oxide synthetase. Seeded EPCs established favorable cell-to-polymer attachment and proliferation into the 3D tubular scaffolds. Both conditioned and static cellular constructs demonstrated positive staining for cluster of differentiation 31, von Willebrand factor, and expression of endothelial nitric oxide synthase. CONCLUSIONS: Human umbilical cord derived EPCs indicated exceptional growth characteristics used for tissue engineering of vascular grafts. These cells demonstrated a constant endothelial phenotype and related functional features. Based on these results EPCs seem to be a promising autologous cell source with regard to cardiovascular tissue engineering, particularly for the repair of congenital defects.

Absorbable Implants↗
PubMed2006

In vitro fabrication of a tissue engineered human cardiovascular patch for future use in cardiovascular surgery.

BACKGROUND: One approach to tissue engineering has been the development of in vitro conditions for the fabrication of functional cardiovascular structures intended for implantation. In this experiment, we developed a pulsatile flow system that provides biochemical and biomechanical signals in order to regulate autologous, human patch-tissue development in vitro. METHODS: We constructed a biodegradable patch scaffold from porous poly-4-hydroxy-butyrate (P4HB; pore size 80 to 150 microm). The scaffold was seeded with pediatric aortic cells. The cell-seeded patch constructs were placed in a self-developed bioreactor for 7 days to observe potential tissue formation under dynamic cell culture conditions. As a control, cell-seeded scaffolds were not conditioned in the bioreactor system. After maturation in vitro, the analysis of the tissue engineered constructs included biochemical, biomechanical, morphologic, and immunohistochemical examination. RESULTS: Macroscopically, all tissue engineered constructs were covered by cells. After conditioning in the bioreactor, the cells were mostly viable, had grown into the pores, and had formed tissue on the patch construct. Electron microscopy showed confluent smooth surfaces. Additionally, we demonstrated the capacity to generate collagen and elastin under in vitro pulsatile flow conditions in biochemical examination. Biomechanical testing showed mechanical properties of the tissue engineered human patch tissue without any statistical differences in strength or resistance to stretch between the static controls and the conditioned patches. Immunohistochemical examination stained positive for alpha smooth muscle actin, collagen type I, and fibronectin. There was minor tissue formation in the nonconditioned control samples. CONCLUSIONS: Porous P4HB may be used to fabricate a biodegradable patch scaffold. Human vascular cells attached themselves to the polymeric scaffold, and extracellular matrix formation was induced under controlled biomechanical and biodynamic stimuli in a self-developed pulsatile bioreactor system.

Absorbable Implants↗
PubMed2006

Tissue engineering of viable pulmonary arteries for surgical correction of congenital heart defects.

BACKGROUND: Tissue-engineered pulmonary arteries could overcome the drawbacks of homografts or prosthetic conduits used in the repair of many congenital cardiac defects. However, the ideal scaffold material for tissue-engineered conduits is still subject of intensive debate. In this study, we evaluated an acellularized allogeneic matrix scaffold for pulmonary artery tissue engineering with and without in-vitro reseeding with autologous endothelial cells in the pulmonary circulation in a growing sheep model. METHODS: Ovine pulmonary arteries (n = 10) were acellularized by trypsin/ethylenediamine tetraacetic acid incubation. Autologous endothelial cells were harvested from carotid arteries, and the pulmonary conduits were seeded with endothelial cells. We implanted in-vitro, autologous, reendothelialized (group A, n = 5) and acellularized pulmonary conduits (group B, n = 5) in the pulmonary circulation. The animals were sacrificed 6 months after the operation. Explanted valves were examined histologically and by immunohistochemistry. RESULTS: The conduit diameter increased in both groups (group A, 44% +/- 11%; group B, 87% +/- 18%; p < 0.05). In group A, however, a proportional increase in diameter was present, whereas in group B, a disproportionate increase resulting in aneurysm formation was observed. Histologically, the conduit wall integrity was destroyed in group B and preserved in group A. In group B, the extracellularmatrix degenerated with a reduced amount of collagens and proteoglycanes. Furthermore, no elastic fibers were detectable. In contrast, the extracellularmatrix in group A was close to native ovine tissue. CONCLUSIONS: Tissue-engineered pulmonary conduits (autologous endothelial cells and allogeneic matrix scaffolds) functioned well in the pulmonary circulation. They demonstrated an increase in diameter and an extracellular matrix comparable to that of native ovine tissue.

Animals↗
PubMed2006

Tissue engineering of autologous human heart valves using cryopreserved vascular umbilical cord cells.

BACKGROUND: Tissue engineering of autologous heart valves with the potential to grow and to remodel represents a promising concept in pediatric cardiovascular surgery. Currently we are exploring the impact of cryopreserved human umbilical cord cells (CHUCCs) for the fabrication of tissue-engineered heart valves for patients diagnosed prenatally with congenital heart lesions, potentially enabling heart valve replacement in the early years of life. METHODS: Human umbilical cord cells were isolated from vascular segments of umbilical cords and cryopreserved in a cell bank. After 12 weeks the cryopreserved cells were again expanded in culture and characterized by histology, immunohistochemistry, and proliferation assays. Trileaflet heart valve scaffolds were fabricated from a porous polymer (P4HB, Tepha Inc, Cambridge, MA) and sequentially seeded with CHUCCs (n = 10). Five of the heart valve constructs were grown for 7 days in a pulse duplicator and, as a control, five constructs were grown under static cell culture conditions for 7 days. Analysis of all tissue-engineered heart valves included histology, immunohistochemistry, electron microscopy, functional analysis, and biomechanical and biochemical examination. RESULTS: We found that CHUCCs remained viable after 12 weeks of cryopreservation and showed a myofibroblast-like morphology that stained positive for alpha-actin and fibroblast specific marker. Histology of the tissue-engineered heart valves showed layered tissue formation, including connective tissue between the inside and the outside of the porous scaffold. Immunohistochemistry was positive for collagen (types I, III, and IV), desmin, laminin, and alpha-actin. Electron microscopy showed that the cells had grown into the pores and formed a confluent tissue layer during maturation in the pulsatile flow system. Biochemical examination showed an increase of extracellular matrix formation in constructs after pulsatile flow exposure compared with the static control group. Functional analysis demonstrated a physiological increase of the intracellular Ca2+ concentration of the recultivated cells and the conditioned constructs after stimulation with histamine. CONCLUSIONS: This study demonstrates in vitro generation of viable and functional human heart valves based on CHUCCs and biomimetic flow culture systems. The CHUCCs demonstrated excellent growth potential and abilities of in vitro tissue formation. These findings suggest the potential benefit of establishing autologous human cell banks for pediatric patients diagnosed intrauterinely with congenital defects that will potentially require heart valve replacement in the early years of life.

Actins↗
PubMed2004

Global gene expression of cells attached to a tissue engineering scaffold.

A goal of tissue engineering is to produce a scaffold material that will guide cells to differentiate and regenerate functional replacement tissue at the site of injury. Little is known about how cells respond on a molecular level to tissue engineering scaffold materials. In this work we used oligonucleotide microarrays to interrogate gene expression profiles associated with cell-biomaterial interactions. We seeded collagen-glycosaminoglycan meshes, a widely used tissue engineering scaffold material, with human IMR-90 fibroblasts and compared transcript levels with control cells grown on tissue culture polystyrene. Genes involved in cell signaling, extracellular matrix remodeling, inflammation, angiogenesis and hypoxia were all activated in cells on the collagen-GAG mesh. Understanding the impact of a scaffold on attached cells will facilitate the design of improved tissue engineering materials.

CD55 Antigens↗
PubMed2005

Craniofacial muscle engineering using a 3-dimensional phosphate glass fibre construct.

The current technique to replace missing craniofacial skeletal muscle is the surgical transfer of local or free flaps. This is associated with donor site morbidity, possible tissue rejection and limited supply. The alternative is to engineer autologous skeletal muscle in vitro, which can then be re-implanted into the patient. A variety of biomaterials have been used to engineer skeletal muscle with limited success. This study investigated the use of phosphate-based glass fibres as a potential scaffold material for the in vitro engineering of craniofacial skeletal muscle. Human masseter (one of the muscles of mastication)--derived cell cultures were used to seed the glass fibres, which were arranged into various configurations. Growth factors and matrix components were to used to manipulate the in vitro environment. Outcome was determined with the aid of microscopy, time-lapse footage, immunofluorescence imaging and CyQUANT proliferation, creatine kinase and protein assays. A 3-dimensional mesh arrangement of the glass fibres was the best at encouraging cell attachment and proliferation. In addition, increasing the density of the seeded cells and using Matrigel and insulin-like growth factor I enhanced the formation of prototypic muscle fibres. In conclusion, phosphate-based glass fibres can support the in vitro engineering of human craniofacial muscle.

Biocompatible Materials↗
PubMed2005

Effect of passage number and matrix characteristics on differentiation of endothelial cells cultured for tissue engineering.

Cells can sense the physical and chemical properties of artificial materials used as scaffolds for tissue engineering and regulate their behavior. Therefore, biomimetic and biospecific molecules are coated on materials to regulate function of cells on the tissue-engineered product. These bioactive molecules can be attached in a defined spectrum, concentration and spatial distribution in order to control adhesion, growth, viability, differentiation, and function of the cells. When autologous cells are used for tissue engineering, initially limited cells obtained may often need an amplification of cell number by passage in tissue culture before they are seeded on a biomaterial or scaffold. We have conducted this study to understand how the characteristics of bioactive molecule coating might affect proliferation, apoptosis and differentiation when endothelial cell (EC) is serially passaged. Proliferation was assessed by proliferating cell nuclear antigen (PCNA) staining along with counting of cells harvested from confluent monolayer. Apoptosis was assessed by Annexin V staining and differentiation by semi quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for von Willebrand factor (vWF) expression and quantification of its release using enzyme linked immunosorbant assay (ELISA), and thrombogenicity by comparing platelet adhesion to EC monolayer Dacron grafts (DG) with specific protein coating. The results indicate that ECs easily lose its proliferation potential when they are cultured repeatedly on gelatin, turn apoptotic and over express the prothrombotic protein- vWF. Whereas, when it is grown on a matrix composed of fibrin, fibronectin, gelatin and vascular EC growth factor (VEGF), the cells retained their ability to proliferate, remained viable and were relatively less thrombogenic, even when passage number progressed. It is concluded that if ECs are grown on the composite matrix that mimics natural vessel scaffold, the cell number can be amplified without affecting its normal physiological function and may be used to generate effective tissue-engineered cardiovascular constructs.

Cell Adhesion↗
PubMed2005

Fabrication and characterization of DTBP-crosslinked chitosan scaffolds for skin tissue engineering.

Chitosan, the deacetylated derivative of chitin, is a promising scaffold material for skin tissue engineering applications. It is biocompatible and biodegradable, and the degradation products are resorbable. However, the rapid degradation of chitosan and its low mechanical strength are concerns that may limit its use. In this study, chitosan with 80%, 90% and 100% degree of deacetylation (DDA) was crosslinked with dimethyl 3-3, dithio bis' propionimidate (DTBP) and compared to uncrosslinked scaffolds. The scaffolds were characterized with respect to important tissue engineering properties. The tensile strength of scaffolds made from 100% DDA chitosan was significantly higher than for scaffolds made from 80% and 90% DDA chitosan. Crosslinking of scaffolds with DTBP increased the tensile strength. Crosslinking with DTBP had no significant effect on water vapour transmission rate (WVTR) or water absorption but had significant effect on the pore size and porosity of the samples. All samples showed a WVTR and pore size distribution suitable for skin tissue engineering; however, the water absorption and porosity were lower than the optimal values for skin tissue engineering. The biodegradation rate of scaffolds crosslinked with DTBP and glutaraldehyde (GTA) were reduced while no significant effect was observed in biodegradation of the samples made from 100% DDA chitosan whether crosslinked or uncrosslinked after 24 days of degradation.

Absorption↗
PubMed2005

A three-dimensional nonlinear finite element analysis of the mechanical behavior of tissue engineered intervertebral discs under complex loads.

The use of tissue-engineering method holds great promise for treating degenerative disc disease [Gan JC, Ducheyne P, Vresilovic E, Shapiro IM. J Biomed Mater Res 2000; 51(4): 596-604]. This concept typically implies that nucleus pulposus (NP) cells are seeded on a scaffold, while the NP tissue is regenerated. Such hybrid implant is inserted into the host intervertebral disc. Because the success of a tissue engineering approach depends on maintenance or restoration of the mechanical function of the intervertebral disc, it is useful to study the initial mechanical performance of the disc after implantation of the hybrid. A three-dimensional finite element model (FEM) of the L2-L3 disc-vertebrae unit has been analyzed. The model took into account the material nonlinearities and it imposed different and complex loading conditions. In this study, we validated the model by comparison of its predictions with several sets of experimental data; we determined the optimal Young's modulus as well as the failure strength for the tissue-engineered scaffold under different loading conditions; and we analyzed the effects of implanted scaffold on the mechanical behavior of the intervertebral disc. The results of this study suggest that a well-designed tissue-engineered scaffold preferably has a modulus in the range of 5-10 MPa and a compressive strength exceeding 1.67 MPa. Implanted scaffolds with such properties can then achieve the goal of restoring the disc height and distributing stress under different loading conditions.

Biomechanical Phenomena↗
PubMed2005

Bioluminescent imaging: emerging technology for non-invasive imaging of bone tissue engineering.

Bone tissue engineering is a multidisciplinary research area in which new strategies are developed to treat patients with large bone defects as occurring during e.g. hip revisions, upon trauma or in spinal fusions. In vivo evaluation of bone formation in animal models is highly relevant for graft evaluation but is time-consuming, invasive and difficult to quantify. As a consequence, most in vivo studies ignore the dynamic nature of bone regeneration and the molecular processes underlying it. In vivo bioluminescent imaging (BLI) is a relatively young research field with great potential that may overcome these problems. BLI encompasses non-invasive imaging of luciferase gene activity using cooled charge coupled device cameras in luciferase transgenic animals or in grafted, luciferase transgenic cells. The imaging procedure is technically simple and quantifiable. Because luciferase expression can be put under the control of tissue-specific regulatory elements, BLI allows non-invasive imaging of processes highly relevant to bone tissue engineering like differentiation, apoptosis, vasculogenesis and inflammation. In this review, we describe the basic principle of BLI and discuss transgenic animals and constructs currently available for application in bone tissue engineering. Furthermore, we reflect on technical developments that will make BLI even more promising for future application in bone tissue engineering research.

Animals↗
PubMed2006

Stem cell-based tissue engineering with silk biomaterials.

Silks are naturally occurring polymers that have been used clinically as sutures for centuries. When naturally extruded from insects or worms, silk is composed of a filament core protein, termed fibroin, and a glue-like coating consisting of sericin proteins. In recent years, silk fibroin has been increasingly studied for new biomedical applications due to the biocompatibility, slow degradability and remarkable mechanical properties of the material. In addition, the ability to now control molecular structure and morphology through versatile processability and surface modification options have expanded the utility for this protein in a range of biomaterial and tissue-engineering applications. Silk fibroin in various formats (films, fibers, nets, meshes, membranes, yarns, and sponges) has been shown to support stem cell adhesion, proliferation, and differentiation in vitro and promote tissue repair in vivo. In particular, stem cell-based tissue engineering using 3D silk fibroin scaffolds has expanded the use of silk-based biomaterials as promising scaffolds for engineering a range of skeletal tissues like bone, ligament, and cartilage, as well as connective tissues like skin. To date fibroin from Bombyx mori silkworm has been the dominant source for silk-based biomaterials studied. However, silk fibroins from spiders and those formed via genetic engineering or the modification of native silk fibroin sequence chemistries are beginning to provide new options to further expand the utility of silk fibroin-based materials for medical applications.

Animals↗
PubMed2006

Fabrication methods of an engineered microenvironment for analysis of cell-biomaterial interactions.

Success in tissue engineering requires an understanding of how cells integrate the signals presented from the microenvironment created by biomaterial scaffolds to alter their responses. Besides the presence of chemical stimuli, there is growing evidence that the spatial organization of cells and tissue within a 3-dimensional (3-D) extracellular matrix (ECM) context is a critical element in controlling cellular function. Therefore, in order to direct cells toward a desirable tissue structure, it is necessary to engineer biomaterials to have spatiotemporal control of the presentation of regulatory signals. Given that, micro-patterning techniques have profited by combining micro-fabrication technology with the chemical conjugation of biologically active molecules to provide new culture systems where cells can be cultured within a specific geometry. The micro-engineered environments have been developed as 2- and 3-D structures, which have proven greatly useful as versatile platforms to study cell, biomaterial, and ECM interactions on both macroscopic and microscopic levels. The main focus of this review is a brief summary of the use of micro-engineered substrates in the analysis of cell-biomaterial interactions with the aim to provide an introductory overview of practical applications available in the literature. In particular, topics regarding (1) the soft-lithography technique to prepare micro-patterned substrates for the spatial control of cell adhesion, (2) biomaterials stiffness-dependent cellular responses, and (3) the microarray techniques for analysis of cell/biomaterials interactions are discussed.

Animals↗