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Engineered Bacteriophages in Cancer Immunotherapy: Emerging Concepts and Potential Integration with CAR-T Cell Therapy.

Due to antigen heterogeneity, restricted immune cell trafficking and an immunosuppressive, nutrient-restricted tumour microenvironment, solid tumours remain resistant to modern immunotherapies. Engineered bacteriophages offer a modular framework to overcome these obstacles: programmable virus-like particles with scalable production. Through genome engineering, capsid decoration with mammalian cell-targeting ligands, or hybrid AAV/phage systems, engineered bacteriophages can display tumour-associated antigens, enhance receptor-mediated uptake and deliver therapeutic payloads such as cytokines, chemokines and suicide genes without naturally infecting mammalian cells. These features support their use as vaccine platforms, immunological adjuvants and targeted gene-delivery vehicles. These may enable more precise, tumour-localized therapeutic intervention. Phages can engage innate immune pathways, including TLR9, TLR3/7/8, cGAS-STING and AIM2, promoting dendritic cell maturation and inflammatory mediators that may convert immunologically "cold" tumours into inflamed microenvironments. Their multivalent antigen display enhances B- and T-cell priming, while cDC1-mediated cross-presentation supports cytotoxic CD8+ T-cell responses and immunological memory. In CAR-T therapy, engineered phages may improve tumour homing through chemokine modulation, support persistence through local cytokine delivery, reduce antigen escape by presenting multiple tumour epitopes, and limit T-cell exhaustion through dominant-negative receptor strategies or local checkpoint blockade. This review summarizes engineering approaches, delivery systems, manufacturing, biodistribution, dosing, and safety issues, including immunogenicity, pre-existing anti-phage antibodies and horizontal gene transfer. It also distinguishes therapeutic engineered phage particles from phage display technologies used for molecular discovery. Despite encouraging results integrating modified bacteriophages with CAR-T cell therapy, the evidence remains mostly preclinical, indicating both substantial translational prospects and crucial obstacles for future clinical development.

CAR-T cell therapy↗

Murine spinal fusion induced by engineered mesenchymal stem cells that conditionally express bone morphogenetic protein-2.

OBJECT: The authors hypothesized that spinal fusion can be achieved and monitored by using cell-mediated gene therapy. Mesenchymal stem cells (MSCs) genetically engineered to express recombinant human bone morphogenetic protein-2 (rhBMP-2) conditionally, were implanted into the paraspinal muscles of mice to establish spinal fusion. The goal was to demonstrate an MSC-based gene therapy platform in which controlled gene expression is used to obtain spinal fusion in a murine model. METHODS: Mesenchymal stem cells expressing the rhBMP-2 gene were injected into the paravertebral muscle in mice. Bone formation in the paraspinal region was longitudinally followed by performing micro-computerized tomography scanning, histological studies, and an analysis of osteocalcin expression to demonstrate the presence of engrafted engineered MSCs. The minimal period of rhBMP-2 expression by the engineered MSCs required to induce fusion was determined. The results of this study demonstrate that genetically engineered MSCs induce bone formation in areas adjacent to and touching the posterior elements of the spine. This newly formed bone fuses the spine, as demonstrated by radiological and histological studies. The authors demonstrate that injected cells induce active osteogenesis at the site of implantation for up to 4 weeks postinjection. They found that a 7-day induction of rhBMP-2 expression in genetically engineered MSCs was sufficient to form new bone tissue, although the quantity of this bone increased as longer expression periods were implemented. CONCLUSIONS: After their injection genetically engineered MSCs can efficiently form new bone in the paraspinal muscle of the mouse to obtain spinal fusion. The extent and quantity of this newly formed bone can be monitored by controlling the duration of rhBMP-2 gene expression.

Animals↗

Effects of copper and cross-linking on the extracellular matrix of tissue-engineered arteries.

In many cases, the mechanical strengths of tissue-engineered arteries do not match the mechanical strengths of native arteries. Ultimate arterial strength is primarily dictated by collagen in the extracellular matrix, but collagen in engineered arteries is not as dense, as organized, or as mature as collagen in native arteries. One step in the maturation process of collagen is the formation of hydroxylysyl pyridinoline (HP) cross-links between and within collagen molecules. HP cross-link formation, which is triggered by the copper-activated enzyme lysyl oxidase, greatly increases collagen fibril stability and enhances tissue strength. Increased cross-link formation, in addition to increased collagen production, may yield a stronger engineered tissue. In this article, the effect of increasing culture medium copper ion concentration on engineered arterial tissue composition and mechanics was investigated. Engineered vessels grown in low copper ion concentrations for the first 4 weeks of culture, followed by higher copper ion concentrations for the last 3 weeks of culture, had significantly elevated levels of cross-link formation compared to those grown in low copper ion concentrations. In contrast, vessels grown in high copper ion concentrations throughout culture failed to develop higher collagen cross-link densities than those grown in low copper ion concentrations. Although the additional cross-linking of collagen in engineered vessels may provide collagen fibril stability and resistance to proteolysis, it failed to enhance global tissue strength.

Amino Acids↗

Optimizing seeding and culture methods to engineer smooth muscle tissue on biodegradable polymer matrices.

The engineering of functional smooth muscle (SM) tissue is critical if one hopes to successfully replace the large number of tissues containing an SM component with engineered equivalents. This study reports on the effects of SM cell (SMC) seeding and culture conditions on the cellularity and composition of SM tissues engineered using biodegradable matrices (5 x 5 mm, 2-mm thick) of polyglycolic acid (PGA) fibers. Cells were seeded by injecting a cell suspension into polymer matrices in tissue culture dishes (static seeding), by stirring polymer matrices and a cell suspension in spinner flasks (stirred seeding), or by agitating polymer matrices and a cell suspension in tubes with an orbital shaker (agitated seeding). The density of SMCs adherent to these matrices was a function of cell concentration in the seeding solution, but under all conditions a larger number (approximately 1 order of magnitude) and more uniform distribution of SMCs adherent to the matrices were obtained with dynamic versus static seeding methods. The dynamic seeding methods, as compared to the static method, also ultimately resulted in new tissues that had a higher cellularity, more uniform cell distribution, and greater elastin deposition. The effects of culture conditions were next studied by culturing cell-polymer constructs in a stirred bioreactor versus static culture conditions. The stirred culture of SMC-seeded polymer matrices resulted in tissues with a cell density of 6.4 +/- 0.8 x 10(8) cells/cm3 after 5 weeks, compared to 2.0 +/- 1.1 x 10(8) cells/cm3 with static culture. The elastin and collagen synthesis rates and deposition within the engineered tissues were also increased by culture in the bioreactors. The elastin content after 5-week culture in the stirred bioreactor was 24 +/- 3%, and both the elastin content and the cellularity of these tissues are comparable to those of native SM tissue. New tissues were also created in vivo when dynamically seeded polymer matrices were implanted in rats for various times. In summary, the system defined by these studies shows promise for engineering a tissue comparable in many respects to native SM. This engineered tissue may find clinical applications and provide a tool to study molecular mechanisms in vascular development.

Animals↗

Renal transfer of genetically engineered cells.

For many years, ex vivo gene transfer has been used for genetic manipulation of various organs. In the kidney, ex vivo gene transfer was reported using mesangial cells and macrophages. In rats, cultured cells injected into the renal artery are accumulated selectively in the glomerulus. With this approach, it is possible to transfer genetically engineered cells to normal and diseased glomeruli. The transfer of genetically engineered cells to glomeruli can be used for several purposes. With the use of resident glomerular cells engineered in vitro, it is possible to examine how the cells that overexpress certain genes behave differently in normal and diseased glomeruli. Both gain-of-function and loss-of-function strategies are useful for this purpose. For the latter, stable expression of antisense cDNA, ribosomes, or dominant-negative mutants is available. By transfer of engineered cells producing secretory, recombinant proteins, it is possible to modify glomerular microenvironment in vivo. Transfer of genes encoding therapeutically relevant molecules could be useful for therapeutic intervention. Transfer of engineered leukocytes to the glomerulus also allows investigation of cross talk between leukocytes and resident cells. Transfer of stimulated leukocytes is useful for investigation of the pathologic actions of infiltrating cells on glomerular structure and function. Leukocytes in which certain gene functions are selectively reinforced or deleted would be useful for elucidation of the exact functions of leukocyte-associated genes in glomerular diseases. This article summarizes current experience with the adoptive transfer of engineered cells to the glomerulus for investigation of and therapy for glomerular diseases.

Animals↗

The U.S. Public Health Service Commissioned Corps: a need for engineers.

In 1798, President John Adams signed the bill creating the Marine Hospital Service to medically care for U.S. merchant seamen. That agency is known today as the U.S. Public Health Service (PHS). In 1918, the PHS Commissioned Corps commissioned sanitary engineers in the Reserve Corps, and in 1930, President Herbert Hoover signed the Parker Act authorizing sanitary engineers to be part of the regular Commissioned Corps. During the world war years, PHS engineers were detailed to improve sanitation for military bases in the United States and abroad. In the 1960s, most PHS engineers served in the Indian Health Service, upgrading sanitation facilities for American Indians and Alaskan Natives. During the 1970s, PHS engineers were involved in providing an integrated and coordinated attack on environmental issues. Today, PHS engineers are involved with many aspects of public health protection and have been detailed around the world to provide emergency assistance in the wake of disasters.

Disaster Planning↗

[Bibliometric analysis on tissue engineering research literatures].

OBJECTIVE: To comprehend the progress of tissue engineering research and speculate its developmental trends. METHODS: MEDLINE search was conducted to retrieve the papers published between 1987 to 1999 under the main headings of tissue engineering. Years, nationalities, languages, journals, authors and heading frequencies of 314 papers were analyzed by bibliometrics. RESULTS: Since 1990, the number of tissue engineering research literatures had doubled, and papers between 1998 and 1999 made up 57.96% of the total papers. All papers came from 15 nations, in 6 languages and 140 journals; 64.97% came from United States and 25.79% from England, Netherlands and Germany; 93.95% was in English; 42.04% was published on 15 journals. Vacanti JP and 19 other authors presented 5 to 24 papers. Heading frequencies were cytology 22.89%, transplantation 13.30%, scaffolds and extracellular matrixes 11.72%, implanting 10.60%, polymers 8.91%, potential applications 8.91%, artificial substitutes 6.88%, tissue culture 6.70% and biogenetics 4.96%. CONCLUSION: Tissue engineering literatures mainly come from United States, England, Netherlands and Germany. English is the major language. J Biomed Mater Res and 14 other journals are important journals about tissue engineering research. Vacanti JP and 19 other authors are prolific authors. Cytology, transplantation, scaffolds and extracellular matrixes and implanting are hot topics and key points on tissue engineering research.

Animals↗

Embryonic development and the principles of tissue engineering.

Tissue engineering has, historically, used empirical methods to devise reparative strategies for optimizing the repair of skeletal tissue defects. The acquired experience and observations indicate that several aspects of successful repair protocols involve the engineered recapitulation of certain embryonic events. A careful study of the details of embryonic limb formation and subsequent differentiation events into its component skeletal tissues suggests that aspects of these tissue formation events can provide guiding principles for the tissue-engineered regeneration of skeletal tissues in adults. A thesis is developed in reviewing selected aspects of embryonic limb formation whereby one could articulate broad tissue engineering principles that should be followed in order to regenerate portions of excised or damaged skeletal tissues. Central to the regeneration of skeletal tissues is the conversion of progenitor cells and tissue into the desired specialized tissue. For mesenchymal tissues, this requires the conversion of groups of mesenchymal cells with their relatively modest extracellular matrix (ECM) into functional skeletal tissues characterized by a voluminous and specialized ECM. Because of the absence of the complex signalling cascade characteristic of early embryonic events, it is improbable that adult tissue reconstruction strategies can recapitulate distinctive morphologies while forming newly differentiated skeletal tissues. Thus, tissue-engineered regeneration protocols must provide the scaffolds and boundaries to establish the contours and edges of reparative tissues and then must functionally and molecularly integrate this neo-tissue with the surrounding host tissue. Consequently, such scaffolds must provide the reparative cells or their progenitors or the specific attachment or binding sites for endogenous reparative cells. The scaffolds must also provide the signals to start the reparative process, the means and signals to expand the reparative cells, the space for the unique and oriented specialized ECM and, lastly, the capacity to functionally integrate this neo-tissue in a seamless manner with the host tissue. Several tissue-engineering principles based on the details of embryonic events provide guides for the development of scientific logics for new reparative strategies for the regeneration of skeletal tissues.

Animals↗

University of Wyoming, College of Engineering, undergraduate design projects to aid Wyoming persons with disabilities.

In Spring 2002 the University of Wyoming received NSF funding from the Division of Bioengineering and Environmental Systems to provide a meaningful design experience for University of Wyoming, College of Engineering students that will directly aid individuals with disabilities within the state of Wyoming. Other universities have participated in this very worthwhile program [1, 2, 3]. To achieve the program purpose, the following objectives were established: Provide engineering students multi-disciplinary, meaningful, community service design projects, Provide persons with disabilities assistive devices to empower them to achieve the maximum individual growth and development and afford them the opportunity to participate in all aspects of life as they choose, Provide engineering students education and awareness on the special needs and challenges of persons with disabilities, and Provide undergraduate engineering students exposure to the biomedical field of engineering. To accomplish these objectives the College of Engineering partnered with three organizations that provide education and service related to disability. Specifically, the college has joined with the Wyoming Institute for Disabilities (WIND) assistive technology program, Wyoming New Options in Technology (WYNOT) and their Sports and Outdoor Assistive Recreation (SOAR) project along with the university's Special Education program. In this paper we will describe how the program was created, developed, and its current status.

Biomedical Engineering↗

Environmental engineering education in Spain.

There is a growing demand for engineers and technologists who show multidisciplinary expertise to deal with environmental issues. As a result of this demand, most countries are adapting their old university programs on environmental engineering education. In Spain an official environmental engineering degree does not yet exist, but the Council of Universities is working to present a proposal, based on Bologna agreement concepts. The paper summarizes not only the future perspectives of environmental engineering education in Spain, but also the evolution of the approach during the last decades, which includes the role of the private initiative, the environmental sciences degree, and the intensification in different traditional engineering degrees. Finally, the paper briefly details and compares the syllabus developed in the only four Spanish universities where environmental engineering is offered as a non-official post-graduate course lasting two years.

Curriculum↗

[Reconstruction of rabbit corneal stroma using tissue engineering technique].

OBJECTIVE: Reconstruct corneal stroma by tissue engineering. METHODS: Primary corneal stromal cells were isolated from newborn rabbit cornea. When the cultured cells reaching confluence, the stromal cells were mixed with polyglycolic acid (PGA) to form a cell-scaffold construct. After 1 week in vitro culture, the constructs were implanted into mother rabbit corneal stroma. Parts of corneal stromal cells were transfected with GFP gene as mark of transplanted cells. Tissues were harvested at 8 weeks for transmission electron microscopy (TEM), histology and Western blot evaluation. In control, PGA alone was implanted into the other cornea. RESULTS: The engineered corneal stroma became transparent gradually over a period of 8 weeks. The histology of engineered stromal lamellar was relatively similar to that of natural one, no significant differences were found in the diameter of cornea collagen fiber [(29.4 +/- 4.7) nm] in experimental rabbits compared with control [(28.5 +/- 3.5) nm], Student's t-test: P = 0.1316 > 0.05. TEM demonstrated that collagen fibrils deposited in engineered stroma had a similar diameter compared to that of normal counterpart. In addition, Western blot showed the positive expression of type I collagen in the collagen fibrils. In contrast, no new stroma tissue was formed when PGA alone implanted. A green colored stroma was observed when engineered with GFP-labeled cells under fluorescence light microscope. CONCLUSION: The results demonstrate that nearly transparent corneal stroma can be obtained by the technique of cornea engineering.

Animals↗

[Fabrication of laryngeal cartilage by means of tissue engineering technique].

OBJECTIVE: To explore the method of fabricating tissue engineered laryngeal cartilage. METHODS: The rib and articular cartilage of infant New Zealand white rabbits were harvested in sterile condition. The chondrocytes were separated by collagenase digestion and cultured in vitro for 3 passage. Serial steps of solution casting, extrusion molding and particulate leaching were used to make larynx-shaped biomaterial models with poly(3-hydroxybutyrate-co-3-hydroxyhexanoate, PHBHH). The chondrocytes were seeded onto PHBHH scaffolds to form cell-PHBHH composites, which were subsequently in vitro for one week. After that, the measure of filling inner space of cell-PHBHH composites together with wrapping total composites using either greater omentum (n = 9) or fascia flap and muscle (also n = 9) in experimental groups was taken to implant the larynx-shaped biomaterial models seeded with chondrocytes into the belly and the back of adult New Zealand white rabbits. Control groups (every group n = 3) were the same measure as experimental groups but without chondrocyte on PHBHH scaffolds. Finally, morphological observation, HE staining & special staining and immunohistochemical test were conducted to assess cartilage regeneration and its shape at different period following implantation. RESULTS: The rate of viable cell in the final cell suspension was (93 +/- 2)% after well-controlled prolongation of digestion trypsin. Similar to that by traditional procedures (94 +/- 2)% (P > 0.05). The larynx-shaped PHBHH models with edges and corners of laryngeal cartilage made by us appeared to be hollow half-trumpet shape and its porosity was more than 90%. It showed that chondrocytes equally attached to the surface of porous PHBHH and filled within porousness with scanning electron microscopic examination. Tissue engineered larynx-shaped specimens could alternatively be harvested with the above mentioned two different implantation measures. The specimens presented to be similar to that before implantation in gross shape. It was demonstrated to be cartilaginous tissue through histological and immunohistochemical examination. Furthermore, There was nearly no difference between two kinds of tissue engineered laryngeal cartilage with two measures of implantation in morphology and histology. CONCLUSIONS: The regeneration of tissue engineered cartilage in vivo is not influenced by the chondrocytes harvested by improvement of well-controlled prolonged digestion with trypsin during in vitro cell culture. It seems that PHBHH may be used as scaffold in cartilage tissue engineering and wrapping together with filling method with either greater omentum or fascia flap and muscle is appropriate for fabricating tissue engineered laryngeal cartilage.

Animals↗

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↗

Tissue engineering with adult stem cells in reconstructive surgery (review).

Tissue engineering is a multidisciplinary field combining biology and engineering along with clinical application to design, manufacture, modify, grow and maintain living tissue. This field has enjoyed tremendous growth in the past 10 years fueled by its potential role in regenerating new tissues and naturally healing injured or diseased organs. Many approaches to tissue engineering have been explored, including ex vivo de novo construction of tissues and strategies of in vivo induction of tissue regeneration. Interventions are hindered by factors such as rejection by the immune system, limited blood supply or morbidity of the donor site. Regardless of the approach, most researchers and clinicians agree that any successful tissue engineering construct will derive from a single unit, the cell. Because the engineering of tissue necessitates a sufficient number of tissue-specific cells with minimal donor site morbidity, a great deal of scientific effort has been directed towards stem cell research and the use of stem cells as a source of cells for new tissues. This review aims at outlining the role of stem cells in tissue engineering, focusing on the use of adult-derived stem cells as applied to the research and practice of plastic surgery.

Animals↗

[Uptake of nickel from industrial wastewater by genetically engineered Escherichia coli JM109].

Heavy metal wastewater poses a serious threat to the environment. In comparison to the existing methods of chemical precipitation, ion exchange and carbon adsorption, biosorption is an attractive alternative for the recovery of heavy metals from industrial effluents. However, nickel ion, different from other heavy metal ions, is a more recalcitrant pollutant and has low affinity to many metal tolerant microorganisms. In this study, Escherichia coli JM109 was genetically engineered to simultaneously express a Ni2+ transport system (the product of nixA gene) andoverexpress metallothionein (MT). NixA protein has a high affinity for Ni2+, and metallothioneins (MTs) are capable of binding a variety of heavy metals including Ni2+ . The Ni2+ bioaccumulation performance of the genetically engineered E. coli JM109 was evaluated. Time-course test showed that the bioaccumulation rate was rapid, and 95% of the accumulation was achieved within the first 10 minutes. The maximum Ni2+ bioaccumulation by genetically engineered E. coli cells was dramatically increased from 1.54 mg/g to 10.11mg/g, a more than five-fold increase than that of the original E. coli strain. The isotherm was of Langmuir type. Within the tested pH range (pH 4-10), the engineered cells displayed more resistance to pH variation, retaining up to 80% of the Ni2+ binding capacity at pH 4, while the original E. coli host cells lost 80% of Ni2+ binding capacity at pH 4. The presence of Na+ and Ca2+ affected Ni2+ bioaccumulation, but the effects were not serious, as 71% and 66% of the Ni2+ binding capacities were retained respectively at the concentrations of 1000 mg/L Na+ and 1000 mg/L Ca2+ . However, Mg2+ exerted a severe adverse effect on Ni2+ bioaccumulation, 83% of Ni2+ accumulating capacity was lost when Mg2+ concentration reached 200 mg/L. The effects of different kinds of heavy metals on Ni2+ accumulating were different. The genetically engineered E. coli cell lost less than 45% of its Ni2+ bioaccumulation activity in the presence of 50 mg/L lead or cadmium, 66% in the presence of 25mg/L mercury and 84% in the presence of 40 mg/L copper. The presence of glucose did not improve Ni2+ uptake. Our study suggests that the genetically engineered E. coli JM109 has potential application for effective and efficient recovery of nickel from aqueous solutions.

Biodegradation, Environmental↗

Effects of copper and cross-linking on the extracellular matrix of tissue-engineered arteries.

In many cases, the mechanical strengths of tissue-engineered arteries do not match the mechanical strengths of native arteries. Ultimate arterial strength is primarily dictated by collagen in the extracellular matrix. but collagen in engineered arteries is not as dense, as organized, or as mature as collagen in native arteries. One step in the maturation process of collagen is the formation of hydroxylysyl pyridinoline (HP) cross-links between and within collagen molecules. HP cross-link formation, which is triggered by the copper-activated enzyme lysyl oxidase, greatly increases collagen fibril stability and enhances tissue strength. Increased cross-link formation, in addition to increased collagen production, may yield a stronger engineered tissue. In this article, the effect of increasing culture medium copper ion concentration on engineered arterial tissue composition and mechanics was investigated. Engineered vessels grown in low copper ion concentrations for the first 4 weeks of culture, followed by higher copper ion concentrations for the last 3 weeks of culture, had significantly elevated levels of cross-link formation compared to those grown in low copper ion concentrations. In contrast, vessels grown in high copper ion concentrations throughout culture failed to develop higher collagen cross-link densities than those grown in low copper ion concentrations. Although the additional cross-linking of collagen in engineered vessels may provide collagen fibril stability and resistance to proteolysis, it failed to enhance global tissue strength.

Amino Acids↗

[Effects of impaction on tissue engineered bone modified by BMP-2 gene].

OBJECTIVE: To observe effects of the direct impaction on the cell survival and the bone formation of the tissue engineered bone modified by the adenovirus mediated human bone morphogenetic protein 2 (Adv-hBMP2) gene and to verify the feasibility of the impacted grafting with it. METHODS: The marrow stromal cells (MSCs) were separated from the canine bone marrow and were cultured. MSCs were transfected with the Adv-hBMP2 gene and combined with the freeze-dried cancellous bone (FDB) to form the tissue engineered bone. Four days after the combination, the tissue engineered bone was impacted in a simulated impactor in vitro and implanted in the mouse. The cell survivals were evaluated with SEM 1 and 4 days after the combination, immediately after the impaction, and 1 and 4 days after the impaction, respectively. The bone formation and the allograft absorption were histologically evaluated respectively. RESULTS: There were multiple layers of the cells and much collagen on FDB before the impaction. Immediately after the impaction, most of the cells on the direct contact area disappeared and there was much debris on the section. Some of the cells died and separated from the surface of FDB at 1 day, the number of the cells decreased but the collagen increased on the surface at 4 days. Histologically, only the fibrous tissue was found in FDB without the cells, the bone formation on FDB was even in distribution and mass in appearance before the impaction, but declined and was mainly on the periphery after the impaction in the Adv-hBMP-2 modified tissue-engineered bone. CONCLUSION: The simulated impaction can decrease the cells survival and the bone formation of the Adv-hBMP-2 modified tissue-engineered bone. The survival cells still function well. It is feasible to use the tissue engineered bone in the impaction graft.

Adenoviridae↗

Interface tissue engineering and the formulation of multiple-tissue systems.

Interface tissue engineering is an exciting field which focuses on the development of tissue engineered grafts capable of promoting integration between different types of tissue and between the implant and surrounding tissue. Focusing on interface tissue engineering, and using the insertion site between the anterior cruciate ligament and bone as an example, this chapter discusses strategies in soft tissue to bone integration as well as current tissue engineering efforts in this area. This review begins with the clinical significance of this problem, followed by a review of existing fixation methods, and tissue engineering efforts aimed at addressing this critical issue. The development of multiphased scaffolds designed for the replacement of more than one type of tissue, as well as novel in vitro co-culture systems will be introduced. Future directions in the field of interface tissue engineering will also be discussed.

Animals↗