Science.gov

Sample records for cornea tissue engineering

  1. Silk film biomaterials for cornea tissue engineering

    PubMed Central

    Lawrence, Brian D.; Marchant, Jeffrey K.; Pindrus, Mariya; Omenetto, Fiorenzo; Kaplan, David L.

    2009-01-01

    Biomaterials for corneal tissue engineering must demonstrate several critical features for potential utility in vivo, including transparency, mechanical integrity, biocompatibility and slow biodegradation. Silk film biomaterials were designed and characterized to meet these functional requirements. Silk protein films were used in a biomimetic approach to replicate corneal stromal tissue architecture. The films were 2 μm thick to emulate corneal collagen lamellae dimensions, and were surface patterned to guide cell alignment. To enhance trans-lamellar diffusion of nutrients and to promote cell-cell interaction, pores with 0.5 to 5.0 μm diameters were introduced into the silk films. Human and rabbit corneal fibroblast proliferation, alignment and corneal extracellular matrix expression on these films in both 2D and 3D cultures was demonstrated. The mechanical properties, optical clarity and surface patterned features of these films, combined with their ability to support corneal cell functions suggest this new biomaterial system offers important potential benefits for corneal tissue regeneration. PMID:19059642

  2. Tissue Engineering the Cornea: The Evolution of RAFT

    PubMed Central

    Levis, Hannah J.; Kureshi, Alvena K.; Massie, Isobel; Morgan, Louise; Vernon, Amanda J.; Daniels, Julie T.

    2015-01-01

    Corneal blindness affects over 10 million people worldwide and current treatment strategies often involve replacement of the defective layer with healthy tissue. Due to a worldwide donor cornea shortage and the absence of suitable biological scaffolds, recent research has focused on the development of tissue engineering techniques to create alternative therapies. This review will detail how we have refined the simple engineering technique of plastic compression of collagen to a process we now call Real Architecture for 3D Tissues (RAFT). The RAFT production process has been standardised, and steps have been taken to consider Good Manufacturing Practice compliance. The evolution of this process has allowed us to create biomimetic epithelial and endothelial tissue equivalents suitable for transplantation and ideal for studying cell-cell interactions in vitro. PMID:25809689

  3. Tissue Engineering the Cornea: The Evolution of RAFT.

    PubMed

    Levis, Hannah J; Kureshi, Alvena K; Massie, Isobel; Morgan, Louise; Vernon, Amanda J; Daniels, Julie T

    2015-01-22

    Corneal blindness affects over 10 million people worldwide and current treatment strategies often involve replacement of the defective layer with healthy tissue. Due to a worldwide donor cornea shortage and the absence of suitable biological scaffolds, recent research has focused on the development of tissue engineering techniques to create alternative therapies. This review will detail how we have refined the simple engineering technique of plastic compression of collagen to a process we now call Real Architecture for 3D Tissues (RAFT). The RAFT production process has been standardised, and steps have been taken to consider Good Manufacturing Practice compliance. The evolution of this process has allowed us to create biomimetic epithelial and endothelial tissue equivalents suitable for transplantation and ideal for studying cell-cell interactions in vitro.

  4. Development and characterization of a full-thickness acellular porcine cornea matrix for tissue engineering.

    PubMed

    Du, Liqun; Wu, Xinyi

    2011-07-01

    Our aim was to produce a natural, acellular matrix from porcine cornea for use as a scaffold in developing a tissue-engineered cornea replacement. Full-thickness, intact porcine corneas were decellularized by immersion in 0.5% (wt/vol) sodium dodecyl sulfate. The resulting acellular matrices were then characterized and examined specifically for completeness of the decellularization process. Histological analyses of decellularized corneal stromas showed that complete cell and α-Gal removal was achieved, while the major structural proteins including collagen type I and IV, laminin, and fibronectin were retained. DAPI staining did not detect any residual DNA within the matrix, and the DNA contents, which reflect the presence of cellular materials, were significantly diminished in the decellularized cornea. The collagen content of the decellularized cornea was well maintained compared with native tissues. Uniaxial tensile testing indicated that decellularization did not significantly compromise the ultimate tensile strength of the tissue (P > 0.05). In vitro cytotoxicity assays using rabbit corneal fibroblast cultures excluded the presence of soluble toxins in the biomaterial. In vivo implantation to rabbit interlamellar stromal pockets showed good biocompability. In summary, a full-thickness natural acellular matrix retaining the major structural components and strength of the cornea has been successfully developed. The matrix is biocompatible with cornea-derived cells and has potential for use in corneal transplantation and tissue-engineering applications.

  5. Control of Scar Tissue Formation in the Cornea: Strategies in Clinical and Corneal Tissue Engineering

    PubMed Central

    Wilson, Samantha L.; El Haj, Alicia J.; Yang, Ying

    2012-01-01

    Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation. PMID:24955637

  6. Control of scar tissue formation in the cornea: strategies in clinical and corneal tissue engineering.

    PubMed

    Wilson, Samantha L; El Haj, Alicia J; Yang, Ying

    2012-09-18

    Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation.

  7. Characterization of tissue-engineered posterior corneas using second- and third-harmonic generation microscopy.

    PubMed

    Jay, Louis; Bourget, Jean-Michel; Goyer, Benjamin; Singh, Kanwarpal; Brunette, Isabelle; Ozaki, Tsuneyuki; Proulx, Stéphanie

    2015-01-01

    Three-dimensional tissues, such as the cornea, are now being engineered as substitutes for the rehabilitation of vision in patients with blinding corneal diseases. Engineering of tissues for translational purposes requires a non-invasive monitoring to control the quality of the resulting biomaterial. Unfortunately, most current methods still imply invasive steps, such as fixation and staining, to clearly observe the tissue-engineered cornea, a transparent tissue with weak natural contrast. Second- and third-harmonic generation imaging are well known to provide high-contrast, high spatial resolution images of such tissues, by taking advantage of the endogenous contrast agents of the tissue itself. In this article, we imaged tissue-engineered corneal substitutes using both harmonic microscopy and classic histopathology techniques. We demonstrate that second- and third-harmonic imaging can non-invasively provide important information regarding the quality and the integrity of these partial-thickness posterior corneal substitutes (observation of collagen network, fibroblasts and endothelial cells). These two nonlinear imaging modalities offer the new opportunity of monitoring the engineered corneas during the entire process of production.

  8. Characterization of Tissue-Engineered Posterior Corneas Using Second- and Third-Harmonic Generation Microscopy

    PubMed Central

    Jay, Louis; Bourget, Jean-Michel; Goyer, Benjamin; Singh, Kanwarpal; Brunette, Isabelle; Ozaki, Tsuneyuki; Proulx, Stéphanie

    2015-01-01

    Three-dimensional tissues, such as the cornea, are now being engineered as substitutes for the rehabilitation of vision in patients with blinding corneal diseases. Engineering of tissues for translational purposes requires a non-invasive monitoring to control the quality of the resulting biomaterial. Unfortunately, most current methods still imply invasive steps, such as fixation and staining, to clearly observe the tissue-engineered cornea, a transparent tissue with weak natural contrast. Second- and third-harmonic generation imaging are well known to provide high-contrast, high spatial resolution images of such tissues, by taking advantage of the endogenous contrast agents of the tissue itself. In this article, we imaged tissue-engineered corneal substitutes using both harmonic microscopy and classic histopathology techniques. We demonstrate that second- and third-harmonic imaging can non-invasively provide important information regarding the quality and the integrity of these partial-thickness posterior corneal substitutes (observation of collagen network, fibroblasts and endothelial cells). These two nonlinear imaging modalities offer the new opportunity of monitoring the engineered corneas during the entire process of production. PMID:25918849

  9. Reconstruction of auto-tissue-engineered lamellar cornea by dynamic culture for transplantation: a rabbit model.

    PubMed

    Wu, Zheng; Zhou, Qiang; Duan, Haoyun; Wang, Xiaoran; Xiao, Jianhui; Duan, Hucheng; Li, Naiyang; Li, Chaoyang; Wan, Pengxia; Liu, Ying; Song, Yiyue; Zhou, Chenjing; Huang, Zheqian; Wang, Zhichong

    2014-01-01

    To construct an auto-tissue-engineered lamellar cornea (ATELC) for transplantation, based on acellular porcine corneal stroma and autologous corneal limbal explants, a dynamic culture process, which composed of a submersion culture, a perfusion culture and a dynamic air-liquid interface culture, was performed using appropriate parameters. The results showed that the ATELC-Dynamic possessed histological structure and DNA content that were similar to native lamellar cornea (NLC, p>0.05). Compared to NLC, the protein contents of zonula occludens-1, desmocollin-2 and integrin β4 in ATELC-Dynamic reached 93%, 89% and 73%, respectively. The basal cells of ATELC-Dynamic showed a better differentiation phenotype (K3-, P63+, ABCG2+) compared with that of ATELC in static air-lift culture (ATELC-Static, K3+, P63-, ABCG2-). Accordingly, the cell-cloning efficiency of ATELC-Dynamic (9.72±3.5%) was significantly higher than that of ATELC-Static (2.13±1.46%, p<0.05). The levels of trans-epithelial electrical resistance, light transmittance and areal modulus variation in ATELC-Dynamic all reached those of NLC (p>0.05). Rabbit lamellar keratoplasty showed that the barrier function of ATELC-Dynamic was intact, and there were no signs of epithelial shedding or neovascularization. Furthermore, the ATELC-Dynamic group had similar optical properties and wound healing processes compared with the NLC group. Thus, the sequential dynamic culture process that was designed according to corneal physiological characteristics could successfully reconstruct an auto-lamellar cornea with favorable morphological characteristics and satisfactory physiological function.

  10. [Regenerative medicine: stem cells, cellular and matricial interactions in the reconstruction of skin and cornea by tissue engineering].

    PubMed

    Larouche, D; Lavoie, A; Proulx, S; Paquet, C; Carrier, P; Beauparlant, A; Auger, F A; Germain, L

    2009-06-01

    Considering that there is a shortage of organ donor, the aim of tissue engineering is to develop substitutes for the replacement of wounded or diseased tissues. Autologous tissue is evidently a preferable transplant material for long-term graft persistence because of the unavoidable rejection reaction occuring against allogeneic transplant. For the production of such substitutes, it is essential to control the culture conditions for post-natal human stem cells. Furthermore, histological organization and functionality of reconstructed tissues must approach those of native organs. For self-renewing tissues such as skin and cornea, tissue engineering strategies must include the preservation of stem cells during the in vitro process as well as after grafting to ensure the long-term regeneration of the transplants. We described a tissue engineering method named the self-assembly approach allowing the production of autologous living organs from human cells without any exogenous biomaterial. This approach is based on the capacity of mesenchymal cells to create in vitro their own extracellular matrix and then reform a tissue. Thereafter, various techniques allow the reorganization of such tissues in more complex organ such as valve leaflets, blood vessels, skin or cornea. These tissues offer the hope of new alternatives for organ transplantation in the future. In this review, the importance of preserving stem cells during in vitro expansion and controlling cell differentiation as well as tissue organization to ensure quality and functionality of tissue-engineered organs will be discussed, while focusing on skin and cornea.

  11. Acellular ostrich corneal stroma used as scaffold for construction of tissue-engineered cornea

    PubMed Central

    Liu, Xian-Ning; Zhu, Xiu-Ping; Wu, Jie; Wu, Zheng-Jie; Yin, Yong; Xiao, Xiang-Hua; Su, Xin; Kong, Bin; Pan, Shi-Yin; Yang, Hua; Cheng, Yan; An, Na; Mi, Sheng-Li

    2016-01-01

    AIM To assess acellular ostrich corneal matrix used as a scaffold to reconstruct a damaged cornea. METHODS A hypertonic saline solution combined with a digestion method was used to decellularize the ostrich cornea. The microstructure of the acellular corneal matrix was observed by transmission electron microscopy (TEM) and hematoxylin and eosin (H&E) staining. The mechanical properties were detected by a rheometer and a tension machine. The acellular corneal matrix was also transplanted into a rabbit cornea and cytokeratin 3 was used to check the immune phenotype. RESULTS The microstructure and mechanical properties of the ostrich cornea were well preserved after the decellularization process. In vitro, the methyl thiazolyl tetrazolium results revealed that extracts of the acellular ostrich corneas (AOCs) had no inhibitory effects on the proliferation of the corneal epithelial or endothelial cells or on the keratocytes. The rabbit lamellar keratoplasty showed that the transplanted AOCs were transparent and completely incorporated into the host cornea while corneal turbidity and graft dissolution occurred in the acellular porcine cornea (APC) transplantation. The phenotype of the reconstructed cornea was similar to a normal rabbit cornea with a high expression of cytokeratin 3 in the superficial epithelial cell layer. CONCLUSION We first used AOCs as scaffolds to reconstruct damaged corneas. Compared with porcine corneas, the anatomical structures of ostrich corneas are closer to those of human corneas. In accordance with the principle that structure determines function, a xenograft lamellar keratoplasty also confirmed that the AOC transplantation generated a superior outcome compared to that of the APC graft. PMID:27158598

  12. The mouse cornea as a transplantation site for live imaging of engineered tissue constructs.

    PubMed

    Poché, Ross A; Saik, Jennifer E; West, Jennifer L; Dickinson, Mary E

    2010-04-01

    The field of tissue engineering aims to recapitulate healthy human organs and 3-D tissue structures in vitro and then transplant these constructs in vivo where they can be effectively integrated within the recipient patient and become perfused by the host circulation. To improve the design of materials for artificial tissue scaffolds, it would be ideal to have a high-throughput imaging system that allows one to directly monitor transplanted tissue constructs in live animals over an extended period of time. By combining such an assay with transgenic, cell-specific fluorescent reporters, one could monitor such parameters as tissue construct perfusion, donor cell survival, and donor-host cell interaction/integration. Here, we describe a protocol for a modified version of the classical corneal micropocket angiogenesis assay, employing it as a live imaging "window" to monitor angiogenic poly(ethylene glycol) (PEG)-based hydrogel tissue constructs.

  13. Tissue engineering of corneal stromal layer with dermal fibroblasts: phenotypic and functional switch of differentiated cells in cornea.

    PubMed

    Zhang, Yan Qing; Zhang, Wen Jie; Liu, Wei; Hu, Xiao Jie; Zhou, Guang Dong; Cui, Lei; Cao, Yilin

    2008-02-01

    Previously, we successfully engineered a corneal stromal layer using corneal stromal cells. However, the limited source and proliferation potential of corneal stromal cells has driven us to search for alternative cell sources for corneal stroma engineering. Based on the idea that the tissue-specific environment may alter cell fate, we proposed that dermal fibroblasts could switch their phenotype to that of corneal stromal cells in the corneal environment. Thus, dermal fibroblasts were harvested from newborn rabbits, seeded on biodegradable polyglycolic acid (PGA) scaffolds, cultured in vitro for 1 week, and then implanted into adult rabbit corneas. After 8 weeks of implantation, nearly transparent corneal stroma was formed, with a histological structure similar to that of its native counterpart. The existence of cells that had been retrovirally labeled with green fluorescence protein (GFP) demonstrated the survival of implanted cells. In addition, all GFP-positive cells that survived expressed keratocan, a specific marker for corneal stromal cells, and formed fine collagen fibrils with a highly organized pattern similar to that of native stroma. However, neither dermal fibroblast-PGA construct pre-incubated in vitro for 3 weeks nor chondrocyte-PGA construct could form transparent stroma. The results demonstrated that neonatal dermal fibroblasts could switch their phenotype in the new tissue environment under restricted conditions. The functional restoration of corneal transparency using dermal fibroblasts suggests that they could be an alternative cell source for corneal stroma engineering.

  14. Value of human amniotic epithelial cells in tissue engineering for cornea.

    PubMed

    Fatimah, Simat Siti; Ng, Sook Luan; Chua, Kien Hui; Hayati, Abdul Rahman; Tan, Ay Eeng; Tan, Geok Chin

    2010-11-01

    Human amniotic epithelial cells (hAECs) are potentially one of the key players in tissue engineering due to their easy availability. The aim of the present study was to develop an optimal isolation and transportation technique, as well as to determine the immunophenotype and epithelial gene expression of hAECs. Amnion was mechanically peeled off from the chorion and digested with trypsin-ethylenediaminetetraacetic acid. The isolated hAECs were cultured in medium containing 10 ng/mL epidermal growth factor until P4. The epithelial gene expression, cell surface antigen and protein expression of hAECs were analyzed by quantitative polymerase chain reaction, flow cytometry and immunocytochemistry. hAECs were also cultured in adipogenic, osteogenic and neurogenic induction media. The best cell yield of hAECs was seen in the digestion of 15 pieces of amnion (2 × 2 cm) and isolated 30 min after digestion with trypsin. F12:Dulbecco's modified eagle medium was the best medium for short term storage at 4 °C. hAECs expressed CD9, CD44, CD73 and CD90, and negligibly expressed CD31, CD34, CD45 and CD117. After serial passage, CK3, CK19 and involucrin gene expressions were upregulated, while p63, CK1 and CK14 gene expressions were downregulated. Sustained gene expressions of integrin β1 and CK18 were observed. At initial culture, these cells might have stem-like properties. However, they differentiated after serial passage. Nonetheless, hAECs have epithelial stem cell characteristics and have the potential to differentiate into corneal epithelial cells. Further investigations are still needed to elucidate the mechanism of differentiation involved and to optimize the culture condition for long term in vitro culture.

  15. Long-Term Cultures of Human Cornea Limbal Explants Form 3D Structures Ex Vivo - Implications for Tissue Engineering and Clinical Applications.

    PubMed

    Szabó, Dóra Júlia; Noer, Agate; Nagymihály, Richárd; Josifovska, Natasha; Andjelic, Sofija; Veréb, Zoltán; Facskó, Andrea; Moe, Morten C; Petrovski, Goran

    2015-01-01

    Long-term cultures of cornea limbal epithelial stem cells (LESCs) were developed and characterized for future tissue engineering and clinical applications. The limbal tissue explants were cultivated and expanded for more than 3 months in medium containing serum as the only growth supplement and without use of scaffolds. Viable 3D cell outgrowth from the explants was observed within 4 weeks of cultivation. The outgrowing cells were examined by immunofluorescent staining for putative markers of stemness (ABCG2, CK15, CK19 and Vimentin), proliferation (p63α, Ki-67), limbal basal epithelial cells (CK8/18) and differentiated cornea epithelial cells (CK3 and CK12). Morphological and immunostaining analyses revealed that long-term culturing can form stratified 3D tissue layers with a clear extracellular matrix deposition and organization (collagen I, IV and V). The LESCs showed robust expression of p63α, ABCG2, and their surface marker fingerprint (CD117/c-kit, CXCR4, CD146/MCAM, CD166/ALCAM) changed over time compared to short-term LESC cultures. Overall, we provide a model for generating stem cell-rich, long-standing 3D cultures from LESCs which can be used for further research purposes and clinical transplantation.

  16. Long-Term Cultures of Human Cornea Limbal Explants Form 3D Structures Ex Vivo – Implications for Tissue Engineering and Clinical Applications

    PubMed Central

    Nagymihály, Richárd; Josifovska, Natasha; Andjelic, Sofija; Veréb, Zoltán; Facskó, Andrea; Moe, Morten C.; Petrovski, Goran

    2015-01-01

    Long-term cultures of cornea limbal epithelial stem cells (LESCs) were developed and characterized for future tissue engineering and clinical applications. The limbal tissue explants were cultivated and expanded for more than 3 months in medium containing serum as the only growth supplement and without use of scaffolds. Viable 3D cell outgrowth from the explants was observed within 4 weeks of cultivation. The outgrowing cells were examined by immunofluorescent staining for putative markers of stemness (ABCG2, CK15, CK19 and Vimentin), proliferation (p63α, Ki-67), limbal basal epithelial cells (CK8/18) and differentiated cornea epithelial cells (CK3 and CK12). Morphological and immunostaining analyses revealed that long-term culturing can form stratified 3D tissue layers with a clear extracellular matrix deposition and organization (collagen I, IV and V). The LESCs showed robust expression of p63α, ABCG2, and their surface marker fingerprint (CD117/c-kit, CXCR4, CD146/MCAM, CD166/ALCAM) changed over time compared to short-term LESC cultures. Overall, we provide a model for generating stem cell-rich, long-standing 3D cultures from LESCs which can be used for further research purposes and clinical transplantation. PMID:26580800

  17. [Eye connective tissues: cornea and vitreous body].

    PubMed

    Labat-Robert, Jacqueline; Pouliquen, Yves; Robert, Ladislas

    2012-01-01

    The authors, ophtalmologist (Y.P.) and basic scientists (J.L.-R and L.R.), collaborated on eye-research since 1962 on normal and pathological aspects of eye tissues, considered as specialized forms of connective tissues, and on specific aspects of the physiology and pathology of the eye. This date coincides with the foundation of the French Society of Connective Tissues, which celebrates the 50th anniversary of its creation. We shall present here some of our work on the ontogenetic and phylogenetic aspects of the cornea, on its structure, function and regulation in normal and pathological states, taken from a large number of publications of our laboratories. Our work on cornea started with the study of the morphogenesis of its lamellar structure, made of collagen fibers and proteoglycans. This led us to the isolation and characterization of structural (or matrix) glycoproteins, a new class of matrix components, present also in all other connective tissues, and to the study of their biosynthesis by keratocytes. Corneal wounds and regeneration were also studied, as well as some corneal pathologies such as keratoconus. The confrontation of quantitative morphological methods with biochemical procedures were to yield important results on the mechanisms of the maintenance of corneal structure and function. Another series of studies concerned the vitreous where we detected, besides previously characterized components, such as hyaluronan and collagens, fibronectin which plays an important role in the adhesion of hyaluronan to the collagen network. Its age-dependent modifications were also studied, with a special focus on the role of reactive oxygen species (ROS)-mediated degradation of hyaluronan, especially important for the aging of the vitreous.

  18. Fourier transform infrared analysis of the thermal modification of human cornea tissue during conductive keratoplasty.

    PubMed

    Zhang, Li; Aksan, Alptekin

    2010-01-01

    This paper presents a study using in vitro Fourier transform infrared spectroscopy (FT-IR) analysis to determine the thermal damage induced to the human cornea by the conductive keratoplasty (CK) procedure. Human cornea tissues were treated with CK at different radiofrequency power (58-64%) and pulse duration (0.6-1.0 s) settings. The cornea tissues were cryo-sectioned and FT-IR analysis was performed to detect the extent of thermal damage by the second-derivative analysis of the infrared (IR) spectral bands corresponding to protein secondary structure. The protein amide I and II spectral bands measured in vitro mainly arose from collagen. The denatured cornea tissue showed a higher beta-sheet content than the native tissue. The extent of the thermal damage created by the CK treatment depended on power and duration settings, with the latter having a stronger effect. With clinical settings (60%, 0.6 s), the thermal damage area was confined within a radius of 100 microm. CK treatment duration had a more significant effect on the damage zone than the power setting.

  19. Tissue Engineering of Corneal Endothelium

    PubMed Central

    Mimura, Tatsuya; Yokoo, Seiichi; Yamagami, Satoru

    2012-01-01

    Human corneal endothelial cells (HCECs) do not replicate after wounding. Therefore, corneal endothelial deficiency can result in irreversible corneal edema. Descemet stripping automated endothelial keratoplasty (DSAEK) allows selective replacement of the diseased corneal endothelium. However, DSAEK requires a donor cornea and the worldwide shortage of corneas limits its application. This review presents current knowledge on the tissue engineering of corneal endothelium using cultured HCECs. We also provide our recent work on tissue engineering for DSAEK grafts using cultured HCECs. We reconstructed DSAEK grafts by seeding cultured DiI-labelled HCECs on collagen sheets. Then HCEC sheets were transplanted onto the posterior stroma after descemetorhexis in the DSAEK group. Severe stromal edema was detected in the control group, but not in the DSAEK group throughout the observation period. Fluorescein microscopy one month after surgery showed numerous DiI-labelled cells on the posterior corneal surface in the DSAEK group. Frozen sections showed a monolayer of DiI-labelled cells on Descemet’s membrane. These findings indicate that cultured adult HCECs, transplanted with DSAEK surgery, maintain corneal transparency after transplantation and suggest the feasibility of performing DSAEK with HCECs to treat endothelial dysfunction. PMID:24955745

  20. Radiofrequency heating of the cornea: an engineering review of electrodes and applicators.

    PubMed

    Berjano, Enrique J; Navarro, Enrique; Ribera, Vicente; Gorris, Javier; Alió, Jorge L

    2007-12-11

    This paper reviews the different applicators and electrodes employed to create localized heating in the cornea by means of the application of radiofrequency (RF) currents. Thermokeratoplasty (TKP) is probably the best known of these techniques and is based on the principle that heating corneal tissue (particularly the central part of the corneal tissue, i.e. the central stroma) causes collagen to shrink, and hence changes the corneal curvature. Firstly, we point out that TKP techniques are a complex challenge from the engineering point of view, due to the fact that it is necessary to create very localized heating in a precise location (central stroma), within a narrow temperature range (from 58 to 76 masculineC). Secondly, we describe the different applicator designs (i.e. RF electrodes) proposed and tested to date. This review is planned from a technical point of view, i.e. the technical developments are classified and described taking into consideration technical criteria, such as energy delivery mode (monopolar versus bipolar), thermal conditions (dry versus cooled electrodes), lesion pattern (focal versus circular lesions), and application placement (surface versus intrastromal).

  1. Radiofrequency Heating of the Cornea: An Engineering Review of Electrodes and Applicators

    PubMed Central

    Berjano, Enrique J; Navarro, Enrique; Ribera, Vicente; Gorris, Javier; Alió, Jorge L

    2007-01-01

    This paper reviews the different applicators and electrodes employed to create localized heating in the cornea by means of the application of radiofrequency (RF) currents. Thermokeratoplasty (TKP) is probably the best known of these techniques and is based on the principle that heating corneal tissue (particularly the central part of the corneal tissue, i.e. the central stroma) causes collagen to shrink, and hence changes the corneal curvature. Firstly, we point out that TKP techniques are a complex challenge from the engineering point of view, due to the fact that it is necessary to create very localized heating in a precise location (central stroma), within a narrow temperature range (from 58 to 76ºC). Secondly, we describe the different applicator designs (i.e. RF electrodes) proposed and tested to date. This review is planned from a technical point of view, i.e. the technical developments are classified and described taking into consideration technical criteria, such as energy delivery mode (monopolar versus bipolar), thermal conditions (dry versus cooled electrodes), lesion pattern (focal versus circular lesions), and application placement (surface versus intrastromal). PMID:19662131

  2. New dimensions in tissue engineering: possible models for human physiology.

    PubMed

    Baar, Keith

    2005-11-01

    Tissue engineering is a discipline of great promise. In some areas, such as the cornea, tissues engineered in the laboratory are already in clinical use. In other areas, where the tissue architecture is more complex, there are a number of obstacles to manoeuvre before clinically relevant tissues can be produced. However, even in areas where clinically relevant tissues are decades away, the tissues being produced at the moment provide powerful new models to aid the understanding of complex physiological processes. This article provides a personal view of the role of tissue engineering in advancing our understanding of physiology, with specific attention being paid to musculoskeletal tissues.

  3. Engineering complex tissues.

    PubMed

    Atala, Anthony; Kasper, F Kurtis; Mikos, Antonios G

    2012-11-14

    Tissue engineering has emerged at the intersection of numerous disciplines to meet a global clinical need for technologies to promote the regeneration of functional living tissues and organs. The complexity of many tissues and organs, coupled with confounding factors that may be associated with the injury or disease underlying the need for repair, is a challenge to traditional engineering approaches. Biomaterials, cells, and other factors are needed to design these constructs, but not all tissues are created equal. Flat tissues (skin); tubular structures (urethra); hollow, nontubular, viscus organs (vagina); and complex solid organs (liver) all present unique challenges in tissue engineering. This review highlights advances in tissue engineering technologies to enable regeneration of complex tissues and organs and to discuss how such innovative, engineered tissues can affect the clinic.

  4. Connective tissue growth factor is not necessary for haze formation in excimer laser wounded mouse corneas

    PubMed Central

    Feng, Xiaodi; Pi, Liya; Sriram, Sriniwas; Schultz, Gregory S.

    2017-01-01

    We sought to determine if connective tissue growth factor (CTGF) is necessary for the formation of corneal haze after corneal injury. Mice with post-natal, tamoxifen-induced, knockout of CTGF were subjected to excimer laser phototherapeutic keratectomy (PTK) and the corneas were allowed to heal. The extent of scaring was observed in non-induced mice, heterozygotes, and full homozygous knockout mice and quantified by macrophotography. The eyes from these mice were collected after euthanization for re-genotyping to control for possible Cre-mosaicism. Primary corneal fibroblasts from CTGF knockout corneas were established in a gel plug assay. The plug was removed, simulating an injury, and the rate of hole closure and the capacity for these cells to form light reflecting cells in response to CTGF and platelet-derived growth factor B (PDGF-B) were tested and compared to wild-type cells. We found that independent of genotype, each group of mice was still capable of forming light reflecting haze in the cornea after laser ablation (p = 0.40). Results from the gel plug closure rate in primary cell cultures of knockout cells were not statistically different from serum starved wild-type cells, independent of treatment. Compared to the serum starved wild-type cells, stimulation with PDGF-BB significantly increased the KO cell culture’s light reflection (p = 0.03). Most interestingly, both reflective cultures were positive for α-SMA, but the cellular morphology and levels of α-SMA were distinct and not in proportion to the light reflection seen. This new work demonstrates that corneas without CTGF can still form sub-epithelial haze, and that the light reflecting phenotype can be reproduced in culture. These data support the possibilities of growth factor redundancy and that multiple pro-haze pathways exist. PMID:28207886

  5. Engineering Complex Tissues

    PubMed Central

    MIKOS, ANTONIOS G.; HERRING, SUSAN W.; OCHAREON, PANNEE; ELISSEEFF, JENNIFER; LU, HELEN H.; KANDEL, RITA; SCHOEN, FREDERICK J.; TONER, MEHMET; MOONEY, DAVID; ATALA, ANTHONY; VAN DYKE, MARK E.; KAPLAN, DAVID; VUNJAK-NOVAKOVIC, GORDANA

    2010-01-01

    This article summarizes the views expressed at the third session of the workshop “Tissue Engineering—The Next Generation,” which was devoted to the engineering of complex tissue structures. Antonios Mikos described the engineering of complex oral and craniofacial tissues as a “guided interplay” between biomaterial scaffolds, growth factors, and local cell populations toward the restoration of the original architecture and function of complex tissues. Susan Herring, reviewing osteogenesis and vasculogenesis, explained that the vascular arrangement precedes and dictates the architecture of the new bone, and proposed that engineering of osseous tissues might benefit from preconstruction of an appropriate vasculature. Jennifer Elisseeff explored the formation of complex tissue structures based on the example of stratified cartilage engineered using stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a problem critical for biological fixation of tendons and ligaments, and the development of a new generation of fixation devices. Rita Kandel discussed the challenges related to the re-creation of the cartilage-bone interface, in the context of tissue engineered joint repair. Frederick Schoen emphasized, in the context of heart valve engineering, the need for including the requirements derived from “adult biology” of tissue remodeling and establishing reliable early predictors of success or failure of tissue engineered implants. Mehmet Toner presented a review of biopreservation techniques and stressed that a new breakthrough in this field may be necessary to meet all the needs of tissue engineering. David Mooney described systems providing temporal and spatial regulation of growth factor availability, which may find utility in virtually all tissue engineering and regeneration applications, including directed in vitro and in vivo vascularization of tissues. Anthony Atala offered a clinician’s perspective for functional tissue

  6. Advancing cardiovascular tissue engineering

    PubMed Central

    Truskey, George A.

    2016-01-01

    Cardiovascular tissue engineering offers the promise of biologically based repair of injured and damaged blood vessels, valves, and cardiac tissue. Major advances in cardiovascular tissue engineering over the past few years involve improved methods to promote the establishment and differentiation of induced pluripotent stem cells (iPSCs), scaffolds from decellularized tissue that may produce more highly differentiated tissues and advance clinical translation, improved methods to promote vascularization, and novel in vitro microphysiological systems to model normal and diseased tissue function. iPSC technology holds great promise, but robust methods are needed to further promote differentiation. Differentiation can be further enhanced with chemical, electrical, or mechanical stimuli. PMID:27303643

  7. Advances in Tissue Engineering

    PubMed Central

    Vacanti, Joseph

    2016-01-01

    Nearly 30 years ago, we reported on a concept now known as Tissue Engineering. Here, we report on some of the advances in this now thriving area of research. In particular, significant advances in tissue engineering of skin, liver, spinal cord, blood vessels, and other areas are discussed. PMID:26711689

  8. Chromosome mutations and tissue regeneration in the cornea after the UV laser irradiation

    NASA Astrophysics Data System (ADS)

    Razhev, Alexander M.; Bagayev, Sergei N.; Lebedeva, Lidya I.; Akhmametyeva, Elena M.; Zhupikov, Andrey A.

    2003-06-01

    In present paper the findings on chromosome mutations, the nature of damage and the repair of the cornea tissue after UV irradiation by excimer lasers at 193, 223 and 248 nm were made. Structural mutations induced by short-pulses UV irradiation were shown to be similar to spontaneous ones by the type, time of formation in the mitotic cycle and location of acentrics. Ten hours after irradiation of the cornea with doses of 0,09 to 1,5 J/cm2 the incidence of cells with chromosome aberrations increased linearly with dose and amounted to 11,7% at 248 nm, 5,5% at 223 nm and 2,6% at 193 nm per 1 J/cm2. No induced chromosome aberrations occurred 72 hour following irradiation. Within the dose range from 3,0 to 18 J/cm2 the cytogenesis effect of radiation was less manifest than that with the doses mentioned above, the frequency of chromosome aberrations being independent of either radiation wavelength or radiation dose and amounted of 2,5 to 3,0%. Thus, large doses of powerful short-pulse UV radiation are safe according to the structural mutation criterion.

  9. A simplified technique for in situ excision of cornea and evisceration of retinal tissue from human ocular globe.

    PubMed

    Parekh, Mohit; Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Camposampiero, Davide; Karali, Marianthi; Ponzin, Diego; Salvalaio, Gianni

    2012-06-12

    Enucleation is the process of retrieving the ocular globe from a cadaveric donor leaving the rest of the globe undisturbed. Excision refers to the retrieval of ocular tissues, especially cornea, by cutting it separate from the ocular globe. Evisceration is the process of removing the internal organs referred here as retina. The ocular globe consists of the cornea, the sclera, the vitreous body, the lens, the iris, the retina, the choroid, muscles etc (Suppl. Figure 1). When a patient is suffering from corneal damage, the cornea needs to be removed and a healthy one must be transplanted by keratoplastic surgeries. Genetic disorders or defects in retinal function can compromise vision. Human ocular globes can be used for various surgical procedures such as eye banking, transplantation of human cornea or sclera and research on ocular tissues. However, there is little information available on human corneal and retinal excision, probably due to the limited accessibility to human tissues. Most of the studies describing similar procedures are performed on animal models. Research scientists rely on the availability of properly dissected and well-conserved ocular tissues in order to extend the knowledge on human eye development, homeostasis and function. As we receive high amount of ocular globes out of which approximately 40% (Table 1) of them are used for research purposes, we are able to perform huge amount of experiments on these tissues, defining techniques to excise and preserve them regularly. The cornea is an avascular tissue which enables the transmission of light onto the retina and for this purpose should always maintain a good degree of transparency. Within the cornea, the limbus region, which is a reservoir of the stem cells, helps the reconstruction of epithelial cells and restricts the overgrowth of the conjunctiva maintaining corneal transparency and clarity. The size and thickness of the cornea are critical for clear vision, as changes in either of them

  10. Optical coherence tomography (OCT) in laser tissue bonding of incisions in the cornea

    NASA Astrophysics Data System (ADS)

    Porat, Yishai; Gabay, Ilan; Varssano, David; Barequet, Irina; Neudorfer, Meira; Rosner, Mordechai; Katzir, Abraham

    2015-03-01

    Temperature controlled laser bonding of the cornea is analyzed in this paper using optical coherence tomography imaging, histological section evaluations and tensile strength measurements. The heat generated to obtain the bonding causes changes to the tissue structure, which appear as a bowl shaped lesion around the heated spot. Optical coherence tomography is established as an appropriate modality for the assessment of these lesions, using the other methods for validation. A quantitative analysis of the lesions attributes is produced, using a dedicated image processing algorithm. By means of this method we observed that the depth of the lesion is the most effective measure in estimating the extent of the tissue reaction to heat. A comparison of the measured lesion depth, produced by different heating profiles, is presented. This comparison shows a linear dependence on both the temperature and the exposure time, within the boundaries of the experiment. The bond strength was evaluated for several set temperatures (with 20 seconds heating time in each case) displaying an optimal value at 70°C. Yet if an incision was successfully bonded, it held a higher burst pressure for a higher temperature value. These findings demonstrate the plausibility of an integrated laser tissue bonding apparatus with an optical coherence tomography probe, which will provide, for the first time, a real time feedback of the tissue structural change, and indicate the bonding progress and end point.

  11. Peptide Amphiphiles in Corneal Tissue Engineering

    PubMed Central

    Miotto, Martina; Gouveia, Ricardo M.; Connon, Che J.

    2015-01-01

    The increasing interest in effort towards creating alternative therapies have led to exciting breakthroughs in the attempt to bio-fabricate and engineer live tissues. This has been particularly evident in the development of new approaches applied to reconstruct corneal tissue. The need for tissue-engineered corneas is largely a response to the shortage of donor tissue and the lack of suitable alternative biological scaffolds preventing the treatment of millions of blind people worldwide. This review is focused on recent developments in corneal tissue engineering, specifically on the use of self-assembling peptide amphiphiles for this purpose. Recently, peptide amphiphiles have generated great interest as therapeutic molecules, both in vitro and in vivo. Here we introduce this rapidly developing field, and examine innovative applications of peptide amphiphiles to create natural bio-prosthetic corneal tissue in vitro. The advantages of peptide amphiphiles over other biomaterials, namely their wide range of functions and applications, versatility, and transferability are also discussed to better understand how these fascinating molecules can help solve current challenges in corneal regeneration. PMID:26258796

  12. In vivo tissue engineering of musculoskeletal tissues.

    PubMed

    McCullen, Seth D; Chow, Andre G Y; Stevens, Molly M

    2011-10-01

    Tissue engineering of musculoskeletal tissues often involves the in vitro manipulation and culture of progenitor cells, growth factors and biomaterial scaffolds. Though in vitro tissue engineering has greatly increased our understanding of cellular behavior and cell-material interactions, this methodology is often unable to recreate tissue with the hierarchical organization and vascularization found within native tissues. Accordingly, investigators have focused on alternative in vivo tissue engineering strategies, whereby the traditional triad (cells, growth factors, scaffolds) or a combination thereof are directly implanted at the damaged tissue site or within ectopic sites capable of supporting neo-tissue formation. In vivo tissue engineering may offer a preferential route for regeneration of musculoskeletal and other tissues with distinct advantages over in vitro methods based on the specific location of endogenous cultivation, recruitment of autologous cells, and patient-specific regenerated tissues.

  13. Neoproteoglycans in tissue engineering

    PubMed Central

    Weyers, Amanda; Linhardt, Robert J.

    2014-01-01

    Proteoglycans, comprised of a core protein to which glycosaminoglycan chains are covalently linked, are an important structural and functional family of macromolecules found in the extracellular matrix. Advances in our understanding of biological interactions have lead to a greater appreciation for the need to design tissue engineering scaffolds that incorporate mimetics of key extracellular matrix components. A variety of synthetic and semisynthetic molecules and polymers have been examined by tissue engineers that serve as structural, chemical and biological replacements for proteoglycans. These proteoglycan mimetics have been referred to as neoproteoglycans and serve as functional and therapeutic replacements for natural proteoglycans that are often unavailable for tissue engineering studies. Although neoproteoglycans have important limitations, such as limited signaling ability and biocompatibility, they have shown promise in replacing the natural activity of proteoglycans through cell and protein binding interactions. This review focuses on the recent in vivo and in vitro tissue engineering applications of three basic types of neoproteoglycan structures, protein–glycosaminoglycan conjugates, nano-glycosaminoglycan composites and polymer–glycosaminoglycan complexes. PMID:23399318

  14. Application of polarization OCT in tissue engineering

    NASA Astrophysics Data System (ADS)

    Yang, Ying; Ahearne, Mark; Bagnaninchi, Pierre O.; Hu, Bin; Hampson, Karen; El Haj, Alicia J.

    2008-02-01

    For tissue engineering of load-bearing tissues, such as bone, tendon, cartilage, and cornea, it is critical to generate a highly organized extracellular matrix. The major component of the matrix in these tissues is collagen, which usually forms a highly hierarchical structure with increasing scale from fibril to fiber bundles. These bundles are ordered into a 3D network to withstand forces such as tensile, compressive or shear. To induce the formation of organized matrix and create a mimic body environment for tissue engineering, in particular, tendon tissue engineering, we have fabricated scaffolds with features to support the formation of uniaxially orientated collagen bundles. In addition, mechanical stimuli were applied to stimulate tissue formation and matrix organization. In parallel, we seek a nondestructive tool to monitor the changes within the constructs in response to these external stimulations. Polarizationsensitive optical coherence tomography (PSOCT) is a non-destructive technique that provides functional imaging, and possesses the ability to assess in depth the organization of tissue. In this way, an engineered tissue construct can be monitored on-line, and correlated with the application of different stimuli by PSOCT. We have constructed a PSOCT using a superluminescent diode (FWHM 52nm) in this study and produced two types of tendon constructs. The matrix structural evolution under different mechanical stimulation has been evaluated by the PSOCT. The results in this study demonstrate that PSOCT was a powerful tool enabling us to monitor non-destructively and real time the progressive changes in matrix organization and assess the impact of various stimuli on tissue orientation and growth.

  15. Craniofacial bone tissue engineering.

    PubMed

    Wan, Derrick C; Nacamuli, Randall P; Longaker, Michael T

    2006-04-01

    Repair and reconstruction of the craniofacial skeleton represents a significant biomedical burden, with thousands of procedures per-formed annually secondary to injuries and congenital malformations. Given the multitude of current approaches, the need for more effective strategies to repair these bone deficits is apparent. This article explores two major modalities for craniofacial bone tissue engineering: distraction osteogenesis and cellular based therapies. Current understanding of the guiding principles for each of these modalities is elaborated on along with the knowledge gained from clinical and investigative studies. By laying this foundation, future directions for craniofacial distraction and cell-based bone engineering have emerged with great promise for the advancement of clinical practice.

  16. Survival and integration of tissue-engineered corneal stroma in a model of corneal ulcer.

    PubMed

    Zhang, Chao; Nie, Xin; Hu, Dan; Liu, Yuan; Deng, Zhihong; Dong, Rui; Zhang, Yongjie; Jin, Yan

    2007-08-01

    Tissue-engineered replacement of diseased or damaged tissue has become a reality for some types of tissue, such as skin and cartilage. Tissue-engineered corneal stroma represents a promising concept to overcome the limitations of cornea replacement with allograft. In this study, porcine cornea was decellularized by a series of extraction methods, and the in vivo biocompatibility of the scaffold was measured subcutaneously in rabbits (n = 8). These were not acutely rejected and no abscesses were observed by hematoxylin and eosin staining at the 8th week, indicating that the scaffolds had good biocompatibility. To investigate the potential value of clinical applications, rabbit stromal keratocytes were implanted onto decellularized scaffolds to fabricate tissue-engineered corneal stroma. Allograft, tissue-engineered corneal stroma, or scaffolds were implanted into a model of corneal ulcer. The survival and reconstruction of corneal transplantation were morphologically evaluated by light and electron microscopy until the 32nd week after implantation. Experiments involving transplantation indicated that the epithelial and stromal defect healed quickly, with improvement in corneal clarity. The integration of the graft was accompanied by neurite ingrowth from the host tissue. By 16 weeks after transplantation, the cornea had gradually regained an intact state similar to that of normal cornea. Our results demonstrate that the tissue-engineered corneal stroma with allogenetic cells is a promising therapeutic method for corneal injury.

  17. Tissue Engineering Research

    DTIC Science & Technology

    2002-01-01

    on Neural Stem Cells ......................................................25 4.1 Scoring System for the Histological Appearance of Full-Thickness...intellectual property. Examples include London’s Imperial College Tissue Engineering Center with its focus on stem cell research and the new Manchester...Moderate Equivalent Allogeneic cells / immunological manipulation Extensive Active in U.S. Modest in EU Little in Japan U.S. Stem cell research Extensive in

  18. Esophageal tissue engineering.

    PubMed

    Luc, Guillaume; Durand, Marlène; Collet, Denis; Guillemot, Fabien; Bordenave, Laurence

    2014-03-01

    Esophageal tissue engineering is still in an early state, and ideal methods have not been developed. Since the beginning of the 20th century, advances have been made in the materials that can be used to produce an esophageal substitute. Three approaches to scaffold-based tissue engineering have yielded good results. The first development concerned non-absorbable constructs based on silicone and collagen. The need to remove the silicone tube is the main disadvantage of this material. Polymeric absorbable scaffolds have been used since the 1990s. The main polymeric material used is poly (glycolic) acid combined with collagen. The problem of stenosis remains prevalent in most studies using an absorbable construct. Finally, decellularized scaffolds have been used since 2000. The promises of this new approach are unfulfilled. Indeed, stenosis occurs when the esophageal defect is circumferential regardless of the scaffold materials. Cell supplementation can decrease the rate of stenosis, but the type(s) of cells and their roles have not been defined. Finally, esophageal tissue engineering cannot provide a functional esophageal substitute, and further development is necessary prior to conducting human clinical studies.

  19. Cornea Transplant

    MedlinePlus

    ... who had several conditions, such as certain central nervous system conditions, infections, and prior eye surgery or eye conditions, or from people who died from an unknown cause. During your cornea transplant On the day of your cornea transplant, you' ...

  20. [Tissue engineering in reconstructive urology].

    PubMed

    Engel, O; Soave, A; Rink, M; Dahlem, R; Hellwinkel, O; Chun, F K; Fisch, M

    2015-05-01

    The term tissue engineering incorporates various techniques for the production of replacement tissues and organs. In urology tissue engineering offers many promising possibilities for the reconstruction of the urinary tract. Currently, buccal mucosa and urothelial cells are most commonly used for tissue engineering of the urinary tract. Various materials have been tested for their suitability as tissue scaffolds. The ideal scaffold, however, has not yet been found. In addition to material sciences and cell culture methods, surgical techniques play an important role in reconstructive urology for the successful implantation of tissue engineered transplants.

  1. Modular Tissue Engineering: Engineering Biological Tissues from the Bottom Up.

    PubMed

    Nichol, Jason W; Khademhosseini, Ali

    2009-01-01

    Tissue engineering creates biological tissues that aim to improve the function of diseased or damaged tissues. To enhance the function of engineered tissues there is a need to generate structures that mimic the intricate architecture and complexity of native organs and tissues. With the desire to create more complex tissues with features such as developed and functional microvasculature, cell binding motifs and tissue specific morphology, tissue engineering techniques are beginning to focus on building modular microtissues with repeated functional units. The emerging field known as modular tissue engineering focuses on fabricating tissue building blocks with specific microarchitectural features and using these modular units to engineer biological tissues from the bottom up. In this review we will examine the promise and shortcomings of "bottom-up" approaches to creating engineered biological tissues. Specifically, we will survey the current techniques for controlling cell aggregation, proliferation and extracellular matrix deposition, as well as approaches to generating shape-controlled tissue modules. We will then highlight techniques utilized to create macroscale engineered biological tissues from modular microscale units.

  2. Tissue engineering and ENT surgery.

    PubMed

    Patel, Nimesh N; Butler, Peter E M; Buttery, Lee; Polak, Julia M; Tolley, Neil S

    2002-03-01

    Tissue engineering is the development of biological substitutes for the repair and regeneration of damaged tissues. We explain the principles of this emerging field of biotechology. The present and potential applications of tissue engineering technologies in ENT surgery are then reviewed.

  3. Tissue bionics: examples in biomimetic tissue engineering.

    PubMed

    Green, David W

    2008-09-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

  4. Electrospun multifunctional tissue engineering scaffolds

    NASA Astrophysics Data System (ADS)

    Wang, Chong; Wang, Min

    2014-03-01

    Tissue engineering holds great promises in providing successful treatments of human body tissue loss that current methods are unable to treat or unable to achieve satisfactory clinical outcomes. In scaffold-based tissue engineering, a highperformance scaffold underpins the success of a tissue engineering strategy and a major direction in the field is to create multifunctional tissue engineering scaffolds for enhanced biological performance and for regenerating complex body tissues. Electrospinning can produce nanofibrous scaffolds that are highly desirable for tissue engineering. The enormous interest in electrospinning and electrospun fibrous structures by the science, engineering and medical communities has led to various developments of the electrospinning technology and wide investigations of electrospun products in many industries, including biomedical engineering, over the past two decades. It is now possible to create novel, multicomponent tissue engineering scaffolds with multiple functions. This article provides a concise review of recent advances in the R & D of electrospun multifunctional tissue engineering scaffolds. It also presents our philosophy and research in the designing and fabrication of electrospun multicomponent scaffolds with multiple functions.

  5. Biomaterials for tissue engineering: summary.

    PubMed

    Christenson, L; Mikos, A G; Gibbons, D F; Picciolo, G L

    1997-01-01

    This article summarizes presentations and discussion at the workshop "Enabling Biomaterial Technology for Tissue Engineering," which was held during the Fifth World Biomaterials Congress in May 1996. Presentations covered the areas of material substrate architecture, barrier effects, and cellular response, including analysis of biomaterials challenges involved in producing specific tissue-engineered products.

  6. Biomaterials for tissue engineering: summary

    NASA Technical Reports Server (NTRS)

    Christenson, L.; Mikos, A. G.; Gibbons, D. F.; Picciolo, G. L.; McIntire, L. V. (Principal Investigator)

    1997-01-01

    This article summarizes presentations and discussion at the workshop "Enabling Biomaterial Technology for Tissue Engineering," which was held during the Fifth World Biomaterials Congress in May 1996. Presentations covered the areas of material substrate architecture, barrier effects, and cellular response, including analysis of biomaterials challenges involved in producing specific tissue-engineered products.

  7. Tissue engineering of reproductive tissues and organs.

    PubMed

    Atala, Anthony

    2012-07-01

    Regenerative medicine and tissue engineering technology may soon offer new hope for patients with serious injuries and end-stage reproductive organ failure. Scientists are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured reproductive tissues. In addition, the stem cell field is advancing, and new discoveries in this field will lead to new therapeutic strategies. For example, newly discovered types of stem cells have been retrieved from uterine tissues such as amniotic fluid and placental stem cells. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous adult cells have already entered the clinic. This article discusses these tissue engineering strategies for various organs in the male and female reproductive tract.

  8. Tissue Engineering of the Penis

    PubMed Central

    Patel, Manish N.; Atala, Anthony

    2011-01-01

    Congenital disorders, cancer, trauma, or other conditions of the genitourinary tract can lead to significant organ damage or loss of function, necessitating eventual reconstruction or replacement of the damaged structures. However, current reconstructive techniques are limited by issues of tissue availability and compatibility. Physicians and scientists have begun to explore tissue engineering and regenerative medicine strategies for repair and reconstruction of the genitourinary tract. Tissue engineering allows the development of biological substitutes which could potentially restore normal function. Tissue engineering efforts designed to treat or replace most organs are currently being undertaken. Most of these efforts have occurred within the past decade. However, before these engineering techniques can be applied to humans, further studies are needed to ensure the safety and efficacy of these new materials. Recent progress suggests that engineered urologic tissues and cell therapy may soon have clinical applicability. PMID:22235188

  9. New Methods in Tissue Engineering

    PubMed Central

    Sheahan, Timothy P.; Rice, Charles M.; Bhatia, Sangeeta N.

    2015-01-01

    New insights in the study of virus and host biology in the context of viral infection are made possible by the development of model systems that faithfully recapitulate the in vivo viral life cycle. Standard tissue culture models lack critical emergent properties driven by cellular organization and in vivo–like function, whereas animal models suffer from limited susceptibility to relevant human viruses and make it difficult to perform detailed molecular manipulation and analysis. Tissue engineering techniques may enable virologists to create infection models that combine the facile manipulation and readouts of tissue culture with the virus-relevant complexity of animal models. Here, we review the state of the art in tissue engineering and describe how tissue engineering techniques may alleviate some common shortcomings of existing models of viral infection, with a particular emphasis on hepatotropic viruses. We then discuss possible future applications of tissue engineering to virology, including current challenges and potential solutions. PMID:25893203

  10. Angiogenesis and Tissue Engineering Research

    DTIC Science & Technology

    2010-08-01

    Aikawa E. Intravital molecular imaging of small- diameter tissue-engineered vascular grafts: A feasibility study.Tissue Eng Part C Methods.2009 Sep 14...Hjortnaes J, Gottlieb D, Figueiredo JL, Melero-Martin J, Kohler RH, Bischoff J, Weissleder R, Mayer J, Aikawa E. Intravital molecular imaging of small...2010 Online Publication Date: April 9, 2010 10 MELERO-MARTIN ET AL. 31 Methods Article Intravital Molecular Imaging of Small-Diameter Tissue-Engineered

  11. Cornea and ocular surface treatment.

    PubMed

    De Miguel, Maria P; Alio, Jorge L; Arnalich-Montiel, Francisco; Fuentes-Julian, Sherezade; de Benito-Llopis, Laura; Amparo, Francisco; Bataille, Laurent

    2010-06-01

    In addition to being a protective shield, the cornea represents two thirds of the eye's refractive power. Corneal pathology can affect one or all of the corneal layers, producing corneal opacity. Although full corneal thickness keratoplasty has been the standard procedure, the ideal strategy would be to replace only the damaged layer. Current difficulties in corneal transplantation, mainly immune rejection and shortage of organ supply, place more emphasis on the development of artificial corneas. Bioengineered corneas range from prosthetic devices that solely address the replacement of the corneal function, to tissue-engineered hydrogels that allow regeneration of the tissue. Recently, major advances in the biology of corneal stem cells have been achieved. However, the therapeutic use of these stem cell types has the disadvantage of needing an intact stem cell compartment, which is usually damaged. In addition, long ex vivo culture is needed to generate enough cell numbers for transplantation. In the near future, combination of advanced biomaterials with cells from abundant outer sources will allow advances in the field. For the former, magnetically aligned collagen is one of the most promising ones. For the latter, different cell types will be optimal: 1) for epithelial replacement: oral mucosal epithelium, ear epidermis, or bone marrow- mesenchymal stem cells, 2) for stromal regeneration: adipose-derived stem cells and 3) for endothelial replacement, the possibility of in vitro directed differentiation of adipose-derived stem cells towards endothelial cells provides an exciting new approach.

  12. Microfluidic hydrogels for tissue engineering.

    PubMed

    Huang, Guo You; Zhou, Li Hong; Zhang, Qian Cheng; Chen, Yong Mei; Sun, Wei; Xu, Feng; Lu, Tian Jian

    2011-03-01

    With advanced properties similar to the native extracellular matrix, hydrogels have found widespread applications in tissue engineering. Hydrogel-based cellular constructs have been successfully developed to engineer different tissues such as skin, cartilage and bladder. Whilst significant advances have been made, it is still challenging to fabricate large and complex functional tissues due mainly to the limited diffusion capability of hydrogels. The integration of microfluidic networks and hydrogels can greatly enhance mass transport in hydrogels and spatiotemporally control the chemical microenvironment of cells, mimicking the function of native microvessels. In this review, we present and discuss recent advances in the fabrication of microfluidic hydrogels from the viewpoint of tissue engineering. Further development of new hydrogels and microengineering technologies will have a great impact on tissue engineering.

  13. Tissue engineering for periodontal regeneration.

    PubMed

    Kao, Richard T; Conte, Greg; Nishimine, Dee; Dault, Scott

    2005-03-01

    As a result of periodontal regeneration research, a series of clinical techniques have emerged that permit tissue engineering to be performed for more efficient regeneration and repair of periodontal defects and improved implant site development. Historically, periodontal regeneration research has focused on a quest for "magic filler" material. This search has led to the development of techniques utilizing autologous bone and bone marrow, allografts, xenografts, and various man-made bone substitutes. Though these techniques have had limited success, the desire for a more effective regenerative approach has resulted in the development of tissue engineering techniques. Tissue engineering is a relatively new field of reconstructive biology which utilizes mechanical, cellular, or biologic mediators to facilitate reconstruction/regeneration of a particular tissue. In periodontology, the concept of tissue engineering had its beginnings with guided tissue regeneration, a mechanical approach utilizing nonresorbable membranes to obtain regeneration in defects. In dental implantology, guided bone regeneration membranes +/- mechanical support are used for bone augmentation of proposed implant placement sites. With the availability of partially purified protein mixture from developing teeth and growth factors from recombinant technology, a new era of tissue engineering whereby biologic mediators can be used for periodontal regeneration. The advantage of recombinant growth factors is this tissue engineering device is consistent in its regenerative capacity, and variations in regenerative response are due to individual healing response and/or poor surgical techniques. In this article, the authors review how tissue engineering has advanced and discuss its impact on the clinical management of both periodontal and osseous defects in preparation for implant placement. An understanding of these new tissue engineering techniques is essential for comprehending today's ever

  14. Biomimetic Materials for Tissue Engineering

    PubMed Central

    Ma, Peter X

    2008-01-01

    Tissue engineering and regenerative medicine is an exciting research area that aims at regenerative alternatives to harvested tissues for transplantation. Biomaterials play a pivotal role as scaffolds to provide three-dimensional templates and synthetic extracellular-matrix environments for tissue regeneration. It is often beneficial for the scaffolds to mimic certain advantageous characteristics of the natural extracellular matrix, or developmental or would healing programs. This article reviews current biomimetic materials approaches in tissue engineering. These include synthesis to achieve certain compositions or properties similar to those of the extracellular matrix, novel processing technologies to achieve structural features mimicking the extracellular matrix on various levels, approaches to emulate cell-extracellular matrix interactions, and biologic delivery strategies to recapitulate a signaling cascade or developmental/would-healing program. The article also provides examples of enhanced cellular/tissue functions and regenerative outcomes, demonstrating the excitement and significance of the biomimetic materials for tissue engineering and regeneration. PMID:18045729

  15. Evaluation of small intestine grafts decellularization methods for corneal tissue engineering.

    PubMed

    Oliveira, Ana Celeste; Garzón, Ingrid; Ionescu, Ana Maria; Carriel, Victor; Cardona, Juan de la Cruz; González-Andrades, Miguel; Pérez, María del Mar; Alaminos, Miguel; Campos, Antonio

    2013-01-01

    Advances in the development of cornea substitutes by tissue engineering techniques have focused on the use of decellularized tissue scaffolds. In this work, we evaluated different chemical and physical decellularization methods on small intestine tissues to determine the most appropriate decellularization protocols for corneal applications. Our results revealed that the most efficient decellularization agents were the SDS and triton X-100 detergents, which were able to efficiently remove most cell nuclei and residual DNA. Histological and histochemical analyses revealed that collagen fibers were preserved upon decellularization with triton X-100, NaCl and sonication, whereas reticular fibers were properly preserved by decellularization with UV exposure. Extracellular matrix glycoproteins were preserved after decellularization with SDS, triton X-100 and sonication, whereas proteoglycans were not affected by any of the decellularization protocols. Tissue transparency was significantly higher than control non-decellularized tissues for all protocols, although the best light transmittance results were found in tissues decellularized with SDS and triton X-100. In conclusion, our results suggest that decellularized intestinal grafts could be used as biological scaffolds for cornea tissue engineering. Decellularization with triton X-100 was able to efficiently remove all cells from the tissues while preserving tissue structure and most fibrillar and non-fibrillar extracellular matrix components, suggesting that this specific decellularization agent could be safely used for efficient decellularization of SI tissues for cornea TE applications.

  16. Polymeric Nanofibers in Tissue Engineering

    PubMed Central

    Dahlin, Rebecca L.; Kasper, F. Kurtis

    2011-01-01

    Polymeric nanofibers can be produced using methods such as electrospinning, phase separation, and self-assembly, and the fiber composition, diameter, alignment, degradation, and mechanical properties can be tailored to the intended application. Nanofibers possess unique advantages for tissue engineering. The small diameter closely matches that of extracellular matrix fibers, and the relatively large surface area is beneficial for cell attachment and bioactive factor loading. This review will update the reader on the aspects of nanofiber fabrication and characterization important to tissue engineering, including control of porous structure, cell infiltration, and fiber degradation. Bioactive factor loading will be discussed with specific relevance to tissue engineering. Finally, applications of polymeric nanofibers in the fields of bone, cartilage, ligament and tendon, cardiovascular, and neural tissue engineering will be reviewed. PMID:21699434

  17. Polymeric nanofibers in tissue engineering.

    PubMed

    Dahlin, Rebecca L; Kasper, F Kurtis; Mikos, Antonios G

    2011-10-01

    Polymeric nanofibers can be produced using methods such as electrospinning, phase separation, and self-assembly, and the fiber composition, diameter, alignment, degradation, and mechanical properties can be tailored to the intended application. Nanofibers possess unique advantages for tissue engineering. The small diameter closely matches that of extracellular matrix fibers, and the relatively large surface area is beneficial for cell attachment and bioactive factor loading. This review will update the reader on the aspects of nanofiber fabrication and characterization important to tissue engineering, including control of porous structure, cell infiltration, and fiber degradation. Bioactive factor loading will be discussed with specific relevance to tissue engineering. Finally, applications of polymeric nanofibers in the fields of bone, cartilage, ligament and tendon, cardiovascular, and neural tissue engineering will be reviewed.

  18. Tissue engineering: A live disc

    NASA Astrophysics Data System (ADS)

    Hukins, David W. L.

    2005-12-01

    A material-cell hybrid device that mimics the anatomic shape of the intervertebral disc has been made and successfully implanted into mice to show that tissue engineering may, in the future, benefit sufferers from back pain.

  19. Mechanobioreactors for Cartilage Tissue Engineering.

    PubMed

    Weber, Joanna F; Perez, Roman; Waldman, Stephen D

    2015-01-01

    Mechanical stimulation is an effective method to increase extracellular matrix synthesis and to improve the mechanical properties of tissue-engineered cartilage constructs. In this chapter, we describe valuable methods of imposing direct mechanical stimuli (compression or shear) to tissue-engineered cartilage constructs as well as some common analytical methods used to quantify the effects of mechanical stimuli after short-term or long-term loading.

  20. The Application of Sheet Technology in Cartilage Tissue Engineering.

    PubMed

    Ge, Yang; Gong, Yi Yi; Xu, Zhiwei; Lu, Yanan; Fu, Wei

    2016-04-01

    Cartilage tissue engineering started to act as a promising, even essential alternative method in the process of cartilage repair and regeneration, considering adult avascular structure has very limited self-renewal capacity of cartilage tissue in adults and a bottle-neck existed in conventional surgical treatment methods. Recent progressions in tissue engineering realized the development of more feasible strategies to treat cartilage disorders. Of these strategies, cell sheet technology has shown great clinical potentials in the regenerative areas such as cornea and esophagus and is increasingly considered as a potential way to reconstruct cartilage tissues for its non-use of scaffolds and no destruction of matrix secreted by cultured cells. Acellular matrix sheet technologies utilized in cartilage tissue engineering, with a sandwich model, can ingeniously overcome the drawbacks that occurred in a conventional acellular block, where cells are often blocked from migrating because of the non-nanoporous structure. Electrospun-based sheets with nanostructures that mimic the natural cartilage matrix offer a level of control as well as manipulation and make them appealing and widely used in cartilage tissue engineering. In this review, we focus on the utilization of these novel and promising sheet technologies to construct cartilage tissues with practical and beneficial functions.

  1. Cell sheet approach for tissue engineering and regenerative medicine.

    PubMed

    Matsuura, Katsuhisa; Utoh, Rie; Nagase, Kenichi; Okano, Teruo

    2014-09-28

    After the biotech medicine era, regenerative medicine is expected to be an advanced medicine that is capable of curing patients with difficult-to-treat diseases and physically impaired function. Our original scaffold-free cell sheet-based tissue engineering technology enables transplanted cells to be engrafted for a long time, while fully maintaining their viability. This technology has already been applied to various diseases in the clinical setting, including the cornea, esophagus, heart, periodontal ligament, and cartilage using autologous cells. Transplanted cell sheets not only replace the injured tissue and compensate for impaired function, but also deliver growth factors and cytokines in a spatiotemporal manner over a prolonged period, which leads to promotion of tissue repair. Moreover, the integration of stem cell biology and cell sheet technology with sufficient vascularization opens possibilities for fabrication of human three-dimensional vascularized dense and intact tissue grafts for regenerative medicine to parenchymal organs.

  2. Scaffolds in Tendon Tissue Engineering

    PubMed Central

    Longo, Umile Giuseppe; Lamberti, Alfredo; Petrillo, Stefano; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Tissue engineering techniques using novel scaffold materials offer potential alternatives for managing tendon disorders. Tissue engineering strategies to improve tendon repair healing include the use of scaffolds, growth factors, cell seeding, or a combination of these approaches. Scaffolds have been the most common strategy investigated to date. Available scaffolds for tendon repair include both biological scaffolds, obtained from mammalian tissues, and synthetic scaffolds, manufactured from chemical compounds. Preliminary studies support the idea that scaffolds can provide an alternative for tendon augmentation with an enormous therapeutic potential. However, available data are lacking to allow definitive conclusion on the use of scaffolds for tendon augmentation. We review the current basic science and clinical understanding in the field of scaffolds and tissue engineering for tendon repair. PMID:22190961

  3. Nanomaterials, Inflammation and Tissue Engineering

    PubMed Central

    Padmanabhan, Jagannath

    2014-01-01

    Nanomaterials exhibit unique properties that are absent in the bulk material because decreasing material size leads to an exponential increase in surface area, surface area to volume ratio, and effective stiffness, resulting in altered physiochemical properties. Diverse categories of nanomaterials such as nanoparticles, nanoporous scaffolds, nanopatterned surfaces, nanofibers and carbon nanotubes can be generated using advanced fabrication and processing techniques. These materials are being increasingly incorporated in tissue engineering scaffolds to facilitate the development of biomimetic substitutes to replace damaged tissues and organs. Long term success of nanomaterials in tissue engineering is contingent upon the inflammatory responses they elicit in vivo. This review seeks to summarize the recent developments in our understanding of biochemical and biophysical attributes of nanomaterials and the inflammatory responses they elicit, with a focus on strategies for nanomaterial design in tissue engineering applications. PMID:25421333

  4. Tissue Engineering Initiative

    DTIC Science & Technology

    2000-08-01

    UNCLASSIFIED AD NUMBER ADB263763 NEW LIMITATION CHANGE TO Approved for public release, distribution unlimited FROM Distribution authorized to U.S...Fort Detrick, MD 21702-5012. AUTHORITY USAMRMC ltr, dtd 15 May 2003 THIS PAGE IS UNCLASSIFIED AD Award Number: DAMD17-99-1-9475 TITLE: Tissue...STATEMENT: Distribution authorized to U.S. Government agencies only (proprietary information, Aug 00). Other requests for this document shall be

  5. Prelude to corneal tissue engineering – Gaining control of collagen organization

    PubMed Central

    Ruberti, Jeffrey W.; Zieske, James D.

    2012-01-01

    By most standard engineering practice principles, it is premature to credibly discuss the “engineering” of a human cornea. A professional design engineer would assert that we still do not know what a cornea is (and correctly so), therefore we cannot possibly build one. The proof resides in the fact that there are no clinically viable corneas based on classical tissue engineering methods available. This is possibly because tissue engineering in the classical sense (seeding a degradable scaffolding with a population synthetically active cells) does not produce conditions which support the generation of organized tissue. Alternative approaches to the problem are in their infancy and include the methods which attempt to recapitulate development or to produce corneal stromal analogs de novo which require minimal remodeling. Nonetheless, tissue engineering efforts, which have been focused on producing the fundamental functional component of a cornea (organized alternating arrays of collagen or “lamellae”) may have already provided valuable new insights and tools relevant to development, growth, remodeling and pathologies associated with connective tissue in general. This is because engineers ask a fundamentally different question (How can that be done?) than do biological scientists (How is that done?). The difference in inquiry has prompted us to closely examine (and to mimic) development as well as investigate collagen physicochemical behavior so that we may exert control over organization both in cell-culture (in vitro) and on the benchtop (de novo). Our initial results indicate that reproducing corneal stroma-like local and long-range organization of collagen may be simpler than we anticipated while controlling spacing and fibril morphology remains difficult, but perhaps not impossible in the (reasonably) near term. PMID:18775789

  6. Bone tissue engineering in osteoporosis.

    PubMed

    Jakob, Franz; Ebert, Regina; Ignatius, Anita; Matsushita, Takashi; Watanabe, Yoshinobu; Groll, Juergen; Walles, Heike

    2013-06-01

    Osteoporosis is a polygenetic, environmentally modifiable disease, which precipitates into fragility fractures of vertebrae, hip and radius and also confers a high risk of fractures in accidents and trauma. Aging and the genetic molecular background of osteoporosis cause delayed healing and impair regeneration. The worldwide burden of disease is huge and steadily increasing while the average life expectancy is also on the rise. The clinical need for bone regeneration applications, systemic or in situ guided bone regeneration and bone tissue engineering, will increase and become a challenge for health care systems. Apart from in situ guided tissue regeneration classical ex vivo tissue engineering of bone has not yet reached the level of routine clinical application although a wealth of scaffolds and growth factors has been developed. Engineering of complex bone constructs in vitro requires scaffolds, growth and differentiation factors, precursor cells for angiogenesis and osteogenesis and suitable bioreactors in various combinations. The development of applications for ex vivo tissue engineering of bone faces technical challenges concerning rapid vascularization for the survival of constructs in vivo. Recent new ideas and developments in the fields of bone biology, materials science and bioreactor technology will enable us to develop standard operating procedures for ex vivo tissue engineering of bone in the near future. Once prototyped such applications will rapidly be tailored for compromised conditions like vitamin D and sex hormone deficiencies, cellular deficits and high production of regeneration inhibitors, as they are prevalent in osteoporosis and in higher age.

  7. Image-guided tissue engineering

    PubMed Central

    Ballyns, Jeffrey J; Bonassar, Lawrence J

    2009-01-01

    Replication of anatomic shape is a significant challenge in developing implants for regenerative medicine. This has lead to significant interest in using medical imaging techniques such as magnetic resonance imaging and computed tomography to design tissue engineered constructs. Implementation of medical imaging and computer aided design in combination with technologies for rapid prototyping of living implants enables the generation of highly reproducible constructs with spatial resolution up to 25 μm. In this paper, we review the medical imaging modalities available and a paradigm for choosing a particular imaging technique. We also present fabrication techniques and methodologies for producing cellular engineered constructs. Finally, we comment on future challenges involved with image guided tissue engineering and efforts to generate engineered constructs ready for implantation. PMID:19583811

  8. Synthetic biology meets tissue engineering

    PubMed Central

    Davies, Jamie A.; Cachat, Elise

    2016-01-01

    Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the ‘embryological cycle’ of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. PMID:27284030

  9. Bioactive glass in tissue engineering

    PubMed Central

    Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

    2011-01-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  10. Polymer concepts in tissue engineering.

    PubMed

    Peter, S J; Miller, M J; Yasko, A W; Yaszemski, M J; Mikos, A G

    1998-01-01

    Traumatic injuries, cancer treatment, and congenital abnormalities are often associated with abnormal bone shape or segmental bone loss. Restoration of normal structure and function in these cases requires replacement of the missing bone that may be accomplished by surgical transfer of natural tissue from an uninjured location elsewhere in the body. However, this procedure is limited by availability, adequate blood supply, and secondary deformities at the donor site. One strategy to overcome these problems is to develop living tissue substitutes based on synthetic biodegradable polymers. Three methods of bone regeneration using biodegradable polymers are being studied in our laboratory: tissue induction, cell transplantation, and fabrication of vascularized bone flaps. Injectable polymers are used for filling skeletal defects and guiding bone tissue growth. Their main advantage is minimizing the surgical intervention or the severity of the surgery. Polymer-cell constructs also hold great promise in the field of tissue engineering. They provide a scaffold on which cells grow and organize themselves. As the cells begin to secrete their own extracellular matrix, the polymer degrades and is eventually eliminated from the body, resulting in completely natural tissue replacement. Bone flaps can be fabricated ectopically into precise shapes and sizes. With an attached vascular supply, these flaps can be transferred into areas deficient in vascularity. This article discusses polymer concepts regarding bone tissue engineering and reviews recent advances of our laboratory on guided bone regeneration using biodegradable polymer scaffolds.

  11. Helicoidal multi-lamellar features of RGD-functionalized silk biomaterials for corneal tissue engineering

    PubMed Central

    Gil, Eun Seok; Mandal, Biman B.; Park, Sang-Hyug; Marchant, Jeffrey K.; Omenetto, Fiorenzo G.; Kaplan, David L.

    2010-01-01

    RGD-coupled silk protein-biomaterial lamellar systems were prepared and studied with human cornea fibroblasts (hCFs) to match functional requirements. A strategy for corneal tissue engineering was pursued to replicate the structural hierarchy of human corneal stroma within thin stacks of lamellae-like tissues, in this case constructed from scaffolds constructed with RGD-coupled, patterned, porous, mechanically robust and transparent silk films. The influence of RGD-coupling on the orientation, proliferation, ECM organization, and gene expression of hCFs was assessed. RGD surface modification enhanced cell attachment, proliferation, alignment and expression of both collagens (type I and V) and proteoglycans (decorin and biglycan). Confocal and histological images of the lamellar systems revealed that the bio-functionalized silk human cornea 3D constructs exhibited integrated corneal stroma tissue with helicoidal multi-lamellar alignment of collagen-rich and proteoglycan-rich extracellular matrix, with transparency of the construct. This biomimetic approach to replicate corneal stromal tissue structural hierarchy and architecture demonstrates a useful strategy for engineering human cornea. Further, this approach can be exploited for other tissue systems due to the pervasive nature of such helicoids in most human tissues. PMID:20801503

  12. Intra-tissue Refractive Index Shaping (IRIS) of the cornea and lens using a low-pulse-energy femtosecond laser oscillator

    PubMed Central

    Ding, Li; Knox, Wayne H.; Bühren, Jens; Nagy, Lana J.; Huxlin, Krystel R.

    2009-01-01

    Purpose To assess the optical effect of high-repetition-rate, low energy femtosecond laser pulses on lightly-fixed corneas and lenses. Methods Eight corneas and eight lenses were extracted post-mortem from normal, adult cats. They were lightly fixed and stored in a solution that minimized swelling and opacification. An 800nm Ti:Sapphire femtosecond laser oscillator with a 27fs pulse duration and 93MHz repetition rate was used to inscribe gratings consisting of 20-40 lines, each 1μm wide, 100μm long and 5μm apart, 100μm below the tissue surface. Refractive index changes in the micromachined regions were calculated immediately and after one month of storage by measuring the intensity distribution of diffracted light when the gratings were irradiated with a 632.8nm He-Ne laser. Results Periodic gratings were created into the stromal layer of the corneas and the cortex of the lenses by adjusting the laser pulse energy until visible plasma luminescence and bubbles were no longer generated. The gratings had low scattering loss and could only be visualized using phase microscopy. Refractive index changes measured 0.005±0.001 to 0.01±0.001 in corneal tissue and 0.015±0.001 to 0.021±0.001 in the lenses. The gratings and refractive index changes were preserved after storing the micromachined corneas and lenses for one month. Conclusions These pilot experiments demonstrate a novel application of low-pulse-energy, MHz femtosecond lasers in modifying the refractive index of transparent ocular tissues without apparent tissue destruction. Although it remains to be verified in living tissues, the stability of this effect suggests that the observed modifications are due to long-term molecular and/or structural changes. PMID:18641284

  13. Engineering functionally graded tissue engineering scaffolds.

    PubMed

    Leong, K F; Chua, C K; Sudarmadji, N; Yeong, W Y

    2008-04-01

    Tissue Engineering (TE) aims to create biological substitutes to repair or replace failing organs or tissues due to trauma or ageing. One of the more promising approaches in TE is to grow cells on biodegradable scaffolds, which act as temporary supports for the cells to attach, proliferate and differentiate; after which the scaffold will degrade, leaving behind a healthy regenerated tissue. Tissues in nature, including human tissues, exhibit gradients across a spatial volume, in which each identifiable layer has specific functions to perform so that the whole tissue/organ can behave normally. Such a gradient is termed a functional gradient. A good TE scaffold should mimic such a gradient, which fulfils the biological and mechanical requirements of the target tissue. Thus, the design and fabrication process of such scaffolds become more complex and the introduction of computer-aided tools will lend themselves well to ease these challenges. This paper reviews the needs and characterization of these functional gradients and the computer-aided systems used to ease the complexity of the scaffold design stage. These include the fabrication techniques capable of building functionally graded scaffolds (FGS) using both conventional and rapid prototyping (RP) techniques. They are able to fabricate both continuous and discrete types of FGS. The challenge in fabricating continuous FGS using RP techniques lies in the development of suitable computer aided systems to facilitate continuous FGS design. What have been missing are the appropriate models that relate the scaffold gradient, e.g. pore size, porosity or material gradient, to the biological and mechanical requirements for the regeneration of the target tissue. The establishment of these relationships will provide the foundation to develop better computer-aided systems to help design a suitable customized FGS.

  14. An Ultra-thin Amniotic Membrane as Carrier in Corneal Epithelium Tissue-Engineering.

    PubMed

    Zhang, Liying; Zou, Dulei; Li, Sanming; Wang, Junqi; Qu, Yangluowa; Ou, Shangkun; Jia, Changkai; Li, Juan; He, Hui; Liu, Tingting; Yang, Jie; Chen, Yongxiong; Liu, Zuguo; Li, Wei

    2016-02-15

    Amniotic membranes (AMs) are widely used as a corneal epithelial tissue carrier in reconstruction surgery. However, the engineered tissue transparency is low due to the translucent thick underlying AM stroma. To overcome this drawback, we developed an ultra-thin AM (UAM) by using collagenase IV to strip away from the epithelial denuded AM (DAM) some of the stroma. By thinning the stroma to about 30 μm, its moist and dry forms were rendered acellular, optically clear and its collagen framework became compacted and inerratic. Engineered rabbit corneal epithelial cell (RCEC) sheets generated through expansion of limbal epithelial cells on UAM were more transparent and thicker than those expanded on DAM. Moreover, ΔNp63 and ABCG2 gene expression was greater in tissue engineered cell sheets expanded on UAM than on DAM. Furthermore, 2 weeks after surgery, the cornea grafted with UAM based cell sheets showed higher transparency and more stratified epithelium than the cornea grafted with DAM based cell sheets. Taken together, tissue engineered corneal epithelium generated on UAM has a preferable outcome because the transplanted tissue is more transparent and better resembles the phenotype of the native tissue than that obtained by using DAM for this procedure. UAM preserves compact layer of the amniotic membrane and maybe an ideal substrate for corneal epithelial tissue engineering.

  15. An Ultra-thin Amniotic Membrane as Carrier in Corneal Epithelium Tissue-Engineering

    PubMed Central

    Zhang, Liying; Zou, Dulei; Li, Sanming; Wang, Junqi; Qu, Yangluowa; Ou, Shangkun; Jia, Changkai; Li, Juan; He, Hui; Liu, Tingting; Yang, Jie; Chen, Yongxiong; Liu, Zuguo; Li, Wei

    2016-01-01

    Amniotic membranes (AMs) are widely used as a corneal epithelial tissue carrier in reconstruction surgery. However, the engineered tissue transparency is low due to the translucent thick underlying AM stroma. To overcome this drawback, we developed an ultra-thin AM (UAM) by using collagenase IV to strip away from the epithelial denuded AM (DAM) some of the stroma. By thinning the stroma to about 30 μm, its moist and dry forms were rendered acellular, optically clear and its collagen framework became compacted and inerratic. Engineered rabbit corneal epithelial cell (RCEC) sheets generated through expansion of limbal epithelial cells on UAM were more transparent and thicker than those expanded on DAM. Moreover, ΔNp63 and ABCG2 gene expression was greater in tissue engineered cell sheets expanded on UAM than on DAM. Furthermore, 2 weeks after surgery, the cornea grafted with UAM based cell sheets showed higher transparency and more stratified epithelium than the cornea grafted with DAM based cell sheets. Taken together, tissue engineered corneal epithelium generated on UAM has a preferable outcome because the transplanted tissue is more transparent and better resembles the phenotype of the native tissue than that obtained by using DAM for this procedure. UAM preserves compact layer of the amniotic membrane and maybe an ideal substrate for corneal epithelial tissue engineering. PMID:26876685

  16. Engineering of implantable liver tissues.

    PubMed

    Sakai, Yasuyuki; Nishikawa, M; Evenou, F; Hamon, M; Huang, H; Montagne, K P; Kojima, N; Fujii, T; Niino, T

    2012-01-01

    In this chapter, from the engineering point of view, we introduce the results from our group and related research on three typical configurations of engineered liver tissues; cell sheet-based tissues, sheet-like macroporous scaffold-based tissues, and tissues based on special scaffolds that comprise a flow channel network. The former two do not necessitate in vitro prevascularization and are thus promising in actual human clinical trials for liver diseases that can be recovered by relatively smaller tissue mass. The third approach can implant a much larger mass but is still not yet feasible. In all cases, oxygen supply is the key engineering factor. For the first configuration, direct oxygen supply using an oxygen-permeable polydimethylsiloxane membrane enables various liver cells to exhibit distinct behaviors, complete double layers of mature hepatocytes and fibroblasts, spontaneous thick tissue formation of hepatocarcinoma cells and fetal hepatocytes. Actual oxygen concentration at the cell level can be strictly controlled in this culture system. Using this property, we found that initially low then subsequently high oxygen concentrations were favorable to growth and maturation of fetal cells. For the second configuration, combination of poly-L: -lactic acid 3D scaffolds and appropriate growth factor cocktails provides a suitable microenvironment for the maturation of cells in vitro but the cell growth is limited to a certain distance from the inner surfaces of the macropores. However, implantation to the mesentery leaves of animals allows the cells again to proliferate and pack the remaining spaces of the macroporous structure, suggesting the high feasibility of 3D culture of hepatocyte progenitors for liver tissue-based therapies. For the third configuration, we proposed a design criterion concerning the dimensions of flow channels based on oxygen diffusion and consumption around the channel. Due to the current limitation in the resolution of 3D

  17. Tissue engineering in urothelium regeneration.

    PubMed

    Vaegler, Martin; Maurer, Sabine; Toomey, Patricia; Amend, Bastian; Sievert, Karl-Dietrich

    2015-03-01

    The development of therapeutic treatments to regenerate urothelium, manufacture tissue equivalents or neourethras for in-vivo application is a significant challenge in the field of tissue engineering. Many studies have focused on urethral defects that, in most cases, inadequately address current therapies. This article reviews the primary tissue engineering strategies aimed at the clinical requirements for urothelium regeneration while concentrating on promising investigations in the use of grafts, cellular preparations, as well as seeded or unseeded natural and synthetic materials. Despite significant progress being made in the development of scaffolds and matrices, buccal mucosa transplants have not been replaced. Recently, graft tissues appear to have an advantage over the use of matrices. These therapies depend on cell isolation and propagation in vitro that require, not only substantial laboratory resources, but also subsequent surgical implant procedures. The choice of the correct cell source is crucial when determining an in-vivo application because of the risks of tissue changes and abnormalities that may result in donor site morbidity. Addressing an appropriately-designed animal model and relevant regulatory issues is of fundamental importance for the principal investigators when a therapy using cellular components has been developed for clinical use.

  18. Developmental biology and tissue engineering.

    PubMed

    Marga, Francoise; Neagu, Adrian; Kosztin, Ioan; Forgacs, Gabor

    2007-12-01

    Morphogenesis implies the controlled spatial organization of cells that gives rise to tissues and organs in early embryonic development. While morphogenesis is under strict genetic control, the formation of specialized biological structures of specific shape hinges on physical processes. Tissue engineering (TE) aims at reproducing morphogenesis in the laboratory, i.e., in vitro, to fabricate replacement organs for regenerative medicine. The classical approach to generate tissues/organs is by seeding and expanding cells in appropriately shaped biocompatible scaffolds, in the hope that the maturation process will result in the desired structure. To accomplish this goal more naturally and efficiently, we set up and implemented a novel TE method that is based on principles of developmental biology and employs bioprinting, the automated delivery of cellular composites into a three-dimensional (3D) biocompatible environment. The novel technology relies on the concept of tissue liquidity according to which multicellular aggregates composed of adhesive and motile cells behave in analogy with liquids: in particular, they fuse. We emphasize the major role played by tissue fusion in the embryo and explain how the parameters (surface tension, viscosity) that govern tissue fusion can be used both experimentally and theoretically to control and simulate the self-assembly of cellular spheroids into 3D living structures. The experimentally observed postprinting shape evolution of tube- and sheet-like constructs is presented. Computer simulations, based on a liquid model, support the idea that tissue liquidity may provide a mechanism for in vitro organ building.

  19. Biomaterials for liver tissue engineering.

    PubMed

    Jain, Era; Damania, Apeksha; Kumar, Ashok

    2014-04-01

    Liver extracellular matrix (ECM) composition, topography and biomechanical properties influence cell-matrix interactions. The ECM presents guiding cues for hepatocyte phenotype maintenance, differentiation and proliferation both in vitro and in vivo. Current understanding of such cell-guiding cues along with advancement of techniques for scaffold fabrication has led to evolution of matrices for liver tissue culture from simple porous scaffolds to more complex 3D matrices with microarchitecture similar to in vivo. Natural and synthetic polymeric biomaterials fabricated in different topographies and porous matrices have been used for hepatocyte culture. Heterotypic and homotypic cell interactions are necessary for developing an adult liver as well as an artificial liver. A high oxygen demand of hepatocytes as well as graded oxygen distribution in liver is another challenging attribute of the normal liver architecture that further adds to the complexity of engineered substrate design. A balanced interplay of cell-matrix interactions along with cell-cell interactions and adequate supply of oxygen and nutrient determines the success of an engineered substrate for liver cells. Techniques devised to incorporate these features of hepatic function and mimic liver architecture range from maintaining liver cells in mm-sized tailor-made scaffolds to a more bottoms up approach that starts from building the microscopic subunit of the whole tissue. In this review, we discuss briefly various biomaterials used for liver tissue engineering with respect to design parameters such as scaffold composition and chemistry, biomechanical properties, topography, cell-cell interactions and oxygenation.

  20. Biomaterials in myocardial tissue engineering

    PubMed Central

    Reis, Lewis A.; Chiu, Loraine L. Y.; Feric, Nicole; Fu, Lara; Radisic, Milica

    2016-01-01

    Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternate sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end-stage heart failure is a heart transplant. In this review we focus on biomaterial approaches to augment injured or impaired myocardium with specific emphasis on: the design criteria for these biomaterials; the types of scaffolds—composed of natural or synthetic biomaterials, or decellularized extracellular matrix—that have been used to develop cardiac patches and tissue models; methods to vascularize scaffolds and engineered tissue, and finally injectable biomaterials (hydrogels)designed for endogenous repair, exogenous repair or as bulking agents to maintain ventricular geometry post-infarct. The challenges facing the field and obstacles that must be overcome to develop truly clinically viable cardiac therapies are also discussed. PMID:25066525

  1. Tissue engineering a human phalanx.

    PubMed

    Landis, W J; Chubinskaya, S; Tokui, T; Wada, Y; Isogai, N; Jacquet, R

    2016-03-21

    A principal purpose of tissue engineering is the augmentation, repair or replacement of diseased or injured human tissue. This study was undertaken to determine whether human biopsies as a cell source could be utilized for successful engineering of human phalanges consisting of both bone and cartilage. This paper reports the use of cadaveric human chondrocytes and periosteum as a model for the development of phalanx constructs. Two factors, osteogenic protein-1 [OP-1/bone morphogenetic protein-7 (BMP7)], alone or combined with insulin-like growth factor (IGF-1), were examined for their potential enhancement of chondrocytes and their secreted extracellular matrices. Design of the study included culture of chondrocytes and periosteum on biodegradable polyglycolic acid (PGA) and poly-l-lactic acid (PLLA)-poly-ε-caprolactone (PCL) scaffolds and subsequent implantation in athymic nu/nu (nude) mice for 5, 20, 40 and 60 weeks. Engineered constructs retrieved from mice were characterized with regard to genotype and phenotype as a function of developmental (implantation) time. Assessments included gross observation, X-ray radiography or microcomputed tomography, histology and gene expression. The resulting data showed that human cell-scaffold constructs could be successfully developed over 60 weeks, despite variability in donor age. Cartilage formation of the distal phalanx models enhanced with both OP-1 and IGF-1 yielded more cells and extracellular matrix (collagen and proteoglycans) than control chondrocytes without added factors. Summary data demonstrated that human distal phalanx models utilizing cadaveric chondrocytes and periosteum were successfully fabricated and OP-1 and OP-1/IGF-1 accelerated construct development and mineralization. The results suggest that similar engineering and transplantation of human autologous tissues in patients are clinically feasible. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Kidney diseases and tissue engineering.

    PubMed

    Moon, Kyung Hyun; Ko, In Kap; Yoo, James J; Atala, Anthony

    2016-04-15

    Kidney disease is a worldwide public health problem. Renal failure follows several disease stages including acute and chronic kidney symptoms. Acute kidney injury (AKI) may lead to chronic kidney disease (CKD), which can progress to end-stage renal disease (ESRD) with a mortality rate. Current treatment options are limited to dialysis and kidney transplantation; however, problems such as donor organ shortage, graft failure and numerous complications remain a concern. To address this issue, cell-based approaches using tissue engineering (TE) and regenerative medicine (RM) may provide attractive approaches to replace the damaged kidney cells with functional renal specific cells, leading to restoration of normal kidney functions. While development of renal tissue engineering is in a steady state due to the complex composition and highly regulated functionality of the kidney, cell therapy using stem cells and primary kidney cells has demonstrated promising therapeutic outcomes in terms of restoration of renal functions in AKI and CKD. In this review, basic components needed for successful renal kidney engineering are discussed, and recent TE and RM approaches to treatment of specific kidney diseases will be presented.

  3. Cardiac Conduction through Engineered Tissue

    PubMed Central

    Choi, Yeong-Hoon; Stamm, Christof; Hammer, Peter E.; Kwaku, Kevin F.; Marler, Jennifer J.; Friehs, Ingeborg; Jones, Mara; Rader, Christine M.; Roy, Nathalie; Eddy, Mau-Thek; Triedman, John K.; Walsh, Edward P.; McGowan, Francis X.; del Nido, Pedro J.; Cowan, Douglas B.

    2006-01-01

    In children, interruption of cardiac atrioventricular (AV) electrical conduction can result from congenital defects, surgical interventions, and maternal autoimmune diseases during pregnancy. Complete AV conduction block is typically treated by implanting an electronic pacemaker device, although long-term pacing therapy in pediatric patients has significant complications. As a first step toward developing a substitute treatment, we implanted engineered tissue constructs in rat hearts to create an alternative AV conduction pathway. We found that skeletal muscle-derived cells in the constructs exhibited sustained electrical coupling through persistent expression and function of gap junction proteins. Using fluorescence in situ hybridization and polymerase chain reaction analyses, myogenic cells in the constructs were shown to survive in the AV groove of implanted hearts for the duration of the animal’s natural life. Perfusion of hearts with fluorescently labeled lectin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding recipient rat cardiomyocytes. Finally, using optical mapping and electrophysiological analyses, we provide evidence of permanent AV conduction through the implant in one-third of recipient animals. Our experiments provide a proof-of-principle that engineered tissue constructs can function as an electrical conduit and, ultimately, may offer a substitute treatment to conventional pacing therapy. PMID:16816362

  4. Human Corneal Endothelial Cells Expanded In Vitro Are a Powerful Resource for Tissue Engineering

    PubMed Central

    Liu, Yongsong; Sun, Hong; Hu, Min; Zhu, Min; Tighe, Sean; Chen, Shuangling; Zhang, Yuan; Su, Chenwei; Cai, Subo; Guo, Ping

    2017-01-01

    Human corneal endothelial cells have two major functions: barrier function mediated by proteins such as ZO-1 and pump function mediated by Na-K-ATPase which help to maintain visual function. However, human corneal endothelial cells are notorious for their limited proliferative capability in vivo and are therefore prone to corneal endothelial dysfunction that eventually may lead to blindness. At present, the only method to cure corneal endothelial dysfunction is by transplantation of a cadaver donor cornea with normal corneal endothelial cells. Due to the global shortage of donor corneas, it is vital to engineer corneal tissue in vitro that could potentially be transplanted clinically. In this review, we summarize the advances in understanding the behavior of human corneal endothelial cells, their current engineering strategy in vitro and their potential applications. PMID:28260988

  5. Biomechanics and mechanobiology in functional tissue engineering.

    PubMed

    Guilak, Farshid; Butler, David L; Goldstein, Steven A; Baaijens, Frank P T

    2014-06-27

    The field of tissue engineering continues to expand and mature, and several products are now in clinical use, with numerous other preclinical and clinical studies underway. However, specific challenges still remain in the repair or regeneration of tissues that serve a predominantly biomechanical function. Furthermore, it is now clear that mechanobiological interactions between cells and scaffolds can critically influence cell behavior, even in tissues and organs that do not serve an overt biomechanical role. Over the past decade, the field of "functional tissue engineering" has grown as a subfield of tissue engineering to address the challenges and questions on the role of biomechanics and mechanobiology in tissue engineering. Originally posed as a set of principles and guidelines for engineering of load-bearing tissues, functional tissue engineering has grown to encompass several related areas that have proven to have important implications for tissue repair and regeneration. These topics include measurement and modeling of the in vivo biomechanical environment; quantitative analysis of the mechanical properties of native tissues, scaffolds, and repair tissues; development of rationale criteria for the design and assessment of engineered tissues; investigation of the effects biomechanical factors on native and repair tissues, in vivo and in vitro; and development and application of computational models of tissue growth and remodeling. Here we further expand this paradigm and provide examples of the numerous advances in the field over the past decade. Consideration of these principles in the design process will hopefully improve the safety, efficacy, and overall success of engineered tissue replacements.

  6. Nanotechnological strategies for engineering complex tissues

    NASA Astrophysics Data System (ADS)

    Dvir, Tal; Timko, Brian P.; Kohane, Daniel S.; Langer, Robert

    2011-01-01

    Tissue engineering aims at developing functional substitutes for damaged tissues and organs. Before transplantation, cells are generally seeded on biomaterial scaffolds that recapitulate the extracellular matrix and provide cells with information that is important for tissue development. Here we review the nanocomposite nature of the extracellular matrix, describe the design considerations for different tissues and discuss the impact of nanostructures on the properties of scaffolds and their uses in monitoring the behaviour of engineered tissues. We also examine the different nanodevices used to trigger certain processes for tissue development, and offer our view on the principal challenges and prospects of applying nanotechnology in tissue engineering.

  7. Nanotechnological strategies for engineering complex tissues

    PubMed Central

    Dvir, Tal; Timko, Brian P.; Kohane, Daniel S.; Langer, Robert

    2014-01-01

    Tissue engineering aims at developing functional substitutes for damaged tissues and organs. Before transplantation, cells are generally seeded on biomaterial scaffolds that recapitulate the extracellular matrix and provide cells with information that is important for tissue development. Here we review the nanocomposite nature of the extracellular matrix, describe the design considerations for different tissues and discuss the impact of nanostructures on the properties of scaffolds and their uses in monitoring the behaviour of engineered tissues. We also examine the different nanodevices used to trigger certain processes for tissue development, and offer our view on the principal challenges and prospects of applying nanotechnology in tissue engineering. PMID:21151110

  8. Biomechanics and mechanobiology in functional tissue engineering

    PubMed Central

    Guilak, Farshid; Butler, David L.; Goldstein, Steven A.; Baaijens, Frank P.T.

    2014-01-01

    The field of tissue engineering continues to expand and mature, and several products are now in clinical use, with numerous other preclinical and clinical studies underway. However, specific challenges still remain in the repair or regeneration of tissues that serve a predominantly biomechanical function. Furthermore, it is now clear that mechanobiological interactions between cells and scaffolds can critically influence cell behavior, even in tissues and organs that do not serve an overt biomechanical role. Over the past decade, the field of “functional tissue engineering” has grown as a subfield of tissue engineering to address the challenges and questions on the role of biomechanics and mechanobiology in tissue engineering. Originally posed as a set of principles and guidelines for engineering of load-bearing tissues, functional tissue engineering has grown to encompass several related areas that have proven to have important implications for tissue repair and regeneration. These topics include measurement and modeling of the in vivo biomechanical environment; quantitative analysis of the mechanical properties of native tissues, scaffolds, and repair tissues; development of rationale criteria for the design and assessment of engineered tissues; investigation of the effects biomechanical factors on native and repair tissues, in vivo and in vitro; and development and application of computational models of tissue growth and remodeling. Here we further expand this paradigm and provide examples of the numerous advances in the field over the past decade. Consideration of these principles in the design process will hopefully improve the safety, efficacy, and overall success of engineered tissue replacements. PMID:24818797

  9. Interface tissue engineering: next phase in musculoskeletal tissue repair.

    PubMed

    Sahoo, Sambit; Teh, Thomas Kh; He, Pengfei; Toh, Siew Lok; Goh, James Ch

    2011-05-01

    Increasing incidence of musculoskeletal injuries coupled with limitations in the current treatment options have necessitated tissue engineering and regenerative medicine- based approaches. Moving forward from engineering isolated musculoskeletal tissues, research strategies are now being increasingly focused on repairing and regenerating the interfaces between dissimilar musculoskeletal tissues with the aim to achieve seamless integration of engineered musculoskeletal tissues. This article reviews the state-of-the-art in the tissue engineering of musculoskeletal tissue interfaces with a focus on Singapore's contribution in this emerging field. Various biomimetic scaffold and cellbased strategies, the use of growth factors, gene therapy and mechanical loading, as well as animal models for functional validation of the tissue engineering strategies are discussed.

  10. Topographical Control of Ocular Cell Types for Tissue Engineering

    PubMed Central

    McHugh, Kevin J.; Saint-Geniez, Magali; Tao, Sarah L.

    2014-01-01

    Visual impairment affects over 285 million people worldwide and has a major impact on an individual’s quality of life. Tissue engineering has the potential to increase quality of life for many of these patients by preventing vision loss or restoring vision using cell-based therapies. However, these strategies will require an understanding of the microenvironmental factors that influence cell behavior. The eye is a well-organized organ whose structural complexity is essential for proper function. Interactions between ocular cells and their highly ordered extracellular matrix are necessary for maintaining key tissue properties including corneal transparency and retinal lamination. Therefore, it is not surprising that culturing these cells in vitro on traditional flat substrates result in irregular morphology. Instead, topographically patterned biomaterials better mimic native extracellular matrix and have been shown to elicit in vivo-like morphology and gene expression which is essential for tissue engineering. Herein we review multiple methods for producing well-controlled topography and discuss optimal biomaterial scaffold design for cells of the cornea, retina, and lens. PMID:23744715

  11. [An experience of dried cornea transplantation].

    PubMed

    Gundorova, R A; Chentsova, E V; Makarov, P V; Kugusheva, A É; Rakova, A V

    2011-01-01

    Sometimes an urgent lamellar keratoplasty remains the only treatment option for corneal defect closure. When fresh donor tissue is absent as it is regular in recent years dried cornea transplantation becomes reasonable. In recent years in ocular trauma department 320 transplantations of dried on silicagel cornea were performed. Analysis of results allows to conclude that use of dried cornea is a promising surgical procedure to preserve the globe and in some cases to prepare the eye with severe trauma for subsequent optic surgery.

  12. Multiscale tissue engineering for liver reconstruction.

    PubMed

    Sudo, Ryo

    2014-01-01

    The liver is a target of in vitro tissue engineering despite its capability to regenerate in vivo. The construction of liver tissues in vitro remains challenging. In this review, conventional 3D cultures of hepatocytes are first discussed. Recent advances in the 3D culturing of liver cells are then summarized in the context of in vitro liver tissue reconstruction at the micro- and macroscales. The application of microfluidics technology to liver tissue engineering has been introduced as a bottom-up approach performed at the microscale, whereas whole-organ bioengineering technology was introduced as a top-down approach performed at the macroscale. Mesoscale approaches are also discussed in considering the integration of micro- and macroscale approaches. Multiple parallel multiscale liver tissue engineering studies are ongoing; however, no tissue-engineered liver that is appropriate for clinical use has yet been realized. The integration of multiscale tissue engineering studies is essential for further understanding of liver reconstruction strategies.

  13. Imaging strategies for tissue engineering applications.

    PubMed

    Nam, Seung Yun; Ricles, Laura M; Suggs, Laura J; Emelianov, Stanislav Y

    2015-02-01

    Tissue engineering has evolved with multifaceted research being conducted using advanced technologies, and it is progressing toward clinical applications. As tissue engineering technology significantly advances, it proceeds toward increasing sophistication, including nanoscale strategies for material construction and synergetic methods for combining with cells, growth factors, or other macromolecules. Therefore, to assess advanced tissue-engineered constructs, tissue engineers need versatile imaging methods capable of monitoring not only morphological but also functional and molecular information. However, there is no single imaging modality that is suitable for all tissue-engineered constructs. Each imaging method has its own range of applications and provides information based on the specific properties of the imaging technique. Therefore, according to the requirements of the tissue engineering studies, the most appropriate tool should be selected among a variety of imaging modalities. The goal of this review article is to describe available biomedical imaging methods to assess tissue engineering applications and to provide tissue engineers with criteria and insights for determining the best imaging strategies. Commonly used biomedical imaging modalities, including X-ray and computed tomography, positron emission tomography and single photon emission computed tomography, magnetic resonance imaging, ultrasound imaging, optical imaging, and emerging techniques and multimodal imaging, will be discussed, focusing on the latest trends of their applications in recent tissue engineering studies.

  14. Imaging Strategies for Tissue Engineering Applications

    PubMed Central

    Nam, Seung Yun; Ricles, Laura M.; Suggs, Laura J.

    2015-01-01

    Tissue engineering has evolved with multifaceted research being conducted using advanced technologies, and it is progressing toward clinical applications. As tissue engineering technology significantly advances, it proceeds toward increasing sophistication, including nanoscale strategies for material construction and synergetic methods for combining with cells, growth factors, or other macromolecules. Therefore, to assess advanced tissue-engineered constructs, tissue engineers need versatile imaging methods capable of monitoring not only morphological but also functional and molecular information. However, there is no single imaging modality that is suitable for all tissue-engineered constructs. Each imaging method has its own range of applications and provides information based on the specific properties of the imaging technique. Therefore, according to the requirements of the tissue engineering studies, the most appropriate tool should be selected among a variety of imaging modalities. The goal of this review article is to describe available biomedical imaging methods to assess tissue engineering applications and to provide tissue engineers with criteria and insights for determining the best imaging strategies. Commonly used biomedical imaging modalities, including X-ray and computed tomography, positron emission tomography and single photon emission computed tomography, magnetic resonance imaging, ultrasound imaging, optical imaging, and emerging techniques and multimodal imaging, will be discussed, focusing on the latest trends of their applications in recent tissue engineering studies. PMID:25012069

  15. Soft tissue engineering in craniomaxillofacial surgery

    PubMed Central

    Kim, Roderick Y; Fasi, Anthony C; Feinberg, Stephen E

    2014-01-01

    Craniofacial soft tissue reconstruction may be required following trauma, tumor resection, and to repair congenital deformities. Recent advances in the field of tissue engineering have significantly widened the reconstructive armamentarium of the surgeon. The successful identification and combination of tissue engineering, scaffold, progenitor cells, and physiologic signaling molecules has enabled the surgeon to design, recreate the missing tissue in its near natural form. This has resolved the issues like graft rejection, wound dehiscence, or poor vascularity. Successfully reconstructed tissue through soft tissue engineering protocols would help surgeon to restore the form and function of the lost tissue in its originality. This manuscript intends to provide a glimpse of the basic principle of tissue engineering, contemporary, and future direction of this field as applied to craniofacial surgery. PMID:24987591

  16. Heterogeneity of collagens in rabbit cornea: type III collagen

    SciTech Connect

    Cintron, C.; Hong, B.S.; Covington, H.I.; Macarak, E.J.

    1988-05-01

    Whole neonate rabbit corneas and adult corneas containing 2-week-old scars were incubated in the presence of (/sup 14/C) glycine. Radiolabeled collagen extracted from the corneas and scar tissue were analyzed by sodium dodecylsulfate/polyacrylamide gel electrophoresis and fluorography to determine the types and relative quantity of collagen polypeptides present and synthesized by these tissues. In addition to other collagen types, type III was found in both neonate cornea and scar tissue from adult cornea, albeit in relatively small quantities. Type III collagen in normal cornea was associated with the residue after pepsin digestion and formic acid extraction of the tissue, and the same type of collagen was extracted from scar tissue after similar treatment. Type III collagen-specific monoclonal antibody bound to developing normal corneas and healing adult tissue sections, as determined by immunofluorescence. Antibody binding was localized to the endothelium and growing Descemet's membrane in fetal and neonate corneas, and restricted to the most posterior region of the corneal scar tissue. Although monoclonal antibody to keratan sulfate, used as a marker for stromal fibroblasts, bound to most of the scar tissue, the antibody failed to bind to the posterior scar tissue positive for type III collagen. We conclude that endothelial cells from fetal and neonate rabbit cornea and endothelium-derived fibroblasts from healing wounds of adult cornea synthesize and deposit type III collagen. Moreover, this collagen appears to be incorporated into the growing Descemet's membrane of normal corneas and narrow posterior portion of the scar tissue.

  17. Nanomaterials for Cardiac Myocyte Tissue Engineering

    PubMed Central

    Amezcua, Rodolfo; Shirolkar, Ajay; Fraze, Carolyn; Stout, David A.

    2016-01-01

    Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials. PMID:28335261

  18. Stem Cells in the Cornea

    PubMed Central

    Hertsenberg, Andrew J.; Funderburgh, James L.

    2017-01-01

    The cornea is the tough, transparent tissue through which light first enters the eye and functions as a barrier to debris and infection as well as two-thirds of the refractive power of the eye. Corneal damage that is not promptly treated will often lead to scarring and vision impairment. Due to the limited options currently available to treat corneal scars, the identification and isolation of stem cells in the cornea has received much attention, as they may have potential for autologous, cell-based approaches to the treatment of damaged corneal tissue. PMID:26310147

  19. Disparate companions: tissue engineering meets cancer research.

    PubMed

    Tilkorn, Daniel J; Lokmic, Zerina; Chaffer, Christine L; Mitchell, Geraldine M; Morrison, Wayne A; Thompson, Erik W

    2010-01-01

    Recreating an environment that supports and promotes fundamental homeostatic mechanisms is a significant challenge in tissue engineering. Optimizing cell survival, proliferation, differentiation, apoptosis and angiogenesis, and providing suitable stromal support and signalling cues are keys to successfully generating clinically useful tissues. Interestingly, those components are often subverted in the cancer setting, where aberrant angiogenesis, cellular proliferation, cell signalling and resistance to apoptosis drive malignant growth. In contrast to tissue engineering, identifying and inhibiting those pathways is a major challenge in cancer research. The recent discovery of adult tissue-specific stem cells has had a major impact on both tissue engineering and cancer research. The unique properties of these cells and their role in tissue and organ repair and regeneration hold great potential for engineering tissue-specific constructs. The emerging body of evidence implicating stem cells and progenitor cells as the source of oncogenic transformation prompts caution when using these cells for tissue-engineering purposes. While tissue engineering and cancer research may be considered as opposed fields of research with regard to their proclaimed goals, the compelling overlap in fundamental pathways underlying these processes suggests that cross-disciplinary research will benefit both fields. In this review article, tissue engineering and cancer research are brought together and explored with regard to discoveries that may be of mutual benefit.

  20. [Chondrocyte mecanobiology. Application in cartilage tissue engineering].

    PubMed

    Stoltz, Jean François; Netter, Patrick; Huselstein, Céline; de Isla, Natalia; Wei Yang, Jing; Muller, Sylvaine

    2005-11-01

    Cartilage is a hydrated connective tissue that withstands and distributes mechanical forces within joints. Chondrocytes utilize mechanical signals to maintain cartilaginous tissue homeostasis. They regulate their metabolic activity through complex biological and biophysical interactions with the extracellular matrix (ECM). Some mechanotransduction mechanisms are known, while many others no doubt remain to be discovered. Various aspects of chondrocyte mechanobiology have been applied to tissue engineering, with the creation of replacement tissue in vitro from bioresorbable or non-bioresorbable scaffolds and harvested cells. The tissues are maintained in a near-physiologic mechanical and biochemical environment. This paper is an overview of both chondrocyte mechanobiology and cartilage tissue engineering

  1. Keratoconus: Tissue Engineering and Biomaterials

    PubMed Central

    Karamichos, Dimitrios; Hjortdal, Jesper

    2014-01-01

    Keratoconus (KC) is a bilateral, asymmetric, corneal disorder that is characterized by progressive thinning, steepening, and potential scarring. The prevalence of KC is stated to be 1 in 2000 persons worldwide; however, numbers vary depending on size of the study and regions. KC appears more often in South Asian, Eastern Mediterranean, and North African populations. The cause remains unknown, although a variety of factors have been considered. Genetics, cellular, and mechanical changes have all been reported; however, most of these studies have proven inconclusive. Clearly, the major problem here, like with any other ocular disease, is quality of life and the threat of vision loss. While most KC cases progress until the third or fourth decade, it varies between individuals. Patients may experience periods of several months with significant changes followed by months or years of no change, followed by another period of rapid changes. Despite the major advancements, it is still uncertain how to treat KC at early stages and prevent vision impairment. There are currently limited tissue engineering techniques and/or “smart” biomaterials that can help arrest the progression of KC. This review will focus on current treatments and how biomaterials may hold promise for the future. PMID:25215423

  2. [Bone grafts using tissue engineering].

    PubMed

    Delloye, C

    2001-01-01

    An overview of bone grafts and, in particular, the allografts is presented. The availability of bone allografts, has promoted their use at the expense of the autograft. However, the loss of the cellular activity in an allograft, makes them less performant than an autograft. The use of an allograft in a small size defect can be advocated provided that the implantation technique is stringent. In case of a large segmental bone defect, an allograft can be considered whereas an autograft is not anymore possible. A massive bone allograft allows an anatomical reconstruction and the preservation of strong tendon insertions. In tumor surgery, a bone allograft has become one of the best options to reshape the skeleton. To offset the poor remodeling of the massive bone allografts, and to improve the take of small size bone allografts, researches are presently carried on, using tissue engineering in order to recover a cellular population. The aim is to combine an acellular bone graft with the cells of the recipient. Cells are procured from the bone marrow. Stromal cells are isolated, cultured, so that they will grow with an osteoblastic phenotype. They can be used alone or in association with a bone graft. It is believed that tomorrow such cellular therapy will become a routine procedure.

  3. 3D Printing for Tissue Engineering.

    PubMed

    Richards, Dylan Jack; Tan, Yu; Jia, Jia; Yao, Hai; Mei, Ying

    2013-10-01

    Tissue engineering aims to fabricate functional tissue for applications in regenerative medicine and drug testing. More recently, 3D printing has shown great promise in tissue fabrication with a structural control from micro- to macro-scale by using a layer-by-layer approach. Whether through scaffold-based or scaffold-free approaches, the standard for 3D printed tissue engineering constructs is to provide a biomimetic structural environment that facilitates tissue formation and promotes host tissue integration (e.g., cellular infiltration, vascularization, and active remodeling). This review will cover several approaches that have advanced the field of 3D printing through novel fabrication methods of tissue engineering constructs. It will also discuss the applications of synthetic and natural materials for 3D printing facilitated tissue fabrication.

  4. 3D Printing for Tissue Engineering

    PubMed Central

    Jia, Jia; Yao, Hai; Mei, Ying

    2016-01-01

    Tissue engineering aims to fabricate functional tissue for applications in regenerative medicine and drug testing. More recently, 3D printing has shown great promise in tissue fabrication with a structural control from micro- to macro-scale by using a layer-by-layer approach. Whether through scaffold-based or scaffold-free approaches, the standard for 3D printed tissue engineering constructs is to provide a biomimetic structural environment that facilitates tissue formation and promotes host tissue integration (e.g., cellular infiltration, vascularization, and active remodeling). This review will cover several approaches that have advanced the field of 3D printing through novel fabrication methods of tissue engineering constructs. It will also discuss the applications of synthetic and natural materials for 3D printing facilitated tissue fabrication. PMID:26869728

  5. Biomimetic strategies for engineering composite tissues.

    PubMed

    Lee, Nancy; Robinson, Jennifer; Lu, Helen

    2016-08-01

    The formation of multiple tissue types and their integration into composite tissue units presents a frontier challenge in regenerative engineering. Tissue-tissue synchrony is crucial in providing structural support for internal organs and enabling daily activities. This review highlights the state-of-the-art in composite tissue scaffold design, and explores how biomimicry can be strategically applied to avoid over-engineering the scaffold. Given the complexity of biological tissues, determining the most relevant parameters for recapitulating native structure-function relationships through strategic biomimicry will reduce the burden for clinical translation. It is anticipated that these exciting efforts in composite tissue engineering will enable integrative and functional repair of common soft tissue injuries and lay the foundation for total joint or limb regeneration.

  6. Engineered neural tissue for peripheral nerve repair.

    PubMed

    Georgiou, Melanie; Bunting, Stephen C J; Davies, Heather A; Loughlin, Alison J; Golding, Jonathan P; Phillips, James B

    2013-10-01

    A new combination of tissue engineering techniques provides a simple and effective method for building aligned cellular biomaterials. Self-alignment of Schwann cells within a tethered type-1 collagen matrix, followed by removal of interstitial fluid produces a stable tissue-like biomaterial that recreates the aligned cellular and extracellular matrix architecture associated with nerve grafts. Sheets of this engineered neural tissue supported and directed neuronal growth in a co-culture model, and initial in vivo tests showed that a device containing rods of rolled-up sheets could support neuronal growth during rat sciatic nerve repair (5 mm gap). Further testing of this device for repair of a critical-sized 15 mm gap showed that, at 8 weeks, engineered neural tissue had supported robust neuronal regeneration across the gap. This is, therefore, a useful new approach for generating anisotropic engineered tissues, and it can be used with Schwann cells to fabricate artificial neural tissue for peripheral nerve repair.

  7. Biodegradable polymeric fiber structures in tissue engineering.

    PubMed

    Tuzlakoglu, Kadriye; Reis, Rui L

    2009-03-01

    Tissue engineering offers a promising new approach to create biological alternatives to repair or restore function of damaged or diseased tissues. To obtain three-dimensional tissue constructs, stem or progenitor cells must be combined with a highly porous three-dimensional scaffold, but many of the structures purposed for tissue engineering cannot meet all the criteria required by an adequate scaffold because of lack of mechanical strength and interconnectivity, as well as poor surface characteristics. Fiber-based structures represent a wide range of morphological and geometric possibilities that can be tailored for each specific tissue-engineering application. The present article overviews the research data on tissue-engineering therapies based on the use of biodegradable fiber architectures as a scaffold.

  8. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2012-10-01

    success of bridging a lateral hemisection in the rat spinal cord with engineered (“stretch-grown”) living nervous tissue constructs 2 . For the current...AD_________________ Award Number: W81XWH-10-1-0941 TITLE: Spinal Cord Repair with Engineered...SUBTITLE Spinal Cord Repair with Engineered Nervous Tissue 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-10-1-0941 5c. PROGRAM ELEMENT NUMBER 6

  9. Collagen in Human Tissues: Structure, Function, and Biomedical Implications from a Tissue Engineering Perspective

    NASA Astrophysics Data System (ADS)

    Balasubramanian, Preethi; Prabhakaran, Molamma P.; Sireesha, Merum; Ramakrishna, Seeram

    The extracellular matrix is a complex biological structure encoded with various proteins, among which the collagen family is the most significant and abundant of all, contributing 30-35% of the whole-body protein. "Collagen" is a generic term for proteins that forms a triple-helical structure with three polypeptide chains, and around 29 types of collagen have been identified up to now. Although most of the members of the collagen family form such supramolecular structures, extensive diversity exists between each type of collagen. The diversity is not only based on the molecular assembly and supramolecular structures of collagen types but is also observed within its tissue distribution, function, and pathology. Collagens possess complex hierarchical structures and are present in various forms such as collagen fibrils (1.5-3.5 nm wide), collagen fibers (50-70 nm wide), and collagen bundles (150-250 nm wide), with distinct properties characteristic of each tissue providing elasticity to skin, softness of the cartilage, stiffness of the bone and tendon, transparency of the cornea, opaqueness of the sclera, etc. There exists an exclusive relation between the structural features of collagen in human tissues (such as the collagen composition, collagen fibril length and diameter, collagen distribution, and collagen fiber orientation) and its tissue-specific mechanical properties. In bone, a transverse collagen fiber orientation prevails in regions of higher compressive stress whereas longitudinally oriented collagen fibers correlate to higher tensile stress. The immense versatility of collagen compels a thorough understanding of the collagen types and this review discusses the major types of collagen found in different human tissues, highlighting their tissue-specific uniqueness based on their structure and mechanical function. The changes in collagen during a specific tissue damage or injury are discussed further, focusing on the many tissue engineering applications for

  10. Strategies for organ level tissue engineering

    PubMed Central

    Rustad, Kristine C; Sorkin, Michael; Levi, Benjamin; Longaker, Michael T

    2010-01-01

    The field of tissue engineering has made considerable strides since it was first described in the late 1980s. The advent and subsequent boom in stem cell biology, emergence of novel technologies for biomaterial development and further understanding of developmental biology have contributed to this accelerated progress. However, continued efforts to translate tissue-engineering strategies into clinical therapies have been hampered by the problems associated with scaling up laboratory methods to produce large, complex tissues. The significant challenges faced by tissue engineers include the production of an intact vasculature within a tissue-engineered construct and recapitulation of the size and complexity of a whole organ. Here we review the basic components necessary for bioengineering organs—biomaterials, cells and bioactive molecules—and discuss various approaches for augmenting these principles to achieve organ level tissue engineering. Ultimately, the successful translation of tissue-engineered constructs into everyday clinical practice will depend upon the ability of the tissue engineer to “scale up” every aspect of the research and development process. PMID:21197216

  11. Nanofibers and their applications in tissue engineering

    PubMed Central

    Vasita, Rajesh; Katti, Dhirendra S

    2006-01-01

    Developing scaffolds that mimic the architecture of tissue at the nanoscale is one of the major challenges in the field of tissue engineering. The development of nanofibers has greatly enhanced the scope for fabricating scaffolds that can potentially meet this challenge. Currently, there are three techniques available for the synthesis of nanofibers: electrospinning, self-assembly, and phase separation. Of these techniques, electrospinning is the most widely studied technique and has also demonstrated the most promising results in terms of tissue engineering applications. The availability of a wide range of natural and synthetic biomaterials has broadened the scope for development of nanofibrous scaffolds, especially using the electrospinning technique. The three dimensional synthetic biodegradable scaffolds designed using nanofibers serve as an excellent framework for cell adhesion, proliferation, and differentiation. Therefore, nanofibers, irrespective of their method of synthesis, have been used as scaffolds for musculoskeletal tissue engineering (including bone, cartilage, ligament, and skeletal muscle), skin tissue engineering, vascular tissue engineering, neural tissue engineering, and as carriers for the controlled delivery of drugs, proteins, and DNA. This review summarizes the currently available techniques for nanofiber synthesis and discusses the use of nanofibers in tissue engineering and drug delivery applications. PMID:17722259

  12. Amelogenin in Enamel Tissue Engineering

    PubMed Central

    2016-01-01

    In this chapter the basic premises, the recent findings and the future challenges in the use of amelogenin for enamel tissue engineering are being discoursed on. Results emerging from the experiments performed to assess the fundamental physicochemical mechanisms of the interaction of amelogenin, the main protein of the enamel matrix, and the growing crystals of apatite, are mentioned, alongside a moderately comprehensive literature review of the subject at hand. The clinical importance of understanding this protein/mineral interaction at the nanoscale are highlighted as well as the potential for tooth enamel to act as an excellent model system for studying some of the essential aspects of biomineralization processes in general. The dominant paradigm stating that amelogenin directs the uniaxial growth of apatite crystals in enamel by slowing down the growth of (hk0) faces on which it adheres is being questioned based on the results demonstrating the ability of amelogenin to promote the nucleation and crystal growth of apatite under constant titration conditions designed to mimic those present in the developing enamel matrix. The role of numerous minor components of the enamel matrix is being highlighted as essential and impossible to compensate for by utilizing its more abundant ingredients only. It is concluded that the three major aspects of amelogenesis outlined hereby – (1) the assembly of amelogenin and other enamel matrix proteins, (2) the proteolytic activity, and (3) crystallization – need to be in precise synergy with each other in order for the grounds for the proper imitation of amelogenesis in the lab to be created. PMID:26545753

  13. Engineered Muscle Actuators: Cells and Tissues

    DTIC Science & Technology

    2007-01-10

    platform. Outcomes by milestone: (1) Develop integrated tissue culture bioreactor systems: completed all but bulk perfusion (2) Develop appropriate...tissue culture perfusion bioreactors (B) Second generation cm-scale hybrid swimming robotic platform & control methodologies (C) Guidance of engineered...integrated tissue culture perfusion bioreactors 1. Employ rapid manufacturing techniques for bioreactors 1. accelerate system development 2. increase number

  14. Optical Coherence Tomography in Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Zhao, Youbo; Yang, Ying; Wang, Ruikang K.; Boppart, Stephen A.

    Tissue engineering holds the promise for a therapeutic solution in regenerative medicine. The primary goal of tissue engineering is the development of physiologically functional and biocompatible tissues/organs being implanted for the repair and replacement of damaged or diseased ones. Given the complexity in the developing processes of engineered tissues, which involves multi-dimensional interactions among cells of different types, three-dimensionally constructed scaffolds, and actively intervening bioreactors, a capable real-time imaging tool is critically required for expanding our knowledge about the developing process of desired tissues or organs. It has been recognized that optical coherence tomography (OCT), an emerging noninvasive imaging technique that provides high spatial resolution (up to the cellular level) and three-dimensional imaging capability, is a promising investigative tool for tissue engineering. This chapter discusses the existing and potential applications of OCT in tissue engineering. Example OCT investigations of the three major components of tissue engineering, i.e., cells, scaffolds, and bioreactors are overviewed. Imaging examples of OCT and its enabling functions and variants, e.g., Doppler OCT, polarization-sensitive OCT, optical coherence microscopy are emphasized. Remaining challenges in the application of OCT to tissue engineering are discussed, and the prospective solutions including the combination of OCT with other high-contrast and high-resolution modalities such as two-photon fluorescence microscopy are suggested as well. It is expected that OCT, along with its functional variants, will make important contributions toward revealing the complex cellular dynamics in engineered tissues as well as help us culture demanding tissue/organ implants that will advance regenerative medicine.

  15. Cardiac tissue engineering: state of the art.

    PubMed

    Hirt, Marc N; Hansen, Arne; Eschenhagen, Thomas

    2014-01-17

    The engineering of 3-dimensional (3D) heart muscles has undergone exciting progress for the past decade. Profound advances in human stem cell biology and technology, tissue engineering and material sciences, as well as prevascularization and in vitro assay technologies make the first clinical application of engineered cardiac tissues a realistic option and predict that cardiac tissue engineering techniques will find widespread use in the preclinical research and drug development in the near future. Tasks that need to be solved for this purpose include standardization of human myocyte production protocols, establishment of simple methods for the in vitro vascularization of 3D constructs and better maturation of myocytes, and, finally, thorough definition of the predictive value of these methods for preclinical safety pharmacology. The present article gives an overview of the present state of the art, bottlenecks, and perspectives of cardiac tissue engineering for cardiac repair and in vitro testing.

  16. Aloe Vera for Tissue Engineering Applications

    PubMed Central

    Rahman, Shekh; Carter, Princeton; Bhattarai, Narayan

    2017-01-01

    Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers. PMID:28216559

  17. Advancing tissue engineering by using electrospun nanofibers.

    PubMed

    Ashammakhi, Nureddin; Ndreu, A; Nikkola, L; Wimpenny, I; Yang, Y

    2008-07-01

    Electrospinning is a versatile technique that enables the development of nanofiber-based scaffolds, from a variety of polymers that may have drug-release properties. Using nanofibers, it is now possible to produce biomimetic scaffolds that can mimic the extracellular matrix for tissue engineering. Interestingly, nanofibers can guide cell growth along their direction. Combining factors like fiber diameter, alignment and chemicals offers new ways to control tissue engineering. In vivo evaluation of nanomats included their degradation, tissue reactions and engineering of specific tissues. New advances made in electrospinning, especially in drug delivery, support the massive potential of these nanobiomaterials. Nevertheless, there is already at least one product based on electrospun nanofibers with drug-release properties in a Phase III clinical trial, for wound dressing. Hopefully, clinical applications in tissue engineering will follow to enhance the success of regenerative therapies.

  18. Aloe Vera for Tissue Engineering Applications.

    PubMed

    Rahman, Shekh; Carter, Princeton; Bhattarai, Narayan

    2017-02-14

    Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers.

  19. Engineering more than a cell: Vascularization Strategies in Tissue Engineering

    PubMed Central

    Phelps, Edward A.; García, Andrés J.

    2010-01-01

    Summary Host integration and performance of engineered tissues have been severely limited by the lack of robust strategies to generate patent vascularization and tissue perfusion. This review highlights a selection of exciting developments in vascularization approaches for tissue engineering research. Current strategies for vascularization in tissue engineering are related to growth factor signaling and delivery, cell transplantation, bioactive smart matrix materials, and directed fabrication. Application of these techniques to in vivo models has resulted in a number of robust host vascular responses, especially with synergistic and engineered bioactive systems. The future outlook of the field includes refinement and development of new technologies for vascularization and combining these techniques with functional repair models for metabolically active tissues and relevant disease states. PMID:20638268

  20. Normal human epithelial cells regulate the size and morphology of tissue-engineered capillaries.

    PubMed

    Rochon, Marie-Hélène; Fradette, Julie; Fortin, Véronique; Tomasetig, Florence; Roberge, Charles J; Baker, Kathleen; Berthod, François; Auger, François A; Germain, Lucie

    2010-05-01

    The survival of thick tissues/organs produced by tissue engineering requires rapid revascularization after grafting. Although capillary-like structures have been reconstituted in some engineered tissues, little is known about the interaction between normal epithelial cells and endothelial cells involved in the in vitro angiogenic process. In the present study, we used the self-assembly approach of tissue engineering to examine this relationship. An endothelialized tissue-engineered dermal substitute was produced by adding endothelial cells to the tissue-engineered dermal substitute produced by the self-assembly approach. The latter consists in culturing fibroblasts in the medium supplemented with serum and ascorbic acid. A network of tissue-engineered capillaries (TECs) formed within the human extracellular matrix produced by dermal fibroblasts. To determine whether epithelial cells modify TECs, the size and form of TECs were studied in the endothelialized tissue-engineered dermal substitute cultured in the presence or absence of epithelial cells. In the presence of normal keratinocytes from skin, cornea or uterine cervix, endothelial cells formed small TECs (cross-sectional area estimated at less than 50 microm(2)) reminiscent of capillaries found in the skin's microcirculation. In contrast, TECs grown in the absence of epithelial cells presented variable sizes (larger than 50 microm(2)), but the addition of keratinocyte-conditioned media or exogenous vascular endothelial growth factor induced their normalization toward a smaller size. Vascular endothelial growth factor neutralization inhibited the effect of keratinocyte-conditioned media. These results provide new direct evidence that normal human epithelial cells play a role in the regulation of the underlying TEC network, and advance our knowledge in tissue engineering for the production of TEC networks in vitro.

  1. Liposomes in tissue engineering and regenerative medicine

    PubMed Central

    Monteiro, Nelson; Martins, Albino; Reis, Rui L.; Neves, Nuno M.

    2014-01-01

    Liposomes are vesicular structures made of lipids that are formed in aqueous solutions. Structurally, they resemble the lipid membrane of living cells. Therefore, they have been widely investigated, since the 1960s, as models to study the cell membrane, and as carriers for protection and/or delivery of bioactive agents. They have been used in different areas of research including vaccines, imaging, applications in cosmetics and tissue engineering. Tissue engineering is defined as a strategy for promoting the regeneration of tissues for the human body. This strategy may involve the coordinated application of defined cell types with structured biomaterial scaffolds to produce living structures. To create a new tissue, based on this strategy, a controlled stimulation of cultured cells is needed, through a systematic combination of bioactive agents and mechanical signals. In this review, we highlight the potential role of liposomes as a platform for the sustained and local delivery of bioactive agents for tissue engineering and regenerative medicine approaches. PMID:25401172

  2. Bone Tissue Engineering: Recent Advances and Challenges

    PubMed Central

    Amini, Ami R.; Laurencin, Cato T.; Nukavarapu, Syam P.

    2013-01-01

    The worldwide incidence of bone disorders and conditions has trended steeply upward and is expected to double by 2020, especially in populations where aging is coupled with increased obesity and poor physical activity. Engineered bone tissue has been viewed as a potential alternative to the conventional use of bone grafts, due to their limitless supply and no disease transmission. However, bone tissue engineering practices have not proceeded to clinical practice due to several limitations or challenges. Bone tissue engineering aims to induce new functional bone regeneration via the synergistic combination of biomaterials, cells, and factor therapy. In this review, we discuss the fundamentals of bone tissue engineering, highlighting the current state of this field. Further, we review the recent advances of biomaterial and cell-based research, as well as approaches used to enhance bone regeneration. Specifically, we discuss widely investigated biomaterial scaffolds, micro- and nano-structural properties of these scaffolds, and the incorporation of biomimetic properties and/or growth factors. In addition, we examine various cellular approaches, including the use of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), adult stem cells, induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), and their clinical application strengths and limitations. We conclude by overviewing the challenges that face the bone tissue engineering field, such as the lack of sufficient vascularization at the defect site, and the research aimed at functional bone tissue engineering. These challenges will drive future research in the field. PMID:23339648

  3. Engineering cell attachments to scaffolds in cartilage tissue engineering

    NASA Astrophysics Data System (ADS)

    Steward, Andrew J.; Liu, Yongxing; Wagner, Diane R.

    2011-04-01

    One of the challenges of tissue engineering, a promising cell-based treatment for damaged or diseased cartilage, is designing the scaffold that provides structure while the tissue regenerates. In addition to the scaffold material's biocompatibility, mechanical properties, and ease of manufacturing, scaffold interactions with the cells must also be considered. In cartilage tissue engineering, a range of scaffolds with various degrees of cell attachment have been proposed, but the attachment density and type have yet to be optimized. Several techniques have been developed to modulate cell adhesion to the scaffold. These studies suggest that the need for cell attachment in cartilage tissue engineering may vary with cell type, stage of differentiation, culture condition, and scaffold material. Further studies will elucidate the role of cell attachment in cartilage regeneration and enhance efforts to engineer cell-based cartilage therapies.

  4. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2011-10-01

    funded grant, we demonstrated proof-of-concept success of bridging a lateral hemisection of the rat spinal cord with engineered (“stretch-grown...AD_________________ Award Number: W81XWH-10-1-0941 TITLE: Spinal Cord Repair with Engineered...5a. CONTRACT NUMBER Spinal Cord Repair with Engineered Nervous Tissue 5b. GRANT NUMBER W81XWH-10-1-0941 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  5. Hard-Soft Tissue Interface Engineering.

    PubMed

    Armitage, Oliver E; Oyen, Michelle L

    2015-01-01

    The musculoskeletal system is comprised of three distinct tissue categories: structural mineralized tissues, actuating muscular soft tissues, and connective tissues. Where connective tissues - ligament, tendon and cartilage - meet with bones, a graded interface in mechanical properties occurs that allows the transmission of load without creating stress concentrations that would cause tissue damage. This interface typically occurs over less than 1 mm and contains a three order of magnitude difference in elastic stiffness, in addition to changes in cell type and growth factor concentrations among others. Like all engineered tissues, the replication of these interfaces requires the production of scaffolds that will provide chemical and mechanical cues, resulting in biologically accurate cellular differentiation. For interface tissues however, the scaffold must provide spatially graded chemical and mechanical cues over sub millimetre length scales. Naturally, this complicates the manufacture of the scaffolds and every stage of their subsequent cell seeding and growth, as each region has different optimal conditions. Given the higher degree of difficulty associated with replicating interface tissues compared to surrounding homogeneous tissues, it is likely that the development of complex musculoskeletal tissue systems will continue to be limited by the engineering of connective tissues interfaces with bone.

  6. Tissue Engineering: Step Ahead in Maxillofacial Reconstruction

    PubMed Central

    Rai, Raj; Raval, Rushik; Khandeparker, Rakshit Vijay Sinai; Chidrawar, Swati K; Khan, Abdul Ahad; Ganpat, Makne Sachin

    2015-01-01

    Within the precedent decade, a new field of “tissue engineering” or “tissue regeneration” emerge that offers an innovative and exhilarating substitute for maxillofacial reconstruction. It offers a new option to supplement existing treatment regimens for reconstruction/regeneration of the oral and craniofacial complex, which includes the teeth, periodontium, bones, soft tissues (oral mucosa, conjunctiva, skin), salivary glands, and the temporomandibular joint (bone and cartilage), as well as blood vessels, muscles, tendons, and nerves. Tissue engineering is based on harvesting the stem cells which are having potential to form an organ. Harvested cells are then transferred into scaffolds that are manufactured in a laboratory to resemble the structure of the desired tissue to be replaced. This article reviews the principles of tissue engineering and its various applications in oral and maxillofacial surgery. PMID:26435634

  7. Tissue engineering: from research to dental clinics

    PubMed Central

    Rosa, Vinicius; Bona, Alvaro Della; Cavalcanti, Bruno Neves; Nör, Jacques Eduardo

    2013-01-01

    Tissue engineering is an interdisciplinary field that combines the principles of engineering, material and biological sciences toward the development of therapeutic strategies and biological substitutes that restore, maintain, replace or improve biological functions. The association of biomaterials, stem cells, growth and differentiation factors have yielded the development of new treatment opportunities in most of the biomedical areas, including Dentistry. The objective of this paper is to present the principles underlying tissue engineering and the current scenario, the challenges and the perspectives of this area in Dentistry. Significance The growth of tissue engineering as a research field have provided a novel set of therapeutic strategies for biomedical applications. The emerging knowledge arisen from studies in the dental area may translate into new methods for caring or improving the alternatives used to treat patients in the daily clinic. PMID:22240278

  8. Tissue engineered constructs for peripheral nerve surgery

    PubMed Central

    Johnson, P. J.; Wood, M. D.; Moore, A. M.; Mackinnon, S. E.

    2013-01-01

    Summary Background Tissue engineering has been defined as “an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ”. Traumatic peripheral nerve injury resulting in significant tissue loss at the zone of injury necessitates the need for a bridge or scaffold for regenerating axons from the proximal stump to reach the distal stump. Methods A review of the literature was used to provide information on the components necessary for the development of a tissue engineered peripheral nerve substitute. Then, a comprehensive review of the literature is presented composed of the studies devoted to this goal. Results Extensive research has been directed toward the development of a tissue engineered peripheral nerve substitute to act as a bridge for regenerating axons from the proximal nerve stump seeking the distal nerve. Ideally this nerve substitute would consist of a scaffold component that mimics the extracellular matrix of the peripheral nerve and a cellular component that serves to stimulate and support regenerating peripheral nerve axons. Conclusions The field of tissue engineering should consider its challenge to not only meet the autograft “gold standard” but also to understand what drives and inhibits nerve regeneration in order to surpass the results of an autograft. PMID:24385980

  9. Biomimetic electrospun nanofibrous structures for tissue engineering

    PubMed Central

    Wang, Xianfeng; Ding, Bin; Li, Bingyun

    2013-01-01

    Biomimetic nanofibrous scaffolds mimicking important features of the native extracellular matrix provide a promising strategy to restore functions or achieve favorable responses for tissue regeneration. This review provides a brief overview of current state-of-the-art research designing and using biomimetic electrospun nanofibers as scaffolds for tissue engineering. It begins with a brief introduction of electrospinning and nanofibers, with a focus on issues related to the biomimetic design aspects. The review next focuses on several typical biomimetic nanofibrous structures (e.g. aligned, aligned to random, spiral, tubular, and sheath membrane) that have great potential for tissue engineering scaffolds, and describes their fabrication, advantages, and applications in tissue engineering. The review concludes with perspectives on challenges and future directions for design, fabrication, and utilization of scaffolds based on electrospun nanofibers. PMID:25125992

  10. Carbon Nanostructures in Bone Tissue Engineering

    PubMed Central

    Perkins, Brian Lee; Naderi, Naghmeh

    2016-01-01

    Background: Recent advances in developing biocompatible materials for treating bone loss or defects have dramatically changed clinicians’ reconstructive armory. Current clinically available reconstructive options have certain advantages, but also several drawbacks that prevent them from gaining universal acceptance. A wide range of synthetic and natural biomaterials is being used to develop tissue-engineered bone. Many of these materials are currently in the clinical trial stage. Methods: A selective literature review was performed for carbon nanostructure composites in bone tissue engineering. Results: Incorporation of carbon nanostructures significantly improves the mechanical properties of various biomaterials to mimic that of natural bone. Recently, carbon-modified biomaterials for bone tissue engineering have been extensively investigated to potentially revolutionize biomaterials for bone regeneration. Conclusion: This review summarizes the chemical and biophysical properties of carbon nanostructures and discusses their functionality in bone tissue regeneration. PMID:28217212

  11. Silk scaffolds for musculoskeletal tissue engineering

    PubMed Central

    Yao, Danyu

    2015-01-01

    The musculoskeletal system, which includes bone, cartilage, tendon/ligament, and skeletal muscle, is becoming the targets for tissue engineering because of the high need for their repair and regeneration. Numerous factors would affect the use of musculoskeletal tissue engineering for tissue regeneration ranging from cells used for scaffold seeding to the manufacture and structures of materials. The essential function of the scaffolds is to convey growth factors as well as cells to the target site to aid the regeneration of the injury. Among the variety of biomaterials used in scaffold engineering, silk fibroin is recognized as an ideal material for its impressive cytocompatibility, slow biodegradability, and excellent mechanical properties. The current review describes the advances made in the fabrication of silk fibroin scaffolds with different forms such as films, particles, electrospun fibers, hydrogels, three-dimensional porous scaffolds, and their applications in the regeneration of musculoskeletal tissues. PMID:26445979

  12. Silk scaffolds for musculoskeletal tissue engineering.

    PubMed

    Yao, Danyu; Liu, Haifeng; Fan, Yubo

    2016-02-01

    The musculoskeletal system, which includes bone, cartilage, tendon/ligament, and skeletal muscle, is becoming the targets for tissue engineering because of the high need for their repair and regeneration. Numerous factors would affect the use of musculoskeletal tissue engineering for tissue regeneration ranging from cells used for scaffold seeding to the manufacture and structures of materials. The essential function of the scaffolds is to convey growth factors as well as cells to the target site to aid the regeneration of the injury. Among the variety of biomaterials used in scaffold engineering, silk fibroin is recognized as an ideal material for its impressive cytocompatibility, slow biodegradability, and excellent mechanical properties. The current review describes the advances made in the fabrication of silk fibroin scaffolds with different forms such as films, particles, electrospun fibers, hydrogels, three-dimensional porous scaffolds, and their applications in the regeneration of musculoskeletal tissues.

  13. Engineering tissue alternatives to animals: applying tissue engineering to basic research and safety testing.

    PubMed

    Holmes, Anthony; Brown, Robert; Shakesheff, Kevin

    2009-07-01

    The focus for the rapid progress in the field of tissue engineering has been the clinical potential of the technology to repair, replace, maintain or enhance the function of a particular tissue or organ. However, tissue engineering has much wider applicability in basic research and safety testing, which is often not recognized owing to the clinical focus of tissue engineers. Using examples from a recent National Centre for the Replacement, Refinement and Reduction of Animals in Research/Biotechnology and Biological Sciences Research Council symposium, which brought together tissue engineers and scientists from other research communities, this review highlights the potential of tissue engineering to provide scientifically robust alternatives to animals to address basic research questions and improve drug and chemical development in the pharmaceutical and chemical industries.

  14. The Expanding World of Tissue Engineering: The Building Blocks and New Applications of Tissue Engineered Constructs

    PubMed Central

    Zorlutuna, Pinar; Vrana, Nihal Engin; Khademhosseini, Ali

    2013-01-01

    The field of tissue engineering has been growing in the recent years as more products have made it to the market and as new uses for the engineered tissues have emerged, motivating many researchers to engage in this multidisciplinary field of research. Engineered tissues are now not only considered as end products for regenerative medicine, but also have emerged as enabling technologies for other fields of research ranging from drug discovery to biorobotics. This widespread use necessitates a variety of methodologies for production of tissue engineered constructs. In this review, these methods together with their non-clinical applications will be described. First, we will focus on novel materials used in tissue engineering scaffolds; such as recombinant proteins and synthetic, self assembling polypeptides. The recent advances in the modular tissue engineering area will be discussed. Then scaffold-free production methods, based on either cell sheets or cell aggregates will be described. Cell sources used in tissue engineering and new methods that provide improved control over cell behavior such as pathway engineering and biomimetic microenvironments for directing cell differentiation will be discussed. Finally, we will summarize the emerging uses of engineered constructs such as model tissues for drug discovery, cancer research and biorobotics applications. PMID:23268388

  15. Engineering superficial zone features in tissue engineered cartilage.

    PubMed

    Chen, Tony; Hilton, Matthew J; Brown, Edward B; Zuscik, Michael J; Awad, Hani A

    2013-05-01

    A major challenge in cartilage tissue engineering is the need to recreate the native tissue's anisotropic extracellular matrix structure. This anisotropy has important mechanical and biological consequences and could be crucial for integrative repair. Here, we report that hydrodynamic conditions that mimic the motion-induced flow fields in between the articular surfaces in the synovial joint induce the formation of a distinct superficial layer in tissue engineered cartilage hydrogels, with enhanced production of cartilage matrix proteoglycan and Type II collagen. Moreover, the flow stimulation at the surface induces the production of the surface zone protein Proteoglycan 4 (aka PRG4 or lubricin). Analysis of second harmonic generation signature of collagen in this superficial layer reveals a highly aligned fibrillar matrix that resembles the alignment pattern in native tissue's surface zone, suggesting that mimicking synovial fluid flow at the cartilage surface in hydrodynamic bioreactors could be key to creating engineered cartilage with superficial zone features.

  16. Engineering complex orthopaedic tissues via strategic biomimicry.

    PubMed

    Qu, Dovina; Mosher, Christopher Z; Boushell, Margaret K; Lu, Helen H

    2015-03-01

    The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

  17. Imaging challenges in biomaterials and tissue engineering.

    PubMed

    Appel, Alyssa A; Anastasio, Mark A; Larson, Jeffery C; Brey, Eric M

    2013-09-01

    Biomaterials are employed in the fields of tissue engineering and regenerative medicine (TERM) in order to enhance the regeneration or replacement of tissue function and/or structure. The unique environments resulting from the presence of biomaterials, cells, and tissues result in distinct challenges in regards to monitoring and assessing the results of these interventions. Imaging technologies for three-dimensional (3D) analysis have been identified as a strategic priority in TERM research. Traditionally, histological and immunohistochemical techniques have been used to evaluate engineered tissues. However, these methods do not allow for an accurate volume assessment, are invasive, and do not provide information on functional status. Imaging techniques are needed that enable non-destructive, longitudinal, quantitative, and three-dimensional analysis of TERM strategies. This review focuses on evaluating the application of available imaging modalities for assessment of biomaterials and tissue in TERM applications. Included is a discussion of limitations of these techniques and identification of areas for further development.

  18. Silk fibroin scaffolds for urologic tissue engineering

    PubMed Central

    Sack, Bryan S.; Mauney, Joshua R.; Estrada, Carlos R.

    2016-01-01

    Urologic tissue engineering efforts have been largely focused on bladder and urethral defect repair. The current surgical gold standard for treatment of poorly compliant pathological bladders and severe urethral stricture disease is enterocystoplasty and onlay urethroplasty with autologous tissue, respectively. The complications associated with autologous tissue use and harvesting have led to efforts to develop tissue-engineered alternatives. Natural and synthetic materials have been used with varying degrees of success, but none has proved consistently reliable for urologic tissue defect repair in humans. Silk fibroin (SF) scaffolds have been tested in bladder and urethral repair because of their favorable biomechanical properties including structural strength, elasticity, biodegradability and biocompatibility. SF scaffolds have been used in multiple animal models, and have demonstrated robust regeneration of smooth muscle and urothelium. The pre-clinical data involving SF scaffolds in urologic defect repair are encouraging and suggest that they hold potential for future clinical use. PMID:26801192

  19. New Era in Health Care: Tissue Engineering

    PubMed Central

    Parveen, S; Krishnakumar, K; Sahoo, SK

    2006-01-01

    Abstract Tissue engineering is a rapidly expanding field, which applies the principles and methods of physical sciences, life sciences and engineering to understand physiological and pathological systems and to modify and create cells and tissues for therapeutic applications. It has emerged as a rapidly expanding ‘interdisciplinary field’ that is a significant potential alternative wherein tissue and organ failure is addressed by implanting natural, synthetic, or semi synthetic tissue or organ mimics that grow into the required functionality or that are fully functional from the start. This review presents in a comprehensive manner the various considerations for the reconstruction of various tissues and organs as well as the various applications of this young emerging field in different disciplines. PMID:24692857

  20. Informing tendon tissue engineering with embryonic development.

    PubMed

    Glass, Zachary A; Schiele, Nathan R; Kuo, Catherine K

    2014-06-27

    Tendon is a strong connective tissue that transduces muscle-generated forces into skeletal motion. In fulfilling this role, tendons are subjected to repeated mechanical loading and high stress, which may result in injury. Tissue engineering with stem cells offers the potential to replace injured/damaged tissue with healthy, new living tissue. Critical to tendon tissue engineering is the induction and guidance of stem cells towards the tendon phenotype. Typical strategies have relied on adult tissue homeostatic and healing factors to influence stem cell differentiation, but have yet to achieve tissue regeneration. A novel paradigm is to use embryonic developmental factors as cues to promote tendon regeneration. Embryonic tendon progenitor cell differentiation in vivo is regulated by a combination of mechanical and chemical factors. We propose that these cues will guide stem cells to recapitulate critical aspects of tenogenesis and effectively direct the cells to differentiate and regenerate new tendon. Here, we review recent efforts to identify mechanical and chemical factors of embryonic tendon development to guide stem/progenitor cell differentiation toward new tendon formation, and discuss the role this work may have in the future of tendon tissue engineering.

  1. Informing tendon tissue engineering with embryonic development

    PubMed Central

    Glass, Zachary A.; Schiele, Nathan R.; Kuo, Catherine K.

    2014-01-01

    Tendon is a strong connective tissue that transduces muscle-generated forces into skeletal motion. In fulfilling this role, tendons are subjected to repeated mechanical loading and high stress, which may result in injury. Tissue engineering with stem cells offers the potential to replace injured/damaged tissue with healthy, new living tissue. Critical to tendon tissue engineering is the induction and guidance of stem cells towards the tendon phenotype. Typical strategies have relied on adult tissue homeostatic and healing factors to influence stem cell differentiation, but have yet to achieve tissue regeneration. A novel paradigm is to use embryonic developmental factors as cues to promote tendon regeneration. Embryonic tendon progenitor cell differentiation in vivo is regulated by a combination of mechanical and chemical factors. We propose that these cues will guide stem cells to recapitulate critical aspects of tenogenesis and effectively direct the cells to differentiate and regenerate new tendon. Here, we review recent efforts to identify mechanical and chemical factors of embryonic tendon development to guide stem/progenitor cell differentiation toward new tendon formation, and discuss the role this work may have in the future of tendon tissue engineering. PMID:24484642

  2. Phototoxicity and the cornea.

    PubMed Central

    Schein, O. D.

    1992-01-01

    The cornea is sensitive to the effects of ultraviolet (UV) light and can suffer both acute and chronic toxicity. Ultraviolet keratitis is associated with relatively short exposures to light sources such as welding arcs or tanning lamps. The corneal effects are seen within a few hours following exposure and typically will resolve within 72 hours. Chronic exposure to environmental UV light may lead to a variety of ocular surface abnormalities that rarely resolve in the absence of therapy. Ultraviolet light, while potentially destructive, also can be used therapeutically. Recently, the photoablative properties of the excimer laser have been used in corneal refractive surgery. This laser uses UV light to break chemical bonds and remove tissue. Corneal phototoxicity is a reflection of the sensitivity of the ocular surface to photochemical injury. Fortunately, effective protection in the form of UV-blocking lenses is widely available. Images Figure 1 Figure 2 Figure 3 PMID:1629921

  3. Nanomaterials for Tissue Engineering In Dentistry

    PubMed Central

    Chieruzzi, Manila; Pagano, Stefano; Moretti, Silvia; Pinna, Roberto; Milia, Egle; Torre, Luigi; Eramo, Stefano

    2016-01-01

    The tissue engineering (TE) of dental oral tissue is facing significant changes in clinical treatments in dentistry. TE is based on a stem cell, signaling molecule, and scaffold triad that must be known and calibrated with attention to specific sectors in dentistry. This review article shows a summary of micro- and nanomorphological characteristics of dental tissues, of stem cells available in the oral region, of signaling molecules usable in TE, and of scaffolds available to guide partial or total reconstruction of hard, soft, periodontal, and bone tissues. Some scaffoldless techniques used in TE are also presented. Then actual and future roles of nanotechnologies about TE in dentistry are presented. PMID:28335262

  4. The materials used in bone tissue engineering

    SciTech Connect

    Tereshchenko, V. P. Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M.

    2015-11-17

    Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

  5. The materials used in bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Tereshchenko, V. P.; Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M.

    2015-11-01

    Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

  6. [The cornea: stasis and dynamics].

    PubMed

    Nishida, Teruo

    2008-03-01

    The physiological roles of the cornea are to conduct external light into the eye, focus it, together with the lens, onto the retina, and to provide rigidity to the entire eyeball. Good vision thus requires maintenance of the transparency and proper refractive shape of the cornea. Although the cornea appears to be a relatively static structure, dynamic processes operate within and around the cornea at the tissue, cell, and molecular level. In this article, I review the mechanisms responsible for maintenance of corneal homeostasis as well as the development of new modes of treatment for various corneal diseases. I. The static cornea: structure and physiological functions. The cornea is derived from ectoderm, so that it can be considered as transparent skin. It is devoid of blood vessels and manifests the highest sensitivity in the entire body. The surface of the cornea is covered by tear fluid, which serves both as a lubricant and as a conduit for regulatory molecules. The cornea is also supplied with oxygen and various nutrients by the aqueous humor and a loop vascular system in addition to tear fluid. The cornea interacts with its surrounding tissues directly as well as indirectly through tear fluid or aqueous humor, with such interactions playing an important role in the regulation of corneal structure and functions. The resident cells of the cornea-epithelial cells, fibroblasts (keratocytes), and endothelial cells--also engage in mutual interactions through network systems. These interactions as well as those with infiltrated cells and regulation by nerves contribute to the maintenance of the normal structure and functions of the cornea as well as to the repair of corneal injuries. II. The dynamic cornea: maintenance of structure and functions by network systems. Developments in laser and computer technology have allowed observation of the cells and collagen fibers within the cornea. Furthermore, progress in cell and molecular biology has allowed characterization

  7. Bioreactor-Based Tumor Tissue Engineering

    PubMed Central

    Guller, A.E.; Grebenyuk, P.N.; Shekhter, A.B.; Zvyagin, A.V.; Deyev, S. M.

    2016-01-01

    This review focuses on modeling of cancer tumors using tissue engineering technology. Tumor tissue engineering (TTE) is a new method of three-dimensional (3D) simulation of malignant neoplasms. Design and development of complex tissue engineering constructs (TECs) that include cancer cells, cell-bearing scaffolds acting as the extracellular matrix, and other components of the tumor microenvironment is at the core of this approach. Although TECs can be transplanted into laboratory animals, the specific aim of TTE is the most realistic reproduction and long-term maintenance of the simulated tumor properties in vitro for cancer biology research and for the development of new methods of diagnosis and treatment of malignant neoplasms. Successful implementation of this challenging idea depends on bioreactor technology, which will enable optimization of culture conditions and control of tumor TECs development. In this review, we analyze the most popular bioreactor types in TTE and the emerging applications. PMID:27795843

  8. Extracellular Matrix Revisited: Roles in Tissue Engineering

    PubMed Central

    2016-01-01

    The extracellular matrix (ECM) is a heterogeneous, connective network composed of fibrous glycoproteins that coordinate in vivo to provide the physical scaffolding, mechanical stability, and biochemical cues necessary for tissue morphogenesis and homeostasis. This review highlights some of the recently raised aspects of the roles of the ECM as related to the fields of biophysics and biomedical engineering. Fundamental aspects of focus include the role of the ECM as a basic cellular structure, for novel spontaneous network formation, as an ideal scaffold in tissue engineering, and its essential contribution to cell sheet technology. As these technologies move from the laboratory to clinical practice, they are bound to shape the vast field of tissue engineering for medical transplantations. PMID:27230457

  9. Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction

    PubMed Central

    Chiara, Gardin; Letizia, Ferroni; Lorenzo, Favero; Edoardo, Stellini; Diego, Stomaci; Stefano, Sivolella; Eriberto, Bressan; Barbara, Zavan

    2012-01-01

    Bone tissue engineering strategies are emerging as attractive alternatives to autografts and allografts in bone tissue reconstruction, in particular thanks to their association with nanotechnologies. Nanostructured biomaterials, indeed, mimic the extracellular matrix (ECM) of the natural bone, creating an artificial microenvironment that promotes cell adhesion, proliferation and differentiation. At the same time, the possibility to easily isolate mesenchymal stem cells (MSCs) from different adult tissues together with their multi-lineage differentiation potential makes them an interesting tool in the field of bone tissue engineering. This review gives an overview of the most promising nanostructured biomaterials, used alone or in combination with MSCs, which could in future be employed as bone substitutes. Recent works indicate that composite scaffolds made of ceramics/metals or ceramics/polymers are undoubtedly more effective than the single counterparts in terms of osteoconductivity, osteogenicity and osteoinductivity. A better understanding of the interactions between MSCs and nanostructured biomaterials will surely contribute to the progress of bone tissue engineering. PMID:22312283

  10. Ebselen Preserves Tissue-Engineered Cell Sheets and their Stem Cells in Hypothermic Conditions

    PubMed Central

    Katori, Ryosuke; Hayashi, Ryuhei; Kobayashi, Yuki; Kobayashi, Eiji; Nishida, Kohji

    2016-01-01

    Clinical trials have been performed using autologous tissue-engineered epithelial cell sheets for corneal regenerative medicine. To improve stem cell-based therapy for convenient clinical practice, new techniques are required for preserving reconstructed tissues and their stem/progenitor cells until they are ready for use. In the present study, we screened potential preservative agents and developed a novel medium for preserving the cell sheets and their stem/progenitor cells; the effects were evaluated with a luciferase-based viability assay. Nrf2 activators, specifically ebselen, could maintain high ATP levels during preservation. Ebselen also showed a strong influence on maintenance of the viability, morphology, and stem cell function of the cell sheets preserved under hypothermia by protecting them from reactive oxygen species-induced damage. Furthermore, ebselen drastically improved the preservation performance of human cornea tissues and their stem cells. Therefore, ebselen shows good potential as a useful preservation agent in regenerative medicine as well as in cornea transplantation. PMID:27966584

  11. Electrical stimulation systems for cardiac tissue engineering.

    PubMed

    Tandon, Nina; Cannizzaro, Christopher; Chao, Pen-Hsiu Grace; Maidhof, Robert; Marsano, Anna; Au, Hoi Ting Heidi; Radisic, Milica; Vunjak-Novakovic, Gordana

    2009-01-01

    We describe a protocol for tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures.

  12. Electrical stimulation systems for cardiac tissue engineering

    PubMed Central

    Tandon, Nina; Cannizzaro, Christopher; Chao, Pen-Hsiu Grace; Maidhof, Robert; Marsano, Anna; Au, Hoi Ting Heidi; Radisic, Milica; Vunjak-Novakovic, Gordana

    2009-01-01

    We describe a protocol for tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures. PMID:19180087

  13. Protein Turnover during in vitro Tissue Engineering

    PubMed Central

    Li, Qiyao; Chang, Zhen; Oliveira, Gisele; Xiong, Maiyer; Smith, Lloyd M.; Frey, Brian L.; Welham, Nathan V.

    2015-01-01

    Repopulating acellular biological scaffolds with phenotypically appropriate cells is a promising approach for regenerating functional tissues and organs. Under this tissue engineering paradigm, reseeded cells are expected to remodel the scaffold by active protein synthesis and degradation; however, the rate and extent of this remodeling remain largely unknown. Here, we present a technique to measure dynamic proteome changes during in vitro remodeling of decellularized tissue by reseeded cells, using vocal fold mucosa as the model system. Decellularization and recellularization were optimized, and a stable isotope labeling strategy was developed to differentiate remnant proteins constituting the original scaffold from proteins newly synthesized by reseeded cells. Turnover of matrix and cellular proteins and the effects of cell-scaffold interaction were elucidated. This technique sheds new light on in vitro tissue remodeling and the process of tissue regeneration, and is readily applicable to other tissue and organ systems. PMID:26724458

  14. Tissue Engineering: Current Strategies and Future Directions

    PubMed Central

    Olson, Jennifer L.; Atala, Anthony

    2011-01-01

    Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, or other clinical issues. Currently, patients with diseased and injured organs are often treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and as the number of new cases of organ failure increases. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured tissues. In addition, the stem cell field is a rapidly advancing part of regenerative medicine, and new discoveries in this field create new options for this type of therapy. For example, new types of stem cells, such as amniotic fluid and placental stem cells that can circumvent the ethical issues associated with embryonic stem cells, have been discovered. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous, adult cells have already entered the clinical setting, indicating that regenerative medicine holds much promise for the future. PMID:22111050

  15. Gene therapy used for tissue engineering applications.

    PubMed

    Heyde, Mieke; Partridge, Kris A; Oreffo, Richard O C; Howdle, Steven M; Shakesheff, Kevin M; Garnett, Martin C

    2007-03-01

    This review highlights the advances at the interface between tissue engineering and gene therapy. There are a large number of reports on gene therapy in tissue engineering, and these cover a huge range of different engineered tissues, different vectors, scaffolds and methodology. The review considers separately in-vitro and in-vivo gene transfer methods. The in-vivo gene transfer method is described first, using either viral or non-viral vectors to repair various tissues with and without the use of scaffolds. The use of a scaffold can overcome some of the challenges associated with delivery by direct injection. The ex-vivo method is described in the second half of the review. Attempts have been made to use this therapy for bone, cartilage, wound, urothelial, nerve tissue regeneration and for treating diabetes using viral or non-viral vectors. Again porous polymers can be used as scaffolds for cell transplantation. There are as yet few comparisons between these many different variables to show which is the best for any particular application. With few exceptions, all of the results were positive in showing some gene expression and some consequent effect on tissue growth and remodelling. Some of the principal advantages and disadvantages of various methods are discussed.

  16. Olfactomedin-like 3 (OLFML3) gene expression in baboon and human ocular tissues: cornea, lens, uvea and retina

    PubMed Central

    Rodríguez-Sánchez, Iràm Pablo; Garza-Rodríguez, Maria Lourdes; Mohamed-Noriega, Karim; Voruganti, Venkata Saroja; Tejero, Maria Elizabeth; Delgado-Enciso, Ivan; Ibave, Diana Cristina Perez; Schlabritz-Loutsevitch, Natalia E.; Mohamed-Noriega, Jibran; Martinez-Fierro, Margarita L; Reséndez-Pérez, Diana; Cole, Shelley A; Cavazos-Adame, Humberto; Comuzzie, Anthony G.; Mohamed-Hamsho, Jesús; Barrera-Saldaña, Hugo Alberto

    2013-01-01

    Background Olfactomedin-like is a polyfunctional polymeric glycoprotein. This family has at least four members. One member of this family is OLFML3, which is preferentially expressed in placenta but is also detected in other adult tissues including the liver and heart. However, the orthologous rat gene is expressed in the iris, sclera, trabecular meshwork, retina, and optic nerve. Methods OLFML3 amplification was performed by RT-PCR from human and baboon ocular tissues. The products were cloned and sequenced. Results We report OFML3 expression in human and baboon eye. The full CDS has 1221 bp, from which a OFR of 406 amino acid was obtained. The baboon OLFML3 gene nucleotidic sequence has 98%, and amino acidic 99% similarity with humans. Conclusions OLFML3 expression in human and baboon ocular tissues and its high similarity make the baboon a powerful model to deduce the physiological and/or metabolic function of this protein in the eye. PMID:23398349

  17. Bioreactor Technology in Cardiovascular Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Mertsching, H.; Hansmann, J.

    Cardiovascular tissue engineering is a fast evolving field of biomedical science and technology to manufacture viable blood vessels, heart valves, myocar-dial substitutes and vascularised complex tissues. In consideration of the specific role of the haemodynamics of human circulation, bioreactors are a fundamental of this field. The development of perfusion bioreactor technology is a consequence of successes in extracorporeal circulation techniques, to provide an in vitro environment mimicking in vivo conditions. The bioreactor system should enable an automatic hydrodynamic regime control. Furthermore, the systematic studies regarding the cellular responses to various mechanical and biochemical cues guarantee the viability, bio-monitoring, testing, storage and transportation of the growing tissue.

  18. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2014-04-01

    in order to minimize scarring and injected dissociated adult DRGs rostral to a dorsal column transection of the spinal cord. From the sensory... columns were dissected and post-fixed overnight in 4% paraformaldehyde, and then spinal cords were dissected from spinal columns and cryoprotected...AD______________ Award Number: W81XWH-10-1-0941 TITLE: Spinal Cord Repair with Engineered Nervous Tissue

  19. Cell–scaffold interaction within engineered tissue

    SciTech Connect

    Chen, Haiping; Liu, Yuanyuan Jiang, Zhenglong; Chen, Weihua; Yu, Yongzhe; Hu, Qingxi

    2014-05-01

    The structure of a tissue engineering scaffold plays an important role in modulating tissue growth. A novel gelatin–chitosan (Gel–Cs) scaffold with a unique structure produced by three-dimensional printing (3DP) technology combining with vacuum freeze-drying has been developed for tissue-engineering applications. The scaffold composed of overall construction, micro-pore, surface morphology, and effective mechanical property. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell–matrix interaction supports the active biocompatibility of the structure. The structure is capable of supporting cell attachment and proliferation. Cells seeded into this structure tend to maintain phenotypic shape and secreted large amounts of extracellular matrix (ECM) and the cell growth decreased the mechanical properties of scaffold. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique structure, which acts to support cell growth. - Highlights: • The scaffold is not only for providing a surface for cell residence but also for determining cell phenotype and retaining structural integrity. • The mechanical property of scaffold can be affected by activities of cell. • The scaffold provides a microenvironment for cell attachment, growth, and migration.

  20. Dentin Matrix Proteins in Bone Tissue Engineering.

    PubMed

    Ravindran, Sriram; George, Anne

    2015-01-01

    Dentin and bone are mineralized tissue matrices comprised of collagen fibrils and reinforced with oriented crystalline hydroxyapatite. Although both tissues perform different functionalities, they are assembled and orchestrated by mesenchymal cells that synthesize both collagenous and noncollagenous proteins albeit in different proportions. The dentin matrix proteins (DMPs) have been studied in great detail in recent years due to its inherent calcium binding properties in the extracellular matrix resulting in tissue calcification. Recent studies have shown that these proteins can serve both as intracellular signaling proteins leading to induction of stem cell differentiation and also function as nucleating proteins in the extracellular matrix. These properties make the DMPs attractive candidates for bone and dentin tissue regeneration. This chapter will provide an overview of the DMPs, their functionality and their proven and possible applications with respect to bone tissue engineering.

  1. Biomimetic nanofibrous scaffolds for bone tissue engineering

    PubMed Central

    Holzwarth, Jeremy M.; Ma, Peter X.

    2011-01-01

    Bone tissue engineering is a highly interdisciplinary field that seeks to tackle the most challenging bone-related clinical issues. The major components of bone tissue engineering are the scaffold, cells, and growth factors. This review will focus on the scaffold and recent advancements in developing scaffolds that can mimic the natural extracellular matrix of bone. Specifically, these novel scaffolds mirror the nanofibrous collagen network that comprises the majority of the non-mineral portion of bone matrix. Using two main fabrication techniques, electrospinning and thermally-induced phase separation, and incorporating bone-like minerals, such as hydroxyapatite, composite nanofibrous scaffolds can improve cell adhesion, stem cell differentiation, and tissue formation. This review will cover the two main processing techniques and how they are being applied to fabricate scaffolds for bone tissue engineering. It will then cover how these scaffolds can enhance the osteogenic capabilities of a variety of cell types and survey the ability of the constructs to support the growth of clinically relevant bone tissue. PMID:21944829

  2. Vascularization in bone tissue engineering constructs

    PubMed Central

    Mercado-Pagán, Ángel E.; Stahl, Alexander M.; Shanjani, Yaser; Yang, Yunzhi

    2016-01-01

    Vascularization of large bone grafts is one of the main challenges of bone tissue engineering (BTE), and has held back the clinical translation of engineered bone constructs for two decades so far. The ultimate goal of vascularized BTE constructs is to provide a bone environment rich in functional vascular networks to achieve efficient osseointegration and accelerate restoration of function after implantation. To attain both structural and vascular integration of the grafts, a large number of biomaterials, cells, and biological cues have been evaluated. This review will present biological considerations for bone function restoration, contemporary approaches for clinical salvage of large bone defects and their limitations, state-of-the-art research on the development of vascularized bone constructs, and perspectives on evaluating and implementing novel BTE grafts in clinical practice. Success will depend on achieving full graft integration at multiple hierarchical levels, both between the individual graft components as well as between the implanted constructs and their surrounding host tissues. The paradigm of vascularized tissue constructs could not only revolutionize the progress of bone tissue engineering, but could also be readily applied to other fields in regenerative medicine for the development of new innovative vascularized tissue designs. PMID:25616591

  3. Drug releasing systems in cardiovascular tissue engineering.

    PubMed

    Spadaccio, Cristiano; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto; Toyoda, Yoshiya; Genovese, Jorge A

    2009-03-01

    Heart disease and atherosclerosis are the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts; however, current artificial grafts carry significant limitations, including thrombosis, infection, limited durability and the inability to grow. Tissue engineering of blood vessels, cardiovascular structures and whole organs is a promising approach for creating replacement tissues to repair congenital defects and/or diseased tissues. In an attempt to surmount the shortcomings of artificial grafts, tissue-engineered cardiovascular graft (TECVG), constructs obtained using cultured autologous vascular cells seeded onto a synthetic biodegradable polymer scaffold, have been developed. Autologous TECVGs have the potential advantages of growth, durability, resistance to infection, and freedom from problems of rejection, thrombogenicity and donor scarcity. Moreover polymers engrafted with growth factors, cytokines, drugs have been developed allowing drug-releasing systems capable of focused and localized delivery of molecules depending on the environmental requirements and the milieu in which the scaffold is placed. A broad range of applications for compound-releasing, tissue-engineered grafts have been suggested ranging from drug delivery to gene therapy. This review will describe advances in the development of drug-delivery systems for cardiovascular applications focusing on the manufacturing techniques and on the compounds delivered by these systems to date.

  4. Drug releasing systems in cardiovascular tissue engineering

    PubMed Central

    Spadaccio, Cristiano; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto; Toyoda, Yoshiya; Genovese, Jorge A

    2009-01-01

    Abstract Heart disease and atherosclerosis are the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts; however, current artificial grafts carry significant limitations, including thrombosis, infection, limited durability and the inability to grow. Tissue engineering of blood vessels, cardiovascular structures and whole organs is a promising approach for creating replacement tissues to repair congenital defects and/or diseased tissues. In an attempt to surmount the shortcomings of artificial grafts, tissue-engineered cardiovascular graft (TECVG), constructs obtained using cultured autologous vascular cells seeded onto a synthetic biodegradable polymer scaffold, have been developed. Autologous TECVGs have the potential advantages of growth, durability, resistance to infection, and freedom from problems of rejection, thrombogenicity and donor scarcity. Moreover polymers engrafted with growth factors, cytokines, drugs have been developed allowing drug-releasing systems capable of focused and localized delivery of molecules depending on the environmental requirements and the milieu in which the scaffold is placed. A broad range of applications for compound-releasing, tissue-engineered grafts have been suggested ranging from drug delivery to gene therapy. This review will describe advances in the development of drug-delivery systems for cardiovascular applications focusing on the manufacturing techniques and on the compounds delivered by these systems to date. PMID:19379142

  5. Tailored Carbon Nanotubes for Tissue Engineering Applications

    PubMed Central

    Veetil, Jithesh V.; Ye, Kaiming

    2008-01-01

    A decade of aggressive researches on carbon nanotubes (CNTs) has paved way for extending these unique nanomaterials into a wide range of applications. In the relatively new arena of nanobiotechnology, a vast majority of applications are based on CNTs, ranging from miniaturized biosensors to organ regeneration. Nevertheless, the complexity of biological systems poses a significant challenge in developing CNT-based tissue engineering applications. This review focuses on the recent developments of CNT-based tissue engineering, where the interaction between living cells/tissues and the nanotubes have been transformed into a variety of novel techniques. This integration has already resulted in a revaluation of tissue engineering and organ regeneration techniques. Some of the new treatments that were not possible previously become reachable now. Because of the advent of surface chemistry, the CNT’s biocompatibility has been significantly improved, making it possible to serve as tissue scaffolding materials to enhance the organ regeneration. The superior mechanic strength and chemical inert also makes it ideal for blood compatible applications, especially for cardiopulmonary bypass surgery. The applications of CNTs in these cardiovascular surgeries led to a remarkable improvement in mechanical strength of implanted catheters and reduced thrombogenecity after surgery. Moreover, the functionalized CNTs have been extensively explored for in vivo targeted drug or gene delivery, which could potentially improve the efficiency of many cancer treatments. However, just like other nanomaterials, the cytotoxicity of CNTs has not been well established. Hence, more extensive cytotoxic studies are warranted while converting the hydrophobic CNTs into biocompatible nanomaterials. PMID:19496152

  6. Biomaterials in Tooth Tissue Engineering: A Review

    PubMed Central

    Sharma, Sarang; Srivastava, Dhirendra; Grover, Shibani; Sharma, Vivek

    2014-01-01

    Biomaterials play a crucial role in the field of tissue engineering. They are utilized for fabricating frameworks known as scaffolds, matrices or constructs which are interconnected porous structures that establish a cellular microenvironment required for optimal tissue regeneration. Several natural and synthetic biomaterials have been utilized for fabrication of tissue engineering scaffolds. Amongst different biomaterials, polymers are the most extensively experimented and employed materials. They can be tailored to provide good interconnected porosity, large surface area, adequate mechanical strengths, varying surface characterization and different geometries required for tissue regeneration. A single type of material may however not meet all the requirements. Selection of two or more biomaterials, optimization of their physical, chemical and mechanical properties and advanced fabrication techniques are required to obtain scaffold designs intended for their final application. Current focus is aimed at designing biomaterials such that they will replicate the local extra cellular environment of the native organ and enable cell-cell and cell-scaffold interactions at micro level required for functional tissue regeneration. This article provides an insight into the different biomaterials available and the emerging use of nano engineering principles for the construction of bioactive scaffolds in tooth regeneration. PMID:24596804

  7. Carbon-based nanomaterials for tissue engineering.

    PubMed

    Ku, Sook Hee; Lee, Minah; Park, Chan Beum

    2013-02-01

    Carbon-based nanomaterials such as graphene sheets and carbon nanotubes possess unique mechanical, electrical, and optical properties that present new opportunities for tissue engineering, a key field for the development of biological alternatives that repair or replace whole or a portion of tissue. Carbon nanomaterials can also provide a similar microenvironment as like a biological extracellular matrix in terms of chemical composition and physical structure, making them a potential candidate for the development of artificial scaffolds. In this review, we summarize recent research advances in the effects of carbon nanomaterial-based substrates on cellular behaviors, including cell adhesion, proliferation, and differentiation into osteo- or neural- lineages. The development of 3D scaffolds based on carbon nanomaterials (or their composites with polymers and inorganic components) is introduced, and the potential of these constructs in tissue engineering, including toxicity issues, is discussed. Future perspectives and emerging challenges are also highlighted.

  8. [Stem cells and tissue engineering techniques].

    PubMed

    Sica, Gigliola

    2013-01-01

    The therapeutic use of stem cells and tissue engineering techniques are emerging in urology. Here, stem cell types, their differentiating potential and fundamental characteristics are illustrated. The cancer stem cell hypothesis is reported with reference to the role played by stem cells in the origin, development and progression of neoplastic lesions. In addition, recent reports of results obtained with stem cells alone or seeded in scaffolds to overcome problems of damaged urinary tract tissue are summarized. Among others, the application of these biotechnologies in urinary bladder, and urethra are delineated. Nevertheless, apart from the ethical concerns raised from the use of embryonic stem cells, a lot of questions need to be solved concerning the biology of stem cells before their widespread use in clinical trials. Further investigation is also required in tissue engineering utilizing animal models.

  9. Multilayered silk scaffolds for meniscus tissue engineering.

    PubMed

    Mandal, Biman B; Park, Sang-Hyug; Gil, Eun S; Kaplan, David L

    2011-01-01

    Removal of injured/damaged meniscus, a vital fibrocartilaginous load-bearing tissue, impairs normal knee function and predisposes patients to osteoarthritis. Meniscus tissue engineering solution is one option to improve outcomes and relieve pain. In an attempt to fabricate knee meniscus grafts three layered wedge shaped silk meniscal scaffold system was engineered to mimic native meniscus architecture. The scaffolds were seeded with human fibroblasts (outside) and chondrocytes (inside) in a spatial separated mode similar to native tissue, in order to generate meniscus-like tissue in vitro. In chondrogenic culture in the presence of TGF-b3, cell-seeded constructs increased in cellularity and extracellular matrix (ECM) content. Histology and Immunohistochemistry confirmed maintenance of chondrocytic phenotype with higher levels of sulfated glycosaminoglycans (sGAG) and collagen types I and II. Improved scaffold mechanical properties along with ECM alignment with time in culture suggest this multiporous silk construct as a useful micro-patterned template for directed tissue growth with respect to form and function of meniscus-like tissue.

  10. Multilayered silk scaffolds for meniscus tissue engineering

    PubMed Central

    Mandal, Biman B.; Park, Sang-Hyug; Gil, Eun Seok

    2010-01-01

    Removal of injured/damaged meniscus, a vital fibrocartilaginous load-bearing tissue, impairs normal knee function and predisposes patients to osteoarthritis. Meniscus tissue engineering solution is one option to improve outcomes and relieve pain. In an attempt to fabricate knee meniscus grafts three layered wedge shaped silk meniscal scaffold system was engineered to mimic native meniscus architecture. The scaffolds were seeded with human fibroblasts (outside) and chondrocytes (inside) in a spatial separated mode similar to native tissue, in order to generate meniscus-like tissue in vitro. In chondrogenic culture in the presence of TGF-b3, cell seeded constructs increased in cellularity and extracellular matrix (ECM) content. Histology and Immunohistochemistry confirmed maintenance of chondrocytic phenotype with higher levels of sulphated glycosaminoglycans (sGAG) and collagen types I and II. Improved scaffold mechanical properties along with ECM alignment with time in culture suggest this multiporous silk construct as a useful micro-patterned template for directed tissue growth with respect to form and function of meniscus-like tissue. PMID:20926132

  11. Stem cell-based meniscus tissue engineering.

    PubMed

    Mandal, Biman B; Park, Sang-Hyug; Gil, Eun Seok; Kaplan, David L

    2011-11-01

    Knee meniscus, a fibrocartilaginous tissue, is characterized by heterogeneity in extracellular matrix (ECM) and biomechanical properties, and critical for orthopedic stability, load transmission, shock absorption, and stress distribution within the knee joint. Most damage to the meniscus cannot be effectively healed by the body due to its partial avascular nature; thus, damage caused by injury or age impairs normal knee function, predisposing patients to osteoarthritis. Meniscus tissue engineering offers a possible solution to this problem by generating replacement tissue that may be implanted into the defect site to mimic the function of natural meniscal tissue. To address this need, a multiporous, multilamellar meniscus was formed using silk protein scaffolds and stem cells. The silk scaffolds were seeded with human bone marrow stem cells and differentiated over time in chondrogenic culture in the presence of transforming growth factor-beta 3 to generate meniscus-like tissue in vitro. High cellularity along with abundant ECM leading to enhanced biomechanics similar to native tissue was found. Higher levels of collagen type I and II, sulfated glycosaminoglycans along with enhanced collagen 1-α1, aggrecan, and SOX9 gene expression further confirmed differentiation and matured cell phenotype. The results of this study are a step forward toward biomechanically competent meniscus engineering, reconstituting both form and function of the native meniscus.

  12. Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model

    PubMed Central

    Kaluzhny, Yulia; Kandárová, Helena; d’Argembeau-Thornton, Laurence; Kearney, Paul; Klausner, Mitchell

    2015-01-01

    To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492. PMID:26325674

  13. Cardiovascular Tissue Engineering: Preclinical Validation to Bedside Application

    PubMed Central

    Best, Cameron; Onwuka, Ekene; Pepper, Victoria; Sams, Malik; Breuer, Jake

    2015-01-01

    Advancements in biomaterial science and available cell sources have spurred the translation of tissue-engineering technology to the bedside, addressing the pressing clinical demands for replacement cardiovascular tissues. Here, the in vivo status of tissue-engineered blood vessels, heart valves, and myocardium is briefly reviewed, illustrating progress toward a tissue-engineered heart for clinical use. PMID:26661524

  14. Multiphasic Scaffolds for Periodontal Tissue Engineering

    PubMed Central

    Ivanovski, S.; Vaquette, C.; Gronthos, S.; Hutmacher, D.W.; Bartold, P.M.

    2014-01-01

    For a successful clinical outcome, periodontal regeneration requires the coordinated response of multiple soft and hard tissues (periodontal ligament, gingiva, cementum, and bone) during the wound-healing process. Tissue-engineered constructs for regeneration of the periodontium must be of a complex 3-dimensional shape and adequate size and demonstrate biomechanical stability over time. A critical requirement is the ability to promote the formation of functional periodontal attachment between regenerated alveolar bone, and newly formed cementum on the root surface. This review outlines the current advances in multiphasic scaffold fabrication and how these scaffolds can be combined with cell- and growth factor–based approaches to form tissue-engineered constructs capable of recapitulating the complex temporal and spatial wound-healing events that will lead to predictable periodontal regeneration. This can be achieved through a variety of approaches, with promising strategies characterized by the use of scaffolds that can deliver and stabilize cells capable of cementogenesis onto the root surface, provide biomechanical cues that encourage perpendicular alignment of periodontal fibers to the root surface, and provide osteogenic cues and appropriate space to facilitate bone regeneration. Progress on the development of multiphasic constructs for periodontal tissue engineering is in the early stages of development, and these constructs need to be tested in large animal models and, ultimately, human clinical trials. PMID:25139362

  15. Multiphasic scaffolds for periodontal tissue engineering.

    PubMed

    Ivanovski, S; Vaquette, C; Gronthos, S; Hutmacher, D W; Bartold, P M

    2014-12-01

    For a successful clinical outcome, periodontal regeneration requires the coordinated response of multiple soft and hard tissues (periodontal ligament, gingiva, cementum, and bone) during the wound-healing process. Tissue-engineered constructs for regeneration of the periodontium must be of a complex 3-dimensional shape and adequate size and demonstrate biomechanical stability over time. A critical requirement is the ability to promote the formation of functional periodontal attachment between regenerated alveolar bone, and newly formed cementum on the root surface. This review outlines the current advances in multiphasic scaffold fabrication and how these scaffolds can be combined with cell- and growth factor-based approaches to form tissue-engineered constructs capable of recapitulating the complex temporal and spatial wound-healing events that will lead to predictable periodontal regeneration. This can be achieved through a variety of approaches, with promising strategies characterized by the use of scaffolds that can deliver and stabilize cells capable of cementogenesis onto the root surface, provide biomechanical cues that encourage perpendicular alignment of periodontal fibers to the root surface, and provide osteogenic cues and appropriate space to facilitate bone regeneration. Progress on the development of multiphasic constructs for periodontal tissue engineering is in the early stages of development, and these constructs need to be tested in large animal models and, ultimately, human clinical trials.

  16. Heart valve and arterial tissue engineering.

    PubMed

    Sarraf, C E; Harris, A B; McCulloch, A D; Eastwood, M

    2003-10-01

    In the industrialized world, cardiovascular disease alone is responsible for almost half of all deaths. Many of the conditions can be treated successfully with surgery, often using transplantation techniques; however, autologous vessels or human-donated organs are in short supply. Tissue engineering aims to create specific, matching grafts by growing cells on appropriate matrices, but there are many steps between the research laboratory and the operating theatre. Neo-tissues must be effective, durable, non-thrombogenic and non-immunogenic. Scaffolds should be bio-compatible, porous (to allow cell/cell communication) and amenable to surgery. In the early days of cardiovascular tissue engineering, autologous or allogenic cells were grown on inert matrices, but patency and thrombogenicity of grafts were disappointing. The current ethos is toward appropriate cell types grown in (most often) a polymeric matrix that degrades at a rate compatible with the cells' production of their own extracellular matrical proteins, thus gradually replacing the graft with a living counterpart. The geometry is crucial. Computer models have been made of valves, and these are used as three-dimensional patterns for mass-production of implant scaffolds. Vessel walls have integral connective tissue architecture, and application of physiological level mechanical forces conditions bio-engineered components to align in precise orientation. This article reviews the concepts involved and successes achieved to date.

  17. Myocardial tissue engineering using electrospun nanofiber composites.

    PubMed

    Kim, Pyung-Hwan; Cho, Je-Yoel

    2016-01-01

    Emerging trends for cardiac tissue engineering are focused on increasing the biocompatibility and tissue regeneration ability of artificial heart tissue by incorporating various cell sources and bioactive molecules. Although primary cardiomyocytes can be successfully implanted, clinical applications are restricted due to their low survival rates and poor proliferation. To develop successful cardiovascular tissue regeneration systems, new technologies must be introduced to improve myocardial regeneration. Electrospinning is a simple, versatile technique for fabricating nanofibers. Here, we discuss various biodegradable polymers (natural, synthetic, and combinatorial polymers) that can be used for fiber fabrication. We also describe a series of fiber modification methods that can increase cell survival, proliferation, and migration and provide supporting mechanical properties by mimicking micro-environment structures, such as the extracellular matrix (ECM). In addition, the applications and types of nanofiber-based scaffolds for myocardial regeneration are described. Finally, fusion research methods combined with stem cells and scaffolds to improve biocompatibility are discussed.

  18. 3D bioprinting for engineering complex tissues.

    PubMed

    Mandrycky, Christian; Wang, Zongjie; Kim, Keekyoung; Kim, Deok-Ho

    2016-01-01

    Bioprinting is a 3D fabrication technology used to precisely dispense cell-laden biomaterials for the construction of complex 3D functional living tissues or artificial organs. While still in its early stages, bioprinting strategies have demonstrated their potential use in regenerative medicine to generate a variety of transplantable tissues, including skin, cartilage, and bone. However, current bioprinting approaches still have technical challenges in terms of high-resolution cell deposition, controlled cell distributions, vascularization, and innervation within complex 3D tissues. While no one-size-fits-all approach to bioprinting has emerged, it remains an on-demand, versatile fabrication technique that may address the growing organ shortage as well as provide a high-throughput method for cell patterning at the micrometer scale for broad biomedical engineering applications. In this review, we introduce the basic principles, materials, integration strategies and applications of bioprinting. We also discuss the recent developments, current challenges and future prospects of 3D bioprinting for engineering complex tissues. Combined with recent advances in human pluripotent stem cell technologies, 3D-bioprinted tissue models could serve as an enabling platform for high-throughput predictive drug screening and more effective regenerative therapies.

  19. Imaging challenges in biomaterials and tissue engineering

    PubMed Central

    Appel, Alyssa A.; Anastasio, Mark A.; Larson, Jeffery C.; Brey, Eric M.

    2013-01-01

    Biomaterials are employed in the fields of tissue engineering and regenerative medicine (TERM) in order to enhance the regeneration or replacement of tissue function and/or structure. The unique environments resulting from the presence of biomaterials, cells, and tissues result in distinct challenges in regards to monitoring and assessing the results of these interventions. Imaging technologies for three-dimensional (3D) analysis have been identified as a strategic priority in TERM research. Traditionally, histological and immunohistochemical techniques have been used to evaluate engineered tissues. However, these methods do not allow for an accurate volume assessment, are invasive, and do not provide information on functional status. Imaging techniques are needed that enable non-destructive, longitudinal, quantitative, and three-dimensional analysis of TERM strategies. This review focuses on evaluating the application of available imaging modalities for assessment of biomaterials and tissue in TERM applications. Included is a discussion of limitations of these techniques and identification of areas for further development. PMID:23768903

  20. Mesenchymal cells for skeletal tissue engineering.

    PubMed

    Panetta, N J; Gupta, D M; Quarto, N; Longaker, M T

    2009-03-01

    Today, surgical intervention remains the mainstay of treatment to intervene upon a multitude of skeletal deficits and defects attributable to congenital malformations, oncologic resection, pathologic degenerative bone destruction, and post-traumatic loss. Despite this significant demand, the tools with which surgeons remain equipped are plagued with a surfeit of inadequacies, often resulting in less than ideal patient outcomes. The failings of current techniques largely arise secondary to their inability to produce a regenerate which closely resembles lost tissue. As such, focus has shifted to the potential of mesenchymal stem cell (MSC)-based skeletal tissue engineering. The successful development of such techniques would represent a paradigm shift from current approaches, carrying with it the potential to regenerate tissues which mimic the form and function of endogenous bone. Lessons learned from investigations probing the endogenous regenerative capacity of skeletal tissues have provided direction to early studies investigating the osteogenic potential of MSC. Additionally, increasing attention is being turned to the role of targeted molecular manipulations in augmenting MSC osteogenesis, as well as the development of an ideal scaffold ''vehicle'' with which to deliver progenitor cells. The following discussion presents the authors' current working knowledge regarding these critical aspects of MSC application in cell-based skeletal tissue engineering strategies, as well as provides insight towards what future steps must be taken to make their clinical translation a reality.

  1. Cardiac tissue engineering in magnetically actuated scaffolds

    NASA Astrophysics Data System (ADS)

    Sapir, Yulia; Polyak, Boris; Cohen, Smadar

    2014-01-01

    Cardiac tissue engineering offers new possibilities for the functional and structural restoration of damaged or lost heart tissue by applying cardiac patches created in vitro. Engineering such functional cardiac patches is a complex mission, involving material design on the nano- and microscale as well as the application of biological cues and stimulation patterns to promote cell survival and organization into a functional cardiac tissue. Herein, we present a novel strategy for creating a functional cardiac patch by combining the use of a macroporous alginate scaffold impregnated with magnetically responsive nanoparticles (MNPs) and the application of external magnetic stimulation. Neonatal rat cardiac cells seeded within the magnetically responsive scaffolds and stimulated by an alternating magnetic field of 5 Hz developed into matured myocardial tissue characterized by anisotropically organized striated cardiac fibers, which preserved its features for longer times than non-stimulated constructs. A greater activation of AKT phosphorylation in cardiac cell constructs after applying a short-term (20 min) external magnetic field indicated the efficacy of magnetic stimulation to actuate at a distance and provided a possible mechanism for its action. Our results point to a synergistic effect of magnetic field stimulation together with nanoparticulate features of the scaffold surface as providing the regenerating environment for cardiac cells driving their organization into functionally mature tissue.

  2. 3D Printing and Biofabrication for Load Bearing Tissue Engineering.

    PubMed

    Jeong, Claire G; Atala, Anthony

    2015-01-01

    Cell-based direct biofabrication and 3D bioprinting is becoming a dominant technological platform and is suggested as a new paradigm for twenty-first century tissue engineering. These techniques may be our next step in surpassing the hurdles and limitations of conventional scaffold-based tissue engineering, and may offer the industrial potential of tissue engineered products especially for load bearing tissues. Here we present a topically focused review regarding the fundamental concepts, state of the art, and perspectives of this new technology and field of biofabrication and 3D bioprinting, specifically focused on tissue engineering of load bearing tissues such as bone, cartilage, osteochondral and dental tissue engineering.

  3. Cardiac tissue engineering using perfusion bioreactor systems

    PubMed Central

    Radisic, Milica; Marsano, Anna; Maidhof, Robert; Wang, Yadong; Vunjak-Novakovic, Gordana

    2009-01-01

    This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is ‘biomimetic’ in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and high-fidelity models for biological research. PMID:18388955

  4. Cell and Tissue Engineering for Liver Disease

    PubMed Central

    Bhatia, Sangeeta N.; Underhill, Gregory H.; Zaret, Kenneth S.; Fox, Ira J.

    2015-01-01

    Despite the tremendous hurdles presented by the complexity of the liver’s structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near and long-term prospects for such cell-based therapies and the unique challenges for clinical translation. PMID:25031271

  5. Cell and tissue engineering for liver disease.

    PubMed

    Bhatia, Sangeeta N; Underhill, Gregory H; Zaret, Kenneth S; Fox, Ira J

    2014-07-16

    Despite the tremendous hurdles presented by the complexity of the liver's structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near- and long-term prospects for such cell-based therapies and the unique challenges for clinical translation.

  6. Strategies for Whole Lung Tissue Engineering

    PubMed Central

    Calle, Elizabeth A.; Ghaedi, Mahboobe; Sundaram, Sumati; Sivarapatna, Amogh; Tseng, Michelle K.

    2014-01-01

    Recent work has demonstrated the feasibility of using decellularized lung extracellular matrix scaffolds to support the engineering of functional lung tissue in vitro. Rendered acellular through the use of detergents and other reagents, the scaffolds are mounted in organ-specific bioreactors where cells in the scaffold are provided with nutrients and appropriate mechanical stimuli such as ventilation and perfusion. Though initial studies are encouraging, a great deal remains to be done to advance the field and transition from rodent lungs to whole human tissue engineered lungs. To do so, a variety of hurdles must be overcome. In particular, a reliable source of human-sized scaffolds, as well as a method of terminal sterilization of scaffolds, must be identified. Continued research in lung cell and developmental biology will hopefully help identify the number and types of cells that will be required to regenerate functional lung tissue. Finally, bioreactor designs must be improved in order to provide more precise ventilation stimuli and vascular perfusion in order to avoid injury to or death of the cells cultivated within the scaffold. Ultimately, the success of efforts to engineer a functional lung in vitro will critically depend on the ability to create a fully endothelialized vascular network that provides sufficient barrier function and alveolar-capillary surface area to exchange gas at rates compatible with healthy lung function. PMID:24691527

  7. Mandibular Tissue Engineering: Past, Present, Future.

    PubMed

    Konopnicki, Sandra; Troulis, Maria J

    2015-12-01

    Almost 2 decades ago, the senior author's (M.T.J.) first article was with our mentor, Dr Leonard B. Kaban, a review article titled "Distraction Osteogenesis: Past, Present, Future." In 1998, many thought it would be impossible to have a remotely activated, small, curvilinear distractor that could be placed using endoscopic techniques. Currently, a U.S. patent for a curvilinear automated device and endoscopic techniques for minimally invasive access for jaw reconstruction exist. With minimally invasive access for jaw reconstruction, the burden to decrease donor site morbidity has increased. Distraction osteogenesis (DO) is an in vivo form of tissue engineering. The DO technique eliminates a donor site, is less invasive, requires a shorter operative time than usual procedures, and can be used for multiple reconstruction applications. Tissue engineering could further reduce morbidity and cost and increase treatment availability. The purpose of the present report was to review our experience with tissue engineering of bone: the past, present, and our vision for the future. The present report serves as a tribute to our mentor and acknowledges Dr Kaban for his incessant tutelage, guidance, wisdom, and boundless vision.

  8. Research progress in liver tissue engineering.

    PubMed

    Zhang, Lei; Guan, Zheng; Ye, Jun-Song; Yin, Yan-Feng; Stoltz, Jean-François; de Isla, Natalia

    2017-01-01

    Liver transplantation is the definitive treatment for patients with end-stage liver diseases (ESLD). However, it is hampered by shortage of liver donor. Liver tissue engineering, aiming at fabricating new livers in vitro, provides a potential resolution for donor shortage. Three elements need to be considered in liver tissue engineering: seeding cell resources, scaffolds and bioreactors. Studies have shown potential cell sources as hepatocytes, hepatic cell line, mesenchymal stem cells and others. They need scaffolds with perfect biocompatiblity, suitable micro-structure and appropriate degradation rate, which are essential charateristics for cell attachment, proliferation and secretion in forming extracellular matrix. The most promising scaffolds in research include decellularized whole liver, collagens and biocompatible plastic. The development and function of cells in scaffold need a microenvironment which can provide them with oxygen, nutrition, growth factors, et al. Bioreactor is expected to fulfill these requirements by mimicking the living condition in vivo. Although there is great progress in these three domains, a large gap stays still between their researches and applications. Herein, we summarized the recent development in these three major fields which are indispensable in liver tissue engineering.

  9. Novel detergent for whole organ tissue engineering.

    PubMed

    Kawasaki, Takanori; Kirita, Yuhei; Kami, Daisuke; Kitani, Tomoya; Ozaki, Chisa; Itakura, Yoko; Toyoda, Masashi; Gojo, Satoshi

    2015-10-01

    Whole organ tissue engineering for various organs, including the heart, lung, liver, and kidney, has demonstrated promising results for end-stage organ failure. However, the sodium dodecyl sulfate (SDS)-based protocol for standard decellularization has drawbacks such as clot formation in vascularized transplantation and poor cell engraftment in recellularization procedures. Preservation of the surface milieu of extracellular matrices (ECMs) might be crucial for organ generation based on decellularization/recellularization engineering. We examined a novel detergent, sodium lauryl ether sulfate (SLES), to determine whether it could overcome the drawbacks associated with SDS using rat heart and kidney. Both organs were perfused in an antegrade fashion with either SLES or SDS. Although immunohistochemistry for collagen I, IV, laminin, and fibronectin showed similar preservation in both detergents, morphological analysis using scanning electron microscopy and an assay of glycosaminoglycan content on ECMs showed that SLES-treated tissues had better-preserved ECMs than SDS-treated tissues. Mesenteric transplantation revealed SLES did not induce significant inflammation, as opposed to SDS. Platelet adhesion to decellularized tissues was significantly reduced with SLES. Overall, SLES could replace older detergents such as SDS in the decellularization process for generation of transplantable recellularized organs.

  10. Tissue Engineering Strategies in Ligament Regeneration

    PubMed Central

    Yilgor, Caglar; Yilgor Huri, Pinar; Huri, Gazi

    2012-01-01

    Ligaments are dense fibrous connective tissues that connect bones to other bones and their injuries are frequently encountered in the clinic. The current clinical approaches in ligament repair and regeneration are limited to autografts, as the gold standard, and allografts. Both of these techniques have their own drawbacks that limit the success in clinical setting; therefore, new strategies are being developed in order to be able to solve the current problems of ligament grafting. Tissue engineering is a novel promising technique that aims to solve these problems, by producing viable artificial ligament substitutes in the laboratory conditions with the potential of transplantation to the patients with a high success rate. Direct cell and/or growth factor injection to the defect site is another current approach aiming to enhance the repair process of the native tissue. This review summarizes the current approaches in ligament tissue engineering strategies including the use of scaffolds, their modification techniques, as well as the use of bioreactors to achieve enhanced regeneration rates, while also discussing the advances in growth factor and cell therapy applications towards obtaining enhanced ligament regeneration. PMID:22242032

  11. Oxygen Delivering Biomaterials for Tissue Engineering

    PubMed Central

    Farris, Ashley L.; Rindone, Alexandra N.; Grayson, Warren L.

    2016-01-01

    Tissue engineering (TE) has provided promising strategies for regenerating tissue defects, but few TE approaches have been translated for clinical applications. One major barrier in TE is providing adequate oxygen supply to implanted tissue scaffolds, since oxygen diffusion from surrounding vasculature in vivo is limited to the periphery of the scaffolds. Moreover, oxygen is also an important signaling molecule for controlling stem cell differentiation within TE scaffolds. Various technologies have been developed to increase oxygen delivery in vivo and enhance the effectiveness of TE strategies. Such technologies include hyperbaric oxygen therapy, perfluorocarbon- and hemoglobin-based oxygen carriers, and oxygen-generating, peroxide-based materials. Here, we provide an overview of the underlying mechanisms and how these technologies have been utilized for in vivo TE applications. Emerging technologies and future prospects for oxygen delivery in TE are also discussed to evaluate the progress of this field towards clinical translation. PMID:27453782

  12. Nanomaterials and nanotechnology for skin tissue engineering

    PubMed Central

    Mohamed, Aezeden; Xing, Malcolm (Mengqiu)

    2012-01-01

    A recent literature review of the field shows that tissue-engineered skin has been in clinical use for the last several decades and that, over this time the technology has advanced rapidly. Despite this progress no synthetic skin yet produced has completely replicated normal, healthy skin. Therefore, researchers must continue to develop materials that successfully overcome the problems with current skin tissue substitutes. This paper is a comprehensive review of the prospects for nanotechnology and nanomaterials to close this gap by mimicking surface properties for reconstruction of a variety of skin tissues. In addition, a number of commercially available products that regenerate different layers of the burn-damaged or chronically wounded skin are reviewed. PMID:22928165

  13. Tissue engineering: state of the art in oral rehabilitation

    PubMed Central

    SCHELLER, E. L.; KREBSBACH, P. H.; KOHN, D. H.

    2009-01-01

    SUMMARY More than 85% of the global population requires repair or replacement of a craniofacial structure. These defects range from simple tooth decay to radical oncologic craniofacial resection. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science and engineering technology. Identification of appropriate scaffolds, cell sources and spatial and temporal signals (the tissue engineering triad) is necessary to optimize development of a single tissue, hybrid organ or interface. Furthermore, combining the understanding of the interactions between molecules of the extracellular matrix and attached cells with an understanding of the gene expression needed to induce differentiation and tissue growth will provide the design basis for translating basic science into rationally developed components of this tissue engineering triad. Dental tissue engineers are interested in regeneration of teeth, oral mucosa, salivary glands, bone and periodontium. Many of these oral structures are hybrid tissues. For example, engineering the periodontium requires growth of alveolar bone, cementum and the periodontal ligament. Recapitulation of biological development of hybrid tissues and interfaces presents a challenge that exceeds that of engineering just a single tissue. Advances made in dental interface engineering will allow these tissues to serve as model systems for engineering other tissues or organs of the body. This review will begin by covering basic tissue engineering principles and strategic design of functional biomaterials. We will then explore the impact of biomaterials design on the status of craniofacial tissue engineering and current challenges and opportunities in dental tissue engineering. PMID:19228277

  14. Scaffold-free tissue engineering: organization of the tissue cytoskeleton and its effects on tissue shape.

    PubMed

    Czajka, Caitlin A; Mehesz, Agnes Nagy; Trusk, Thomas C; Yost, Michael J; Drake, Christopher J

    2014-05-01

    Work described herein characterizes tissues formed using scaffold-free, non-adherent systems and investigates their utility in modular approaches to tissue engineering. Immunofluorescence analysis revealed that all tissues formed using scaffold-free, non-adherent systems organize tissue cortical cytoskeletons that appear to be under tension. Tension in these tissues was also evident when modules (spheroids) were used to generate larger tissues. Real-time analysis of spheroid fusion in unconstrained systems illustrated modular motion that is compatible with alterations in tensions, due to the process of disassembly/reassembly of the cortical cytoskeletons required for module fusion. Additionally, tissues generated from modules placed within constrained linear molds, which restrict modular motion, deformed upon release from molds. That tissue deformation is due in full or in part to imbalanced cortical actin cytoskeleton tensions resulting from the constraints imposed by mold systems is suggested from our finding that treatment of forming tissues with Y-27632, a selective inhibitor of ROCK phosphorylation, reduced tissue deformation. Our studies suggest that the deformation of scaffold-free tissues due to tensions mediated via the tissue cortical cytoskeleton represents a major and underappreciated challenge to modular tissue engineering.

  15. The Application of Tissue Engineering Procedures to Repair the Larynx

    ERIC Educational Resources Information Center

    Ringel, Robert L.; Kahane, Joel C.; Hillsamer, Peter J.; Lee, Annie S.; Badylak, Stephen F.

    2006-01-01

    The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice,…

  16. Biomaterial systems for orthopedic tissue engineering

    NASA Astrophysics Data System (ADS)

    Spoerke, Erik David

    2003-06-01

    The World Health Organization has estimated that one out of seven Americans suffers from a musculoskeletal impairment, annually incurring 28.6 million musculoskeletal injuries---more than half of all injuries. Bone tissue engineering has evolved rapidly to address this continued health concern. In the last decade, the focus of orthopedic biomaterials design has shifted from the use of common engineering metals and plastics to smart materials designed to mimic nature and elicit favorable bioresponse. Working within this new paradigm, this thesis explores unique chemical and materials systems for orthopedic tissue engineering. Improving on current titanium implant technologies, porous titanium scaffolds were utilized to better approximate the mechanical and structural properties of natural bone. These foam scaffolds were enhanced with bioactive coatings, designed to enhance osteoblastic implant colonization. The biopolymer poly(L-lysine) was incorporated into both hydroxypatite and octacalcium phosphate mineral phases to create modified organoapatite and pLys-CP coatings respectively. These coatings were synthesized and characterized on titanium surfaces, including porous structures such as titanium mesh and titanium foam. In addition, in vitro osteoblastic cell culture experiments probed the biological influences of these coatings. Organoapatite (OA) accelerated preosteoblastic colonization of titanium mesh and improved cellular ingrowth into titanium foam. Alternatively, the thin, uniform pLys-CP coating demonstrated significant potential as a substrate for chemically binding biological molecules and supramolecular assemblies. Biologically, pLys-CP demonstrated enhanced cellular attachment over titanium and inorganic calcium phosphate controls. Supramolecular self-assembled nanofiber assemblies were also explored both as stand-alone tissue engineering gels and as titanium coatings. Self-supporting nanofiber gels induced accelerated, biomimetic mineralization

  17. Orthopaedic tissue engineering and bone regeneration.

    PubMed

    Dickson, Glenn; Buchanan, Fraser; Marsh, David; Harkin-Jones, Eileen; Little, Uel; McCaigue, Mervyn

    2007-01-01

    Orthopaedic tissue engineering combines the application of scaffold materials, cells and the release of growth factors. It has been described as the science of persuading the body to reconstitute or repair tissues that have failed to regenerate or heal spontaneously. In the case of bone regeneration 3-D scaffolds are used as a framework to guide tissue regeneration. Mesenchymal cells obtained from the patient via biopsy are grown on biomaterials in vitro and then implanted at a desired site in the patient's body. Medical implants that encourage natural tissue regeneration are generally considered more desirable than metallic implants that may need to be removed by subsequent intervention. Numerous polymeric materials, from natural and artificial sources, are under investigation as substitutes for skeletal elements such as cartilage and bone. For bone regeneration, cells (obtained mainly from bone marrow aspirate or as primary cell outgrowths from bone biopsies) can be combined with biodegradable polymeric materials and/or ceramics and absorbed growth factors so that osteoinduction is facilitated together with osteoconduction; through the creation of bioactive rather than bioinert scaffold constructs. Relatively rapid biodegradation enables advantageous filling with natural tissue while loss of polymer strength before mass is disadvantageous. Innovative solutions are required to address this and other issues such as the biocompatibility of material surfaces and the use of appropriate scaffold topography and porosity to influence bone cell gene expression.

  18. Molecular trafficking in tissue engineered cartilage constructs

    NASA Astrophysics Data System (ADS)

    de Rosa, Enrica

    2005-03-01

    Tissue processing in vitro requires an effective trafficking of biologically active agents within three-dimensional constructs for induction of appropriate and enhanced cellular growth, biosynthesis and tissue remodeling. Moreover, nutrients and waste products need to move freely through the cellular constructs to minimize the presence of regions with necrotic and/or apoptotic cells. In tissue-engineered cartilage, for example, during the time of culture, cells seeded within the three-dimensional constructs lay-down their own extracellular matrix and this may lead to a heterogeneous distribution of transport properties both in time and space. In this work the diffusion coefficient of BSA and 500kDa dextran has been measured with FRAP thecnique in agarose gel chondrocytes constructs at different position and time during the culture. The diffusion coefficient of both molecular probes within the developing tissue well correlated with the ECM production and assembly. Moreover the comparision between BSA and dextran transport parameters revealed a selective hindrance effect of the neo tissue on high interacting molecules.

  19. Craniofacial Tissue Engineering by Stem Cells

    PubMed Central

    Mao, J.J.; Giannobile, W.V.; Helms, J.A.; Hollister, S.J.; Krebsbach, P.H.; Longaker, M.T.; Shi, S.

    2008-01-01

    Craniofacial tissue engineering promises the regeneration or de novo formation of dental, oral, and craniofacial structures lost to congenital anomalies, trauma, and diseases. Virtually all craniofacial structures are derivatives of mesenchymal cells. Mesenchymal stem cells are the offspring of mesenchymal cells following asymmetrical division, and reside in various craniofacial structures in the adult. Cells with characteristics of adult stem cells have been isolated from the dental pulp, the deciduous tooth, and the periodontium. Several craniofacial structures—such as the mandibular condyle, calvarial bone, cranial suture, and subcutaneous adipose tissue—have been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches. As a departure from the reliance of current clinical practice on durable materials such as amalgam, composites, and metallic alloys, biological therapies utilize mesenchymal stem cells, delivered or internally recruited, to generate craniofacial structures in temporary scaffolding biomaterials. Craniofacial tissue engineering is likely to be realized in the foreseeable future, and represents an opportunity that dentistry cannot afford to miss. PMID:17062735

  20. Dendronized polyaniline nanotubes for cardiac tissue engineering.

    PubMed

    Moura, Renata Mendes; de Queiroz, Alvaro Antonio Alencar

    2011-05-01

    Today, nanobiomaterials represent a very important class of biomaterials because they differ dramatically in their bulk precursors. The properties of these materials are determined by the size and morphology, thus creating a fascinating line in their physicochemical properties. Polyaniline nanotubes (PANINTs) are one of the most promising nanobiomaterials for cardiac tissue engineering applications due to their electroactive properties. The biocompatibility and low hydrophilic properties of PANINTs can be improved by their functionalization with the highly hydrophilic polyglycerol dendrimers (PGLDs). Hydrophilicity plays a fundamental role in tissue regeneration and fundamental forces that govern the process of cell adhesion and proliferation. In this work, the biocompatible properties and cardiomyocyte proliferation onto PANINTs modified by PGLD are described. PGLDs were immobilized onto PANINTs via surface-initiated anionic ring-opening polymerization of glycidol. The microstructure and morphology of PGLD-PANINTs was determined by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), respectively. The cardiac cell growth on the PGLD-PANINTs was investigated. The PGLD-coated PANINTs showed noncytotoxic effects to Chinese hamster ovary cells. It was observed that the application of microcurrent stimulates the differentiation of cardiac cells cultured on PGLD-PANINTs scaffolds. The electroactive and biocompatible results of PGLD-PANINTs observed in this work demonstrate the potential of this nanobiomaterial for the culture of cardiac cells and open the possibility of using this material as a biocompatible electroactive three-dimensional matrix in cardiac tissue engineering.

  1. Tumor Engineering: The Other Face of Tissue Engineering

    SciTech Connect

    Ghajar, Cyrus M; Bissell, Mina J

    2010-03-09

    Advances in tissue engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function for a given tissue.We believe that the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of 'tumor engineering', that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physical scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment. In 1993, Vacanti and Langer cast a spotlight on the growing gap between patients in need of organ transplants and the amount of available donor organs; they reaffirmed that tissue engineering could eventually address this problem by 'applying principles of engineering and the life sciences toward the development of biological substitutes. Mortality figures and direct health care costs for cancer patients rival those of patients who experience organ failure. Cancer is the second leading cause of death in the United States (Source: American Cancer Society) and it is estimated that direct medical costs for cancer patients approach $100B yearly in the United States alone (Source: National Cancer Institute). In addition, any promising therapy that emerges from the laboratory costs roughly $1.7B to take from bench to bedside. Whereas we have indeed waged war on cancer, the

  2. Elastomeric PGS scaffolds in arterial tissue engineering.

    PubMed

    Lee, Kee-Won; Wang, Yadong

    2011-04-08

    Cardiovascular disease is one of the leading cause of mortality in the US and especially, coronary artery disease increases with an aging population and increasing obesity. Currently, bypass surgery using autologous vessels, allografts, and synthetic grafts are known as a commonly used for arterial substitutes. However, these grafts have limited applications when an inner diameter of arteries is less than 6 mm due to low availability, thrombotic complications, compliance mismatch, and late intimal hyperplasia. To overcome these limitations, tissue engineering has been successfully applied as a promising alternative to develop small-diameter arterial constructs that are nonthrombogenic, robust, and compliant. Several previous studies have developed small-diameter arterial constructs with tri-lamellar structure, excellent mechanical properties and burst pressure comparable to native arteries. While high tensile strength and burst pressure by increasing collagen production from a rigid material or cell sheet scaffold, these constructs still had low elastin production and compliance, which is a major problem to cause graft failure after implantation. Considering these issues, we hypothesized that an elastometric biomaterial combined with mechanical conditioning would provide elasticity and conduct mechanical signals more efficiently to vascular cells, which increase extracellular matrix production and support cellular orientation. The objective of this report is to introduce a fabrication technique of porous tubular scaffolds and a dynamic mechanical conditioning for applying them to arterial tissue engineering. We used a biodegradable elastomer, poly (glycerol sebacate) (PGS) for fabricating porous tubular scaffolds from the salt fusion method. Adult primary baboon smooth muscle cells (SMCs) were seeded on the lumen of scaffolds, which cultured in our designed pulsatile flow bioreactor for 3 weeks. PGS scaffolds had consistent thickness and randomly distributed macro

  3. Porous titanium bases for osteochondral tissue engineering

    PubMed Central

    Nover, Adam B.; Lee, Stephanie L.; Georgescu, Maria S.; Howard, Daniel R.; Saunders, Reuben A.; Yu, William T.; Klein, Robert W.; Napolitano, Anthony P.; Ateshian, Gerard A.

    2015-01-01

    Tissue engineering of osteochondral grafts may offer a cell-based alternative to native allografts, which are in short supply. Previous studies promote the fabrication of grafts consisting of a viable cell-seeded hydrogel integrated atop a porous, bone-like metal. Advantages of the manufacturing process have led to the evaluation of porous titanium as the bone-like base material. Here, porous titanium was shown to support the growth of cartilage to produce native levels of Young’s modulus, using a clinically relevant cell source. Mechanical and biochemical properties were similar or higher for the osteochondral constructs compared to chondral-only controls. Further investigation into the mechanical influence of the base on the composite material suggests that underlying pores may decrease interstitial fluid pressurization and applied strains, which may be overcome by alterations to the base structure. Future studies aim to optimize titanium-based tissue engineered osteochondral constructs to best match the structural architecture and strength of native grafts. Statement of Significance The studies described in this manuscript follow up on previous studies from our lab pertaining to the fabrication of osteochondral grafts that consist of a bone-like porous metal and a chondrocyte-seeded hydrogel. Here, tissue engineered osteochondral grafts were cultured to native stiffness using adult chondrocytes, a clinically relevant cell source, and a porous titanium base, a material currently used in clinical implants. This porous titanium is manufactured via selective laser melting, offering the advantages of precise control over shape, pore size, and orientation. Additionally, this manuscript describes the mechanical influence of the porous base, which may have applicability to porous bases derived from other materials. PMID:26320541

  4. Cells and materials for liver tissue engineering.

    PubMed

    Li, Yuan-Sheng; Harn, Horng-Jyh; Hsieh, Dean-Kuo; Wen, Tung-Chou; Subeq, Yi-Maun; Sun, Li-Yi; Lin, Shinn-Zong; Chiou, Tzyy-Wen

    2013-01-01

    Liver transplantation is currently the most efficacious treatment for end-stage liver diseases. However, one main problem with liver transplantation is the limited number of donor organs that are available. Therefore, liver tissue engineering based on cell transplantation that combines materials to mimic the liver is under investigation with the goal of restoring normal liver functions. Tissue engineering aims to mimic the interactions among cells with a scaffold. Particular materials or a matrix serve as a scaffold and provide a three-dimensional environment for cell proliferation and interaction. Moreover, the scaffold plays a role in regulating cell maturation and function via these interactions. In cultures of hepatic lineage cells, regulation of cell proliferation and specific function using biocompatible synthetic, biodegradable bioderived matrices, protein-coated materials, surface-modified nanofibers, and decellularized biomatrix has been demonstrated. Furthermore, beneficial effects of addition of growth factor cocktails to a flow bioreactor or coculture system on cell viability and function have been observed. In addition, a system for growing stem cells, liver progenitor cells, and primary hepatocytes for transplantation into animal models was developed, which produces hepatic lineage cells that are functional and that show long-term proliferation following transplantation. The major limitation of cells proliferated with matrix-based transplantation systems is the high initial cell loss and dysfunction, which may be due to the absence of blood flow and the changes in nutrients. Thus, the development of vascular-like scaffold structures, the formation of functional bile ducts, and the maintenance of complex metabolic functions remain as major problems in hepatic tissue engineering and will need to be addressed to enable further advances toward clinical applications.

  5. Tumor Engineering: The Other Face of Tissue Engineering

    PubMed Central

    2010-01-01

    Advances in tissue engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function for a given tissue. We believe that the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of ‘tumor engineering’, that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physical scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment. PMID:20214448

  6. Piezoelectric polymers as biomaterials for tissue engineering applications.

    PubMed

    Ribeiro, Clarisse; Sencadas, Vítor; Correia, Daniela M; Lanceros-Méndez, Senentxu

    2015-12-01

    Tissue engineering often rely on scaffolds for supporting cell differentiation and growth. Novel paradigms for tissue engineering include the need of active or smart scaffolds in order to properly regenerate specific tissues. In particular, as electrical and electromechanical clues are among the most relevant ones in determining tissue functionality in tissues such as muscle and bone, among others, electroactive materials and, in particular, piezoelectric ones, show strong potential for novel tissue engineering strategies, in particular taking also into account the existence of these phenomena within some specific tissues, indicating their requirement also during tissue regeneration. This referee reports on piezoelectric materials used for tissue engineering applications. The most used materials for tissue engineering strategies are reported together with the main achievements, challenges and future needs for research and actual therapies. This review provides thus a compilation of the most relevant results and strategies and a start point for novel research pathways in the most relevant and challenging open questions.

  7. Cryogenic 3D printing for tissue engineering.

    PubMed

    Adamkiewicz, Michal; Rubinsky, Boris

    2015-12-01

    We describe a new cryogenic 3D printing technology for freezing hydrogels, with a potential impact to tissue engineering. We show that complex frozen hydrogel structures can be generated when the 3D object is printed immersed in a liquid coolant (liquid nitrogen), whose upper surface is maintained at the same level as the highest deposited layer of the object. This novel approach ensures that the process of freezing is controlled precisely, and that already printed frozen layers remain at a constant temperature. We describe the device and present results which illustrate the potential of the new technology.

  8. Periodontics--tissue engineering and the future.

    PubMed

    Douglass, Gordon L

    2005-03-01

    Periodontics has a long history of utilizing advances in science to expand and improve periodontal therapies. Recently the American Academy of Periodontology published the findings of the Contemporary Science Workshop, which conducted state-of-the-art evidence-based reviews of current and emerging areas in periodontics. The findings of this workshop provide the basis for an evidence-based approach to periodontal therapy. While the workshop evaluated all areas of periodontics, it is in the area of tissue engineering that the most exciting advances are becoming a reality.

  9. Distilling complexity to advance cardiac tissue engineering

    PubMed Central

    Ogle, Brenda M.; Bursac, Nenad; Domian, Ibrahim; Huang, Ngan F; Menasché, Philippe; Murry, Charles; Pruitt, Beth; Radisic, Milica; Wu, Joseph C; Wu, Sean M; Zhang, Jianyi; Zimmermann, Wolfram-Hubertus; Vunjak-Novakovic, Gordana

    2016-01-01

    The promise of cardiac tissue engineering is in the ability to recapitulate in vitro the functional aspects of healthy heart and disease pathology as well as to design replacement muscle for clinical therapy. Parts of this promise have been realized; others have not. In a meeting of scientists in this field, five central challenges or “big questions” were articulated that, if addressed, could substantially advance the current state-of-the-art in modeling heart disease and realizing heart repair. PMID:27280684

  10. Tissue Engineering Considerations in Dental Pulp Regeneration

    PubMed Central

    Nosrat, Ali; Kim, Jong Ryul; Verma, Prashant; S. Chand, Priya

    2014-01-01

    Regenerative endodontic procedure is introduced as a biologically based treatment for immature teeth with pulp necrosis. Successful clinical and radiographic outcomes following regenerative procedures have been reported in landmark case reports. Retrospective studies have shown that this conservative treatment allows for continued root development and increases success and survival rate of the treated teeth compared to other treatment options. Although the goal of treatment is regeneration of a functional pulp tissue, histological analyses show a different outcome. Developing predictable protocols would require the use of key elements for tissue engineering: stem cells, bioactive scaffolds, and growth factors. In this study we will review the evidence based steps and outcomes of regenerative endodontics. PMID:24396373

  11. Combined additive manufacturing approaches in tissue engineering.

    PubMed

    Giannitelli, S M; Mozetic, P; Trombetta, M; Rainer, A

    2015-09-01

    Advances introduced by additive manufacturing (AM) have significantly improved the control over the microarchitecture of scaffolds for tissue engineering. This has led to the flourishing of research works addressing the optimization of AM scaffolds microarchitecture to optimally trade-off between conflicting requirements (e.g. mechanical stiffness and porosity level). A fascinating trend concerns the integration of AM with other scaffold fabrication methods (i.e. "combined" AM), leading to hybrid architectures with complementary structural features. Although this innovative approach is still at its beginning, significant results have been achieved in terms of improved biological response to the scaffold, especially targeting the regeneration of complex tissues. This review paper reports the state of the art in the field of combined AM, posing the accent on recent trends, challenges, and future perspectives.

  12. Biopreservation of cells and engineered tissues.

    PubMed

    Acker, Jason P

    2007-01-01

    The development of effective preservation and long-term storage techniques is a critical requirement for the successful clinical and commercial application of emerging cell-based technologies. Biopreservation is the process of preserving the integrity and functionality of cells, tissues and organs held outside the native environment for extended storage times. Biopreservation can be categorized into four different areas on the basis of the techniques used to achieve biological stability and to ensure a viable state following long-term storage. These include in vitro culture, hypothermic storage, cryopreservation and desiccation. In this chapter, an overview of these four techniques is presented with an emphasis on the recent developments that have been made using these technologies for the biopreservation of cells and engineered tissues.

  13. Tissue Engineering Organs for Space Biology Research

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.; Shansky, J.; DelTatto, M.; Lee, P.; Meir, J.

    1999-01-01

    Long-term manned space flight requires a better understanding of skeletal muscle atrophy resulting from microgravity. Atrophy most likely results from changes at both the systemic level (e.g. decreased circulating growth hormone, increased circulating glucocorticoids) and locally (e.g. decreased myofiber resting tension). Differentiated skeletal myofibers in tissue culture have provided a model system over the last decade for gaining a better understanding of the interactions of exogenous growth factors, endogenous growth factors, and muscle fiber tension in regulating protein turnover rates and muscle cell growth. Tissue engineering these cells into three dimensional bioartificial muscle (BAM) constructs has allowed us to extend their use to Space flight studies for the potential future development of countermeasures.

  14. Myocardial tissue engineering using electrospun nanofiber composites

    PubMed Central

    Kim, Pyung-Hwan; Cho, Je-Yoel

    2016-01-01

    Emerging trends for cardiac tissue engineering are focused on increasing the biocompatibility and tissue regeneration ability of artificial heart tissue by incorporating various cell sources and bioactive molecules. Although primary cardiomyocytes can be successfully implanted, clinical applications are restricted due to their low survival rates and poor proliferation. To develop successful cardiovascular tissue regeneration systems, new technologies must be introduced to improve myocardial regeneration. Electrospinning is a simple, versatile technique for fabricating nanofibers. Here, we discuss various biodegradable polymers (natural, synthetic, and combinatorial polymers) that can be used for fiber fabrication. We also describe a series of fiber modification methods that can increase cell survival, proliferation, and migration and provide supporting mechanical properties by mimicking micro-environment structures, such as the extracellular matrix (ECM). In addition, the applications and types of nanofiber-based scaffolds for myocardial regeneration are described. Finally, fusion research methods combined with stem cells and scaffolds to improve biocompatibility are discussed. [BMB Reports 2016; 49(1): 26-36] PMID:26497579

  15. Capillary Force Lithography for Cardiac Tissue Engineering

    PubMed Central

    Macadangdang, Jesse; Lee, Hyun Jung; Carson, Daniel; Jiao, Alex; Fugate, James; Pabon, Lil; Regnier, Michael; Murry, Charles; Kim, Deok-Ho

    2014-01-01

    Cardiovascular disease remains the leading cause of death worldwide1. Cardiac tissue engineering holds much promise to deliver groundbreaking medical discoveries with the aims of developing functional tissues for cardiac regeneration as well as in vitro screening assays. However, the ability to create high-fidelity models of heart tissue has proven difficult. The heart’s extracellular matrix (ECM) is a complex structure consisting of both biochemical and biomechanical signals ranging from the micro- to the nanometer scale2. Local mechanical loading conditions and cell-ECM interactions have recently been recognized as vital components in cardiac tissue engineering3-5. A large portion of the cardiac ECM is composed of aligned collagen fibers with nano-scale diameters that significantly influences tissue architecture and electromechanical coupling2. Unfortunately, few methods have been able to mimic the organization of ECM fibers down to the nanometer scale. Recent advancements in nanofabrication techniques, however, have enabled the design and fabrication of scalable scaffolds that mimic the in vivo structural and substrate stiffness cues of the ECM in the heart6-9. Here we present the development of two reproducible, cost-effective, and scalable nanopatterning processes for the functional alignment of cardiac cells using the biocompatible polymer poly(lactide-co-glycolide) (PLGA)8 and a polyurethane (PU) based polymer. These anisotropically nanofabricated substrata (ANFS) mimic the underlying ECM of well-organized, aligned tissues and can be used to investigate the role of nanotopography on cell morphology and function10-14. Using a nanopatterned (NP) silicon master as a template, a polyurethane acrylate (PUA) mold is fabricated. This PUA mold is then used to pattern the PU or PLGA hydrogel via UV-assisted or solvent-mediated capillary force lithography (CFL), respectively15,16. Briefly, PU or PLGA pre-polymer is drop dispensed onto a glass coverslip and the PUA

  16. Patterned melt electrospun substrates for tissue engineering.

    PubMed

    Dalton, Paul D; Joergensen, Nanna T; Groll, Juergen; Moeller, Martin

    2008-09-01

    Tissue engineering scaffolds can be built with patterning techniques that allow discrete placement of structures. In this study, electrospun fibres are collected in focused spots; the patterning and drawing of a cell adhesive scaffold is shown. Blends of biodegradable poly(ethylene glycol)-block-poly(epsilon-caprolactone) (PEG-b-PCL) and PCL were melt electrospun onto glass collectors, and the optimal electrospinning parameters determined. The quality of the fibre was largely influenced by the flow rate of the melt to the spinneret; however, this can be adjusted with the voltage. A collection distance between 3 cm and 5 cm was optimal, and at 10 cm the fibres became unfocused in their deposition although the diameter remained similar (0.96 +/- 0.19 microm). Aligned lines of electrospun fibres 200-400 microm in width could be applied onto the slide with an x-y stage, continuously and discretely. Lines of electrospun fibres could be applied on top of one another and were very uniform in diameter. Fibroblasts adhered primarily in the fibre region, due to the poor cell adhesion to the PEG substrate. Improvements in depositing hydrophilic electrospun fibres that wet and adhere to in vitro substrates and the use of stage automation for the writing interface could provide scaffold-building devices suitable for tissue engineering applications.

  17. Silk: A Potential Medium for Tissue Engineering

    PubMed Central

    Sobajo, Cassandra; Behzad, Farhad; Yuan, Xue-Feng; Bayat, Ardeshir

    2008-01-01

    Objective: Human skin is a complex bilayered organ that serves as a protective barrier against the environment. The loss of integrity of skin by traumatic experiences such as burns and ulcers may result in considerable disability or ultimately death. Therefore, in skin injuries, adequate dermal substitutes are among primary care targets, aimed at replacing the structural and functional properties of native skin. To date, there are very few single application tissue-engineered dermal constructs fulfilling this criterion. Silk produced by the domestic silkworm, Bombyx mori, has a long history of use in medicine. It has recently been increasingly investigated as a promising biomaterial for dermal constructs. Silk contains 2 fibrous proteins, sericin and fibroin. Each one exhibits unique mechanical and biological properties. Methods: Comprehensive review of randomized-controlled trials investigating current dermal constructs and the structures and properties of silk-based constructs on wound healing. Results: This review revealed that silk-fibroin is regarded as the most promising biomaterial, providing options for the construction of tissue-engineered skin. Conclusion: The research available indicates that silk fibroin is a suitable biomaterial scaffold for the provision of adequate dermal constructs. PMID:18997857

  18. A multilayer tissue engineered meniscus substitute.

    PubMed

    Halili, Albana Ndreu; Hasirci, Nesrin; Hasirci, Vasif

    2014-04-01

    Various methods have been tried to treat the main meniscus problem, meniscal tears, for which we believe tissue engineering could be a viable solution. In this study, a three dimensional, collagen-based meniscus substitute was prepared by tissue engineering using human fibrochondrocytes and a collagen based-scaffold. This construct was made with 3 different collagen-based foams interspaced with two electrospun nano/microfibrous mats. The top layer was made of collagen type I-chondroitin sulfate-hyaluronic acid (Coll-CS-HA), and the middle and the bottom layers were made of only collagen type I with different porosities and thus with different mechanical properties. The mats of aligned fibers were a blend of collagen type I and poly(L-lactic acid-co-glycolic acid) (PLGA). After seeding with human fibrochondrocytes, cell attachment, proliferation, and production of extracellular matrix and glucoseaminoglycan were studied. Cell seeding had a positive effect on the compressive properties of foams and the 3D construct. The 3D construct with all its 5 layers had better mechanical properties than the individual foams.

  19. Synthetic cornea: biocompatibility and optics

    NASA Astrophysics Data System (ADS)

    Parel, Jean-Marie A.; Kaminski, Stefan; Fernandez, Viviana; Alfonso, E.; Lamar, Peggy; Lacombe, Emmanuel; Duchesne, Bernard; Dubovy, Sander; Manns, Fabrice; Rol, Pascal O.

    2002-06-01

    Purpose. Experimentally find a method to provide a safe surgical technique and an inexpensive and long lasting mesoplant for the restoration of vision in patients with bilateral corneal blindness due to ocular surface and stromal diseases. Methods. Identify the least invasive and the safest surgical technique for synthetic cornea implantation. Identify the most compatible biomaterials and the optimal shape a synthetic cornea must have to last a long time when implanted in vivo. Results. Penetrating procedures were deemed too invasive, time consuming, difficult and prone to long term complications. Therefore a non-penetrating delamination technique with central trephination was developed to preserve the integrity of Descemet's membrane and the anterior segment. Even though this approach limits the number of indications, it is acceptable since the majority of patients only have opacities in the stroma. The prosthesis was designed to fit in the removed tissue plane with its skirt fitted under the delaminated stroma. To improve retention, the trephination wall was made conical with the smallest opening on the anterior surface and a hat-shaped mesoplant was made to fit. The skirt was perforated in its perimeter to allow passage of nutrients and tissues ingrowths. To simplify the fabrication procedure, the haptic and optic were made of the same polymer. The intrastromal biocompatibility of several hydrogels was found superior to current clinically used PMMA and PTFE materials. Monobloc mesoplants made of 4 different materials were implanted in rabbits and followed weekly until extrusion occurred. Some remained optically clear allowing for fundus photography. Conclusions. Hydrogel synthetic corneas can be made to survive for periods longer than 1 year. ArF excimer laser photoablation studies are needed to determine the refractive correction potential of these mesoplants. A pilot FDA clinical trial is needed to assess the mesoplant efficacy and very long-term stability.

  20. An overview of recent patents on musculoskeletal interface tissue engineering.

    PubMed

    Rao, Rohit T; Browe, Daniel P; Lowe, Christopher J; Freeman, Joseph W

    2016-01-01

    Interface tissue engineering involves the development of engineered grafts that promote integration between multiple tissue types. Musculoskeletal tissue interfaces are critical to the safe and efficient transmission of mechanical forces between multiple musculoskeletal tissues, e.g., between ligament and bone tissue. However, these interfaces often do not physiologically regenerate upon injury, resulting in impaired tissue function. Therefore, interface tissue engineering approaches are considered to be particularly relevant for the structural restoration of musculoskeletal tissues interfaces. In this article, we provide an overview of the various strategies used for engineering musculoskeletal tissue interfaces with a specific focus on the recent important patents that have been issued for inventions that were specifically designed for engineering musculoskeletal interfaces as well as those that show promise to be adapted for this purpose.

  1. Photocrosslinkable Gelatin Hydrogel for Epidermal Tissue Engineering.

    PubMed

    Zhao, Xin; Lang, Qi; Yildirimer, Lara; Lin, Zhi Yuan; Cui, Wenguo; Annabi, Nasim; Ng, Kee Woei; Dokmeci, Mehmet R; Ghaemmaghami, Amir M; Khademhosseini, Ali

    2016-01-07

    Natural hydrogels are promising scaffolds to engineer epidermis. Currently, natural hydrogels used to support epidermal regeneration are mainly collagen- or gelatin-based, which mimic the natural dermal extracellular matrix but often suffer from insufficient and uncontrollable mechanical and degradation properties. In this study, a photocrosslinkable gelatin (i.e., gelatin methacrylamide (GelMA)) with tunable mechanical, degradation, and biological properties is used to engineer the epidermis for skin tissue engineering applications. The results reveal that the mechanical and degradation properties of the developed hydrogels can be readily modified by varying the hydrogel concentration, with elastic and compressive moduli tuned from a few kPa to a few hundred kPa, and the degradation times varied from a few days to several months. Additionally, hydrogels of all concentrations displayed excellent cell viability (>90%) with increasing cell adhesion and proliferation corresponding to increases in hydrogel concentrations. Furthermore, the hydrogels are found to support keratinocyte growth, differentiation, and stratification into a reconstructed multilayered epidermis with adequate barrier functions. The robust and tunable properties of GelMA hydrogels suggest that the keratinocyte laden hydrogels can be used as epidermal substitutes, wound dressings, or substrates to construct various in vitro skin models.

  2. Tissue engineering skeletal muscle for orthopaedic applications

    NASA Technical Reports Server (NTRS)

    Payumo, Francis C.; Kim, Hyun D.; Sherling, Michael A.; Smith, Lee P.; Powell, Courtney; Wang, Xiao; Keeping, Hugh S.; Valentini, Robert F.; Vandenburgh, Herman H.

    2002-01-01

    With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.

  3. Tissue engineering of cartilage in space

    PubMed Central

    Freed, Lisa E.; Langer, Robert; Martin, Ivan; Pellis, Neal R.; Vunjak-Novakovic, Gordana

    1997-01-01

    Tissue engineering of cartilage, i.e., the in vitro cultivation of cartilage cells on synthetic polymer scaffolds, was studied on the Mir Space Station and on Earth. Specifically, three-dimensional cell-polymer constructs consisting of bovine articular chondrocytes and polyglycolic acid scaffolds were grown in rotating bioreactors, first for 3 months on Earth and then for an additional 4 months on either Mir (10−4–10−6 g) or Earth (1 g). This mission provided a unique opportunity to study the feasibility of long-term cell culture flight experiments and to assess the effects of spaceflight on the growth and function of a model musculoskeletal tissue. Both environments yielded cartilaginous constructs, each weighing between 0.3 and 0.4 g and consisting of viable, differentiated cells that synthesized proteoglycan and type II collagen. Compared with the Earth group, Mir-grown constructs were more spherical, smaller, and mechanically inferior. The same bioreactor system can be used for a variety of controlled microgravity studies of cartilage and other tissues. These results may have implications for human spaceflight, e.g., a Mars mission, and clinical medicine, e.g., improved understanding of the effects of pseudo-weightlessness in prolonged immobilization, hydrotherapy, and intrauterine development. PMID:9391122

  4. Textile Technologies and Tissue Engineering: A Path Toward Organ Weaving.

    PubMed

    Akbari, Mohsen; Tamayol, Ali; Bagherifard, Sara; Serex, Ludovic; Mostafalu, Pooria; Faramarzi, Negar; Mohammadi, Mohammad Hossein; Khademhosseini, Ali

    2016-04-06

    Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, microarchitecture, and mechanical properties of the fabrics play important roles in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted.

  5. Textile Technologies and Tissue Engineering: A Path Towards Organ Weaving

    PubMed Central

    Akbari, Mohsen; Tamayol, Ali; Bagherifard, Sara; Serex, Ludovic; Mostafalu, Pooria; Faramarzi, Negar; Mohammadi, Mohammad Hossein

    2016-01-01

    Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, pore size and mechanical properties of the fabrics play important role in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted. PMID:26924450

  6. Quantitative Ultrasound for Nondestructive Characterization of Engineered Tissues and Biomaterials.

    PubMed

    Dalecki, Diane; Mercado, Karla P; Hocking, Denise C

    2016-03-01

    Non-invasive, non-destructive technologies for imaging and quantitatively monitoring the development of artificial tissues are critical for the advancement of tissue engineering. Current standard techniques for evaluating engineered tissues, including histology, biochemical assays and mechanical testing, are destructive approaches. Ultrasound is emerging as a valuable tool for imaging and quantitatively monitoring the properties of engineered tissues and biomaterials longitudinally during fabrication and post-implantation. Ultrasound techniques are rapid, non-invasive, non-destructive and can be easily integrated into sterile environments necessary for tissue engineering. Furthermore, high-frequency quantitative ultrasound techniques can enable volumetric characterization of the structural, biological, and mechanical properties of engineered tissues during fabrication and post-implantation. This review provides an overview of ultrasound imaging, quantitative ultrasound techniques, and elastography, with representative examples of applications of these ultrasound-based techniques to the field of tissue engineering.

  7. Natural and Genetically Engineered Proteins for Tissue Engineering

    PubMed Central

    Gomes, Sílvia; Leonor, Isabel B.; Mano, João F.; Reis, Rui L.

    2011-01-01

    To overcome the limitations of traditionally used autografts, allografts and, to a lesser extent, synthetic materials, there is the need to develop a new generation of scaffolds with adequate mechanical and structural support, control of cell attachment, migration, proliferation and differentiation and with bio-resorbable features. This suite of properties would allow the body to heal itself at the same rate as implant degradation. Genetic engineering offers a route to this level of control of biomaterial systems. The possibility of expressing biological components in nature and to modify or bioengineer them further, offers a path towards multifunctional biomaterial systems. This includes opportunities to generate new protein sequences, new self-assembling peptides or fusions of different bioactive domains or protein motifs. New protein sequences with tunable properties can be generated that can be used as new biomaterials. In this review we address some of the most frequently used proteins for tissue engineering and biomedical applications and describe the techniques most commonly used to functionalize protein-based biomaterials by combining them with bioactive molecules to enhance biological performance. We also highlight the use of genetic engineering, for protein heterologous expression and the synthesis of new protein-based biopolymers, focusing the advantages of these functionalized biopolymers when compared with their counterparts extracted directly from nature and modified by techniques such as physical adsorption or chemical modification. PMID:22058578

  8. The Role of Bioreactors in Tissue Engineering for Musculoskeletal Applications

    PubMed Central

    Oragui, Emeka; Nannaparaju, Madhusudhan; Khan, Wasim S

    2011-01-01

    Tissue engineering involves using the principles of biology, chemistry and engineering to design a ‘neotissue’ that augments a malfunctioning in vivo tissue. The main requirements for functional engineered tissue include reparative cellular components that proliferate on a biocompatible scaffold grown within a bioreactor that provides specific biochemical and physical signals to regulate cell differentiation and tissue assembly. We discuss the role of bioreactors in tissue engineering and evaluate the principles of bioreactor design. We evaluate the methods of cell stimulation and review the bioreactors in common use today. PMID:21886691

  9. Multilayered Electrospun Scaffolds for Tendon Tissue Engineering

    PubMed Central

    Chainani, Abby; Hippensteel, Kirk J.; Kishan, Alysha; Garrigues, N. William; Ruch, David S.; Guilak, Farshid

    2013-01-01

    Full-thickness rotator cuff tears are one of the most common causes of shoulder pain in people over the age of 65. High retear rates and poor functional outcomes are common after surgical repair, and currently available extracellular matrix scaffold patches have limited abilities to enhance new tendon formation. In this regard, tissue-engineered scaffolds may provide a means to improve repair of rotator cuff tears. Electrospinning provides a versatile method for creating nanofibrous scaffolds with controlled architectures, but several challenges remain in its application to tissue engineering, such as cell infiltration through the full thickness of the scaffold as well as control of cell growth and differentiation. Previous studies have shown that ligament-derived extracellular matrix may enhance differentiation toward a tendon or ligament phenotype by human adipose stem cells (hASCs). In this study, we investigated the use of tendon-derived extracellular matrix (TDM)-coated electrospun multilayered scaffolds compared to fibronectin (FN) or phosphate-buffered saline (PBS) coating for use in rotator cuff tendon tissue engineering. Multilayered poly(ɛ-caprolactone) scaffolds were prepared by sequentially collecting electrospun layers onto the surface of a grounded saline solution into a single scaffold. Scaffolds were then coated with TDM, FN, or PBS and seeded with hASCs. Scaffolds were maintained without exogenous growth factors for 28 days in culture and evaluated for protein content (by immunofluorescence and biochemical assay), markers of tendon differentiation, and tensile mechanical properties. The collagen content was greatest by day 28 in TDM-scaffolds. Gene expression of type I collagen, decorin, and tenascin C increased over time, with no effect of scaffold coating. Sulfated glycosaminoglycan and dsDNA contents increased over time in culture, but there was no effect of scaffold coating. The Young's modulus did not change over time, but yield strain

  10. Tissue Engineering-Current Challenges and Expanding Opportunities

    NASA Astrophysics Data System (ADS)

    Griffith, Linda G.; Naughton, Gail

    2002-02-01

    Tissue engineering can be used to restore, maintain, or enhance tissues and organs. The potential impact of this field, however, is far broader-in the future, engineered tissues could reduce the need for organ replacement, and could greatly accelerate the development of new drugs that may cure patients, eliminating the need for organ transplants altogether.

  11. Tissue engineering in endodontics: root canal revascularization.

    PubMed

    Palit Madhu Chanda; Hegde, K Sundeep; Bhat, Sham S; Sargod, Sharan S; Mantha, Somasundar; Chattopadhyay, Sayan

    2014-01-01

    Root canal revascularization attempts to make necrotic tooth alive by the use of certain simple clinical protocols. Earlier apexification was the treatment of choice for treating and preserving immature permanent teeth that have lost pulp vitality. This procedure promoted the formation of apical barrier to seal the root canal of immature teeth and nonvital filling materials contained within root canal space. However with the success of root canal revascularization to regenerate the pulp dentin complex of necrotic immature tooth has made us to rethink if apexification is at the beginning of its end. The objective of this review is to discuss the new concepts of tissue engineering in endodontics and the clinical steps of root canal revascularization.

  12. Tissue engineering scaffolds electrospun from cotton cellulose.

    PubMed

    He, Xu; Cheng, Long; Zhang, Ximu; Xiao, Qiang; Zhang, Wei; Lu, Canhui

    2015-01-22

    Nonwovens of cellulose nanofibers were fabricated by electrospinning of cotton cellulose in its LiCl/DMAc solution. The key factors associated with the electrospinning process, including the intrinsic properties of cellulose solutions, the rotating speed of collector and the applied voltage, were systematically investigated. XRD data indicated the electrospun nanofibers were almost amorphous. When increasing the rotating speed of the collector, preferential alignment of fibers along the drawing direction and improved molecular orientation were revealed by scanning electron microscope and polarized FTIR, respectively. Tensile tests indicated the strength of the nonwovens along the orientation direction could be largely improved when collected at a higher speed. In light of the excellent biocompatibility and biodegradability as well as their unique porous structure, the nonwovens were further assessed as potential tissue engineering scaffolds. Cell culture experiments demonstrated human dental follicle cells could proliferate rapidly not only on the surface but also in the entire scaffold.

  13. Conducting scaffolds for liver tissue engineering.

    PubMed

    Rad, Armin Tahmasbi; Ali, Naushad; Kotturi, Hari Shankar R; Yazdimamaghani, Mostafa; Smay, Jim; Vashaee, Daryoosh; Tayebi, Lobat

    2014-11-01

    It is known that there is a correlation between a cell membrane potential and the proliferation of the cell. The high proliferation capacity of liver cells can also be attributed to its specific cell membrane potential as liver cell is recognized as one of the most depolarized of all differentiated cells. We hypothesized that this phenomenon can be emphasized by growing liver cells in conducting scaffolds that can increase the electrical communication among the cells. In this article, using tissue engineering techniques, we grew hepatocyte cells in scaffolds with various compositions. It was found that the scaffolds containing conducting polymer of poly (3,4-ethylenedioxythiophene) (PEDOT) provide the best condition for attachment and proliferation of the cells. More specifically, the blend of hyaluronan, PEDOT, and collagen (I) as dopants in gelatin-chitosan-based scaffold presented the best cell/scaffold interactions for regeneration of liver cells.

  14. Tissue engineering of biphasic joint cartilage transplants.

    PubMed

    Kreklau, B; Sittinger, M; Mensing, M B; Voigt, C; Berger, G; Burmester, G R; Rahmanzadeh, R; Gross, U

    1999-09-01

    In isolated posttraumatic or idiopathic joint defects the chondral layers and adjacent subchondral spongy bone are usually destructed. For regeneration we suggest the in vitro formation of a cartilage-coated biomaterial carriers (biphases) in order to fill the correspondingjoint defects. In this study Biocoral, a natural coralline material made of calcium carbonate, and calcite, a synthetic calcium carbonate, were used as supports for the cultivation of bovine chondrocytes in a three-dimensional polymer fleece. The cell-polymer-structure was affixed to the biomaterial with a fibrin-cell-solution. The artificial cartilage formed a new matrix and fused with the underlying biomaterial. The results indicate a promising technical approach to anchor tissue engineered cartilage in joint defects.

  15. Oriented collagen nanocoatings for tissue engineering.

    PubMed

    Pastorino, Laura; Dellacasa, Elena; Scaglione, Silvia; Giulianelli, Massimo; Sbrana, Francesca; Vassalli, Massimo; Ruggiero, Carmelina

    2014-02-01

    Collagens are among the most widely present and important proteins composing the human total body, providing strength and structural stability to various tissues, from skin to bone. In this paper, we report an innovative approach to bioactivate planar surfaces with oriented collagen molecules to promote cells proliferation and alignment. The Langmuir-Blodgett technique was used to form a stable collagen film at the air-water interface and the Langmuir-Schaefer deposition was adopted to transfer it to the support surface. The deposition process was monitored by estimating the mass of the protein layers after each deposition step. Collagen films were then structurally characterized by atomic force, scanning electron and fluorescent microscopies. Finally, collagen films were functionally tested in vitro. To this aim, 3T3 cells were seeded onto the silicon supports either modified or not (control) by collagen film deposition. Cells adhesion and proliferation on collagen films were found to be greater than those on control both after 1 (p<0.05) and 7 days culture. Moreover, the functionalization of the substrate surface triggered a parallel orientation of cells when cultured on it. In conclusion, these data demonstrated that the Langmuir-Schaefer technique can be successfully used for the deposition of oriented collagen films for tissue engineering applications.

  16. Tissue Engineered Constructs: Perspectives on Clinical Translation

    PubMed Central

    Lu, Lichun; Arbit, Harvey M.; Herrick, James L.; Segovis, Suzanne Glass; Maran, Avudaiappan; Yaszemski, Michael J.

    2015-01-01

    In this article, a “bedside to bench and back” approach for developing tissue engineered medical products (TEMPs) for clinical applications is reviewed. The driving force behind this approach is unmet clinical needs. Preclinical research, both in vitro and in vivo using small and large animal models, will help find solutions to key research questions. In clinical research, ethical issues regarding the use of cells and tissues, their sources, donor consent, as well as clinical trials are important considerations. Regulatory issues, at both institutional and government levels, must be addressed prior to the translation of TEMPs to clinical practice. TEMPs are regulated as drugs, biologics, devices, or combination products by the US Food and Drug Administration (FDA). Depending on the mode of regulation, applications for TEMP introduction must be filed with the FDA to demonstrate safety and effectiveness in premarket clinical studies, followed by 510(k) premarket clearance or premarket approval (for medical devices), biologics license application approval (for biologics), or New Drug Application approval (for drugs). A case study on nerve cuffs is presented to illustrate the regulatory process. Finally, perspectives on commercialization such as finding a company partner and funding issues, as well as physician culture change, are presented. PMID:25711151

  17. Controlling the Porosity and Microarchitecture of Hydrogels for Tissue Engineering

    PubMed Central

    Annabi, Nasim; Nichol, Jason W.; Zhong, Xia; Ji, Chengdong; Koshy, Sandeep; Khademhosseini, Ali

    2010-01-01

    Tissue engineering holds great promise for regeneration and repair of diseased tissues, making the development of tissue engineering scaffolds a topic of great interest in biomedical research. Because of their biocompatibility and similarities to native extracellular matrix, hydrogels have emerged as leading candidates for engineered tissue scaffolds. However, precise control of hydrogel properties, such as porosity, remains a challenge. Traditional techniques for creating bulk porosity in polymers have demonstrated success in hydrogels for tissue engineering; however, often the conditions are incompatible with direct cell encapsulation. Emerging technologies have demonstrated the ability to control porosity and the microarchitectural features in hydrogels, creating engineered tissues with structure and function similar to native tissues. In this review, we explore the various technologies for controlling the porosity and microarchitecture within hydrogels, and demonstrate successful applications of combining these techniques. PMID:20121414

  18. Macrophages modulate engineered human tissues for enhanced vascularization and healing

    PubMed Central

    Spiller, Kara L.; Freytes, Donald O.; Vunjak-Novakovic, Gordana

    2014-01-01

    Tissue engineering is increasingly based on recapitulating human physiology, through integration of biological principles into engineering designs. In spite of all progress in engineering functional human tissues, we are just beginning to develop effective methods for establishing blood perfusion and controlling the inflammatory factors following implantation into the host. Functional vasculature largely determines tissue survival and function in vivo. The inflammatory response is a major regulator of vascularization and overall functionality of engineered tissues, through the activity of different types of macrophages and the cytokines they secrete. We discuss cell-scaffold-bioreactor systems for harnessing the inflammatory response for enhanced tissue vascularization and healing. To this end, inert scaffolds that have been considered for many decades a “gold standard” in regenerative medicine are beginning to be replaced by a new generation of “smart” tissue engineering systems designed to actively mediate tissue survival and function. PMID:25331098

  19. Optimization of electrical stimulation parameters for cardiac tissue engineering.

    PubMed

    Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo; Park, Hyoungshin; Vunjak-Novakovic, Gordana

    2011-06-01

    In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile engineered cardiac tissues. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, were thus used in tissue engineering studies. Engineered cardiac tissues stimulated at 3 V/cm amplitude and 3 Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43 and the best-developed contractile behaviour. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering.

  20. The use of nanoscaffolds and dendrimers in tissue engineering.

    PubMed

    Gorain, Bapi; Tekade, Muktika; Kesharwani, Prashant; Iyer, Arun K; Kalia, Kiran; Tekade, Rakesh Kumar

    2017-02-20

    To avoid tissue rejection during organ transplantation, research has focused on the use of tissue engineering to regenerate required tissues or organs for patients. The biomedical applications of hyperbranched, multivalent, structurally uniform, biocompatible dendrimers in tissue engineering include the mimicking of natural extracellular matrices (ECMs) in the 3D microenvironment. Dendrimers are unimolecular architects that can incorporate a variety of biological and/or chemical substances in a 3D architecture to actively support the scaffold microenvironment during cell growth. Here, we review the use of dendritic delivery systems in tissue engineering. We discuss the available literature, highlighting the 3D architecture and preparation of these nanoscaffolds, and also review challenges to, and advances in, the use dendrimers in tissue engineering. Advances in the manufacturing of dendritic nanoparticles and scaffold architectures have resulted in the successful incorporation of dendritic scaffolds in tissue engineering.

  1. Functional tissue engineering of ligament healing

    PubMed Central

    2010-01-01

    Ligaments and tendons are dense connective tissues that are important in transmitting forces and facilitate joint articulation in the musculoskeletal system. Their injury frequency is high especially for those that are functional important, like the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) of the knee as well as the glenohumeral ligaments and the rotator cuff tendons of the shoulder. Because the healing responses are different in these ligaments and tendons after injury, the consequences and treatments are tissue- and site-specific. In this review, we will elaborate on the injuries of the knee ligaments as well as using functional tissue engineering (FTE) approaches to improve their healing. Specifically, the ACL of knee has limited capability to heal, and results of non-surgical management of its midsubstance rupture have been poor. Consequently, surgical reconstruction of the ACL is regularly performed to gain knee stability. However, the long-term results are not satisfactory besides the numerous complications accompanied with the surgeries. With the rapid development of FTE, there is a renewed interest in revisiting ACL healing. Approaches such as using growth factors, stem cells and scaffolds have been widely investigated. In this article, the biology of normal and healing ligaments is first reviewed, followed by a discussion on the issues related to the treatment of ACL injuries. Afterwards, current promising FTE methods are presented for the treatment of ligament injuries, including the use of growth factors, gene delivery, and cell therapy with a particular emphasis on the use of ECM bioscaffolds. The challenging areas are listed in the future direction that suggests where collection of energy could be placed in order to restore the injured ligaments and tendons structurally and functionally. PMID:20492676

  2. Biomimetic nanoclay scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Ambre, Avinash Harishchandra

    Tissue engineering offers a significant potential alternative to conventional methods for rectifying tissue defects by evoking natural regeneration process via interactions between cells and 3D porous scaffolds. Imparting adequate mechanical properties to biodegradable scaffolds for bone tissue engineering is an important challenge and extends from molecular to macroscale. This work focuses on the use of sodium montmorillonite (Na-MMT) to design polymer composite scaffolds having enhanced mechanical properties along with multiple interdependent properties. Materials design beginning at the molecular level was used in which Na-MMT clay was modified with three different unnatural amino acids and further characterized using Fourier Transform Infrared (FTIR) spectroscopy, X-ray diffraction (XRD). Based on improved bicompatibility with human osteoblasts (bone cells) and intermediate increase in d-spacing of MMT clay (shown by XRD), 5-aminovaleric acid modified clay was further used to prepare biopolymer (chitosan-polygalacturonic acid complex) scaffolds. Osteoblast proliferation in biopolymer scaffolds containing 5-aminovaleric acid modified clay was similar to biopolymer scaffolds containing hydroxyapatite (HAP). A novel process based on biomineralization in bone was designed to prepare 5-aminovaleric acid modified clay capable of imparting multiple properties to the scaffolds. Bone-like apatite was mineralized in modified clay and a novel nanoclay-HAP hybrid (in situ HAPclay) was obtained. FTIR spectroscopy indicated a molecular level organic-inorganic association between the intercalated 5-aminovaleric acid and mineralized HAP. Osteoblasts formed clusters on biopolymer composite films prepared with different weight percent compositions of in situ HAPclay. Human MSCs formed mineralized nodules on composite films and mineralized extracellular matrix (ECM) in composite scaffolds without the use of osteogenic supplements. Polycaprolactone (PCL), a synthetic polymer, was

  3. Bioreactors for Tissue Engineering of Cartilage

    NASA Astrophysics Data System (ADS)

    Concaro, S.; Gustavson, F.; Gatenholm, P.

    The cartilage regenerative medicine field has evolved during the last decades. The first-generation technology, autologous chondrocyte transplantation (ACT) involved the transplantation of in vitro expanded chondrocytes to cartilage defects. The second generation involves the seeding of chondrocytes in a three-dimensional scaffold. The technique has several potential advantages such as the ability of arthroscopic implantation, in vitro pre-differentiation of cells and implant stability among others (Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L, N Engl J Med 331(14):889-895, 1994; Henderson I, Francisco R, Oakes B, Cameron J, Knee 12(3):209-216, 2005; Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A, Clin Orthop (374):212-234, 2000; Nagel-Heyer S, Goepfert C, Feyerabend F, Petersen JP, Adamietz P, Meenen NM, et al. Bioprocess Biosyst Eng 27(4):273-280, 2005; Portner R, Nagel-Heyer S, Goepfert C, Adamietz P, Meenen NM, J Biosci Bioeng 100(3):235-245, 2005; Nagel-Heyer S, Goepfert C, Adamietz P, Meenen NM, Portner R, J Biotechnol 121(4):486-497, 2006; Heyland J, Wiegandt K, Goepfert C, Nagel-Heyer S, Ilinich E, Schumacher U, et al. Biotechnol Lett 28(20):1641-1648, 2006). The nutritional requirements of cells that are synthesizing extra-cellular matrix increase along the differentiation process. The mass transfer must be increased according to the tissue properties. Bioreactors represent an attractive tool to accelerate the biochemical and mechanical properties of the engineered tissues providing adequate mass transfer and physical stimuli. Different reactor systems have been [5] developed during the last decades based on different physical stimulation concepts. Static and dynamic compression, confined and nonconfined compression-based reactors have been described in this review. Perfusion systems represent an attractive way of culturing constructs under dynamic conditions. Several groups showed increased matrix

  4. STUDIES ON THE CORNEA

    PubMed Central

    Kaye, Gordon I.; Pappas, George D.

    1962-01-01

    Physiological studies have demonstrated that ions, as well as large molecules such as hemoglobin or fluorescein, can diffuse across and within the cornea. Most of the substrates for corneal metabolism are obtained from aqueous humor filling the anterior chamber. In order to receive its nutrients and in order to maintain its normal conditions of hydration, the avascular cornea must transport relatively large amounts of solute and solvent across the cellular layers which cover this structure. It has been suggested in the past that there may be a morphological basis for the transport of large amounts of solvents and solutes by cells by the mechanism of pinocytosis. The use of electron-opaque markers to study fluid movements at the electron microscope magnification level was described by Wissig (29). The present study describes the fine structure of the normal rabbit cornea and the pathways of transport of colloidal particles by the cornea in vivo. Rabbit corneas were exposed in vivo to suspensions of saccharated iron oxide, thorium dioxide, or ferritin by injection of the material into the anterior chamber. In other experiments thorium dioxide or saccharated iron oxide was injected into the corneal stroma, producing a small bleb. Particles presented at the aqueous humor surface of the rabbit corneal endothelium are first attached to the cell surface and then pinocytosed. It appears that the particles are carried around the terminal bar by an intracellular pathway involving the pinocytosis of the particles and their subsequent transport in vesicles to the lateral cell margin basal to the terminal bar. Particles introduced at the basal surface of the endothelium (via blebs in the corneal stroma) are apparently carried through the endothelial cells in membrane-bounded vesicles without appearing in the intercellular space. There appears to be free diffusion of these particles through Descemet's membrane and the corneal stroma. The stromal cells take up large quantities of

  5. Tissue engineering strategies to study cartilage development, degeneration and regeneration.

    PubMed

    Bhattacharjee, Maumita; Coburn, Jeannine; Centola, Matteo; Murab, Sumit; Barbero, Andrea; Kaplan, David L; Martin, Ivan; Ghosh, Sourabh

    2015-04-01

    Cartilage tissue engineering has primarily focused on the generation of grafts to repair cartilage defects due to traumatic injury and disease. However engineered cartilage tissues have also a strong scientific value as advanced 3D culture models. Here we first describe key aspects of embryonic chondrogenesis and possible cell sources/culture systems for in vitro cartilage generation. We then review how a tissue engineering approach has been and could be further exploited to investigate different aspects of cartilage development and degeneration. The generated knowledge is expected to inform new cartilage regeneration strategies, beyond a classical tissue engineering paradigm.

  6. Micro- and nanotechnology in cardiovascular tissue engineering.

    PubMed

    Zhang, Boyang; Xiao, Yun; Hsieh, Anne; Thavandiran, Nimalan; Radisic, Milica

    2011-12-09

    While in nature the formation of complex tissues is gradually shaped by the long journey of development, in tissue engineering constructing complex tissues relies heavily on our ability to directly manipulate and control the micro-cellular environment in vitro. Not surprisingly, advancements in both microfabrication and nanofabrication have powered the field of tissue engineering in many aspects. Focusing on cardiac tissue engineering, this paper highlights the applications of fabrication techniques in various aspects of tissue engineering research: (1) cell responses to micro- and nanopatterned topographical cues, (2) cell responses to patterned biochemical cues, (3) controlled 3D scaffolds, (4) patterned tissue vascularization and (5) electromechanical regulation of tissue assembly and function.

  7. From in vitro to in situ tissue engineering.

    PubMed

    Sengupta, Debanti; Waldman, Stephen D; Li, Song

    2014-07-01

    In vitro tissue engineering enables the fabrication of functional tissues for tissue replacement. In addition, it allows us to build useful physiological and pathological models for mechanistic studies. However, the translation of in vitro tissue engineering into clinical therapies presents a number of technical and regulatory challenges. It is possible to circumvent the complexity of developing functional tissues in vitro by taking an in situ tissue engineering approach that uses the body as a native bioreactor to regenerate tissues. This approach harnesses the innate regenerative potential of the body and directs the appropriate cells to the site of injury. This review surveys the biomaterial-, cell-, and chemical factor-based strategies to engineer tissue in vitro and in situ.

  8. Computer-aided tissue engineering: overview, scope and challenges.

    PubMed

    Sun, Wei; Darling, Andrew; Starly, Binil; Nam, Jae

    2004-02-01

    Advances in computer-aided technology and its application with biology, engineering and information science to tissue engineering have evolved a new field of computer-aided tissue engineering (CATE). This emerging field encompasses computer-aided design (CAD), image processing, manufacturing and solid free-form fabrication (SFF) for modelling, designing, simulation and manufacturing of biological tissue and organ substitutes. The present Review describes some salient advances in this field, particularly in computer-aided tissue modeling, computer-aided tissue informatics and computer-aided tissue scaffold design and fabrication. Methodologies of development of CATE modelling from high-resolution non-invasive imaging and image-based three-dimensional reconstruction, and various reconstructive techniques for CAD-based tissue modelling generation will be described. The latest development in SFF to tissue engineering and a framework of bio-blueprint modelling for three-dimensional cell and organ printing will also be introduced.

  9. Gelatin-GAG electrospun nanofibrous scaffold for skin tissue engineering: fabrication and modeling of process parameters.

    PubMed

    Pezeshki-Modaress, Mohamad; Mirzadeh, Hamid; Zandi, Mojgan

    2015-03-01

    Electrospinning is a very useful technique for producing polymeric nanofibers by applying electrostatic forces. In this study, fabrication of novel gelatin/GAG nanofibrous mats and also the optimization of electrospinning process using response surface methodology were reported. At optimization section, gelatin/GAG blend ratio, applied voltage and feeding rate, their individual and interaction effects on the mean fiber diameter (MFD) and standard deviation of fiber diameter (SDF) were investigated. The obtained model for MFD has a quadratic relationship with gelatin/GAG blend ratio, applied voltage and feeding rate. The interactions of blend ratio and applied voltage and also applied voltage and flow rate were found significant but the interactions of blend ratio and flow rate were ignored. The optimum condition for gelatin/GAG electrospinning was also introduced using the model obtained in this study. The potential use of optimized electrospun mat in skin tissue engineering was evaluated using culturing of human dermal fibroblast cells (HDF). The SEM micrographs of HDF cells on the nanofibrous structure show that fibroblast cells can highly attach, grow and populate on the fabricated scaffold surface. The electrospun gelatin/GAG nanofibrous mats have a potential for using as scaffold for skin, cartilage and cornea tissue engineering.

  10. Utilizing stem cells for three-dimensional neural tissue engineering.

    PubMed

    Knowlton, Stephanie; Cho, Yongku; Li, Xue-Jun; Khademhosseini, Ali; Tasoglu, Savas

    2016-05-26

    Three-dimensional neural tissue engineering has made great strides in developing neural disease models and replacement tissues for patients. However, the need for biomimetic tissue models and effective patient therapies remains unmet. The recent push to expand 2D neural tissue engineering into the third dimension shows great potential to advance the field. Another area which has much to offer to neural tissue engineering is stem cell research. Stem cells are well known for their self-renewal and differentiation potential and have been shown to give rise to tissues with structural and functional properties mimicking natural organs. Application of these capabilities to 3D neural tissue engineering may be highly useful for basic research on neural tissue structure and function, engineering disease models, designing tissues for drug development, and generating replacement tissues with a patient's genetic makeup. Here, we discuss the vast potential, as well as the current challenges, unique to integration of 3D fabrication strategies and stem cells into neural tissue engineering. We also present some of the most significant recent achievements, including nerve guidance conduits to facilitate better healing of nerve injuries, functional 3D biomimetic neural tissue models, physiologically relevant disease models for research purposes, and rapid and effective screening of potential drugs.

  11. Nerve repulsion by the lens and cornea during cornea innervation is dependent on Robo-Slit signaling and diminishes with neuron age.

    PubMed

    Schwend, Tyler; Lwigale, Peter Y; Conrad, Gary W

    2012-03-01

    The cornea, the most densely innervated tissue on the surface of the body, becomes innervated in a series of highly coordinated developmental events. During cornea development, chick trigeminal nerve growth cones reach the cornea margin at embryonic day (E)5, where they are initially repelled for days from E5 to E8, instead encircling the corneal periphery in a nerve ring prior to entering on E9. The molecular events coordinating growth cone guidance during cornea development are poorly understood. Here we evaluated a potential role for the Robo-Slit nerve guidance family. We found that Slits 1, 2 and 3 expression in the cornea and lens persisted during all stages of cornea innervation examined. Robo1 expression was developmentally regulated in trigeminal cell bodies, expressed robustly during nerve ring formation (E5-8), then later declining concurrent with projection of growth cones into the cornea. In this study we provide in vivo and in vitro evidence that Robo-Slit signaling guides trigeminal nerves during cornea innervation. Transient, localized inhibition of Robo-Slit signaling, by means of beads loaded with inhibitory Robo-Fc protein implanted into the developing eyefield in vivo, led to disorganized nerve ring formation and premature cornea innervation. Additionally, when trigeminal explants (source of neurons) were oriented adjacent to lens vesicles or corneas (source of repellant molecules) in organotypic tissue culture both lens and cornea tissues strongly repelled E7 trigeminal neurites, except in the presence of inhibitory Robo-Fc protein. In contrast, E10 trigeminal neurites were not as strongly repelled by cornea, and presence of Robo-Slit inhibitory protein had no effect. In full, these findings suggest that nerve repulsion from the lens and cornea during nerve ring formation is mediated by Robo-Slit signaling. Later, a shift in nerve guidance behavior occurs, in part due to molecular changes in trigeminal neurons, including Robo1 downregulation

  12. Hydrogel scaffolds for tissue engineering: Progress and challenges

    PubMed Central

    El-Sherbiny, Ibrahim M.; Yacoub, Magdi H.

    2013-01-01

    Designing of biologically active scaffolds with optimal characteristics is one of the key factors for successful tissue engineering. Recently, hydrogels have received a considerable interest as leading candidates for engineered tissue scaffolds due to their unique compositional and structural similarities to the natural extracellular matrix, in addition to their desirable framework for cellular proliferation and survival. More recently, the ability to control the shape, porosity, surface morphology, and size of hydrogel scaffolds has created new opportunities to overcome various challenges in tissue engineering such as vascularization, tissue architecture and simultaneous seeding of multiple cells. This review provides an overview of the different types of hydrogels, the approaches that can be used to fabricate hydrogel matrices with specific features and the recent applications of hydrogels in tissue engineering. Special attention was given to the various design considerations for an efficient hydrogel scaffold in tissue engineering. Also, the challenges associated with the use of hydrogel scaffolds were described. PMID:24689032

  13. Bioengineered Corneas Grafted as Alternatives to Human Donor Corneas in Three High-Risk Patients

    PubMed Central

    Buznyk, Oleksiy; Pasyechnikova, Nataliya; Islam, M Mirazul; Iakymenko, Stanislav; Fagerholm, Per; Griffith, May

    2015-01-01

    Corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues. In this early observational study, we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure. These patients suffered from corneal ulcers and recurrent erosions preoperatively. The implants provided relief from pain and discomfort, restored corneal integrity by promoting endogenous regeneration of corneal tissues, and improved vision in two of three patients. Such implants could in the future be alternatives to donor corneas for high-risk patients, and therefore, merits further testing in a clinical trial. PMID:25996570

  14. Scaffolding in tissue engineering: general approaches and tissue-specific considerations

    PubMed Central

    Leong, K. W.

    2008-01-01

    Scaffolds represent important components for tissue engineering. However, researchers often encounter an enormous variety of choices when selecting scaffolds for tissue engineering. This paper aims to review the functions of scaffolds and the major scaffolding approaches as important guidelines for selecting scaffolds and discuss the tissue-specific considerations for scaffolding, using intervertebral disc as an example. PMID:19005702

  15. Bioactive polymers for cardiac tissue engineering

    NASA Astrophysics Data System (ADS)

    Wall, Samuel Thomas

    2007-05-01

    Prevalent in the US and worldwide, acute myocardial infarctions (AMI) can cause ischemic injuries to the heart that persist and lead to progressive degradation of the organ. Tissue engineering techniques exploiting biomaterials present a hopeful means of treating these injuries, either by mechanically stabilizing the injured ventricle, or by fostering cell growth to replace myocytes lost to damage. This thesis describes the development and testing of a synthetic extracellular matrix for cardiac tissue engineering applications. The first stage of this process was using an advanced finite element model of an injured ovine left ventricle to evaluate the potential benefits of injecting synthetic materials into the heart. These simulations indicated that addition of small amounts non-contractile material (on the order of 1--5% total wall volume) to infarct border zone regions reduced pathological systolic fiber stress to levels near those found in normal remote regions. Simulations also determined that direct addition to the infarct itself caused increases in ventricle ejection fraction while the underlying performance of the pump, ascertained by the Starling relation, was not improved. From these theoretical results, biomaterials were developed specifically for injection into the injured myocardium, and were characterized and tested for their mechanical properties and ability to sustain the proliferation of a stem cell population suitable for transplantation. Thermoresponsive synthetic copolymer hydrogels consisting of N-isopropylacrylamide and acrylic acid, p(NIPAAm-co-AAc), crosslinked with protease degradable amino acid sequences and modified with integrin binding ligands were synthesized, characterized in vitro, and used for myocardial implantation. These injectable materials could maintain a population of bone marrow derived mesenchymal stem cells in both two dimensional and three dimensional culture, and when tested in vivo in a murine infarct model they

  16. Cardiovascular tissue engineering I. Perfusion bioreactors: a review.

    PubMed

    Mironov, Vladimir; Kasyanov, Vladimir A; Yost, Michael J; Visconti, Richard; Twal, Waleed; Trusk, Thomas; Wen, Xuejun; Ozolanta, Iveta; Kadishs, Arnolds; Prestwich, Glenn D; Terracio, Louis; Markwald, Roger R

    2006-01-01

    Tissue engineering is a fast-evolving field of biomedical science and technology with future promise to manufacture living tissues and organs for replacement, repair, and regeneration of diseased organs. Owing to the specific role of hemodynamics in the development, maintenance, and functioning of the cardiovascular system, bioreactors are a fundamental of cardiovascular tissue engineering. The development of perfusion bioreactor technology for cardiovascular tissue engineering is a direct sequence of previous historic successes in extracorporeal circulation techniques. Bioreactors provide a fluidic environment for tissue engineered tissue and organs, and guarantee their viability, maturation, biomonitoring, testing, storage, and transportation. There are different types of bioreactors and they vary greatly in their size, complexity, and functional capabilities. Although progress in design and functional properties of perfusion bioreactors for tissue engineered blood vessels, heart valves, and myocardial patches is obvious, there are some challenges and insufficiently addressed issues, and room for bioreactor design improvement and performance optimization. These challenges include creating a triple perfusion bioreactor for vascularized tubular tissue engineered cardiac construct; designing and manufacturing fluidics-based perfused minibioreactors; incorporation of systematic mathematical modeling and computer simulation based on computational fluid dynamics into the bioreactor designing process; and development of automatic systems of hydrodynamic regime control. Designing and engineering of built-in noninvasive biomonitoring systems is another important challenge. The optimal and most efficient perfusion and conditioning regime, which accelerates tissue maturation of tissue-engineered constructs also remains to be determined. This is a first article in a series of reviews on critical elements of cardiovascular tissue engineering technology describing the current

  17. [Strategies to choose scaffold materials for tissue engineering].

    PubMed

    Gao, Qingdong; Zhu, Xulong; Xiang, Junxi; Lü, Yi; Li, Jianhui

    2016-02-01

    Current therapies of organ failure or a wide range of tissue defect are often not ideal. Transplantation is the only effective way for long time survival. But it is hard to meet huge patients demands because of donor shortage, immune rejection and other problems. Tissue engineering could be a potential option. Choosing a suitable scaffold material is an essential part of it. According to different sources, tissue engineering scaffold materials could be divided into three types which are natural and its modified materials, artificial and composite ones. The purpose of tissue engineering scaffold is to repair the tissues or organs damage, so could reach the ideal recovery in its function and structure aspect. Therefore, tissue engineering scaffold should even be as close as much to the original tissue or organs in function and structure. We call it "organic scaffold" and this strategy might be the drastic perfect substitute for the tissues or organs in concern. Optimized organization with each kind scaffold materials could make up for biomimetic structure and function of the tissue or organs. Scaffold material surface modification, optimized preparation procedure and cytosine sustained-release microsphere addition should be considered together. This strategy is expected to open new perspectives for tissue engineering. Multidisciplinary approach including material science, molecular biology, and engineering might find the most ideal tissue engineering scaffold. Using the strategy of drawing on each other strength and optimized organization with each kind scaffold material to prepare a multifunctional biomimetic tissue engineering scaffold might be a good method for choosing tissue engineering scaffold materials. Our research group had differentiated bone marrow mesenchymal stem cells into bile canaliculi like cells. We prepared poly(L-lactic acid)/poly(ε-caprolactone) biliary stent. The scaffold's internal played a part in the long-term release of cytokines which

  18. Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds.

    PubMed

    Gershlak, Joshua R; Hernandez, Sarah; Fontana, Gianluca; Perreault, Luke R; Hansen, Katrina J; Larson, Sara A; Binder, Bernard Y K; Dolivo, David M; Yang, Tianhong; Dominko, Tanja; Rolle, Marsha W; Weathers, Pamela J; Medina-Bolivar, Fabricio; Cramer, Carole L; Murphy, William L; Gaudette, Glenn R

    2017-05-01

    Despite significant advances in the fabrication of bioengineered scaffolds for tissue engineering, delivery of nutrients in complex engineered human tissues remains a challenge. By taking advantage of the similarities in the vascular structure of plant and animal tissues, we developed decellularized plant tissue as a prevascularized scaffold for tissue engineering applications. Perfusion-based decellularization was modified for different plant species, providing different geometries of scaffolding. After decellularization, plant scaffolds remained patent and able to transport microparticles. Plant scaffolds were recellularized with human endothelial cells that colonized the inner surfaces of plant vasculature. Human mesenchymal stem cells and human pluripotent stem cell derived cardiomyocytes adhered to the outer surfaces of plant scaffolds. Cardiomyocytes demonstrated contractile function and calcium handling capabilities over the course of 21 days. These data demonstrate the potential of decellularized plants as scaffolds for tissue engineering, which could ultimately provide a cost-efficient, "green" technology for regenerating large volume vascularized tissue mass.

  19. Bioreactors Drive Advances in Tissue Engineering

    NASA Technical Reports Server (NTRS)

    2012-01-01

    It was an unlikely moment for inspiration. Engineers David Wolf and Ray Schwarz stopped by their lab around midday. Wolf, of Johnson Space Center, and Schwarz, with NASA contractor Krug Life Sciences (now Wyle Laboratories Inc.), were part of a team tasked with developing a unique technology with the potential to enhance medical research. But that wasn t the focus at the moment: The pair was rounding up colleagues interested in grabbing some lunch. One of the lab s other Krug engineers, Tinh Trinh, was doing something that made Wolf forget about food. Trinh was toying with an electric drill. He had stuck the barrel of a syringe on the bit; it spun with a high-pitched whirr when he squeezed the drill s trigger. At the time, a multidisciplinary team of engineers and biologists including Wolf, Schwarz, Trinh, and project manager Charles D. Anderson, who formerly led the recovery of the Apollo capsules after splashdown and now worked for Krug was pursuing the development of a technology called a bioreactor, a cylindrical device used to culture human cells. The team s immediate goal was to grow human kidney cells to produce erythropoietin, a hormone that regulates red blood cell production and can be used to treat anemia. But there was a major barrier to the technology s success: Moving the liquid growth media to keep it from stagnating resulted in turbulent conditions that damaged the delicate cells, causing them to quickly die. The team was looking forward to testing the bioreactor in space, hoping the device would perform more effectively in microgravity. But on January 28, 1986, the Space Shuttle Challenger broke apart shortly after launch, killing its seven crewmembers. The subsequent grounding of the shuttle fleet had left researchers with no access to space, and thus no way to study the effects of microgravity on human cells. As Wolf looked from Trinh s syringe-capped drill to where the bioreactor sat on a workbench, he suddenly saw a possible solution to both

  20. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2013-10-01

    transplanted nervous tissue constructs on...recovery of motor function. Specific Aim 2: Evaluation of the survival and integration of transplanted living nervous tissue constructs and host... Nervous Tissue PRINCIPAL INVESTIGATOR: Douglas H. Smith, M.D. CONTRACTING

  1. Preclinical imaging in bone tissue engineering.

    PubMed

    Ventura, Manuela; Boerman, Otto C; de Korte, Chris; Rijpkema, Mark; Heerschap, Arend; Oosterwijk, Egbert; Jansen, John A; Walboomers, X Frank

    2014-12-01

    Since X-rays were discovered, in 1895, and since the first radiological image of a hand, bone tissue has been the subject of detailed medical imaging. However, advances in bone engineering, including the increased complexity of implant scaffolds, currently also underline the limits of X-ray imaging. Therefore, advanced follow-up imaging methods are pivotal to develop. The field of noninvasive, high-sensitivity, and high-resolution anatomical and functional imaging techniques (optical, ultrasound, positron emission tomography, single-photon emission computed tomography, magnetic resonance, etc.) offers a wide variety of tools that potentially could be considered as alternatives, or at least supportive, to the most commonly used X-ray computed tomography. Moreover, dedicated preclinical scanners have become available, with sensitivity and resolution even higher than clinical scanners, thus favoring a quick translation from preclinical to clinical applications. Furthermore, the armamentarium of bone-specific probes and contrast agents for each of this imaging modalities is constantly growing. This review focuses on such preclinical imaging tools, each with its respective strengths and weaknesses, used alone or in combination. Especially, multimodal imaging will dramatically contribute to improve the knowledge on bone healing regenerative processes.

  2. Acellular organ scaffolds for tumor tissue engineering

    NASA Astrophysics Data System (ADS)

    Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

    2015-12-01

    Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

  3. Tissue engineering strategies for the regeneration of orthopedic interfaces.

    PubMed

    Lu, Helen H; Subramony, Siddarth D; Boushell, Margaret K; Zhang, Xinzhi

    2010-06-01

    A major focus in the field of orthopedic tissue engineering is the development of tissue engineered bone and soft tissue grafts with biomimetic functionality to allow for their translation to the clinical setting. One of the most significant challenges of this endeavor is promoting the biological fixation of these grafts with each other as well as the implant site. Such fixation requires strategic biomimicry to be incorporated into the scaffold design in order to re-establish the critical structure-function relationship of the native soft tissue-to-bone interface. The integration of distinct tissue types (e.g. bone and soft tissues such as cartilage, ligaments, or tendons), necessitates a multi-phased or stratified scaffold with distinct yet continuous tissue regions accompanied by a gradient of mechanical properties. This review discusses tissue engineering strategies for regenerating common tissue-to-tissue interfaces (ligament-to-bone, tendon-to-bone, or cartilage-to-bone), and the strategic biomimicry implemented in stratified scaffold design for multi-tissue regeneration. Potential challenges and future directions in this emerging field will also be presented. It is anticipated that interface tissue engineering will enable integrative soft tissue repair, and will be instrumental for the development of complex musculoskeletal tissue systems with biomimetic complexity and functionality.

  4. Recent progress in interfacial tissue engineering approaches for osteochondral defects.

    PubMed

    Castro, Nathan J; Hacking, S Adam; Zhang, Lijie Grace

    2012-08-01

    This review provides a brief synopsis of the anatomy and physiology of the osteochondral interface, scaffold-based and non-scaffold based approaches for engineering both tissues independently as well as recent developments in the manufacture of gradient constructs. Novel manufacturing techniques and nanotechnology will be discussed with potential application in osteochondral interfacial tissue engineering.

  5. Functional tissue engineering: Ten more years of progress.

    PubMed

    Guilak, Farshid; Baaijens, Frank P T

    2014-06-27

    "Functional tissue engineering" is a subset of the field of tissue engineering that was proposed by the United States National Committee on Biomechanics over a decade ago in order to place more emphasis on the roles of biomechanics and mechanobiology in tissue repair and regeneration. Over the past decade, there have been tremendous advances in this area, pointing out the critical role that biomechanical factors can play in the engineered repair of virtually all tissue and organ systems. In this special issue of the Journal of Biomechanics, we present a series of articles that address a broad array of the fundamental topics of functional tissue engineering, including: (1) measurement and modeling of the in vivo biomechanical environment and history in native and repair tissues; (2) further understanding of the biomechanical properties of native tissues across all geometric scales, in the context of repair or regeneration; (3) prioritization of specific biomechanical properties as design criteria; (4) development of biomaterials, scaffolds, and engineered tissues with prescribed biomechanical properties; (5) development of success criteria based on appropriate outcome measures; (6) investigation of the effects of mechanical factors on tissue repair in vivo; (7) investigation of the mechanisms by which physical factors may enhance tissue regeneration in vitro; and (8) development and validation of computational models of tissue growth and remodeling. These articles represent the tremendous expansion of this field in recent years, and emphasize the critical roles that biomechanics and mechanobiology play in controlling tissue repair and regeneration.

  6. Scaffolds based bone tissue engineering: the role of chitosan.

    PubMed

    Costa-Pinto, Ana Rita; Reis, Rui L; Neves, Nuno M

    2011-10-01

    As life expectancy increases, malfunction or loss of tissue caused by injury or disease leads to reduced quality of life in many patients at significant socioeconomic cost. Even though major progress has been made in the field of bone tissue engineering, present therapies, such as bone grafts, still have limitations. Current research on biodegradable polymers is emerging, combining these structures with osteogenic cells, as an alternative to autologous bone grafts. Different types of biodegradable materials have been proposed for the preparation of three-dimensional porous scaffolds for bone tissue engineering. Among them, natural polymers are one of the most attractive options, mainly due to their similarities with extracellular matrix, chemical versatility, good biological performance, and inherent cellular interactions. In this review, special attention is given to chitosan as a biomaterial for bone tissue engineering applications. An extensive literature survey was performed on the preparation of chitosan scaffolds and their in vitro biological performance as well as their potential to facilitate in vivo bone regeneration. The present review also aims to offer the reader a general overview of all components needed to engineer new bone tissue. It gives a brief background on bone biology, followed by an explanation of all components in bone tissue engineering, as well as describing different tissue engineering strategies. Moreover, also discussed are the typical models used to evaluate in vitro functionality of a tissue-engineered construct and in vivo models to assess the potential to regenerate bone tissue are discussed.

  7. Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

    PubMed

    Thavornyutikarn, Boonlom; Chantarapanich, Nattapon; Sitthiseripratip, Kriskrai; Thouas, George A; Chen, Qizhi

    Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

  8. Is tissue engineering a new paradigm in medicine? Consequences for the ethical evaluation of tissue engineering research.

    PubMed

    Trommelmans, Leen; Selling, Joseph; Dierickx, Kris

    2009-11-01

    Ex-vivo tissue engineering is a quickly developing medical technology aiming to regenerate tissue through the introduction of an ex-vivo created tissue construct instead of restoring the damaged tissue to some level of functionality. Tissue engineering is considered by some as a new medical paradigm. We analyse this claim and identify tissue engineering's fundamental characteristics, focusing on the aim of the intervention and on the complexity and continuity of the process. We inquire how these features have an impact not only on the scientific research itself but also on the ethical evaluation of this research. We suggest that viewing tissue engineering as a new medical paradigm allows us to develop a wider perspective for successful investigation instead of focusing on isolated steps of the tissue engineering process in an anecdotal way, which may lead to an inadequate ethical evaluation. We argue that the concept of tissue engineering as a paradigm may benefit the way we address the ethical challenges presented by tissue engineering.

  9. Re-epithelialization: a key element in tracheal tissue engineering.

    PubMed

    Zhang, Hengyi; Fu, Wei; Xu, Zhiwei

    2015-11-01

    Trachea-tissue engineering is a thriving new field in regenerative medicine that is reaching maturity and yielding numerous promising results. In view of the crucial role that the epithelium plays in the trachea, re-epithelialization of tracheal substitutes has gradually emerged as the focus of studies in tissue-engineered trachea. Recent progress in our understanding of stem cell biology, growth factor interactions and transplantation immunobiology offer the prospect of optimization of a tissue-engineered tracheal epithelium. In addition, advances in cell culture technology and successful applications of clinical transplantation are opening up new avenues for the construction of a tissue-engineered tracheal epithelium. Therefore, this review summarizes current advances, unresolved obstacles and future directions in the reconstruction of a tissue-engineered tracheal epithelium.

  10. Powder-based 3D printing for bone tissue engineering.

    PubMed

    Brunello, G; Sivolella, S; Meneghello, R; Ferroni, L; Gardin, C; Piattelli, A; Zavan, B; Bressan, E

    2016-01-01

    Bone tissue engineered 3-D constructs customized to patient-specific needs are emerging as attractive biomimetic scaffolds to enhance bone cell and tissue growth and differentiation. The article outlines the features of the most common additive manufacturing technologies (3D printing, stereolithography, fused deposition modeling, and selective laser sintering) used to fabricate bone tissue engineering scaffolds. It concentrates, in particular, on the current state of knowledge concerning powder-based 3D printing, including a description of the properties of powders and binder solutions, the critical phases of scaffold manufacturing, and its applications in bone tissue engineering. Clinical aspects and future applications are also discussed.

  11. Clinical translation of controlled protein delivery systems for tissue engineering

    PubMed Central

    Spiller, Kara L.; Vunjak-Novakovic, Gordana

    2013-01-01

    Strategies that utilize controlled release of drugs and proteins for tissue engineering have enormous potential to regenerate damaged organs and tissues. The multiple advantages of controlled release strategies merit overcoming the significant challenges to translation, including high costs and long, difficult regulatory pathways. This review highlights the potential of controlled release of proteins for tissue engineering and regenerative medicine. We specifically discuss treatment modalities that have reached preclinical and clinical trials, with emphasis on controlled release systems for bone tissue engineering, the most advanced application with several products already in clinic. Possible strategies to address translational and regulatory concerns are also discussed. PMID:25787736

  12. Current progress in 3D printing for cardiovascular tissue engineering.

    PubMed

    Mosadegh, Bobak; Xiong, Guanglei; Dunham, Simon; Min, James K

    2015-03-16

    3D printing is a technology that allows the fabrication of structures with arbitrary geometries and heterogeneous material properties. The application of this technology to biological structures that match the complexity of native tissue is of great interest to researchers. This mini-review highlights the current progress of 3D printing for fabricating artificial tissues of the cardiovascular system, specifically the myocardium, heart valves, and coronary arteries. In addition, how 3D printed sensors and actuators can play a role in tissue engineering is discussed. To date, all the work with building 3D cardiac tissues have been proof-of-principle demonstrations, and in most cases, yielded products less effective than other traditional tissue engineering strategies. However, this technology is in its infancy and therefore there is much promise that through collaboration between biologists, engineers and material scientists, 3D bioprinting can make a significant impact on the field of cardiovascular tissue engineering.

  13. Bioreactor Development for Lung Tissue Engineering

    PubMed Central

    Panoskaltsis-Mortari, Angela

    2015-01-01

    Rationale Much recent interest in lung bioengineering by pulmonary investigators, industry and the organ transplant field has seen a rapid growth of bioreactor development ranging from the microfluidic scale to the human-sized whole lung systems. A comprehension of the findings from these models is needed to provide the basis for further bioreactor development. Objective The goal was to comprehensively review the current state of bioreactor development for the lung. Methods A search using PubMed was done for published, peer-reviewed papers using the keywords “lung” AND “bioreactor” or “bioengineering” or “tissue engineering” or “ex vivo perfusion”. Main Results Many new bioreactors ranging from the microfluidic scale to the human-sized whole lung systems have been developed by both academic and commercial entities. Microfluidic, lung-mimic and lung slice cultures have the advantages of cost-efficiency and high throughput analyses ideal for pharmaceutical and toxicity studies. Perfused/ventilated rodent whole lung systems can be adapted for mid-throughput studies of lung stem/progenitor cell development, cell behavior, understanding and treating lung injury and for preliminary work that can be translated to human lung bioengineering. Human-sized ex vivo whole lung bioreactors incorporating perfusion and ventilation are amenable to automation and have been used for whole lung decellularization and recellularization. Clinical scale ex vivo lung perfusion systems have been developed for lung preservation and reconditioning and are currently being evaluated in clinical trials. Conclusions Significant advances in bioreactors for lung engineering have been made at both the microfluidic and the macro scale. The most advanced are closed systems that incorporate pressure-controlled perfusion and ventilation and are amenable to automation. Ex vivo lung perfusion systems have advanced to clinical trials for lung preservation and reconditioning. The biggest

  14. Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

    PubMed Central

    Nguyen, Lonnissa H.; Annabi, Nasim; Nikkhah, Mehdi; Bae, Hojae; Binan, Loïc; Park, Sangwon; Kang, Yunqing

    2012-01-01

    Significant advances have been made in bone tissue engineering (TE) in the past decade. However, classical bone TE strategies have been hampered mainly due to the lack of vascularization within the engineered bone constructs, resulting in poor implant survival and integration. In an effort toward clinical success of engineered constructs, new TE concepts have arisen to develop bone substitutes that potentially mimic native bone tissue structure and function. Large tissue replacements have failed in the past due to the slow penetration of the host vasculature, leading to necrosis at the central region of the engineered tissues. For this reason, multiple microscale strategies have been developed to induce and incorporate vascular networks within engineered bone constructs before implantation in order to achieve successful integration with the host tissue. Previous attempts to engineer vascularized bone tissue only focused on the effect of a single component among the three main components of TE (scaffold, cells, or signaling cues) and have only achieved limited success. However, with efforts to improve the engineered bone tissue substitutes, bone TE approaches have become more complex by combining multiple strategies simultaneously. The driving force behind combining various TE strategies is to produce bone replacements that more closely recapitulate human physiology. Here, we review and discuss the limitations of current bone TE approaches and possible strategies to improve vascularization in bone tissue substitutes. PMID:22765012

  15. The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

    PubMed Central

    Butler, David L.; Goldstein, Steven A.; Guo, X. Edward; Kamm, Roger; Laurencin, Cato T.; McIntire, Larry V.; Mow, Van C.; Nerem, Robert M.; Sah, Robert L.; Soslowsky, Louis J.; Spilker, Robert L.; Tranquillo, Robert T.

    2009-01-01

    Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges. PMID:19583462

  16. MECHANICAL DESIGN CRITERIA FOR INTERVERTEBRAL DISC TISSUE ENGINEERING

    PubMed Central

    Nerurkar, Nandan L.; Elliott, Dawn M.; Mauck, Robert L.

    2009-01-01

    Due to the inability of current clinical practices to restore function to degenerated intervertebral discs, the arena of disc tissue engineering has received substantial attention in recent years. Despite tremendous growth and progress in this field, translation to clinical implementation has been hindered by a lack of well-defined functional benchmarks. Because successful replacement of the disc is contingent upon replication of some or all of its complex mechanical behaviour, it is critically important that disc mechanics be well characterized in order to establish discrete functional goals for tissue engineering. In this review, the key functional signatures of the intervertebral disc are discussed and used to propose a series of native tissue benchmarks to guide the development of engineered replacement tissues. These benchmarks include measures of mechanical function under tensile, compressive and shear deformations for the disc and its substructures. In some cases, important functional measures are identified that have yet to be measured in the native tissue. Ultimately, native tissue benchmark values are compared to measurements that have been made on engineered disc tissues, identifying measures where functional equivalence was achieved, and others where there remain opportunities for advancement. Several excellent reviews exist regarding disc composition and structure, as well as recent tissue engineering strategies; therefore this review will remain focused on the functional aspects of disc tissue engineering. PMID:20080239

  17. Optimization of Electrical Stimulation Parameters for Cardiac Tissue Engineering

    PubMed Central

    Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo; Park, Hyoungshin; Vunjak-Novakovic, Gordana

    2010-01-01

    In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile cardiac tissue constrcuts. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation, to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, and were thus used in tissue engineering studies. Cardiac tissues stimulated at 3V/cm amplitude and 3Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43, and the best developed contractile behavior. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering. PMID:21604379

  18. Bioreactors in tissue engineering - principles, applications and commercial constraints.

    PubMed

    Hansmann, Jan; Groeber, Florian; Kahlig, Alexander; Kleinhans, Claudia; Walles, Heike

    2013-03-01

    Bioreactor technology is vital for tissue engineering. Usually, bioreactors are used to provide a tissue-specific physiological in vitro environment during tissue maturation. In addition to this most obvious application, bioreactors have the potential to improve the efficiency of the overall tissue-engineering concept. To date, a variety of bioreactor systems for tissue-specific applications have been developed. Of these, some systems are already commercially available. With bioreactor technology, various functional tissues of different types were generated and cultured in vitro. Nevertheless, these efforts and achievements alone have not yet led to many clinically successful tissue-engineered implants. We review possible applications for bioreactor systems within a tissue-engineering process and present basic principles and requirements for bioreactor development. Moreover, the use of bioreactor systems for the expansion of clinically relevant cell types is addressed. In contrast to cell expansion, for the generation of functional three-dimensional tissue equivalents, additional physical cues must be provided. Therefore, bioreactors for musculoskeletal tissue engineering are discussed. Finally, bioreactor technology is reviewed in the context of commercial constraints.

  19. Heterogeneity of collagens in rabbit cornea: type VI collagen

    SciTech Connect

    Cintron, C.; Hong, B.S.

    1988-05-01

    Normal adult rabbit corneas were digested with 5% pepsin and their collagens extracted with acetic acid. Collagen extracts were fractionated by differential salt precipitation. The 2.5 M NaCl fraction was then redissolved with tris buffer and precipitated with sodium acetate. The precipitate contained a high-molecular-weight disulfide-bonded aggregate which, upon reduction with mercaptoethanol, was converted into three distinct polypeptides having molecular weights between 45 and 66 Kd. These physical characteristics, together with the susceptibility of these polypeptides to collagenase and their amino acid composition, identified the high molecular weight aggregate as type VI collagen. Corneas from neonate rabbits and adult corneas containing 2-week-old scars were organ cultured in the presence of (/sup 14/C) glycine to incorporate radiolabel into collagen. Tissues were digested with 0.02% pepsin and their collagens extracted with formic acid. The total radioactivity of the extracts and tissue residues was determined before the collagens were separated by SDS-polyacrylamide slab gel electrophoresis. Radioactive collagen polypeptides bands were then stained with Coomassie blue, processed for fluorography, and analyzed by densitometry. The results show that: (1) type VI collagen is synthesized by neonate corneas and healing adult corneas; (2) it is not readily solubilized from either corneal tissue by 0.02% pepsin digestion and formic acid extraction; and (3) the proportion of type VI collagen deposited in scar tissue is markedly lower than that found in neonate corneas.

  20. Ethical considerations in tissue engineering research: Case studies in translation.

    PubMed

    Baker, Hannah B; McQuilling, John P; King, Nancy M P

    2016-04-15

    Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of "modest translational distance" and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology.

  1. Microfluidic systems for stem cell-based neural tissue engineering.

    PubMed

    Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

    2016-07-05

    Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

  2. Cell-Based Strategies for Meniscus Tissue Engineering

    PubMed Central

    Niu, Wei; Guo, Weimin; Han, Shufeng; Zhu, Yun; Liu, Shuyun; Guo, Quanyi

    2016-01-01

    Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering. PMID:27274735

  3. Nano scaffolds and stem cell therapy in liver tissue engineering

    NASA Astrophysics Data System (ADS)

    Montaser, Laila M.; Fawzy, Sherin M.

    2015-08-01

    Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

  4. Human stem cells and articular cartilage tissue engineering.

    PubMed

    Stoltz, J-F; Huselstein, C; Schiavi, J; Li, Y Y; Bensoussan, D; Decot, V; De Isla, N

    2012-12-01

    Injuries to articular cartilage are one of the most challenging issues of musculoskeletal medicine due to the poor intrinsic ability of this tissue for repair. Despite progress in orthopaedic surgery, cell-based surgical therapies such as autologous chondrocyte transplantation (ACT) have been in clinical use for cartilage repair for over a decade but this approach has shown mixed results. Moreover, the lack of efficient modalities of treatment for large chondral defects has prompted research on cartilage tissue engineering combining cells, scaffold materials and environmental factors. This paper focuses on the main parameters in tissue engineering and in particular, on the potential of mesenchymal stem cells (MSCs) as an alternative to cells derived from patient tissues in autologous transplantation and tissue engineering. We discussed the prospects of using autologous chondrocytes or MSCs in regenerative medicine and summarized the advantages and disadvantages of these cells in articular cartilage engineering.

  5. Perspectives of gene therapy in stem cell tissue engineering.

    PubMed

    Goessler, Ulrich Reinhart; Riedel, Katrin; Hormann, Karl; Riedel, Frank

    2006-01-01

    Tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain or improve tissue function. It is hoped that forming tissue de novo will overcome many problems in plastic surgery associated with such areas as wound healing and the immunogenicity of transplanted tissue that lead to dysfunctional repair. Gene therapy is the science of the transfer of genetic material into individuals for therapeutic purposes by altering cellular function or structure at the molecular level. Recently, tissue engineering has been used in conjunction with gene therapy as a hybrid approach. This combination of stem-cell-based tissue engineering with gene therapy has the potential to provide regenerative tissue cells within an environment of optimal regulatory protein expression and would have many benefits in various areas such as the transplantation of skin, cartilage or bone. The aim of this review is to outline tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery.

  6. Mesoscopic Fluorescence Molecular Tomography for Evaluating Engineered Tissues

    PubMed Central

    Ozturk, Mehmet S.; Chen, Chao-Wei; Ji, Robin; Zhao, Lingling; Nguyen, Bao-Ngoc B.; Fisher, John P.; Chen, Yu; Intes, Xavier

    2015-01-01

    Optimization of regenerative medicine strategies includes the design of biomaterials, development of cell-seeding methods, and control of cell-biomaterial interactions within the engineered tissues. Among these steps, one paramount challenge is to non-destructively image the engineered tissues in their entirety to assess structure, function, and molecular expression. It is especially important to be able to enable cell phenotyping and monitor the distribution and migration of cells throughout the bulk scaffold. Advanced fluorescence microscopic techniques are commonly employed to perform such tasks; however, they are limited to superficial examination of tissue constructs. Therefore, the field of tissue engineering and regenerative medicine would greatly benefit from the development of molecular imaging techniques which are capable of non-destructive imaging of three-dimensional cellular distribution and maturation within a tissue-engineered scaffold beyond the limited depth of current microscopic techniques. In this review, we focus on an emerging depth-resolved optical mesoscopic imaging technique, termed Laminar Optical Tomography (LOT) or Mesoscopic Fluorescence Molecular Tomography (MFMT), which enables longitudinal imaging of cellular distribution in thick tissue engineering constructs at depths of a few millimeters and with relatively high resolution. The physical principle, image formation, and instrumentation of LOT/MFMT systems are introduced. Representative applications in tissue engineering include imaging the distribution of human mesenchymal stem cells (hMSCs) embedded in hydrogels, imaging of bio-printed tissues, and in vivo applications. PMID:26645079

  7. Osseous differentiation of human fat tissue grafts: From tissue engineering to tissue differentiation

    PubMed Central

    Bondarava, Maryna; Cattaneo, Chiara; Ren, Bin; Thasler, Wolfgang E.; Jansson, Volkmar; Müller, Peter E.; Betz, Oliver B.

    2017-01-01

    Conventional bone tissue engineering approaches require isolation and in vitro propagation of autologous cells, followed by seeding on a variety of scaffolds. Those protracted procedures impede the clinical applications. Here we report the transdifferentiation of human fat tissue fragments retrieved from subcutaneous fat into tissue with bone characteristics in vitro without prior cell isolation and propagation. 3D collagen-I cultures of human fat tissue were cultivated either in growth medium or in osteogenic medium (OM) with or without addition of Bone Morphogenetic Proteins (BMPs) BMP-2, BMP-7 or BMP-9. Ca2+ depositions were observed after two weeks of osteogenic induction which visibly increased when either type of BMP was added. mRNA levels of alkaline phosphatase (ALP) and osteocalcin (OCN) increased when cultured in OM alone but addition of BMP-2, BMP-7 or BMP-9 caused significantly higher expression levels of ALP and OCN. Immunofluorescent staining for OCN, osteopontin and sclerostin supported the observed real-time-PCR data. BMP-9 was the most effective osteogenic inducer in this system. Our findings reveal that tissue regeneration can be remarkably simplified by omitting prior cell isolation and propagation, therefore removing significant obstacles on the way to clinical applications of much needed regeneration treatments. PMID:28054585

  8. Cell sheet-based tissue engineering for fabricating 3-dimensional heart tissues.

    PubMed

    Shimizu, Tatsuya

    2014-01-01

    In addition to stem cell biology, tissue engineering is an essential research field for regenerative medicine. In contrast to cell injection, bioengineered tissue transplantation minimizes cell loss and has the potential to repair tissue defects. A popular approach is scaffold-based tissue engineering, which utilizes a biodegradable polymer scaffold for seeding cells; however, new techniques of cell sheet-based tissue engineering have been developed. Cell sheets are harvested from temperature-responsive culture dishes by simply lowering the temperature. Monolayer or stacked cell sheets are transplantable directly onto damaged tissues and cell sheet transplantation has already been clinically applied. Cardiac cell sheet stacking produces pulsatile heart tissue; however, lack of vasculature limits the viable tissue thickness to 3 layers. Multistep transplantation of triple-layer cardiac cell sheets cocultured with endothelial cells has been used to form thick vascularized cardiac tissue in vivo. Furthermore, in vitro functional blood vessel formation within 3-dimensional (3D) tissues has been realized by successfully imitating in vivo conditions. Triple-layer cardiac cell sheets containing endothelial cells were layered on vascular beds and the constructs were media-perfused using novel bioreactor systems. Interestingly, cocultured endothelial cells migrate into the vascular beds and form perfusable blood vessels. An in vitro multistep procedure has also enabled the fabrication of thick, vascularized heart tissues. Cell sheet-based tissue engineering has revealed great potential to fabricate 3D cardiac tissues and should contribute to future treatment of severe heart diseases and human tissue model production.

  9. Development of Hydrogels and Biomimetic Regulators as Tissue Engineering Scaffolds

    PubMed Central

    Shi, Junbin; Xing, Malcolm M. Q.; Zhong, Wen

    2012-01-01

    This paper reviews major research and development issues relating to hydrogels as scaffolds for tissue engineering, the article starts with a brief introduction of tissue engineering and hydrogels as extracellular matrix mimics, followed by a description of the various types of hydrogels and preparation methods, before a discussion of the physical and chemical properties that are important to their application. There follows a short comment on the trends of future research and development. Throughout the discussion there is an emphasis on the genetic understanding of bone tissue engineering application. PMID:24957963

  10. Review: Polymeric-Based 3D Printing for Tissue Engineering.

    PubMed

    Wu, Geng-Hsi; Hsu, Shan-Hui

    Three-dimensional (3D) printing, also referred to as additive manufacturing, is a technology that allows for customized fabrication through computer-aided design. 3D printing has many advantages in the fabrication of tissue engineering scaffolds, including fast fabrication, high precision, and customized production. Suitable scaffolds can be designed and custom-made based on medical images such as those obtained from computed tomography. Many 3D printing methods have been employed for tissue engineering. There are advantages and limitations for each method. Future areas of interest and progress are the development of new 3D printing platforms, scaffold design software, and materials for tissue engineering applications.

  11. Micro and Nano-mediated 3D Cardiac Tissue Engineering

    DTIC Science & Technology

    2009-10-01

    Micro and Nano -mediated 3D Cardiac Tissue Engineering PRINCIPAL INVESTIGATOR:  Rashid Bashir, PhD, PI  Brian Cunningham, PhD, co-PI  Hyunjoon...SUBTITLE Micro and Nano -mediated 3D Cardiac Tissue Engineering 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0701 5c. PROGRAM ELEMENT...Optical  Characterization (Cunningham) Mechano‐Biology  of Cardiac Cells (Saif) Micro / Nano ‐ Medicated  Cardiac Tissue  Engineering Dr. M. Gibb, Head of

  12. Progress and opportunities for tissue-engineered skin

    NASA Astrophysics Data System (ADS)

    MacNeil, Sheila

    2007-02-01

    Tissue-engineered skin is now a reality. For patients with extensive full-thickness burns, laboratory expansion of skin cells to achieve barrier function can make the difference between life and death, and it was this acute need that drove the initiation of tissue engineering in the 1980s. A much larger group of patients have ulcers resistant to conventional healing, and treatments using cultured skin cells have been devised to restart the wound-healing process. In the laboratory, the use of tissue-engineered skin provides insight into the behaviour of skin cells in healthy skin and in diseases such as vitiligo, melanoma, psoriasis and blistering disorders.

  13. Polysaccharide-based strategies for heart tissue engineering.

    PubMed

    Silva, Amanda K A; Juenet, Maya; Meddahi-Pellé, Anne; Letourneur, Didier

    2015-02-13

    Polysaccharides are abundant biomolecules in nature presenting important roles in a wide variety of living systems processes. Considering the structural and biological functions of polysaccharides, their properties have raised interest for tissue engineering. Herein, we described the latest advances in cardiac tissue engineering mediated by polysaccharides. We reviewed the data already obtained in vitro and in vivo in this field with several types of polysaccharides. Cardiac injection, intramyocardial in situ polymerization strategies, and scaffold-based approaches involving polysaccharides for heart tissue engineering are thus discussed.

  14. Tissue-Engineering for the Study of Cardiac Biomechanics

    PubMed Central

    Ma, Stephen P.; Vunjak-Novakovic, Gordana

    2016-01-01

    The notion that both adaptive and maladaptive cardiac remodeling occurs in response to mechanical loading has informed recent progress in cardiac tissue engineering. Today, human cardiac tissues engineered in vitro offer complementary knowledge to that currently provided by animal models, with profound implications to personalized medicine. We review here recent advances in the understanding of the roles of mechanical signals in normal and pathological cardiac function, and their application in clinical translation of tissue engineering strategies to regenerative medicine and in vitro study of disease. PMID:26720588

  15. Assessment of tissue ingrowth rates in polyurethane scaffolds for tissue engineering.

    PubMed

    Ramrattan, Navin N; Heijkants, Ralf G J C; van Tienen, Tony G; Schouten, Arend Jan; Veth, Rene P H; Buma, Pieter

    2005-01-01

    The continuous development of new biomaterials for tissue engineering and the enhancement of tissue ingrowth into existing scaffolds, using growth factors, create the necessity for developing adequate tools to assess tissue ingrowth rates into porous biomaterials. Current histomorphometric techniques evaluating rates of tissue ingrowth tend either to measure the overall tissue content in an entire sample or to depend on the user to indicate a front of tissue ingrowth. Neither method is particularly suitable for the assessment of tissue ingrowth rates, as these methods either lack the sensitivity required or are problematic when there is a tissue ingrowth gradient rather than an obvious tissue ingrowth front. This study describes a histomorphometric method that requires little observer input, is sensitive, and renders detailed information for the assessment of tissue ingrowth rates into porous biomaterials. This is achieved by examining a number of computer-defined concentric zones, which are based on the distance of a pixel from the scaffold edge. Each zone is automatically analyzed for tissue content, eliminating the need for user definition of a tissue ingrowth front and thus reducing errors and observer dependence. Tissue ingrowth rates in two biodegradable polyurethane scaffolds (Estane and polycaprolactone-polyurethane [PCLPU]) specifically designed for tissue engineering of the knee meniscus were assessed. Samples were subcutaneously implanted in rats with follow-up until 6 months. Especially at the earlier follow-up points, PCLPU scaffolds showed significantly higher tissue ingrowth rates than Estane scaffolds, making the PCLPU scaffold a promising candidate for further studies investigating meniscus tissue engineering.

  16. A Review of Three-Dimensional Printing in Tissue Engineering.

    PubMed

    Sears, Nick A; Seshadri, Dhruv R; Dhavalikar, Prachi S; Cosgriff-Hernandez, Elizabeth

    2016-08-01

    Recent advances in three-dimensional (3D) printing technologies have led to a rapid expansion of applications from the creation of anatomical training models for complex surgical procedures to the printing of tissue engineering constructs. In addition to achieving the macroscale geometry of organs and tissues, a print layer thickness as small as 20 μm allows for reproduction of the microarchitectures of bone and other tissues. Techniques with even higher precision are currently being investigated to enable reproduction of smaller tissue features such as hepatic lobules. Current research in tissue engineering focuses on the development of compatible methods (printers) and materials (bioinks) that are capable of producing biomimetic scaffolds. In this review, an overview of current 3D printing techniques used in tissue engineering is provided with an emphasis on the printing mechanism and the resultant scaffold characteristics. Current practical challenges and technical limitations are emphasized and future trends of bioprinting are discussed.

  17. Tissue Contraction Force Microscopy for Optimization of Engineered Cardiac Tissue

    PubMed Central

    Schaefer, Jeremy A.

    2016-01-01

    We developed a high-throughput screening assay that allows for relative comparison of the twitch force of millimeter-scale gel-based cardiac tissues. This assay is based on principles taken from traction force microscopy and uses fluorescent microspheres embedded in a soft polydimethylsiloxane (PDMS) substrate. A gel-forming cell suspension is simply pipetted onto the PDMS to form hemispherical cardiac tissue samples. Recordings of the fluorescent bead movement during tissue pacing are used to determine the maximum distance that the tissue can displace the elastic PDMS substrate. In this study, fibrin gel hemispheres containing human induced pluripotent stem cell-derived cardiomyocytes were formed on the PDMS and allowed to culture for 9 days. Bead displacement values were measured and compared to direct force measurements to validate the utility of the system. The amplitude of bead displacement correlated with direct force measurements, and the twitch force generated by the tissues was the same in 2 and 4 mg/mL fibrin gels, even though the 2 mg/mL samples visually appear more contractile if the assessment were made on free-floating samples. These results demonstrate the usefulness of this assay as a screening tool that allows for rapid sample preparation, data collection, and analysis in a simple and cost-effective platform. PMID:26538167

  18. Building off-the-shelf tissue-engineered composites.

    PubMed

    Burg, Timothy; Cass, Cheryl A P; Groff, Richard; Pepper, Matthew; Burg, Karen J L

    2010-04-28

    Rapid advances in technology have created the realistic possibility of personalized medicine. In 2000, Time magazine listed tissue engineering as one of the 'hottest 10 career choices'. However, in the past decade, only a handful of tissue-engineered products were translated to the clinical market and none were financially viable. The reality of complex business planning and the high-investment, high-technology environment was not apparent, and the promise of tissue engineering was overstated. In the meantime, biologists were steadily applying three-dimensional benchtop tissue-culture systems for cellular research, but the systems were gelatinous and thus limited in their ability to facilitate the development of complex tissues. Now, the bioengineering literature has seen an emergence of literature describing biofabrication of tissues and organs. However, if one looks closely, again, the viable products appear distant. 'Rapid' prototyping to reproduce the intricate patterns of whole organs using large volumes of cellular components faces daunting challenges. Homogenous forms are being labelled 'tissues', but, in fact, do not represent the heterogeneous structure of the native biological system. In 2003, we disclosed the concept of combining rapid prototyping techniques with tissue engineering technologies to facilitate precision development of heterogeneous complex tissue-test systems, i.e. systems to be used for drug discovery and the study of cellular behaviour, biomedical devices and progression of disease. The focus of this paper is on the challenges we have faced since that time, moving this concept towards reality, using the case of breast tissue as an example.

  19. Tendon tissue engineering: progress, challenges, and translation to the clinic.

    PubMed

    Shearn, J T; Kinneberg, K R; Dyment, N A; Galloway, M T; Kenter, K; Wylie, C; Butler, D L

    2011-06-01

    The tissue engineering field has made great strides in understanding how different aspects of tissue engineered constructs (TECs) and the culture process affect final tendon repair. However, there remain significant challenges in developing strategies that will lead to a clinically effective and commercially successful product. In an effort to increase repair quality, a better understanding of normal development, and how it differs from adult tendon healing, may provide strategies to improve tissue engineering. As tendon tissue engineering continues to improve, the field needs to employ more clinically relevant models of tendon injury such as degenerative tendons. We need to translate successes to larger animal models to begin exploring the clinical implications of our treatments. By advancing the models used to validate our TECs, we can help convince our toughest customer, the surgeon, that our products will be clinically efficacious. As we address these challenges in musculoskeletal tissue engineering, the field still needs to address the commercialization of products developed in the laboratory. TEC commercialization faces numerous challenges because each injury and patient is unique. This review aims to provide tissue engineers with a summary of important issues related to engineering tendon repairs and potential strategies for producing clinically successful products.

  20. Cell Sheet-Based Tissue Engineering for Organizing Anisotropic Tissue Constructs Produced Using Microfabricated Thermoresponsive Substrates.

    PubMed

    Takahashi, Hironobu; Okano, Teruo

    2015-11-18

    In some native tissues, appropriate microstructures, including orientation of the cell/extracellular matrix, provide specific mechanical and biological functions. For example, skeletal muscle is made of oriented myofibers that is responsible for the mechanical function. Native artery and myocardial tissues are organized three-dimensionally by stacking sheet-like tissues of aligned cells. Therefore, to construct any kind of complex tissue, the microstructures of cells such as myotubes, smooth muscle cells, and cardiomyocytes also need to be organized three-dimensionally just as in the native tissues of the body. Cell sheet-based tissue engineering allows the production of scaffold-free engineered tissues through a layer-by-layer construction technique. Recently, using microfabricated thermoresponsive substrates, aligned cells are being harvested as single continuous cell sheets. The cell sheets act as anisotropic tissue units to build three-dimensional tissue constructs with the appropriate anisotropy. This cell sheet-based technology is straightforward and has the potential to engineer a wide variety of complex tissues. In addition, due to the scaffold-free cell-dense environment, the physical and biological cell-cell interactions of these cell sheet constructs exhibit unique cell behaviors. These advantages will provide important clues to enable the production of well-organized tissues that closely mimic the structure and function of native tissues, required for the future of tissue engineering.

  1. Self-synthesized extracellular matrix contributes to mature adipose tissue regeneration in a tissue engineering chamber.

    PubMed

    Zhan, Weiqing; Chang, Qiang; Xiao, Xiaolian; Dong, Ziqing; Zeng, Zhaowei; Gao, Jianhua; Lu, Feng

    2015-01-01

    The development of an engineered adipose tissue substitute capable of supporting reliable, predictable, and complete fat tissue regeneration would be of value in plastic and reconstructive surgery. For adipogenesis, a tissue engineering chamber provides an optimized microenvironment that is both efficacious and reproducible; however, for reasons that remain unclear, tissues regenerated in a tissue engineering chamber consist mostly of connective rather than adipose tissue. Here, we describe a chamber-based system for improving the yield of mature adipose tissue and discuss the potential mechanism of adipogenesis in tissue-chamber models. Adipose tissue flaps with independent vascular pedicles placed in chambers were implanted into rabbits. Adipose volume increased significantly during the observation period (week 1, 2, 3, 4, 16). Histomorphometry revealed mature adipose tissue with signs of adipose tissue remolding. The induced engineered constructs showed high-level expression of adipogenic (peroxisome proliferator-activated receptor γ), chemotactic (stromal cell-derived factor 1a), and inflammatory (interleukin 1 and 6) genes. In our system, the extracellular matrix may have served as a scaffold for cell migration and proliferation, allowing mature adipose tissue to be obtained in a chamber microenvironment without the need for an exogenous scaffold. Our results provide new insights into key elements involved in the early development of adipose tissue regeneration.

  2. Toward clinical application of tissue-engineered cartilage.

    PubMed

    Fulco, Ilario; Largo, René Denis; Miot, Sylvie; Wixmerten, Anke; Martin, Ivan; Schaefer, Dirk J; Haug, Martin Dieter

    2013-04-01

    Since the late 1960s, surgeons and scientists envisioned use of tissue engineering to provide an alternative treatment for tissue and organ damage by combining biological and synthetic components in such a way that a long-lasting repair was established. In addition to the treatment, the patient would also benefit from reduced donor site morbidity and operation time as compared with the standard procedures. Tremendous efforts in basic research have been done since the late 1960s to better understand chondrocyte biology and cartilage maturation and to fulfill the growing need for tissue-engineered cartilage in reconstructive, trauma, and orthopedic surgery. Starting from the first successful generation of engineered cartilaginous tissue, scientists strived to improve the properties of the cartilaginous constructs by characterizing different cell sources, modifying the environmental factors influencing cell expansion and differentiation and applying physical stimuli to modulate the mechanical properties of the construct. All these efforts have finally led to a clinical phase I trial to show the safety and feasibility of using tissue-engineered cartilage in reconstructive facial surgery. However, to bring tissue engineering into routine clinical applications and commercialize tissue-engineered grafts, further research is necessary to achieve a cost-effective, standardized, safe, and regulatory compliant process.

  3. Multiscale assembly for tissue engineering and regenerative medicine

    PubMed Central

    Inci, Fatih; Tasoglu, Savas; Erkmen, Burcu; Demirci, Utkan

    2015-01-01

    Our understanding of cell biology and its integration with materials science has led to technological innovations in the bioengineering of tissue-mimicking grafts that can be utilized in clinical and pharmaceutical applications. Bio-engineering of native-like multiscale building blocks provides refined control over the cellular microenvironment, thus enabling functional tissues. In this review, we focus on assembling building blocks from the biomolecular level to the millimeter scale. We also provide an overview of techniques for assembling molecules, cells, spheroids, and microgels and achieving bottom-up tissue engineering. Additionally, we discuss driving mechanisms for self- and guided assembly to create micro-to-macro scale tissue structures. PMID:25796488

  4. Biodegradable and biocompatible polymers for tissue engineering application: a review.

    PubMed

    Asghari, Fatemeh; Samiei, Mohammad; Adibkia, Khosro; Akbarzadeh, Abolfazl; Davaran, Soodabeh

    2017-03-01

    Since so many years ago, tissue damages that are caused owing to various reasons attract scientists' attention to find a practical way to treat. In this regard, many studies were conducted. Nano scientists also suggested some ways and the newest one is called tissue engineering. They use biodegradable polymers in order to replace damaged structures in tissues to make it practical. Biodegradable polymers are dominant scaffolding materials in tissue engineering field. In this review, we explained about biodegradable polymers and their application as scaffolds.

  5. Improving the moisturizing properties of collagen film by surface grafting of chondroitin sulfate for corneal tissue engineering.

    PubMed

    Liu, Yang; Lv, Huilin; Ren, Li; Xue, Guanhua; Wang, Yingjun

    2016-01-01

    Cornea disease is the second cause of blindness and keratoplasty is the most commonly performed option for visual rehabilitation of patients with corneal blindness. However, the clinical treatment has been drastically limited due to a severe shortage of high-quality donor corneas. Although collagen film with outstanding biocompatibility has promising application in corneal tissue engineering, the moisturizing properties of collagen-based materials must be further improved to satisfy the requirements of clinical applications. This paper describes a novel collagen-based film with high moisture capacity reinforced by surface grafting of chondroitin sulfate. The collagen-chondroitin sulfate (abbreviated as Col-CS) film was analyzed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy and its hydrophilic property, moisture retention, optical property, and mechanical performance had been tested. The moisture-retaining capacity is found to be improved with the introduction of chondroitin sulfate, and the Col-CS membrane performs better mechanical properties than the collagen film. Moreover, the modified film proves excellent biocompatibility for the proliferation of human corneal epithelial cells in vitro. This Col-CS film with good moisturizing properties can reduce the risk of xerophthalmia and is expected to increase the implant success rate in clinic patients with corneal defects.

  6. Bone Tissue Engineering Challenges in Oral & Maxillofacial Surgery.

    PubMed

    Smith, Brandon T; Shum, Jonathan; Wong, Mark; Mikos, Antonios G; Young, Simon

    2015-01-01

    Over the past decades, there has been a substantial amount of innovation and research into tissue engineering and regenerative approaches for the craniofacial region. This highly complex area presents many unique challenges for tissue engineers. Recent research indicates that various forms of implantable biodegradable scaffolds may play a beneficial role in the clinical treatment of craniofacial pathological conditions. Additionally, the direct delivery of bioactive molecules may further increase de novo bone formation. While these strategies offer an exciting glimpse into potential future treatments, there are several challenges that still must be overcome. In this chapter, we will highlight both current surgical approaches for craniofacial reconstruction and recent advances within the field of bone tissue engineering. The clinical challenges and limitations of these strategies will help contextualize and inform future craniofacial tissue engineering strategies.

  7. Soft Tissue Engineering with Micronized-Gingival Connective Tissues.

    PubMed

    Noda, Sawako; Sumita, Yoshinori; Ohba, Seigo; Yamamoto, Hideyuki; Asahina, Izumi

    2017-02-24

    The free gingival graft (FGG) and connective tissue graft (CTG) are currently considered to be the gold standards for keratinized gingival tissue reconstruction and augmentation. However, these procedures have some disadvantages in harvesting large grafts, such as donor-site morbidity as well as insufficient gingival width and thickness at the recipient site post-treatment. To solve these problems, we focused on an alternative strategy using micronized tissue transplantation (micro-graft). In this study, we first investigated whether transplantation of micronized gingival connective tissues (MGCTs) promotes skin wound healing. MGCTs (≤100 µm) were obtained by mincing a small piece (8 mm(3) ) of porcine keratinized gingiva using the RIGENERA system. The MGCTs were then transplanted to a full skin defect (5 mm in diameter) on the dorsal surface of immunodeficient mice after seeding to an atelocollagen matrix. Transplantations of atelocollagen matrixes with and without micronized dermis were employed as experimental controls. The results indicated that MGCTs markedly promote the vascularization and epithelialization of the defect area 14 days after transplantation compared to the experimental controls. After 21 days, complete wound closure with low contraction was obtained only in the MGCT grafts. Tracking analysis of transplanted MGCTs revealed that some mesenchymal cells derived from MGCTs can survive during healing and may function to assist in wound healing. We propose here that micro-grafting with MGCTs represents an alternative strategy for keratinized tissue reconstruction that is characterized by low morbidity and ready availability. This article is protected by copyright. All rights reserved.

  8. Gene therapy progress and prospects: in tissue engineering.

    PubMed

    Polak, J; Hench, L

    2005-12-01

    Tissue engineering (TE) has existed for several years as an area spanning many disciplines, including medicine and engineering. The use of stem cells as a biological basis for TE coupled with advances in materials science has opened up an entirely new chapter in medicine and holds the promise of major contributions to the repair, replacement and regeneration of damaged tissues and organs. In this article, we review the spectrum of stem cells and scaffolds being investigated for their potential applications in medicine.

  9. Micro and Nano-mediated 3D Cardiac Tissue Engineering

    DTIC Science & Technology

    2011-10-01

    AD_________________ Award Number: W81XWH-08-1-0701 TITLE: Micro and Nano -mediated 3D Cardiac...5a. CONTRACT NUMBER Micro and Nano -mediated 3D Cardiac Tissue Engineering 5b. GRANT NUMBER W81XWH-08-1-0701 5c. PROGRAM ELEMENT NUMBER 6...TATRC-funded Micro and Nano -mediated 3D Cardiac Tissue Engineering is a project of the University of Illinois Center for Nanoscale Science and

  10. Low-intensity pulsed ultrasound in dentofacial tissue engineering.

    PubMed

    Tanaka, Eiji; Kuroda, Shingo; Horiuchi, Shinya; Tabata, Akira; El-Bialy, Tarek

    2015-04-01

    Oral and maxillofacial diseases affect millions of people worldwide and hence tissue engineering can be considered an interesting and clinically relevant approach to regenerate orofacial tissues after being affected by different diseases. Among several innovations for tissue regeneration, low-intensity pulsed ultrasound (LIPUS) has been used extensively in medicine as a therapeutic, operative, and diagnostic tool. LIPUS is accepted to promote bone fracture repair and regeneration. Furthermore, the effect of LIPUS on soft tissues regeneration has been paid much attention, and many studies have performed to evaluate the potential use of LIPUS to tissue engineering soft tissues. The present article provides an overview about the status of LIPUS stimulation as a tool to be used to enhance regeneration/tissue engineering. This review consists of five parts. Part 1 is a brief introduction of the acoustic description of LIPUS and mechanical action. In Part 2, biological problems in dentofacial tissue engineering are proposed. Part 3 explores biologic mechanisms of LIPUS to cells and tissues in living body. In Part 4, the effectiveness of LIPUS on cell metabolism and tissue regeneration in dentistry are summarized. Finally, Part 5 relates the possibility of clinical application of LIPUS in orthodontics. The present review brings out better understanding of the bioeffect of LIPUS therapy on orofacial tissues which is essential to the successful integration of management remedies for tissue regeneration/engineering. To develop an evidence-based approach to clinical management and treatment of orofacial degenerative diseases using LIPUS, we would like to be in full pursuit of LIPUS biotherapy. Still, there are many challenges for this relatively new strategy, but the up to date achievements using it promises to go far beyond the present possibilities.

  11. Fiber-Based Tissue Engineering: Progress, Challenges, and Opportunities

    PubMed Central

    Tamayol, Ali; Akbari, Mohsen; Annabi, Nasim; Paul, Arghya; Khademhosseini, Ali; Juncker, David

    2013-01-01

    Tissue engineering aims to improve the function of diseased or damaged organs by creating biological substitutes. To fabricate a functional tissue, the engineered construct should mimic the physiological environment including its structural, topographical, and mechanical properties. Moreover, the construct should facilitate nutrients and oxygen diffusion as well as removal of metabolic waste during tissue regeneration. In the last decade, fiber-based techniques such as weaving, knitting, braiding, as well as electrospinning, and direct writing have emerged as promising platforms for making 3D tissue constructs that can address the above mentioned challenges. Here, we critically review the techniques used to form cell-free and cell-laden fibers and to assemble them into scaffolds. We compare their mechanical properties, morphological features and biological activity. We discuss current challenges and future opportunities of fiber-based tissue engineering (FBTE) for use in research and clinical practice. PMID:23195284

  12. Advances in polymeric systems for tissue engineering and biomedical applications.

    PubMed

    Ravichandran, Rajeswari; Sundarrajan, Subramanian; Venugopal, Jayarama Reddy; Mukherjee, Shayanti; Ramakrishna, Seeram

    2012-03-01

    The characteristics of tissue engineered scaffolds are major concerns in the quest to fabricate ideal scaffolds for tissue engineering applications. The polymer scaffolds employed for tissue engineering applications should possess multifunctional properties such as biocompatibility, biodegradability and favorable mechanical properties as it comes in direct contact with the body fluids in vivo. Additionally, the polymer system should also possess biomimetic architecture and should support stem cell adhesion, proliferation and differentiation. As the progress in polymer technology continues, polymeric biomaterials have taken characteristics more closely related to that desired for tissue engineering and clinical needs. Stimuli responsive polymers also termed as smart biomaterials respond to stimuli such as pH, temperature, enzyme, antigen, glucose and electrical stimuli that are inherently present in living systems. This review highlights the exciting advancements in these polymeric systems that relate to biological and tissue engineering applications. Additionally, several aspects of technology namely scaffold fabrication methods and surface modifications to confer biological functionality to the polymers have also been discussed. The ultimate objective is to emphasize on these underutilized adaptive behaviors of the polymers so that novel applications and new generations of smart polymeric materials can be realized for biomedical and tissue engineering applications.

  13. Textile Processes for Engineering Tissues with Biomimetic Architectures and Properties.

    PubMed

    Fallahi, Afsoon; Khademhosseini, Ali; Tamayol, Ali

    2016-09-01

    Textile technologies in which fibers containing biological factors and cells are formed and assembled into constructs with biomimetic properties have attracted significant attention in the field of tissue engineering. This Forum article highlights the most prominent advances of the field in the areas of fiber fabrication and construct engineering.

  14. Application of the cell sheet technique in tissue engineering

    PubMed Central

    CHEN, GUANGNAN; QI, YIYING; NIU, LIE; DI, TUOYU; ZHONG, JINWEI; FANG, TINGTING; YAN, WEIQI

    2015-01-01

    The development and application of the tissue engineering technique has shown a significant potential in regenerative medicine. However, the limitations of conventional tissue engineering methods (cell suspensions, scaffolds and/or growth factors) restrict its application in certain fields. The novel cell sheet technique can overcome such disadvantages. Cultured cells can be harvested as intact sheets without the use of proteolytic enzymes, such as trypsin or dispase, which can result in cell damage and loss of differentiated phenotypes. The cell sheet is a complete layer, which contains extracellular matrix, ion channel, growth factor receptors, nexin and other important cell surface proteins. Mesenchymal stem cells (MSCs), which have the potential for multiple differentiation, are promising candidate seed cells for tissue engineering. The MSC sheet technique may have potential in the fields of regenerative medicine and tissue engineering in general. Additionally, induced pluripotent stem cell and embryonic stem cell-derived cell sheets have been proposed for tissue regeneration. Currently, the application of cell sheet for tissue reconstruction includes: Direct recipient sites implantation, superposition of cell sheets to construct three-dimensional structure for implantation, or cell sheet combined with scaffolds. The present review discusses the progress in cell sheet techniques, particularly stem cell sheet techniques, in tissue engineering. PMID:26623011

  15. Natural Polymer-Cell Bioconstructs for Bone Tissue Engineering.

    PubMed

    Titorencu, Irina; Albu, Madalina Georgiana; Nemecz, Miruna; Jinga, Victor V

    2017-01-01

    The major goal of bone tissue engineering is to develop bioconstructs which substitute the functionality of damaged natural bone structures as much as possible if critical-sized defects occur. Scaffolds that mimic the structure and composition of bone tissue and cells play a pivotal role in bone tissue engineering applications. First, composition, properties and in vivo synthesis of bone tissue are presented for the understanding of bone formation. Second, potential sources of osteoprogenitor cells have been investigated for their capacity to induce bone repair and regeneration. Third, taking into account that the main property to qualify one scaffold as a future bioconstruct for bone tissue engineering is the biocompatibility, the assessments which prove it are reviewed in this paper. Forth, various types of natural polymer- based scaffolds consisting in proteins, polysaccharides, minerals, growth factors etc, are discussed, and interaction between scaffolds and cells which proved bone tissue engineering concept are highlighted. Finally, the future perspectives of natural polymer-based scaffolds for bone tissue engineering are considered.

  16. Stem Cell Sources for Vascular Tissue Engineering and Regeneration

    PubMed Central

    Bajpai, Vivek K.

    2012-01-01

    This review focuses on the stem cell sources with the potential to be used in vascular tissue engineering and to promote vascular regeneration. The first clinical studies using tissue-engineered vascular grafts are already under way, supporting the potential of this technology in the treatment of cardiovascular and other diseases. Despite progress in engineering biomaterials with the appropriate mechanical properties and biological cues as well as bioreactors for generating the correct tissue microenvironment, the source of cells that make up the vascular tissues remains a major challenge for tissue engineers and physicians. Mature cells from the tissue of origin may be difficult to obtain and suffer from limited proliferative capacity, which may further decline as a function of donor age. On the other hand, multipotent and pluripotent stem cells have great potential to provide large numbers of autologous cells with a great differentiation capacity. Here, we discuss the adult multipotent as well as embryonic and induced pluripotent stem cells, their differentiation potential toward vascular lineages, and their use in engineering functional and implantable vascular tissues. We also discuss the associated challenges that need to be addressed in order to facilitate the transition of this technology from the bench to the bedside. PMID:22571595

  17. Gene therapy in the cornea: 2005--present.

    PubMed

    Mohan, Rajiv R; Tovey, Jonathan C K; Sharma, Ajay; Tandon, Ashish

    2012-01-01

    Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat corneal abnormalities has begun to surface. Identification of next generation viral and nanoparticle vectors, characterization of delivered gene levels, localization, and duration in the cornea, and significant success in controlling corneal disorders, particularly fibrosis and angiogenesis, in experimental animal disease models, with no major side effects have propelled gene therapy a step closer toward establishing gene-based therapies for corneal blindness. Recently, researchers have assessed the delivery of therapeutic genes for corneal diseases and disorders due to trauma, infections, chemical, mechanical, and surgical injury, and/or abnormal wound healing. This review provides an update on the developments in gene therapy for corneal diseases and discusses the barriers that hinder its utilization for delivering genes in the cornea.

  18. UVA system for human cornea irradiation

    NASA Astrophysics Data System (ADS)

    Pereira, Fernando R. A.; Stefani, Mario; Otoboni, José A.; Richter, Eduardo H.; Rossi, Giuliano; Mota, Alessandro D.; Ventura, Liliane

    2009-02-01

    According to recent studies, an increase in corneal stiffness is a promising alternative for avoiding ectasias and for stagnating keratoconus of grades 1 and 2. The clinical treatment consists essentially of instilling Riboflavin (vitamin B2), in the cornea and then irradiating the corneal tissue, with UVA (365nm) radiation at 3mW/cm2 for 30min. This procedure provides collagen cross-linking in the corneal surface, increasing its stiffness. This work presents a system for UVA irradiation of the corneas at a peak wavelength of 365nm with adjustable power up to 5mW. The system has closed loop electronics to control the emitted power with 20% precision from the sated power output. The system is a prototype for performing corneal cross-linking and has been clinically tested. The closed loop electronics is a differential from the equipments available on the market.

  19. Stratified scaffold design for engineering composite tissues.

    PubMed

    Mosher, Christopher Z; Spalazzi, Jeffrey P; Lu, Helen H

    2015-08-01

    A significant challenge to orthopaedic soft tissue repair is the biological fixation of autologous or allogeneic grafts with bone, whereby the lack of functional integration between such grafts and host bone has limited the clinical success of anterior cruciate ligament (ACL) and other common soft tissue-based reconstructive grafts. The inability of current surgical reconstruction to restore the native fibrocartilaginous insertion between the ACL and the femur or tibia, which minimizes stress concentration and facilitates load transfer between the soft and hard tissues, compromises the long-term clinical functionality of these grafts. To enable integration, a stratified scaffold design that mimics the multiple tissue regions of the ACL interface (ligament-fibrocartilage-bone) represents a promising strategy for composite tissue formation. Moreover, distinct cellular organization and phase-specific matrix heterogeneity achieved through co- or tri-culture within the scaffold system can promote biomimetic multi-tissue regeneration. Here, we describe the methods for fabricating a tri-phasic scaffold intended for ligament-bone integration, as well as the tri-culture of fibroblasts, chondrocytes, and osteoblasts on the stratified scaffold for the formation of structurally contiguous and compositionally distinct regions of ligament, fibrocartilage and bone. The primary advantage of the tri-phasic scaffold is the recapitulation of the multi-tissue organization across the native interface through the layered design. Moreover, in addition to ease of fabrication, each scaffold phase is similar in polymer composition and therefore can be joined together by sintering, enabling the seamless integration of each region and avoiding delamination between scaffold layers.

  20. Challenges and opportunities for tissue-engineering polarized epithelium.

    PubMed

    Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

    2014-02-01

    The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

  1. Three-dimensional bioprinting in tissue engineering and regenerative medicine.

    PubMed

    Gao, Guifang; Cui, Xiaofeng

    2016-02-01

    With the advances of stem cell research, development of intelligent biomaterials and three-dimensional biofabrication strategies, highly mimicked tissue or organs can be engineered. Among all the biofabrication approaches, bioprinting based on inkjet printing technology has the promises to deliver and create biomimicked tissue with high throughput, digital control, and the capacity of single cell manipulation. Therefore, this enabling technology has great potential in regenerative medicine and translational applications. The most current advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review, including vasculature, muscle, cartilage, and bone. In addition, the benign side effect of bioprinting to the printed mammalian cells can be utilized for gene or drug delivery, which can be achieved conveniently during precise cell placement for tissue construction. With layer-by-layer assembly, three-dimensional tissues with complex structures can be printed using converted medical images. Therefore, bioprinting based on thermal inkjet is so far the most optimal solution to engineer vascular system to the thick and complex tissues. Collectively, bioprinting has great potential and broad applications in tissue engineering and regenerative medicine. The future advances of bioprinting include the integration of different printing mechanisms to engineer biphasic or triphasic tissues with optimized scaffolds and further understanding of stem cell biology.

  2. The Role of Bioreactors in Ligament and Tendon Tissue Engineering.

    PubMed

    Mace, James; Wheelton, Andy; Khan, Wasim S; Anand, Sanj

    2016-01-01

    Bioreactors are pivotal to the emerging field of tissue engineering. The formation of neotissue from pluripotent cell lineages potentially offers a source of tissue for clinical use without the significant donor site morbidity associated with many contemporary surgical reconstructive procedures. Modern bioreactor design is becoming increasingly complex to provide a both an expandable source of readily available pluripotent cells and to facilitate their controlled differentiation into a clinically applicable ligament or tendon like neotissue. This review presents the need for such a method, challenges in the processes to engineer neotissue and the current designs and results of modern bioreactors in the pursuit of engineered tendon and ligament.

  3. Therapeutic efficiency of tissue-engineered human corneal endothelium transplants on rabbit primary corneal endotheliopathy.

    PubMed

    Fan, Ting-jun; Zhao, Jun; Hu, Xiu-zhong; Ma, Xi-ya; Zhang, Wen-bo; Yang, Chao-zhong

    2011-06-01

    To evaluate the therapeutic efficiency of tissue-engineered human corneal endothelia (TE-HCEs) on rabbit primary corneal endotheliopathy (PCEP), TE-HCEs reconstructed with monoclonal human corneal endothelial cells (mcHCECs) and modified denuded amniotic membranes (mdAMs) were transplanted into PCEP models of New Zealand white rabbits using penetrating keratoplasty. The TE-HCEs were examined using diverse techniques including slit-lamp biomicroscopy observation and pachymeter and tonometer measurements in vivo, and fluorescent microscopy, alizarin red staining, paraffin sectioning, scanning and transmission electron microscopy observations in vitro. The corneas of transplanted eyes maintained transparency for as long as 200 d without obvious edema or immune rejection. The corneal thickness of transplanted eyes decreased gradually after transplanting, reaching almost the thickness of normal eyes after 156 d, while the TE-HCE non-transplanted eyes were turbid and showed obvious corneal edema. The polygonal corneal endothelial cells in the transplanted area originated from the TE-HCE transplant. An intact monolayer corneal endothelium had been reconstructed with the morphology, cell density and structure similar to those of normal rabbit corneal endothelium. In conclusion, the transplanted TE-HCE can reconstruct the integrality of corneal endothelium and restore corneal transparency and thickness in PCEP rabbits. The TE-HCE functions normally as an endothelial barrier and pump and promises to be an equivalent of HCE for clinical therapy of human PCEP.

  4. Liver tissue engineering: promises and prospects of new technology.

    PubMed

    Zheng, Ming-Hua; Ye, Chao; Braddock, Martin; Chen, Yong-Ping

    2010-05-01

    Today, many patients suffer from acute liver failure and hepatoma. This is an area of high unmet clinical need as these conditions are associated with very high mortality. There is an urgent need to develop techniques that will enable liver tissue engineering or generate a bioartificial liver, which will maintain or improve liver function or offer the possibility of liver replacement. Liver tissue engineering is an innovative way of constructing an implantable liver and has the potential to alleviate the shortage of organ donors for orthotopic liver transplantation. In this review we describe, from an engineering perspective, progress in the field of liver tissue engineering, including three main aspects involving cell sources, scaffolds and vascularization.

  5. Cell Microenvironment Engineering and Monitoring for Tissue Engineering and Regenerative Medicine: The Recent Advances

    PubMed Central

    Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul

    2014-01-01

    In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future. PMID:25143954

  6. Characterization of electrical stimulation electrodes for cardiac tissue engineering.

    PubMed

    Tandon, Nina; Cannizzaro, Chris; Figallo, Elisa; Voldman, Joel; Vunjak-Novakovic, Gordana

    2006-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. The goal of this study was to assess the conditions of electrical stimulation with respect to the electrode geometry, material properties and charge-transfer characteristics at the electrode-electrolyte interface. We compared various biocompatible materials, including nanoporous carbon, stainless steel, titanium and titanium nitride, for use in cardiac tissue engineering bioreactors. The faradaic and non-faradaic charge transfer mechanisms were assessed by electrochemical impedance spectroscopy (EIS), studying current injection characteristics, and examining surface properties of electrodes with scanning electron microscopy. Carbon electrodes were found to have the best current injection characteristics. However, these electrodes require careful handling because of their limited mechanical strength. The efficacy of various electrodes for use in 2-D and 3-D cardiac tissue engineering systems with neonatal rat cardiomyocytes is being determined by assessing cell viability, amplitude of contractions, excitation thresholds, maximum capture rate, and tissue morphology.

  7. Biomaterial based cardiac tissue engineering and its applications

    PubMed Central

    Huyer, Locke Davenport; Montgomery, Miles; Zhao, Yimu; Xiao, Yun; Conant, Genevieve; Korolj, Anastasia; Radisic, Milica

    2015-01-01

    Cardiovascular disease is a leading cause of death worldwide, necessitating the development of effective treatment strategies. A myocardial infarction involves the blockage of a coronary artery leading to depletion of nutrient and oxygen supply to cardiomyocytes and massive cell death in a region of the myocardium. Cardiac tissue engineering is the growth of functional cardiac tissue in vitro on biomaterial scaffolds for regenerative medicine application. This strategy relies on the optimization of the complex relationship between cell networks and biomaterial properties. In this review, we discuss important biomaterial properties for cardiac tissue engineering applications, such as elasticity, degradation, and induced host response, and their relationship to engineered cardiac cell environments. With these properties in mind, we also emphasize in vitro use of cardiac tissues for high-throughput drug screening and disease modelling. PMID:25989939

  8. Photo Cleavable Polymers for Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Apostol, Monica

    We have found that P4VP and PMMA thin films can be etched with UVA radiation. Furthermore, we also found that dermal fibroblasts could be cultured successfully on the P4VP polymer, with a doubling time comparable to tissue culture Petri dish standards. Consequently we were able to grow tissue on P4VP substrates which could easily be lifted using UVA radiation. The cells that were removed were then re-plated at a lower density and a series of assays was performed at 3 and 6 days. While only a small amount of damage was discernable at day 3 nearly complete recovery was observed at day 6. The technique was also used to pattern areas within the tissue, where other types of cells could be inserted. In order to demonstrate the technique, a hybrid tissue layer was produced, where the dermal fibroblasts in a circular area at the center of the sample were removed via exposure through a mask. A keratinocyte layer was inserted which adhere to the fibroblast layer forming a tissue with integrated layers of two distinct cell types. We also investigated the effects of coated TiO2 particles on cells exposed to UVC. We found that as expected, cells were adversely affected by exposure to UVC and died even after exposure to as little as 3.5 J/cm 2. Addition of 0.4mg/ml TiO2 particles that were uncoated did not provide protection, and the cells died at the same rate. Addition of 4mg/ml of coated TiO2 on the other hand, did not affect cell viability in the absence of UV light and increased the viability after exposure to UVC radiation. In fact the cells containing the coated particles were indistinguishable for the unexposed control samples even after exposure to as much as 7.1J/cm 2 of UVC.

  9. Image-based metrology of porous tissue engineering scaffolds

    NASA Astrophysics Data System (ADS)

    Rajagopalan, Srinivasan; Robb, Richard A.

    2006-03-01

    Tissue engineering is an interdisciplinary effort aimed at the repair and regeneration of biological tissues through the application and control of cells, porous scaffolds and growth factors. The regeneration of specific tissues guided by tissue analogous substrates is dependent on diverse scaffold architectural indices that can be derived quantitatively from the microCT and microMR images of the scaffolds. However, the randomness of pore-solid distributions in conventional stochastic scaffolds presents unique computational challenges. As a result, image-based characterization of scaffolds has been predominantly qualitative. In this paper, we discuss quantitative image-based techniques that can be used to compute the metrological indices of porous tissue engineering scaffolds. While bulk averaged quantities such as porosity and surface are derived directly from the optimal pore-solid delineations, the spatially distributed geometric indices are derived from the medial axis representations of the pore network. The computational framework proposed (to the best of our knowledge for the first time in tissue engineering) in this paper might have profound implications towards unraveling the symbiotic structure-function relationship of porous tissue engineering scaffolds.

  10. Electrical stimulation: a novel tool for tissue engineering.

    PubMed

    Balint, Richard; Cassidy, Nigel J; Cartmell, Sarah H

    2013-02-01

    New advances in tissue engineering are being made through the application of different types of electrical stimuli to influence cell proliferation and differentiation. Developments made in the last decade have allowed us to improve the structure and functionality of tissue-engineered products through the use of growth factors, hormones, drugs, physical stimuli, bioreactor use, and two-dimensional (2-D) and three-dimensional (3-D) artificial extracellular matrices (with various material properties and topography). Another potential type of stimulus is electricity, which is important in the physiology and development of the majority of all human tissues. Despite its great potential, its role in tissue regeneration and its ability to influence cell migration, orientation, proliferation, and differentiation has rarely been considered in tissue engineering. This review highlights the importance of endogenous electrical stimulation, gathering the current knowledge on its natural occurrence and role in vivo, discussing the novel methods of delivering this stimulus and examining its cellular and tissue level effects, while evaluating how the technique could benefit the tissue engineering discipline in the future.

  11. Cell patterning for liver tissue engineering via dielectrophoretic mechanisms.

    PubMed

    Yahya, Wan Nurlina Wan; Kadri, Nahrizul Adib; Ibrahim, Fatimah

    2014-07-02

    Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP) force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration.

  12. Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

    PubMed Central

    Yahya, Wan Nurlina Wan; Kadri, Nahrizul Adib; Ibrahim, Fatimah

    2014-01-01

    Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP) force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration. PMID:24991941

  13. Periodontal tissue engineering and regeneration: current approaches and expanding opportunities.

    PubMed

    Chen, Fa-Ming; Jin, Yan

    2010-04-01

    The management of periodontal tissue defects that result from periodontitis represents a medical and socioeconomic challenge. Concerted efforts have been and still are being made to accelerate and augment periodontal tissue and bone regeneration, including a range of regenerative surgical procedures, the development of a variety of grafting materials, and the use of recombinant growth factors. More recently, tissue-engineering strategies, including new cell- and/or matrix-based dimensions, are also being developed, analyzed, and employed for periodontal regenerative therapies. Tissue engineering in periodontology applies the principles of engineering and life sciences toward the development of biological techniques that can restore lost alveolar bone, periodontal ligament, and root cementum. It is based on an understanding of the role of periodontal formation and aims to grow new functional tissues rather than to build new replacements of periodontium. Although tissue engineering has merged to create more opportunities for predictable and optimal periodontal tissue regeneration, the technique and design for preclinical and clinical studies remain in their early stages. To date, the reconstruction of small- to moderate-sized periodontal bone defects using engineered cell-scaffold constructs is technically feasible, and some of the currently developed concepts may represent alternatives for certain ideal clinical scenarios. However, the predictable reconstruction of the normal structure and functionality of a tooth-supporting apparatus remains challenging. This review summarizes current regenerative procedures for periodontal healing and regeneration and explores their progress and difficulties in clinical practice, with particular emphasis placed upon current challenges and future possibilities associated with tissue-engineering strategies in periodontal regenerative medicine.

  14. Current approaches to electrospun nanofibers for tissue engineering.

    PubMed

    Rim, Nae Gyune; Shin, Choongsoo S; Shin, Heungsoo

    2013-02-01

    The ultimate goal of tissue engineering is to replace damaged tissues by applying engineering technology and the principles of life sciences. To successfully engineer a desirable tissue, three main elements of cells, scaffolds and growth factors need to be harmonized. Biomaterial-based scaffolds serve as a critical platform both to support cell adhesion and to deliver growth factors. Various methods of fabricating scaffolds have been investigated. One recently developed method that is growing in popularity is called electrospinning. Electrospinning is known for its capacity to make fibrous and porous structures that are similar to natural extracellular matrix (ECM). Other advantages to electrospinning include its ability to create relatively large surface to volume ratios, its ability to control fiber size from micro- to nano-scales and its versatility in material choice. Although early work with electrospun fibers has shown promise in the regeneration of certain types of tissues, further modification of their chemical, biological and mechanical properties would permit future advancements. In this paper, current approaches to the development of modular electrospun fibers as scaffolds for tissue engineering are discussed. Their chemical and physical characteristics can be tuned for the regeneration of specific target tissues by co-spinning of multiple materials and by post-modification of the surface of electrospun fibers. In addition, topology or structure can also be controlled to elicit specific responses from cells and tissues. The selection of proper polymers, suitable surface modification techniques and the control of the dimension and arrangement of the fibrous structure of electrospun fibers can offer versatility and tissue specificity, and therefore provide a blueprint for specific tissue engineering applications.

  15. Cnidarians biomineral in tissue engineering: a review.

    PubMed

    Vago, Razi

    2008-01-01

    Biomineralization is the process by which organisms precipitate minerals. Crystals formed in this way are exploited by the organisms for a variety of purposes, including mechanical support and protection of soft tissue. Skeletal precipitation, via millions of years of evolution, has produced a wide variety of architectural configurations and material properties. It is exactly these properties that now attract the attention of researchers searching for new materials for a variety of biomedical applications.

  16. Scaffolds for hand tissue engineering: the importance of surface topography.

    PubMed

    Kloczko, E; Nikkhah, D; Yildirimer, L

    2015-11-01

    Tissue engineering is believed to have great potential for the reconstruction of the hand after trauma, congenital absence and tumours. Due to the presence of multiple distinct tissue types, which together function in a precisely orchestrated fashion, the hand counts among the most complex structures to regenerate. As yet the achievements have been limited. More recently, the focus has shifted towards scaffolds, which provide a three-dimensional framework to mimic the natural extracellular environment for specific cell types. In particular their surface structures (or topographies) have become a key research focus to enhance tissue-specific cell attachment and growth into fully functioning units. This article reviews the current understanding in hand tissue engineering before focusing on the potential for scaffold topographical features on micro- and nanometre scales to achieve better functional regeneration of individual and composite tissues.

  17. Superior Tissue Evolution in Slow-Degrading Scaffolds for Valvular Tissue Engineering.

    PubMed

    Brugmans, Marieke M C P; Soekhradj-Soechit, R Sarita; van Geemen, Daphne; Cox, Martijn; Bouten, Carlijn V C; Baaijens, Frank P T; Driessen-Mol, Anita

    2016-01-01

    Synthetic polymers are widely used to fabricate porous scaffolds for the regeneration of cardiovascular tissues. To ensure mechanical integrity, a balance between the rate of scaffold absorption and tissue formation is of high importance. A higher rate of tissue formation is expected in fast-degrading materials than in slow-degrading materials. This could be a result of synthetic cells, which aim to compensate for the fast loss of mechanical integrity of the scaffold by deposition of collagen fibers. Here, we studied the effect of fast-degrading polyglycolic acid scaffolds coated with poly-4-hydroxybutyrate (PGA-P4HB) and slow-degrading poly-ɛ-caprolactone (PCL) scaffolds on amount of tissue, composition, and mechanical characteristics in time, and compared these engineered values with values for native human heart valves. Electrospun PGA-P4HB and PCL scaffolds were either kept unseeded in culture or were seeded with human vascular-derived cells. Tissue formation, extracellular matrix (ECM) composition, remaining scaffold weight, tissue-to-scaffold weight ratio, and mechanical properties were analyzed every week up to 6 weeks. Mass of unseeded PCL scaffolds remained stable during culture, whereas PGA-P4HB scaffolds degraded rapidly. When seeded with cells, both scaffold types demonstrated increasing amounts of tissue with time, which was more pronounced for PGA-P4HB-based tissues during the first 2 weeks; however, PCL-based tissues resulted in the highest amount of tissue after 6 weeks. This study is the first to provide insight into the tissue-to-scaffold weight ratio, therewith allowing for a fair comparison between engineered tissues cultured on scaffolds as well as between native heart valve tissues. Although the absolute amount of ECM components differed between the engineered tissues, the ratio between ECM components was similar after 6 weeks. PCL-based tissues maintained their shape, whereas the PGA-P4HB-based tissues deformed during culture. After 6 weeks

  18. An Adipoinductive Role of Inflammation in Adipose Tissue Engineering: Key Factors in the Early Development of Engineered Soft Tissues

    PubMed Central

    Lilja, Heidi E.; Morrison, Wayne A.; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W.

    2013-01-01

    Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue. PMID:23231040

  19. An adipoinductive role of inflammation in adipose tissue engineering: key factors in the early development of engineered soft tissues.

    PubMed

    Lilja, Heidi E; Morrison, Wayne A; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W; Abberton, Keren M

    2013-05-15

    Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

  20. Noninvasive optical coherence tomography monitoring of structure and hydration changes of human corneas in different preservation media

    NASA Astrophysics Data System (ADS)

    Wu, Yicong; Clarke, Dominic; Mathew, Aby; Nicoud, Ian; Li, Xingde

    2011-02-01

    The influence of different tissue preservation (a test solution under development and a standard storage solution) on human cornea morphology, refractive index and hydration was assessed noninvasively by ultrahigh-resolution optical coherence tomography (OCT) over time. For 28 days' or 15 days' storage in the preservation media, corneas in the two media exhibited different structural changes with different onset times including epithelial desquamation, edema-induced cornea thickening and change in tissue refractive index. It was found that the variation of the group refractive index over time was only about 2%, while 25% variation of hydration was observed in the storage and subsequent return to normothermic conditions in both preservation media. The results suggest the two media involved different but correlated preservation mechanisms. This study demonstrates that the noncontact, noninvasive, and high-resolution OCT is a powerful tool for noninvasive characterization of tissue morphological changes and hydration process and for assessment of the effects of preservation media on stored tissue integrity. Engineers.

  1. Bioglass Activated Skin Tissue Engineering Constructs for Wound Healing.

    PubMed

    Yu, Hongfei; Peng, Jinliang; Xu, Yuhong; Chang, Jiang; Li, Haiyan

    2016-01-13

    Wound healing is a complicated process, and fibroblast is a major cell type that participates in the process. Recent studies have shown that bioglass (BG) can stimulate fibroblasts to secrete a multitude of growth factors that are critical for wound healing. Therefore, we hypothesize that BG can stimulate fibroblasts to have a higher bioactivity by secreting more bioactive growth factors and proteins as compared to untreated fibroblasts, and we aim to construct a bioactive skin tissue engineering graft for wound healing by using BG activated fibroblast sheet. Thus, the effects of BG on fibroblast behaviors were studied, and the bioactive skin tissue engineering grafts containing BG activated fibroblasts were applied to repair the full skin lesions on nude mouse. Results showed that BG stimulated fibroblasts to express some critical growth factors and important proteins including vascular endothelial growth factor, basic fibroblast growth factor, epidermal growth factor, collagen I, and fibronectin. In vivo results revealed that fibroblasts in the bioactive skin tissue engineering grafts migrated into wound bed, and the migration ability of fibroblasts was stimulated by BG. In addition, the bioactive BG activated fibroblast skin tissue engineering grafts could largely increase the blood vessel formation, enhance the production of collagen I, and stimulate the differentiation of fibroblasts into myofibroblasts in the wound site, which would finally accelerate wound healing. This study demonstrates that the BG activated skin tissue engineering grafts contain more critical growth factors and extracellular matrix proteins that are beneficial for wound healing as compared to untreated fibroblast cell sheets.

  2. Tissue engineering a surrogate niche for metastatic cancer cells.

    PubMed

    Seib, F Philipp; Berry, Janice E; Shiozawa, Yusuke; Taichman, Russell S; Kaplan, David L

    2015-05-01

    In breast and prostate cancer patients, the bone marrow is a preferred site of metastasis. We hypothesized that we could use tissue-engineering strategies to lure metastasizing cancer cells to tissue-engineered bone marrow. First, we generated highly porous 3D silk scaffolds that were biocompatible and amenable to bone morphogenetic protein 2 functionalization. Control and functionalized silk scaffolds were subcutaneously implanted in mice and bone marrow development was followed. Only functionalized scaffolds developed cancellous bone and red bone marrow, which appeared as early as two weeks post-implantation and further developed over the 16-week study period. This tissue-engineered bone marrow microenvironment could be readily manipulated in situ to understand the biology of bone metastasis. To test the ability of functionalized scaffolds to serve as a surrogate niche for metastasis, human breast cancer cells were injected into the mammary fat pads of mice. The treatment of animals with scaffolds had no significant effect on primary tumor growth. However, extensive metastasis was observed in functionalized scaffolds, and the highest levels for scaffolds that were in situ manipulated with receptor activator of nuclear factor kappa-B ligand (RANKL). We also applied this tissue-engineered bone marrow model in a prostate cancer and experimental metastasis setting. In summary, we were able to use tissue-engineered bone marrow to serve as a target or "trap" for metastasizing cancer cells.

  3. Skeletal muscle tissue engineering: strategies for volumetric constructs

    PubMed Central

    Cittadella Vigodarzere, Giorgio; Mantero, Sara

    2014-01-01

    Skeletal muscle tissue is characterized by high metabolic requirements, defined structure and high regenerative potential. As such, it constitutes an appealing platform for tissue engineering to address volumetric defects, as proven by recent works in this field. Several issues common to all engineered constructs constrain the variety of tissues that can be realized in vitro, principal among them the lack of a vascular system and the absence of reliable cell sources; as it is, the only successful tissue engineering constructs are not characterized by active function, present limited cellular survival at implantation and possess low metabolic requirements. Recently, functionally competent constructs have been engineered, with vascular structures supporting their metabolic requirements. In addition to the use of biochemical cues, physical means, mechanical stimulation and the application of electric tension have proven effective in stimulating the differentiation of cells and the maturation of the constructs; while the use of co-cultures provided fine control of cellular developments through paracrine activity. This review will provide a brief analysis of some of the most promising improvements in the field, with particular attention to the techniques that could prove easily transferable to other branches of tissue engineering. PMID:25295011

  4. Tissue-engineering strategies to repair joint tissue in osteoarthritis: nonviral gene-transfer approaches.

    PubMed

    Madry, Henning; Cucchiarini, Magali

    2014-10-01

    Loss of articular cartilage is a common clinical consequence of osteoarthritis (OA). In the past decade, substantial progress in tissue engineering, nonviral gene transfer, and cell transplantation have provided the scientific foundation for generating cartilaginous constructs from genetically modified cells. Combining tissue engineering with overexpression of therapeutic genes enables immediate filling of a cartilage defect with an engineered construct that actively supports chondrogenesis. Several pioneering studies have proved that spatially defined nonviral overexpression of growth-factor genes in constructs of solid biomaterials or hydrogels is advantageous compared with gene transfer or scaffold alone, both in vitro and in vivo. Notably, these investigations were performed in models of focal cartilage defects, because advanced cartilage-repair strategies based on the principles of tissue engineering have not advanced sufficiently to enable resurfacing of extensively degraded cartilage as therapy for OA. These studies serve as prototypes for future technological developments, because they raise the possibility that cartilage constructs engineered from genetically modified chondrocytes providing autocrine and paracrine stimuli could similarly compensate for the loss of articular cartilage in OA. Because cartilage-tissue-engineering strategies are already used in the clinic, combining tissue engineering and nonviral gene transfer could prove a powerful approach to treat OA.

  5. Tissue Engineered Bone Grafts: Biological Requirements, Tissue Culture and Clinical Relevance

    PubMed Central

    Fröhlich, Mirjam; Grayson, Warren L.; Wan, Leo Q.; Marolt, Darja; Drobnic, Matej; Vunjak-Novakovic, Gordana

    2009-01-01

    The tremendous need for bone tissue in numerous clinical situations and the limited availability of suitable bone grafts are driving the development of tissue engineering approaches to bone repair. In order to engineer viable bone grafts, one needs to understand the mechanisms of native bone development and fracture healing, as these processes should ideally guide the selection of optimal conditions for tissue culture and implantation. Engineered bone grafts have been shown to have capacity for osteogenesis, osteoconduction, osteoinduction and osteointegration - functional connection between the host bone and the graft. Cells from various anatomical sources in conjunction with scaffolds and osteogenic factors have been shown to form bone tissue in vitro. The use of bioreactor systems to culture cells on scaffolds before implantation further improved the quality of the resulting bone grafts. Animal studies confirmed the capability of engineered grafts to form bone and integrate with the host tissues. However, the vascularization of bone remains one of the hurdles that need to be overcome if clinically sized, fully viable bone grafts are to be engineered and implanted. We discuss here the biological guidelines for tissue engineering of bone, the bioreactor cultivation of human mesenchymal stem cells on three-dimensional scaffolds, and the need for vascularization and functional integration of bone grafts following implantation. PMID:19075755

  6. Biocompatible magnetic core-shell nanocomposites for engineered magnetic tissues

    NASA Astrophysics Data System (ADS)

    Rodriguez-Arco, Laura; Rodriguez, Ismael A.; Carriel, Victor; Bonhome-Espinosa, Ana B.; Campos, Fernando; Kuzhir, Pavel; Duran, Juan D. G.; Lopez-Lopez, Modesto T.

    2016-04-01

    The inclusion of magnetic nanoparticles into biopolymer matrixes enables the preparation of magnetic field-responsive engineered tissues. Here we describe a synthetic route to prepare biocompatible core-shell nanostructures consisting of a polymeric core and a magnetic shell, which are used for this purpose. We show that using a core-shell architecture is doubly advantageous. First, gravitational settling for core-shell nanocomposites is slower because of the reduction of the composite average density connected to the light polymer core. Second, the magnetic response of core-shell nanocomposites can be tuned by changing the thickness of the magnetic layer. The incorporation of the composites into biopolymer hydrogels containing cells results in magnetic field-responsive engineered tissues whose mechanical properties can be controlled by external magnetic forces. Indeed, we obtain a significant increase of the viscoelastic moduli of the engineered tissues when exposed to an external magnetic field. Because the composites are functionalized with polyethylene glycol, the prepared bio-artificial tissue-like constructs also display excellent ex vivo cell viability and proliferation. When implanted in vivo, the engineered tissues show good biocompatibility and outstanding interaction with the host tissue. Actually, they only cause a localized transitory inflammatory reaction at the implantation site, without any effect on other organs. Altogether, our results suggest that the inclusion of magnetic core-shell nanocomposites into biomaterials would enable tissue engineering of artificial substitutes whose mechanical properties could be tuned to match those of the potential target tissue. In a wider perspective, the good biocompatibility and magnetic behavior of the composites could be beneficial for many other applications.The inclusion of magnetic nanoparticles into biopolymer matrixes enables the preparation of magnetic field-responsive engineered tissues. Here we

  7. Tuna cornea as biomaterial for cardiac applications.

    PubMed

    Parravicini, Roberto; Cocconcelli, Flavio; Verona, Alessandro; Parravicini, Valeriano; Giuliani, Enrico; Barbieri, Alberto

    2012-01-01

    Among available biomaterials, cornea is almost completely devoid of cells and is composed only of collagen fibers oriented in an orderly pattern, which contributes to low antigenicity. Thunnus thynnus, the Atlantic bluefin tuna, is a fish with large eyes that can withstand pressures of approximately 10 MPa. We evaluated the potential of this tuna cornea in cardiac bioimplantation. Eyes from freshly caught Atlantic bluefin tuna were harvested and preserved in a fixative solution. Sterilized samples of corneal stroma were embedded in paraffin and stained with hematoxylin and eosin, and the histologic features were studied. Physical and mechanical resistance tests were performed in comparison with bovine pericardial strips and porcine mitral valves. Corneal material was implanted subcutaneously in 7 rats, to evaluate in vivo calcification rates. Mitral valves made from tuna corneal leaflets were implanted in 9 sheep. We found that the corneal tissue consisted only of parallel collagen fibers without evidence of vascular or neural structures. In tensile strength, the tuna corneal specimens were substantially similar to bovine pericardium. After 23 days, the rat-implanted samples showed no calcium or calcium salt deposition. Hydrodynamic and fatigue testing of valve prototypes yielded acceptable functional and long-term behavioral results. In the sheep, valvular performance was stable during the 180-day follow-up period, with no instrumental sign of calcification at the end of observation. We conclude that low antigenicity and favorable physical properties qualify tuna cornea as a potential material for durable bioimplantation. Further study is warranted.

  8. From stem to roots: Tissue engineering in endodontics

    PubMed Central

    Kala, M.; Banthia, Priyank; Banthia, Ruchi

    2012-01-01

    The vitality of dentin-pulp complex is fundamental to the life of tooth and is a priority for targeting clinical management strategies. Loss of the tooth, jawbone or both, due to periodontal disease, dental caries, trauma or some genetic disorders, affects not only basic mouth functions but aesthetic appearance and quality of life. One novel approach to restore tooth structure is based on biology: regenerative endodontic procedure by application of tissue engineering. Regenerative endodontics is an exciting new concept that seeks to apply the advances in tissue engineering to the regeneration of the pulp-dentin complex. The basic logic behind this approach is that patient-specific tissue-derived cell populations can be used to functionally replace integral tooth tissues. The development of such ‘test tube teeth’ requires precise regulation of the regenerative events in order to achieve proper tooth size and shape, as well as the development of new technologies to facilitate these processes. This article provides an extensive review of literature on the concept of tissue engineering and its application in endodontics, providing an insight into the new developmental approaches on the horizon. Key words:Regenerative, tissue engineering, stem cells, scaffold. PMID:24558528

  9. Coaxial electrospun fibers: applications in drug delivery and tissue engineering.

    PubMed

    Lu, Yang; Huang, Jiangnan; Yu, Guoqiang; Cardenas, Romel; Wei, Suying; Wujcik, Evan K; Guo, Zhanhu

    2016-09-01

    Coelectrospinning and emulsion electrospinning are two main methods for preparing core-sheath electrospun nanofibers in a cost-effective and efficient manner. Here, physical phenomena and the effects of solution and processing parameters on the coaxial fibers are introduced. Coaxial fibers with specific drugs encapsulated in the core can exhibit a sustained and controlled release. Their exhibited high surface area and three-dimensional nanofibrous network allows the electrospun fibers to resemble native extracellular matrices. These features of the nanofibers show that they have great potential in drug delivery and tissue engineering applications. Proteins, growth factors, antibiotics, and many other agents have been successfully encapsulated into coaxial fibers for drug delivery. A main advantage of the core-sheath design is that after the process of electrospinning and release, these drugs remain bioactive due to the protection of the sheath. Applications of coaxial fibers as scaffolds for tissue engineering include bone, cartilage, cardiac tissue, skin, blood vessels and nervous tissue, among others. A synopsis of novel coaxial electrospun fibers, discussing their applications in drug delivery and tissue engineering, is covered pertaining to proteins, growth factors, antibiotics, and other drugs and applications in the fields of bone, cartilage, cardiac, skin, blood vessel, and nervous tissue engineering, respectively. WIREs Nanomed Nanobiotechnol 2016, 8:654-677. doi: 10.1002/wnan.1391 For further resources related to this article, please visit the WIREs website.

  10. Role of morphogenetic proteins in skeletal tissue engineering and regeneration.

    PubMed

    Reddi, A H

    1998-03-01

    Morphogenesis is the developmental cascade of pattern formation and body plan establishment, culminating in the adult form. It has formed the basis for the emerging discipline of tissue engineering, which uses principles of molecular developmental biology and morphogenesis gleaned through studies on inductive signals, responding stem cells, and the extracellular matrix to design and construct spare parts that restore function to the human body. Among the many organs in the body, bone has considerable powers for regeneration and is a prototype model for tissue engineering. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and has permitted the isolation of bone morphogens, such as bone morphogenetic proteins (BMPs), from demineralized adult bone matrix. BMPs initiate, promote, and maintain chondrogenesis and osteogenesis, but are also involved in the morphogenesis of organs other than bone. The symbiosis of the mechanisms underlying bone induction and differentiation is critical for tissue engineering and is governed by both biomechanics (physical forces) and context (microenvironment/extracellular matrix), which can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion glycoproteins, including fibronectins and laminin. Rules of tissue architecture elucidated in bone morphogenesis may provide insights into tissue engineering and be universally applicable for all organs/tissues, including bones and joints.

  11. Extracellular Matrix Scaffolds for Tissue Engineering and Regenerative Medicine.

    PubMed

    Yi, Sheng; Ding, Fei; Gong, Leiiei; Gu, Xiaosong

    2017-01-01

    The extracellular matrix is produced by the resident cells in tissues and organs, and secreted into the surrounding medium to provide biophysical and biochemical support to the surrounding cells due to its content of diverse bioactive molecules. Recently, the extracellular matrix has been used as a promising approach for tissue engineering. Emerging studies demonstrate that extracellular matrix scaffolds are able to create a favorable regenerative microenvironment, promote tissue-specific remodeling, and act as an inductive template for the repair and functional reconstruction of skin, bone, nerve, heart, lung, liver, kidney, small intestine, and other organs. In the current review, we will provide a critical overview of the structure and function of various types of extracellular matrix, the construction of three-dimensional extracellular matrix scaffolds, and their tissue engineering applications, with a focus on translation of these novel tissue engineered products to the clinic. We will also present an outlook on future perspectives of the extracellular matrix in tissue engineering and regenerative medicine.

  12. Injectable biodegradable materials for orthopedic tissue engineering.

    PubMed

    Temenoff, J S; Mikos, A G

    2000-12-01

    The large number of orthopedic procedures performed each year, including many performed arthroscopically, have led to great interest in injectable biodegradable materials for regeneration of bone and cartilage. A variety of materials have been developed for these applications, including ceramics, naturally derived substances and synthetic polymers. These materials demonstrate overall biocompatibility and appropriate mechanical properties, as well as promote tissue formation, thus providing an important step towards minimally invasive orthopedic procedures. This review provides a comparison of these materials based on mechanical properties, biocompatibility and regeneration efficacy. Advantages and disadvantages of each material are explained and design criteria for injectable biodegradable systems are provided.

  13. Dielectric relaxation of normothermic and hypothermic rat corneas.

    PubMed

    Marzec, E; Sosnowski, P; Olszewski, J; Krauss, H; Bahloul, K; Samborski, W; Krawczyk-Wasielewska, A

    2015-02-01

    This paper aims at the presentation of the results of in vitro research on the dielectric properties of the cornea specimen collected from the rats subjected to in vivo hypothermia. The average values of the relative permittivity and dielectric loss are about 40% higher for the hypothermic cornea than those for the normothermic tissue at the same water content of 12% for both samples and at 25°C. Whereas, at 50°C this effect of increase in the dielectric properties of the hypothermic cornea when compared to the normothermic one is observed clearly only in the relative permittivity of about 19%. In the temperature range of 25-50°C, the activation energy of conductivity associated with the release of loosely bound water takes the average values of 45kJ/mol and 30kJ/mol for the normothermic and hypothermic corneas, respectively. The study provided information on dielectric polarization and conductance mechanisms in the cornea which may be helpful in interpreting clinical results of human cornea examination, currently obtained by means of such electrodiagnostic methods as conductive keratoplasty, electroretinography or electrooculography.

  14. Orthopaedic Interface Tissue Engineering for the Biological Fixation of Soft Tissue Grafts

    PubMed Central

    Moffat, Kristen L .; Wang, I-Ning Elaine; Rodeo, Scott A.; Lu, Helen H.

    2012-01-01

    Interface tissue engineering is a promising new strategy aimed at the regeneration of tissue interfaces and ultimately enabling the biological fixation of soft tissue grafts utilized in orthopaedic repair and sports medicine. Many ligaments and tendons with direct insertions into subchondral bone exhibit a complex enthesis consisting of several distinct yet continuous regions of soft tissue, noncalcified fibrocartilage, calcified fibrocartilage and bone. Regeneration of this multi-tissue interface will be critical for functional graft integration and improving long term clinical outcome. This review will highlight current knowledge of the structure-function relationship at the interface, the mechanism of interface regeneration, and the strategic biomimicry implemented in stratified scaffold design for interface tissue engineering and multi-tissue regeneration. Potential challenges and future directions in this emerging field will also be discussed. It is anticipated that interface tissue engineering will lead to the design of a new generation of integrative fixation devices for soft tissue repair, and it will be instrumental for the development of integrated musculoskeletal tissue systems with biomimetic complexity and functionality. PMID:19064172

  15. Nanostructured materials for applications in drug delivery and tissue engineering*

    PubMed Central

    GOLDBERG, MICHAEL; LANGER, ROBERT; JIA, XINQIAO

    2010-01-01

    Research in the areas of drug delivery and tissue engineering has witnessed tremendous progress in recent years due to their unlimited potential to improve human health. Meanwhile, the development of nanotechnology provides opportunities to characterize, manipulate and organize matter systematically at the nanometer scale. Biomaterials with nano-scale organizations have been used as controlled release reservoirs for drug delivery and artificial matrices for tissue engineering. Drug-delivery systems can be synthesized with controlled composition, shape, size and morphology. Their surface properties can be manipulated to increase solubility, immunocompatibility and cellular uptake. The limitations of current drug delivery systems include suboptimal bioavailability, limited effective targeting and potential cytotoxicity. Promising and versatile nano-scale drug-delivery systems include nanoparticles, nanocapsules, nanotubes, nanogels and dendrimers. They can be used to deliver both small-molecule drugs and various classes of biomacromolecules, such as peptides, proteins, plasmid DNA and synthetic oligodeoxynucleotides. Whereas traditional tissue-engineering scaffolds were based on hydrolytically degradable macroporous materials, current approaches emphasize the control over cell behaviors and tissue formation by nano-scale topography that closely mimics the natural extracellular matrix (ECM). The understanding that the natural ECM is a multifunctional nanocomposite motivated researchers to develop nanofibrous scaffolds through electrospinning or self-assembly. Nanocomposites containing nanocrystals have been shown to elicit active bone growth. Drug delivery and tissue engineering are closely related fields. In fact, tissue engineering can be viewed as a special case of drug delivery where the goal is to accomplish controlled delivery of mammalian cells. Controlled release of therapeutic factors in turn will enhance the efficacy of tissue engineering. From a materials

  16. Nanoscale hydroxyapatite particles for bone tissue engineering.

    PubMed

    Zhou, Hongjian; Lee, Jaebeom

    2011-07-01

    Hydroxyapatite (HAp) exhibits excellent biocompatibility with soft tissues such as skin, muscle and gums, making it an ideal candidate for orthopedic and dental implants or components of implants. Synthetic HAp has been widely used in repair of hard tissues, and common uses include bone repair, bone augmentation, as well as coating of implants or acting as fillers in bone or teeth. However, the low mechanical strength of normal HAp ceramics generally restricts its use to low load-bearing applications. Recent advancements in nanoscience and nanotechnology have reignited investigation of nanoscale HAp formation in order to clearly define the small-scale properties of HAp. It has been suggested that nano-HAp may be an ideal biomaterial due to its good biocompatibility and bone integration ability. HAp biomedical material development has benefited significantly from advancements in nanotechnology. This feature article looks afresh at nano-HAp particles, highlighting the importance of size, crystal morphology control, and composites with other inorganic particles for biomedical material development.

  17. Gene therapy and tissue engineering for sports medicine.

    PubMed

    Huard, Johnny; Li, Yong; Peng, Hairong; Fu, Freddie H

    2003-02-01

    Sports injuries usually involve tissues that display a limited capacity for healing. The treatment of sports injuries has improved over the past 10 to 20 years through sophisticated rehabilitation programs, novel operative techniques, and advances in the field of biomechanical research. Despite this considerable progress, no optimal solution has been found for treatment of various sports-related injuries, including muscle injuries, ligament and tendon ruptures, central meniscal tears, cartilage lesions, and delayed bone fracture healing. New biological approaches focus on the treatment of these injuries with growth factors to stimulate and hasten the healing process. Gene therapy using the transfer of defined genes encoding therapeutic proteins represents a promising way to efficiently deliver suitable growth factors into the injured tissue. Tissue engineering, which may eventually be combined with gene therapy, may potentially result in the creation of tissues or scaffolds for regeneration of tissue defects following trauma. In this article we will discuss why gene therapy and tissue engineering are becoming increasingly important in modern orthopaedic sports medicine practice. We then will review recent research achievements in the area of gene therapy and tissue engineering for sports-related injuries, and highlight the potential clinical applications of this technology in the treatment of patients with musculoskeletal problems following sports-related injuries.

  18. Bone mechanobiology, gravity and tissue engineering: effects and insights.

    PubMed

    Ruggiu, Alessandra; Cancedda, Ranieri

    2015-12-01

    Bone homeostasis strongly depends on fine tuned mechanosensitive regulation signals from environmental forces into biochemical responses. Similar to the ageing process, during spaceflights an altered mechanotransduction occurs as a result of the effects of bone unloading, eventually leading to loss of functional tissue. Although spaceflights represent the best environment to investigate near-zero gravity effects, there are major limitations for setting up experimental analysis. A more feasible approach to analyse the effects of reduced mechanostimulation on the bone is represented by the 'simulated microgravity' experiments based on: (1) in vitro studies, involving cell cultures studies and the use of bioreactors with tissue engineering approaches; (2) in vivo studies, based on animal models; and (3) direct analysis on human beings, as in the case of the bed rest tests. At present, advanced tissue engineering methods allow investigators to recreate bone microenvironment in vitro for mechanobiology studies. This group and others have generated tissue 'organoids' to mimic in vitro the in vivo bone environment and to study the alteration cells can go through when subjected to unloading. Understanding the molecular mechanisms underlying the bone tissue response to mechanostimuli will help developing new strategies to prevent loss of tissue caused by altered mechanotransduction, as well as identifying new approaches for the treatment of diseases via drug testing. This review focuses on the effects of reduced gravity on bone mechanobiology by providing the up-to-date and state of the art on the available data by drawing a parallel with the suitable tissue engineering systems.

  19. Jellyfish collagen scaffolds for cartilage tissue engineering.

    PubMed

    Hoyer, Birgit; Bernhardt, Anne; Lode, Anja; Heinemann, Sascha; Sewing, Judith; Klinger, Matthias; Notbohm, Holger; Gelinsky, Michael

    2014-02-01

    Porous scaffolds were engineered from refibrillized collagen of the jellyfish Rhopilema esculentum for potential application in cartilage regeneration. The influence of collagen concentration, salinity and temperature on fibril formation was evaluated by turbidity measurements and quantification of fibrillized collagen. The formation of collagen fibrils with a typical banding pattern was confirmed by atomic force microscopy and transmission electron microscopy analysis. Porous scaffolds from jellyfish collagen, refibrillized under optimized conditions, were fabricated by freeze-drying and subsequent chemical cross-linking. Scaffolds possessed an open porosity of 98.2%. The samples were stable under cyclic compression and displayed an elastic behavior. Cytotoxicity tests with human mesenchymal stem cells (hMSCs) did not reveal any cytotoxic effects of the material. Chondrogenic markers SOX9, collagen II and aggrecan were upregulated in direct cultures of hMSCs upon chondrogenic stimulation. The formation of typical extracellular matrix components was further confirmed by quantification of sulfated glycosaminoglycans.

  20. Stem Cells and Scaffolds for Vascularizing Engineered Tissue Constructs

    NASA Astrophysics Data System (ADS)

    Luong, E.; Gerecht, S.

    The clinical impact of tissue engineering depends upon our ability to direct cells to form tissues with characteristic structural and mechanical properties from the molecular level up to organized tissue. Induction and creation of functional vascular networks has been one of the main goals of tissue engineering either in vitro, for the transplantation of prevascularized constructs, or in vivo, for cellular organization within the implantation site. In most cases, tissue engineering attempts to recapitulate certain aspects of normal development in order to stimulate cell differentiation and functional tissue assembly. The induction of tissue growth generally involves the use of biodegradable and bioactive materials designed, ideally, to provide a mechanical, physical, and biochemical template for tissue regeneration. Human embryonic stem cells (hESCs), derived from the inner cell mass of a developing blastocyst, are capable of differentiating into all cell types of the body. Specifically, hESCs have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. Human ESC-derived endothelial progenitor cells (EPCs) and endothelial cells have substantial potential for microvessel formation, in vitro and in vivo. Human adult EPCs are being isolated to understand the fundamental biology of how these cells are regulated as a population and to explore whether these cells can be differentiated and reimplanted as a cellular therapy in order to arrest or even reverse damaged vasculature. This chapter focuses on advances made toward the generation and engineering of functional vascular tissue, focusing on both the scaffolds - the synthetic and biopolymer materials - and the cell sources - hESCs and hEPCs.

  1. Synthetic biodegradable functional polymers for tissue engineering: a brief review.

    PubMed

    BaoLin, Guo; Ma, Peter X

    2014-04-01

    Scaffolds play a crucial role in tissue engineering. Biodegradable polymers with great processing flexibility are the predominant scaffolding materials. Synthetic biodegradable polymers with well-defined structure and without immunological concerns associated with naturally derived polymers are widely used in tissue engineering. The synthetic biodegradable polymers that are widely used in tissue engineering, including polyesters, polyanhydrides, polyphosphazenes, polyurethane, and poly (glycerol sebacate) are summarized in this article. New developments in conducting polymers, photoresponsive polymers, amino-acid-based polymers, enzymatically degradable polymers, and peptide-activated polymers are also discussed. In addition to chemical functionalization, the scaffold designs that mimic the nano and micro features of the extracellular matrix (ECM) are presented as well, and composite and nanocomposite scaffolds are also reviewed.

  2. Keeping an Eye on Decellularized Corneas: A Review of Methods, Characterization and Applications

    PubMed Central

    Wilson, Samantha L.; Sidney, Laura E.; Dunphy, Siobhán E.; Rose, James B.; Hopkinson, Andrew

    2013-01-01

    The worldwide limited availability of suitable corneal donor tissue has led to the development of alternatives, including keratoprostheses (Kpros) and tissue engineered (TE) constructs. Despite advances in bioscaffold design, there is yet to be a corneal equivalent that effectively mimics both the native tissue ultrastructure and biomechanical properties. Human decellularized corneas (DCs) could offer a safe, sustainable source of corneal tissue, increasing the donor pool and potentially reducing the risk of immune rejection after corneal graft surgery. Appropriate, human-specific, decellularization techniques and high-resolution, non-destructive analysis systems are required to ensure reproducible outputs can be achieved. If robust treatment and characterization processes can be developed, DCs could offer a supplement to the donor corneal pool, alongside superior cell culture systems for pharmacology, toxicology and drug discovery studies. PMID:24956084

  3. Harnessing wound healing and regeneration for tissue engineering.

    PubMed

    Metcalfe, A D; Ferguson, M W J

    2005-04-01

    Biomedical science has made major advances in understanding how cells grow into functioning tissue and the signalling mechanisms used to achieve this are slowly being dissected. Tissue engineering is the application of that knowledge to the building or repairing of organs, including skin, the largest organ in the body. Generally, engineered tissue is a combination of living cells and a supporting matrix. Besides serving as burn coverings, engineered skin substitutes can help patients with diabetic foot ulcers. Today, most of these ulcers are treated with an approach that includes antibiotics, glucose control, special shoes and frequent cleaning and bandaging. The results of such treatments are often disappointing and ineffectual, and scarring remains a major problem, mechanically, cosmetically and psychologically. Within our group we are attempting to address this by investigating novel approaches to skin tissue engineering. We are identifying novel therapeutic manipulations to improve the degree of integration between a tissue engineered dermal construct and the host by both molecular manipulation of growth factors but also by understanding and harnessing mechanisms of regenerative biology. For the purpose of this summary, we will concentrate primarily on the latter of these two approaches in that we have identified a novel mouse mutant that completely and perfectly regenerates skin and cartilaginous components following ear injury. This experimental animal will allow us to characterize not only novel genes involved in the regeneration process but also to utilize cells from such animals in artificial skin equivalents to assess their behaviour compared with normal cells. This approach should allow us to create a tissue-engineered substitute, which more closely resembles the normal regional microanatomy and physiology of the skin, allowing better integration to the host with minimal or no scarring.

  4. Stem cells, tissue engineering and periodontal regeneration.

    PubMed

    Han, J; Menicanin, D; Gronthos, S; Bartold, P M

    2014-06-01

    The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We consider and describe the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.

  5. Electrospun nanofibers for neural tissue engineering

    NASA Astrophysics Data System (ADS)

    Xie, Jingwei; MacEwan, Matthew R.; Schwartz, Andrea G.; Xia, Younan

    2010-01-01

    Biodegradable nanofibers produced by electrospinning represent a new class of promising scaffolds to support nerve regeneration. We begin with a brief discussion on the electrospinning of nanofibers and methods for controlling the structure, porosity, and alignment of the electrospun nanofibers. The methods include control of the nanoscale morphology and microscale alignment of the nanofibers, as well as the fabrication of macroscale, three-dimensional tubular structures. We then highlight recent studies that utilize electrospun nanofibers to manipulate biological processes relevant to nervous tissue regeneration, including stem cell differentiation, guidance of neurite extension, and peripheral nerve injury treatments. The main objective of this feature article is to provide valuable insights into methods for investigating the mechanisms of neurite growth on novel nanofibrous scaffolds and optimization of the nanofiber scaffolds and conduits for repairing peripheral nerve injuries.

  6. Physical non-viral gene delivery methods for tissue engineering.

    PubMed

    Mellott, Adam J; Forrest, M Laird; Detamore, Michael S

    2013-03-01

    The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that "fits-all" cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications.

  7. The Use of Adipose Tissue-Derived Progenitors in Bone Tissue Engineering - a Review

    PubMed Central

    Bhattacharya, Indranil; Ghayor, Chafik; Weber, Franz E.

    2016-01-01

    2500 years ago, Hippocrates realized that bone can heal without scaring. The natural healing potential of bone is, however, restricted to small defects. Extended bone defects caused by trauma or during tumor resections still pose a huge problem in orthopedics and cranio-maxillofacial surgery. Bone tissue engineering strategies using stem cells, growth factors, and scaffolds could overcome the problems with the treatment of extended bone defects. In this review, we give a short overview on bone tissue engineering with emphasis on the use of adipose tissue-derived stem cells and small molecules. PMID:27781021

  8. Cartilage tissue engineering using PHBV and PHBV/Bioglass scaffolds.

    PubMed

    Zhou, Mingshu; Yu, Dong

    2014-07-01

    Scaffolds have an important role in cartilage tissue engineering. Poly(hydroxybutyrate‑co‑hydroxyvalerate) (PHBV) has been demonstrated to have potential as a scaffold for the three dimensional construction of engineered cartilage tissue. However, the poor hydrophilicity and mechanical strength associated with PHBV affects its clinical applications as a scaffold in cartilage tissue engineering. The incorporation of Bioglass (BG) into PHBV has been shown to improve the hydrophilicity and mechanical strength of PHBV matrices. Therefore, this study aimed to compare the properties of PHBV scaffolds and PHBV scaffolds containing 10% BG (w/w) (PHBV/10% BG) and to investigate the effects of these scaffolds on the properties of engineered cartilage in vivo. Rabbit auricular chondrocytes were seeded onto PHBV and PHBV/10% BG scaffolds. Differences in cartilage regeneration were compared between the neocartilage grown on the PHBV and the PHBV/10% BG scaffolds after 10 weeks of in vivo transplantation. The incorporation of BG into PHBV was observed to improve the hydrophilicity and compressive strength of the scaffold. Furthermore, after 10 weeks incubation in vivo, the cartilage‑like tissue formed using the PHBV/10% BG scaffolds was observed to be thicker, exhibit enhanced biomechanical properties and have a higher cartilage matrix content than that generated using the pure PHBV scaffolds. The results of this study demonstrate that the incorporation of BG into PHBV may generate composite scaffolds with improved properties for cartilage engineering.

  9. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  10. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myoribers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postmitotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  11. Design of electrical stimulation bioreactors for cardiac tissue engineering.

    PubMed

    Tandon, N; Marsano, A; Cannizzaro, C; Voldman, J; Vunjak-Novakovic, G

    2008-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering.

  12. Design of Electrical Stimulation Bioreactors for Cardiac Tissue Engineering

    PubMed Central

    Tandon, N.; Marsano, A.; Cannizzaro, C.; Voldman, J.; Vunjak-Novakovic, G.

    2009-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering. PMID:19163486

  13. Review: tissue engineering for regeneration of articular cartilage.

    PubMed

    Temenoff, J S; Mikos, A G

    2000-03-01

    Joint pain due to cartilage degeneration is a serious problem, affecting people of all ages. Although many techniques, often surgical, are currently employed to treat this affliction, none have had complete success. Recent advances in biology and materials science have pushed tissue engineering to the forefront of new cartilage repair techniques. This review seeks to condense information for the biomaterialist interested in developing materials for this application. Articular cartilage anatomy, types of injury, and current repair methods are explained. The need for biomaterials, current commonly used materials for tissue-engineered cartilage, and considerations in scale-up of cell-biomaterial constructs are summarized.

  14. Growth factor delivery for oral and periodontal tissue engineering

    PubMed Central

    Kaigler, Darnell; Cirelli, Joni A; Giannobile, William V

    2008-01-01

    The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. Growth factors are critical to the development, maturation, maintenance and repair of craniofacial tissues, as they establish an extracellular environment that is conducive to cell and tissue growth. Tissue-engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. These materials have been constructed into devices that can be used as vehicles for delivery of cells, growth factors and DNA. In this review, different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral- and tooth-supporting structures, namely the periodontium and alveolar bone. PMID:16948560

  15. Functional tissue engineering of the liver and islets.

    PubMed

    Ohashi, Kazuo; Okano, Teruo

    2014-01-01

    Cell-based therapies by using hepatocytes and islets have recently been evaluated as a new therapeutic modality for patients with many forms of liver diseases and insulin-deficient diabetes mellitus. In most of the recently conducted clinical trials, cells have been delivered into liver vasculatures by infusing them through the portal circulation. More recently, tissue engineering-based approaches have spurred significant interests, using hepatocytes and islets in which small but functional new tissues would be created in vivo. Under circumstances in which a higher level of cell engraftment could be obtained, these approaches could provide therapeutic effects. Considerable efforts have been given to sustaining engineered tissues and maintaining their therapeutic effects. This review highlights several strategies that can achieve a higher level of cell survival for creating new functional liver and islet tissues.

  16. Outlook for Tissue Engineering of the Tympanic Membrane

    PubMed Central

    Villar-Fernandez, Maria A.; Lopez-Escamez, Jose A.

    2015-01-01

    Tympanic membrane perforation is a common problem leading to hearing loss. Despite the autoregenerative activity of the eardrum, chronic perforations require surgery using different materials, from autologous tissue - fascia, cartilage, fat or perichondrium - to paper patch. However, both, surgical procedures (myringoplasty or tympanoplasty) and the materials employed, have a number of limitations. Therefore, the advances in this field are incorporating the principles of tissue engineering, which includes the use of scaffolds, biomolecules and cells. This discipline allows the development of new biocompatible materials that reproduce the structure and mechanical properties of the native tympanic membrane, while it seeks to implement new therapeutic approaches that can be performed in an outpatient setting. Moreover, the creation of an artificial tympanic membrane commercially available would reduce the duration of the surgery and costs. The present review analyzes the current treatment of tympanic perforations and examines the techniques of tissue engineering, either to develop bioartificial constructs, or for tympanic regeneration by using different scaffold materials, bioactive molecules and cells. Finally, it considers the aspects regarding the design of scaffolds, release of biomolecules and use of cells that must be taken into account in the tissue engineering of the eardrum. The possibility of developing new biomaterials, as well as constructs commercially available, makes tissue engineering a discipline with great potential, capable of overcoming the drawbacks of current surgical procedures. PMID:26557361

  17. Chitosan composites for bone tissue engineering--an overview.

    PubMed

    Venkatesan, Jayachandran; Kim, Se-Kwon

    2010-08-02

    Bone contains considerable amounts of minerals and proteins. Hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂] is one of the most stable forms of calcium phosphate and it occurs in bones as major component (60 to 65%), along with other materials including collagen, chondroitin sulfate, keratin sulfate and lipids. In recent years, significant progress has been made in organ transplantation, surgical reconstruction and the use of artificial prostheses to treat the loss or failure of an organ or bone tissue. Chitosan has played a major role in bone tissue engineering over the last two decades, being a natural polymer obtained from chitin, which forms a major component of crustacean exoskeleton. In recent years, considerable attention has been given to chitosan composite materials and their applications in the field of bone tissue engineering due to its minimal foreign body reactions, an intrinsic antibacterial nature, biocompatibility, biodegradability, and the ability to be molded into various geometries and forms such as porous structures, suitable for cell ingrowth and osteoconduction. The composite of chitosan including hydroxyapatite is very popular because of the biodegradability and biocompatibility in nature. Recently, grafted chitosan natural polymer with carbon nanotubes has been incorporated to increase the mechanical strength of these composites. Chitosan composites are thus emerging as potential materials for artificial bone and bone regeneration in tissue engineering. Herein, the preparation, mechanical properties, chemical interactions and in vitro activity of chitosan composites for bone tissue engineering will be discussed.

  18. Tissue engineering in cleft palate and other congenital malformations.

    PubMed

    Panetta, Nicholas J; Gupta, Deepak M; Slater, Bethany J; Kwan, Matthew D; Liu, Karen J; Longaker, Michael T

    2008-05-01

    Contributions from multidisciplinary investigations have focused attention on the potential of tissue engineering to yield novel therapeutics. Congenital malformations, including cleft palate, craniosynostosis, and craniofacial skeletal hypoplasias represent excellent targets for the implementation of tissue engineering applications secondary to the technically challenging nature and inherent inadequacies of current reconstructive interventions. Apropos to the search for answers to these clinical conundrums, studies have focused on elucidating the molecular signals driving the biologic activity of the aforementioned maladies. These investigations have highlighted multiple signaling pathways, including Wnt, fibroblast growth factor, transforming growth factor-beta, and bone morphogenetic proteins, that have been found to play critical roles in guided tissue development. Furthermore, a comprehensive knowledge of these pathways will be of utmost importance to the optimization of future cell-based tissue engineering strategies. The scope of this review encompasses a discussion of the molecular biology involved in the development of cleft palate and craniosynostosis. In addition, we include a discussion of craniofacial distraction osteogenesis and how its applied forces influence cell signaling to guide endogenous bone regeneration. Finally, this review discusses the future role of cell-based tissue engineering in the treatment of congenital malformations.

  19. Cryopreservation of Cell/Scaffold Tissue-Engineered Constructs

    PubMed Central

    Costa, Pedro F.; Dias, Ana F.; Reis, Rui L.

    2012-01-01

    The aim of this work was to study the effect of cryopreservation over the functionality of tissue-engineered constructs, analyzing the survival and viability of cells seeded, cultured, and cryopreserved onto 3D scaffolds. Further, it also evaluated the effect of cryopreservation over the properties of the scaffold material itself since these are critical for the engineering of most tissues and in particular, tissues such as bone. For this purpose, porous scaffolds, namely fiber meshes based on a starch and poly(caprolactone) blend were seeded with goat bone marrow stem cells (GBMSCs) and cryopreserved for 7 days. Discs of the same material seeded with GBMSCs were also used as controls. After this period, these samples were analyzed and compared to samples collected before the cryopreservation process. The obtained results demonstrate that it is possible to maintain cell viability and scaffolds properties upon cryopreservation of tissue-engineered constructs based on starch scaffolds and goat bone marrow mesenchymal cells using standard cryopreservation methods. In addition, the outcomes of this study suggest that the greater porosity and interconnectivity of scaffolds favor the retention of cellular content and cellular viability during cryopreservation processes, when compared with nonporous discs. These findings indicate that it might be possible to prepare off-the-shelf engineered tissue substitutes and preserve them to be immediately available upon request for patients' needs. PMID:22676448

  20. Tissue-engineered lymphatic graft for the treatment of lymphedema

    PubMed Central

    Kanapathy, Muholan; Patel, Nikhil M.; Kalaskar, Deepak M.; Mosahebi, Afshin; Mehrara, Babak J.; Seifalian, Alexander M.

    2015-01-01

    Background Lymphedema is a chronic debilitating condition and curative treatment is yet to be found. Tissue engineering approach, which combines cellular components, scaffold, and molecular signals hold great potential in the treatment of secondary lymphedema with the advent of lymphatic graft to reconstruct damaged collecting lymphatic vessel. This review highlights the ideal characteristics of lymphatic graft, the limitation and challenges faced, and the approaches in developing tissue-engineered lymphatic graft. Methods Literature on tissue engineering of lymphatic system and lymphatic tissue biology was reviewed. Results The prime challenge in the design and manufacturing of this graft is producing endothelialized conduit with intraluminal valves. Suitable scaffold material is needed to ensure stability and functionality of the construct. Endothelialization of the construct can be enhanced via biofunctionalization and nanotopography, which mimics extracellular matrix. Nanocomposite polymers with improved performance over existing biomaterials are likely to benefit the development of lymphatic graft. Conclusions With the in-depth understanding of tissue engineering, nanotechnology, and improved knowledge on the biology of lymphatic regeneration, the aspiration to develop successful lymphatic graft is well achievable. PMID:25248852

  1. Biomimetic Polymers for Cardiac Tissue Engineering

    PubMed Central

    2016-01-01

    Heart failure is a morbid disorder characterized by progressive cardiomyocyte (CM) dysfunction and death. Interest in cell-based therapies is growing, but sustainability of injected CMs remains a challenge. To mitigate this, we developed an injectable biomimetic Reverse Thermal Gel (RTG) specifically engineered to support long-term CM survival. This RTG biopolymer provided a solution-based delivery vehicle of CMs, which transitioned to a gel-based matrix shortly after reaching body temperature. In this study we tested the suitability of this biopolymer to sustain CM viability. The RTG was biomolecule-functionalized with poly-l-lysine or laminin. Neonatal rat ventricular myocytes (NRVM) and adult rat ventricular myocytes (ARVM) were cultured in plain-RTG and biomolecule-functionalized-RTG both under 3-dimensional (3D) conditions. Traditional 2D biomolecule-coated dishes were used as controls. We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia. Regarding cell contraction, in both RTG and RTG-lysine, beating cells were recorded after 21 days. Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days. These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform. PMID:27073119

  2. X-ray Phase Contrast Imaging of Calcified Tissue and Biomaterial Structure in Bioreactor Engineered Tissues

    SciTech Connect

    Appel, Alyssa A.; Larson, Jeffery C.; Garson, III, Alfred B.; Guan, Huifeng; Zhong, Zhong; Nguyen, Bao-Ngoc; Fisher, John P.; Anastasio, Mark A.; Brey, Eric M.

    2014-11-04

    Tissues engineered in bioreactor systems have been used clinically to replace damaged tissues and organs. In addition, these systems are under continued development for many tissue engineering applications. The ability to quantitatively assess material structure and tissue formation is critical for evaluating bioreactor efficacy and for preimplantation assessment of tissue quality. These techniques allow for the nondestructive and longitudinal monitoring of large engineered tissues within the bioreactor systems and will be essential for the translation of these strategies to viable clinical therapies. X-ray Phase Contrast (XPC) imaging techniques have shown tremendous promise for a number of biomedical applications owing to their ability to provide image contrast based on multiple X-ray properties, including absorption, refraction, and scatter. In this research, mesenchymal stem cell-seeded alginate hydrogels were prepared and cultured under osteogenic conditions in a perfusion bioreactor. The constructs were imaged at various time points using XPC microcomputed tomography (µCT). Imaging was performed with systems using both synchrotron- and tube-based X-ray sources. XPC µCT allowed for simultaneous three-dimensional (3D) quantification of hydrogel size and mineralization, as well as spatial information on hydrogel structure and mineralization. Samples were processed for histological evaluation and XPC showed similar features to histology and quantitative analysis consistent with the histomorphometry. Furthermore, these results provide evidence of the significant potential of techniques based on XPC for noninvasive 3D imaging engineered tissues grown in bioreactors.

  3. Formation of vascularized meniscal tissue by combining gene therapy with tissue engineering.

    PubMed

    Hidaka, Chisa; Ibarra, Clemente; Hannafin, Jo A; Torzilli, Peter A; Quitoriano, Mannix; Jen, Shih-Shi; Warren, Russell F; Crystal, Ronald G

    2002-02-01

    Ingrowth of host blood vessels into engineered tissues has potential benefits for successful transplantation of engineered tissues as well as healing of surrounding host tissues. In particular, the use of a vascularized bioengineered tissue could be beneficial for treating injuries to the meniscus, a structure in the knee where the lack of a vascular supply is associated with an inadequate healing response. In this study, gene transfer using an adenovirus vector encoding the hepatocyte growth factor gene (AdHGF) was used to induce blood vessel formation in tissue-engineered meniscus. Bovine meniscal cells were treated with AdHGF, a vector encoding a marker gene E. coli beta-galactosidase (Adbetagal), or no virus. Cells were seeded onto poly-glycolic acid felt scaffolds and then transplanted into the subcutaneous pouch of athymic nude mice for 8 weeks. Expression of the marker gene and HGF was detectable for several weeks after gene transfer. Ink injection studies showed that AdHGF-treated meniscal cells formed tissue which contained fourfold more blood vessels at 2 weeks (p < 0.02) and 2.5-fold more blood vessels at 8 weeks (p < 0.001) posttransplantation than controls. This study demonstrates the feasibility of using adenovirus-mediated gene transfer to engineer a blood supply in the bioengineered meniscal tissue.

  4. Decellularized matrices for cardiovascular tissue engineering

    PubMed Central

    Moroni, Francesco; Mirabella, Teodelinda

    2014-01-01

    Cardiovascular disease (CVD) is one of the leading causes of death in the Western world. The replacement of damaged vessels and valves has been practiced since the 1950’s. Synthetic grafts, usually made of bio-inert materials, are long-lasting and mechanically relevant, but fail when it comes to “biointegration”. Decellularized matrices, instead, can be considered biological grafts capable of stimulating in vivo migration and proliferation of endothelial cells (ECs), recruitment and differentiation of mural cells, finally, culminating in the formation of a biointegrated tissue. Decellularization protocols employ osmotic shock, ionic and non-ionic detergents, proteolitic digestions and DNase/RNase treatments; most of them effectively eliminate the cellular component, but show limitations in preserving the native structure of the extracellular matrix (ECM). In this review, we examine the current state of the art relative to decellularization techniques and biological performance of decellularized heart, valves and big vessels. Furthermore, we focus on the relevance of ECM components, native and resulting from decellularization, in mediating in vivo host response and determining repair and regeneration, as opposed to graft corruption. PMID:24660110

  5. Adipose-derived stem cells and periodontal tissue engineering.

    PubMed

    Tobita, Morikuni; Mizuno, Hiroshi

    2013-01-01

    Innovative developments in the multidisciplinary field of tissue engineering have yielded various implementation strategies and the possibility of functional tissue regeneration. Technologic advances in the combination of stem cells, biomaterials, and growth factors have created unique opportunities to fabricate tissues in vivo and in vitro. The therapeutic potential of human multipotent mesenchymal stem cells (MSCs), which are harvested from bone marrow and adipose tissue, has generated increasing interest in a wide variety of biomedical disciplines. These cells can differentiate into a variety of tissue types, including bone, cartilage, fat, and nerve tissue. Adipose-derived stem cells have some advantages compared with other sources of stem cells, most notably that a large number of cells can be easily and quickly isolated from adipose tissue. In current clinical therapy for periodontal tissue regeneration, several methods have been developed and applied either alone or in combination, such as enamel matrix proteins, guided tissue regeneration, autologous/allogeneic/xenogeneic bone grafts, and growth factors. However, there are various limitations and shortcomings for periodontal tissue regeneration using current methods. Recently, periodontal tissue regeneration using MSCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because the various secreted growth factors from MSCs might not only promote the regeneration of periodontal tissue but also encourage neovascularization of the damaged tissues. Adipose-derived stem cells are especially effective for neovascularization compared with other MSC sources. In this review, the possibility and potential of adipose-derived stem cells for regenerative medicine are introduced. Of particular interest, periodontal tissue regeneration with adipose-derived stem cells is discussed.

  6. Hydrogel Bioprinted Microchannel Networks for Vascularization of Tissue Engineering Constructs

    PubMed Central

    Bertassoni, Luiz E.; Cecconi, Martina; Manoharan, Vijayan; Nikkhah, Mehdi; Hjortnaes, Jesper; Cristino, Ana Luiza; Barabaschi, Giada; Demarchi, Danilo; Dokmeci, Mehmet R.; Yang, Yunzhi; Khademhosseini, Ali

    2014-01-01

    Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photo cross linkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly (ethylene glycol-co-lactide) acrylate (SPELA), poly (ethylene glycol) dimethacrylate (PEGDMA) and poly (ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip. PMID:24860845

  7. An exploratory survey on the views of European tissue engineers concerning the ethical issues of tissue engineering research.

    PubMed

    Trommelmans, Leen; Selling, Joseph; Dierickx, Kris

    2009-09-01

    We present the first exploratory survey about the views of tissue engineers on the ethical issues of tissue engineering (TE), conducted among participants of a large European TE consortium. We analyzed the topics for which ethical guidance is necessary and the preferred dissemination channels, which are relevant issues and goals of clinical trials with human tissue-engineered products, and which information is to be given to trial participants. The need for comprehensive, specific ethical guidance of TE is a first key finding of this survey. Second, it becomes clear that little clarity exists on some crucial issues in the setup and conduct of clinical trials in TE. Identifying the unique features of TE and their repercussions for the ethical conduct of TE research and therapy is necessary. Third, prospective trial participants are to be informed about a wide variety of issues before taking part in the trial.

  8. Growing Tissues in Real and Simulated Microgravity: New Methods for Tissue Engineering

    PubMed Central

    Wehland, Markus; Pietsch, Jessica; Aleshcheva, Ganna; Wise, Petra; van Loon, Jack; Ulbrich, Claudia; Magnusson, Nils E.; Infanger, Manfred; Bauer, Johann

    2014-01-01

    Tissue engineering in simulated (s-) and real microgravity (r-μg) is currently a topic in Space medicine contributing to biomedical sciences and their applications on Earth. The principal aim of this review is to highlight the advances and accomplishments in the field of tissue engineering that could be achieved by culturing cells in Space or by devices created to simulate microgravity on Earth. Understanding the biology of three-dimensional (3D) multicellular structures is very important for a more complete appreciation of in vivo tissue function and advancing in vitro tissue engineering efforts. Various cells exposed to r-μg in Space or to s-μg created by a random positioning machine, a 2D-clinostat, or a rotating wall vessel bioreactor grew in the form of 3D tissues. Hence, these methods represent a new strategy for tissue engineering of a variety of tissues, such as regenerated cartilage, artificial vessel constructs, and other organ tissues as well as multicellular cancer spheroids. These aggregates are used to study molecular mechanisms involved in angiogenesis, cancer development, and biology and for pharmacological testing of, for example, chemotherapeutic drugs or inhibitors of neoangiogenesis. Moreover, they are useful for studying multicellular responses in toxicology and radiation biology, or for performing coculture experiments. The future will show whether these tissue-engineered constructs can be used for medical transplantations. Unveiling the mechanisms of microgravity-dependent molecular and cellular changes is an up-to-date requirement for improving Space medicine and developing new treatment strategies that can be translated to in vivo models while reducing the use of laboratory animals. PMID:24597549

  9. Growing tissues in real and simulated microgravity: new methods for tissue engineering.

    PubMed

    Grimm, Daniela; Wehland, Markus; Pietsch, Jessica; Aleshcheva, Ganna; Wise, Petra; van Loon, Jack; Ulbrich, Claudia; Magnusson, Nils E; Infanger, Manfred; Bauer, Johann

    2014-12-01

    Tissue engineering in simulated (s-) and real microgravity (r-μg) is currently a topic in Space medicine contributing to biomedical sciences and their applications on Earth. The principal aim of this review is to highlight the advances and accomplishments in the field of tissue engineering that could be achieved by culturing cells in Space or by devices created to simulate microgravity on Earth. Understanding the biology of three-dimensional (3D) multicellular structures is very important for a more complete appreciation of in vivo tissue function and advancing in vitro tissue engineering efforts. Various cells exposed to r-μg in Space or to s-μg created by a random positioning machine, a 2D-clinostat, or a rotating wall vessel bioreactor grew in the form of 3D tissues. Hence, these methods represent a new strategy for tissue engineering of a variety of tissues, such as regenerated cartilage, artificial vessel constructs, and other organ tissues as well as multicellular cancer spheroids. These aggregates are used to study molecular mechanisms involved in angiogenesis, cancer development, and biology and for pharmacological testing of, for example, chemotherapeutic drugs or inhibitors of neoangiogenesis. Moreover, they are useful for studying multicellular responses in toxicology and radiation biology, or for performing coculture experiments. The future will show whether these tissue-engineered constructs can be used for medical transplantations. Unveiling the mechanisms of microgravity-dependent molecular and cellular changes is an up-to-date requirement for improving Space medicine and developing new treatment strategies that can be translated to in vivo models while reducing the use of laboratory animals.

  10. Excimer laser ablation of the cornea

    NASA Astrophysics Data System (ADS)

    Pettit, George H.; Ediger, Marwood N.; Weiblinger, Richard P.

    1995-03-01

    Pulsed ultraviolet laser ablation is being extensively investigated clinically to reshape the optical surface of the eye and correct vision defects. Current knowledge of the laser/tissue interaction and the present state of the clinical evaluation are reviewed. In addition, the principal findings of internal Food and Drug Administration research are described in some detail, including a risk assessment of the laser-induced-fluorescence and measurement of the nonlinear optical properties of cornea during the intense UV irradiation. Finally, a survey is presented of the alternative laser technologies being explored for this ophthalmic application.

  11. Bioreactors for Connective Tissue Engineering: Design and Monitoring Innovations

    NASA Astrophysics Data System (ADS)

    Haj, A. J. El; Hampson, K.; Gogniat, G.

    The challenges for the tissue engineering of connective tissue lie in creating off-the-shelf tissue constructs which are capable of providing organs for transplantation. These strategies aim to grow a complex tissue with the appropri ate mechanical integrity necessary for functional load bearing. Monolayer culture systems lack correlation with the in vivo environment and the naturally occur ring cell phenotypes. Part of the development of more recent models is to create growth environments or bioreactors which enable three-dimensional culture. Evidence suggests that in order to grow functional load-bearing tissues in a bioreactor, the cells must experience mechanical loading stimuli similar to that experienced in vivo which sets out the requirements for mechanical loading bioreactors. An essential part of developing new bioreactors for tissue growth is identifying ways of routinely and continuously measuring neo-tissue formation and in order to fully identify the successful generation of a tissue implant, the appropriate on-line monitoring must be developed. New technologies are being developed to advance our efforts to grow tissue ex vivo. The bioreactor is a critical part of these develop ments in supporting growth of biological implants and combining this with new advances in the detection of tissue formation allows us to refine our protocols and move nearer to off-the-shelf implants for clinical applications.

  12. A Novel Albumin-Based Tissue Scaffold for Autogenic Tissue Engineering Applications

    NASA Astrophysics Data System (ADS)

    Li, Pei-Shan; -Liang Lee, I.; Yu, Wei-Lin; Sun, Jui-Sheng; Jane, Wann-Neng; Shen, Hsin-Hsin

    2014-07-01

    Tissue scaffolds provide a framework for living tissue regeneration. However, traditional tissue scaffolds are exogenous, composed of metals, ceramics, polymers, and animal tissues, and have a defined biocompatibility and application. This study presents a new method for obtaining a tissue scaffold from blood albumin, the major protein in mammalian blood. Human, bovine, and porcine albumin was polymerised into albumin polymers by microbial transglutaminase and was then cast by freeze-drying-based moulding to form albumin tissue scaffolds. Scanning electron microscopy and material testing analyses revealed that the albumin tissue scaffold possesses an extremely porous structure, moderate mechanical strength, and resilience. Using a culture of human mesenchymal stem cells (MSCs) as a model, we showed that MSCs can be seeded and grown in the albumin tissue scaffold. Furthermore, the albumin tissue scaffold can support the long-term osteogenic differentiation of MSCs. These results show that the albumin tissue scaffold exhibits favourable material properties and good compatibility with cells. We propose that this novel tissue scaffold can satisfy essential needs in tissue engineering as a general-purpose substrate. The use of this scaffold could lead to the development of new methods of artificial fabrication of autogenic tissue substitutes.

  13. A novel albumin-based tissue scaffold for autogenic tissue engineering applications.

    PubMed

    Li, Pei-Shan; Lee, I-Liang; Yu, Wei-Lin; Sun, Jui-Sheng; Jane, Wann-Neng; Shen, Hsin-Hsin

    2014-07-18

    Tissue scaffolds provide a framework for living tissue regeneration. However, traditional tissue scaffolds are exogenous, composed of metals, ceramics, polymers, and animal tissues, and have a defined biocompatibility and application. This study presents a new method for obtaining a tissue scaffold from blood albumin, the major protein in mammalian blood. Human, bovine, and porcine albumin was polymerised into albumin polymers by microbial transglutaminase and was then cast by freeze-drying-based moulding to form albumin tissue scaffolds. Scanning electron microscopy and material testing analyses revealed that the albumin tissue scaffold possesses an extremely porous structure, moderate mechanical strength, and resilience. Using a culture of human mesenchymal stem cells (MSCs) as a model, we showed that MSCs can be seeded and grown in the albumin tissue scaffold. Furthermore, the albumin tissue scaffold can support the long-term osteogenic differentiation of MSCs. These results show that the albumin tissue scaffold exhibits favourable material properties and good compatibility with cells. We propose that this novel tissue scaffold can satisfy essential needs in tissue engineering as a general-purpose substrate. The use of this scaffold could lead to the development of new methods of artificial fabrication of autogenic tissue substitutes.

  14. A Novel Albumin-Based Tissue Scaffold for Autogenic Tissue Engineering Applications

    PubMed Central

    Li, Pei-Shan; -Liang Lee, I.; Yu, Wei-Lin; Sun, Jui-Sheng; Jane, Wann-Neng; Shen, Hsin-Hsin

    2014-01-01

    Tissue scaffolds provide a framework for living tissue regeneration. However, traditional tissue scaffolds are exogenous, composed of metals, ceramics, polymers, and animal tissues, and have a defined biocompatibility and application. This study presents a new method for obtaining a tissue scaffold from blood albumin, the major protein in mammalian blood. Human, bovine, and porcine albumin was polymerised into albumin polymers by microbial transglutaminase and was then cast by freeze-drying-based moulding to form albumin tissue scaffolds. Scanning electron microscopy and material testing analyses revealed that the albumin tissue scaffold possesses an extremely porous structure, moderate mechanical strength, and resilience. Using a culture of human mesenchymal stem cells (MSCs) as a model, we showed that MSCs can be seeded and grown in the albumin tissue scaffold. Furthermore, the albumin tissue scaffold can support the long-term osteogenic differentiation of MSCs. These results show that the albumin tissue scaffold exhibits favourable material properties and good compatibility with cells. We propose that this novel tissue scaffold can satisfy essential needs in tissue engineering as a general-purpose substrate. The use of this scaffold could lead to the development of new methods of artificial fabrication of autogenic tissue substitutes. PMID:25034369

  15. Bioceramics and Scaffolds: A Winning Combination for Tissue Engineering.

    PubMed

    Baino, Francesco; Novajra, Giorgia; Vitale-Brovarone, Chiara

    2015-01-01

    In the last few decades, we have assisted to a general increase of elder population worldwide associated with age-related pathologies. Therefore, there is the need for new biomaterials that can substitute damaged tissues, stimulate the body's own regenerative mechanisms, and promote tissue healing. Porous templates referred to as "scaffolds" are thought to be required for three-dimensional tissue growth. Bioceramics, a special set of fully, partially, or non-crystalline ceramics (e.g., calcium phosphates, bioactive glasses, and glass-ceramics) that are designed for the repair and reconstruction of diseased parts of the body, have high potential as scaffold materials. Traditionally, bioceramics have been used to fill and restore bone and dental defects (repair of hard tissues). More recently, this category of biomaterials has also revealed promising applications in the field of soft-tissue engineering. Starting with an overview of the fundamental requirements for tissue engineering scaffolds, this article provides a detailed picture on recent developments of porous bioceramics and composites, including a summary of common fabrication technologies and a critical analysis of structure-property and structure-function relationships. Areas of future research are highlighted at the end of this review, with special attention to the development of multifunctional scaffolds exploiting therapeutic ion/drug release and emerging applications beyond hard tissue repair.

  16. Tissue engineering osteochondral implants for temporomandibular joint repair.

    PubMed

    Schek, R M; Taboas, J M; Hollister, S J; Krebsbach, P H

    2005-11-01

    Tissue engineering has provided an alternative to traditional strategies to repair and regenerate temporomandibular joints (TMJ). A successful strategy to engineer osteochondral tissue, such as that found in the TMJ, will produce tissue that is both biologically and mechanically functional. Image-based design (IBD) and solid free-form (SFF) fabrication can be used to generate scaffolds that are load bearing and match patient and defect site geometry. The objective of this study was to demonstrate how scaffold design, materials, and biological factors can be used in an integrated approach to regenerate a multi-tissue interface. IBD and SFF were first used to create biomimetic scaffolds with appropriate bulk geometry and microarchitecture. Biphasic composite scaffolds were then manufactured with the same techniques and used to simultaneously generate bone and cartilage in discrete regions and provide for the development of a stable interface between cartilage and subchondral bone. Poly-l-lactic acid/hydroxyapatite composite scaffolds were differentially seeded with fibroblasts transduced with an adenovirus expressing bone morphogenetic protein-7 in the ceramic phase and fully differentiated chondrocytes in the polymeric phase, and were subcutaneously implanted into mice. Following implantation in the ectopic site, the biphasic scaffolds promoted the simultaneous growth of bone, cartilage, and a mineralized interface tissue. Within the ceramic phase, the pockets of tissue generated included blood vessels, marrow stroma, and adipose tissue. This combination of IBD and SFF-fabricated biphasic scaffolds with gene and cell therapy is a promising approach to regenerate osteochondral defects and, ultimately, the TMJ.

  17. Cell Therapy and Tissue Engineering from and toward the Uterus.

    PubMed

    Cervelló, Irene; Santamaría, Xavier; Miyazaki, Kaoru; Maruyama, Tetsuo; Simón, Carlos

    2015-09-01

    Regenerative medicine offers the potential for replacement or repair of different types of cells within damaged tissues or the tissues themselves, typically through cell therapy or tissue engineering. Stem cells are critical to these approaches; indeed, the involvement of bone marrow in the differentiation of stem cells to nonhematopoietic cells is well demonstrated. Further, the contribution of bone marrow-derived stem cells in promoting neoangiogenesis has been demonstrated not only in animal models, but also in human clinical trials with an excellent safety profile. Recent evidence indicates that the endometrium is a tissue with the potential for regeneration through such approaches. The presence of donor cells in the endometrium of women receiving bone marrow transplantation suggests a hematopoietic source with the ability to renew this tissue. Here we describe the role of cell therapy with bone marrow-derived stem cells in treating endometrial dysfunction in Asherman syndrome and/or endometrial atrophy in human and murine models. Additionally, the emerging field of tissue engineering has recently been applied in the reproductive tissues-beyond the endometrium-with elegant studies involving humans and animal models.

  18. Bioceramics and Scaffolds: A Winning Combination for Tissue Engineering

    PubMed Central

    Baino, Francesco; Novajra, Giorgia; Vitale-Brovarone, Chiara

    2015-01-01

    In the last few decades, we have assisted to a general increase of elder population worldwide associated with age-related pathologies. Therefore, there is the need for new biomaterials that can substitute damaged tissues, stimulate the body’s own regenerative mechanisms, and promote tissue healing. Porous templates referred to as “scaffolds” are thought to be required for three-dimensional tissue growth. Bioceramics, a special set of fully, partially, or non-crystalline ceramics (e.g., calcium phosphates, bioactive glasses, and glass–ceramics) that are designed for the repair and reconstruction of diseased parts of the body, have high potential as scaffold materials. Traditionally, bioceramics have been used to fill and restore bone and dental defects (repair of hard tissues). More recently, this category of biomaterials has also revealed promising applications in the field of soft-tissue engineering. Starting with an overview of the fundamental requirements for tissue engineering scaffolds, this article provides a detailed picture on recent developments of porous bioceramics and composites, including a summary of common fabrication technologies and a critical analysis of structure–property and structure–function relationships. Areas of future research are highlighted at the end of this review, with special attention to the development of multifunctional scaffolds exploiting therapeutic ion/drug release and emerging applications beyond hard tissue repair. PMID:26734605

  19. A high throughput mechanical screening device for cartilage tissue engineering.

    PubMed

    Mohanraj, Bhavana; Hou, Chieh; Meloni, Gregory R; Cosgrove, Brian D; Dodge, George R; Mauck, Robert L

    2014-06-27

    Articular cartilage enables efficient and near-frictionless load transmission, but suffers from poor inherent healing capacity. As such, cartilage tissue engineering strategies have focused on mimicking both compositional and mechanical properties of native tissue in order to provide effective repair materials for the treatment of damaged or degenerated joint surfaces. However, given the large number design parameters available (e.g. cell sources, scaffold designs, and growth factors), it is difficult to conduct combinatorial experiments of engineered cartilage. This is particularly exacerbated when mechanical properties are a primary outcome, given the long time required for testing of individual samples. High throughput screening is utilized widely in the pharmaceutical industry to rapidly and cost-effectively assess the effects of thousands of compounds for therapeutic discovery. Here we adapted this approach to develop a high throughput mechanical screening (HTMS) system capable of measuring the mechanical properties of up to 48 materials simultaneously. The HTMS device was validated by testing various biomaterials and engineered cartilage constructs and by comparing the HTMS results to those derived from conventional single sample compression tests. Further evaluation showed that the HTMS system was capable of distinguishing and identifying 'hits', or factors that influence the degree of tissue maturation. Future iterations of this device will focus on reducing data variability, increasing force sensitivity and range, as well as scaling-up to even larger (96-well) formats. This HTMS device provides a novel tool for cartilage tissue engineering, freeing experimental design from the limitations of mechanical testing throughput.

  20. A High Throughput Mechanical Screening Device for Cartilage Tissue Engineering

    PubMed Central

    Mohanraj, Bhavana; Hou, Chieh; Meloni, Greg R.; Cosgrove, Brian D.; Dodge, George R.; Mauck, Robert L.

    2014-01-01

    Articular cartilage enables efficient and near-frictionless load transmission, but suffers from poor inherent healing capacity. As such, cartilage tissue engineering strategies have focused on mimicking both compositional and mechanical properties of native tissue in order to provide effective repair materials for the treatment of damaged or degenerated joint surfaces. However, given the large number design parameters available (e.g. cell sources, scaffold designs, and growth factors), it is difficult to conduct combinatorial experiments of engineered cartilage. This is particularly exacerbated when mechanical properties are a primary outcome given the long time required for testing of individual samples. High throughput screening is utilized widely in the pharmaceutical industry to rapidly and cost-effectively assess the effects of thousands of compounds for therapeutic discovery. Here we adapted this approach to develop a high throughput mechanical screening (HTMS) system capable of measuring the mechanical properties of up to 48 materials simultaneously. The HTMS device was validated by testing various biomaterials and engineered cartilage constructs and by comparing the HTMS results to those derived from conventional single sample compression tests. Further evaluation showed that the HTMS system was capable of distinguishing and identifying ‘hits’, or factors that influence the degree of tissue maturation. Future iterations of this device will focus on reducing data variability, increasing force sensitivity and range, as well as scaling-up to even larger (96-well) formats. This HTMS device provides a novel tool for cartilage tissue engineering, freeing experimental design from the limitations of mechanical testing throughput. PMID:24275442

  1. Computer-aided tissue engineering of a human vertebral body.

    PubMed

    Wettergreen, M A; Bucklen, B S; Sun, W; Liebschner, M A K

    2005-10-01

    Tissue engineering is developing into a less speculative science involving the careful interplay of numerous design parameters and multidisciplinary professionals. Problem solving abilities and state of the art research tools are required to develop solutions for a wide variety of clinical issues. One area of particular interest is orthopedic biomechanics, a field that is responsible for the treatment of over 700,000 vertebral fractures in the United States alone last year. Engineers are currently lacking the technology and knowledge required to govern the subsistence of cells in vivo, let alone the knowledge to create a functional tissue replacement for a whole organ. Despite this, advances in computer-aided tissue engineering are continually growing. Using a combinatory approach to scaffold design, patient-specific implants may be constructed. Computer-aided design, optimization of geometry using voxel finite element models or other optimization routines, creation of a library of architectures with specific material properties, rapid prototyping, and determination of a defect site using imaging modalities highlight the current availability of design resources. This study proposes a novel methodology from start to finish which could, in the future, be used to design a tissue-engineered construct for the replacement of an entire vertebral body.

  2. Hydrogels for ocular drug delivery and tissue engineering

    PubMed Central

    Fathi, Marzieh; Barar, Jaleh; Aghanejad, Ayuob; Omidi, Yadollah

    2015-01-01

    Hydrogels, as crosslinked polymeric three dimensional networks, possess unique structure and behavior in response to the internal and/or external stimuli. As a result, they offer great prospective applications in drug delivery, cell therapy and human tissue engineering. Here, we highlight the potential of hydrogels in prolonged intraocular drug delivery and ocular surface therapy using stem cells incorporated hydrogels. PMID:26929918

  3. The importance of new processing techniques in tissue engineering.

    PubMed

    Lu, L; Mikos, A G

    1996-11-01

    The use of polymer scaffolds in tissue engineering is reviewed and processing techniques are examined. The discussion of polymer-scaffold processing explains fiber bonding, solvent casting and particulate leaching, membrane lamination, melt molding, polymer/ceramic fiber composite-foam processing, phase separation, and high-pressure processing.

  4. Liver tissue engineering and cell sources: issues and challenges.

    PubMed

    Palakkan, Anwar A; Hay, David C; Anil Kumar, P R; Kumary, T V; Ross, James A

    2013-05-01

    Liver diseases are of major concern as they now account for millions of deaths annually. As a result of the increased incidence of liver disease, many patients die on the transplant waiting list, before a donor organ becomes available. To meet the huge demand for donor liver, alternative approaches using liver tissue engineering principles are being actively pursued. Even though adult hepatocytes, the primary cells of the liver are most preferred for tissue engineering of liver, their limited availability, isolation from diseased organs, lack of in vitro propagation and deterioration of function acts as a major drawback to their use. Various approaches have been taken to prevent the functional deterioration of hepatocytes including the provision of an adequate extracellular matrix and co-culture with non-parenchymal cells of liver. Great progress has also been made to differentiate human stem cells to hepatocytes and to use them for liver tissue engineering applications. This review provides an overview of recent challenges, issues and cell sources with regard to liver tissue engineering.

  5. The importance of new processing techniques in tissue engineering

    NASA Technical Reports Server (NTRS)

    Lu, L.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1996-01-01

    The use of polymer scaffolds in tissue engineering is reviewed and processing techniques are examined. The discussion of polymer-scaffold processing explains fiber bonding, solvent casting and particulate leaching, membrane lamination, melt molding, polymer/ceramic fiber composite-foam processing, phase separation, and high-pressure processing.

  6. Efficient in vivo Vascularization of Tissue Engineering Scaffolds

    PubMed Central

    Hegen, Anja; Blois, Anna; Tiron, Crina E.; Hellesøy, Monica; Micklem, David R.; Nör, Jacques E.; Akslen, Lars A.; Lorens, James B.

    2010-01-01

    The success of tissue engineering depends on the rapid and efficient formation of a functional blood vasculature. Adult blood vessels comprise endothelial cells and peri-vascular mural cells that assemble into patent tubules ensheathed by a basement membrane during angiogenesis. Using individual vessel components, we characterized intra-scaffold microvessel self-assembly efficiency in a physiological in vivo tissue engineering implant context. Primary human microvascular endothelial- and vascular smooth muscle cells were seeded at different ratios in poly-L lactic acid (PLLA) scaffolds enriched with basement membrane proteins (Matrigel) and implanted subcutaneously into immunocompromised mice. Temporal intra-scaffold microvessel formation, anastomosis and perfusion were monitored by immunohistochemical, flow cytometric and in vivo multiphoton fluorescence microscopy analysis. Vascularization in the tissue engineering context was strongly enhanced in the implants seeded with a complete complement of blood vessel components: Human microvascular endothelial and vascular smooth muscle cells in vivo assembled a patent microvasculature within Matrigel-enriched PLLA scaffolds that anastomosed with the host circulation during the first week of implantation. Multiphoton fluorescence angiographic analysis of the intra-scaffold microcirculation showed a uniform, branched microvascular network. 3-D image reconstruction analysis of hPASMC distribution within vascularized implants was non-random and displayed a preferential peri-vascular localization. Hence, efficient microvessel self-assembly, anastomosis and establishment of a functional microvasculture in the native hypoxic in vivo tissue engineering context is promoted by providing a complete set of vascular components. PMID:20865694

  7. Extracellular matrix production in vitro in cartilage tissue engineering.

    PubMed

    Chen, Jie-Lin; Duan, Li; Zhu, Weimin; Xiong, Jianyi; Wang, Daping

    2014-04-05

    Cartilage tissue engineering is arising as a technique for the repair of cartilage lesions in clinical applications. However, fibrocartilage formation weakened the mechanical functions of the articular, which compromises the clinical outcomes. Due to the low proliferation ability, dedifferentiation property and low production of cartilage-specific extracellular matrix (ECM) of the chondrocytes, the cartilage synthesis in vitro has been one of the major limitations for obtaining high-quality engineered cartilage constructs. This review discusses cells, biomaterial scaffolds and stimulating factors that can facilitate the cartilage-specific ECM production and accumulation in the in vitro culture system. Special emphasis has been put on the factors that affect the production of ECM macromolecules such as collagen type II and proteoglycans in the review, aiming at providing new strategies to improve the quality of tissue-engineered cartilage.

  8. Alginate composites for bone tissue engineering: a review.

    PubMed

    Venkatesan, Jayachandran; Bhatnagar, Ira; Manivasagan, Panchanathan; Kang, Kyong-Hwa; Kim, Se-Kwon

    2015-01-01

    Bone is a complex and hierarchical tissue consisting of nano hydroxyapatite and collagen as major portion. Several attempts have been made to prepare the artificial bone so as to replace the autograft and allograft treatment. Tissue engineering is a promising approach to solve the several issues and is also useful in the construction of artificial bone with materials including polymer, ceramics, metals, cells and growth factors. Composites consisting of polymer-ceramics, best mimic the natural functions of bone. Alginate, an anionic polymer owing enormous biomedical applications, is gaining importance particularly in bone tissue engineering due to its biocompatibility and gel forming properties. Several composites such as alginate-polymer (PLGA, PEG and chitosan), alginate-protein (collagen and gelatin), alginate-ceramic, alginate-bioglass, alginate-biosilica, alginate-bone morphogenetic protein-2 and RGD peptides composite have been investigated till date. These alginate composites show enhanced biochemical significance in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, alkaline phosphatase increase, excellent mineralization and osteogenic differentiation. Hence, alginate based composite biomaterials will be promising for bone tissue regeneration. This review will provide a broad overview of alginate preparation and its applications towards bone tissue engineering.

  9. Additive manufacturing techniques for the production of tissue engineering constructs.

    PubMed

    Mota, Carlos; Puppi, Dario; Chiellini, Federica; Chiellini, Emo

    2015-03-01

    'Additive manufacturing' (AM) refers to a class of manufacturing processes based on the building of a solid object from three-dimensional (3D) model data by joining materials, usually layer upon layer. Among the vast array of techniques developed for the production of tissue-engineering (TE) scaffolds, AM techniques are gaining great interest for their suitability in achieving complex shapes and microstructures with a high degree of automation, good accuracy and reproducibility. In addition, the possibility of rapidly producing tissue-engineered constructs meeting patient's specific requirements, in terms of tissue defect size and geometry as well as autologous biological features, makes them a powerful way of enhancing clinical routine procedures. This paper gives an extensive overview of different AM techniques classes (i.e. stereolithography, selective laser sintering, 3D printing, melt-extrusion-based techniques, solution/slurry extrusion-based techniques, and tissue and organ printing) employed for the development of tissue-engineered constructs made of different materials (i.e. polymeric, ceramic and composite, alone or in combination with bioactive agents), by highlighting their principles and technological solutions.

  10. Novel opportunities and challenges offered by nanobiomaterials in tissue engineering

    PubMed Central

    Gelain, Fabrizio

    2008-01-01

    Over the last decades, tissue engineering has demonstrated an unquestionable potential to regenerate damaged tissues and organs. Some tissue-engineered solutions recently entered the clinics (eg, artificial bladder, corneal epithelium, engineered skin), but most of the pathologies of interest are still far from being solved. The advent of stem cells opened the door to large-scale production of “raw living matter” for cell replacement and boosted the overall sector in the last decade. Still reliable synthetic scaffolds fairly resembling the nanostructure of extracellular matrices, showing mechanical properties comparable to those of the tissues to be regenerated and capable of being modularly functionalized with biological active motifs, became feasible only in the last years thanks to newly introduced nanotechnology techniques of material design, synthesis, and characterization. Nanostructured synthetic matrices look to be the next generation scaffolds, opening new powerful pathways for tissue regeneration and introducing new challenges at the same time. We here present a detailed overview of the advantages, applications, and limitations of nanostructured matrices with a focus on both electrospun and self-assembling scaffolds. PMID:19337410

  11. Metal mesh scaffold for tissue engineering of membranes.

    PubMed

    Alavi, S Hamed; Kheradvar, Arash

    2012-04-01

    Engineering of the membrane-like tissue structures to be utilized in highly dynamic loading environments such as the cardiovascular system has been a challenge in the past decade. Scaffolds are critical components of the engineered tissue membranes and allow them being formed in vitro and remain secure in vivo when implanted in the body. Several approaches have been taken to develop scaffolds for tissue membranes. However, all methods entail limitations due to structural vulnerability, short-term functionality, and mechanical properties of the resulted membrane constructs. To overcome these issues, we have developed a novel hybrid scaffold made of an extra thin layer of metal mesh tightly enclosed by biological matrix components. This approach retains all the advantages of using biological scaffolds while developing a strong extracellular matrix that can stand various types of loads after implantation inside the body.

  12. Chitosan-based scaffolds for bone tissue engineering

    PubMed Central

    Levengood, Sheeny Lan; Zhang, Miqin

    2014-01-01

    Bone defects requiring grafts to promote healing are frequently occurring and costly problems in health care. Chitosan, a biodegradable, naturally occurring polymer, has drawn considerable attention in recent years as scaffolding material in tissue engineering and regenerative medicine. Chitosan is especially attractive as a bone scaffold material because it supports the attachment and proliferation of osteoblast cells as well as formation of mineralized bone matrix. In this review, we discuss the fundamentals of bone tissue engineering and the unique properties of chitosan as a scaffolding material to treat bone defects for hard tissue regeneration. We present the common methods for fabrication and characterization of chitosan scaffolds, and discuss the influence of material preparation and addition of polymeric or ceramic components or biomolecules on chitosan scaffold properties such as mechanical strength, structural integrity, and functional bone regeneration. Finally, we highlight recent advances in development of chitosan-based scaffolds with enhanced bone regeneration capability. PMID:24999429

  13. Microstereolithography-based computer-aided manufacturing for tissue engineering.

    PubMed

    Cho, Dong-Woo; Kang, Hyun-Wook

    2012-01-01

    Various solid freeform fabrication technologies have been introduced for constructing three-dimensional (3-D) freeform structures. Of these, microstereolithography (MSTL) technology performs the best in 3-D space because it not only has high resolution, but also fast fabrication speed. Using this technology, 3-D structures with mesoscale size and microscale resolution are achievable. Many researchers have been trying to apply this technology to tissue engineering to construct medically applicable scaffolds, which require a 3-D shape that fits a defect with a mesoscale size and microscale inner architecture for efficient regeneration of artificial tissue. This chapter introduces the principles of MSTL technology and representative systems. It includes fabrication and computer-aided design/computer-aided manufacturing (CAD/CAM) processes to show the automation process by which measurements from medical images are used to fabricate the required 3-D shape. Then, various tissue engineering applications based on MSTL are summarized.

  14. Biofunctionalisation of polymeric scaffolds for neural tissue engineering.

    PubMed

    Wang, T Y; Forsythe, J S; Parish, C L; Nisbet, D R

    2012-11-01

    Patients who experience injury to the central or peripheral nervous systems invariably suffer from a range of dysfunctions due to the limited ability for repair and reconstruction of damaged neural tissue. Whilst some treatment strategies can provide symptomatic improvement of motor and cognitive function, they fail to repair the injured circuits and rarely offer long-term disease modification. To this end, the biological molecules, used in combination with neural tissue engineering scaffolds, may provide feasible means to repair damaged neural pathways. This review will focus on three promising classes of neural tissue engineering scaffolds, namely hydrogels, electrospun nanofibres and self-assembling peptides. Additionally, the importance and methods for presenting biologically relevant molecules such as, neurotrophins, extracellular matrix proteins and protein-derived sequences that promote neuronal survival, proliferation and neurite outgrowth into the lesion will be discussed.

  15. Mathematical modeling in wound healing, bone regeneration and tissue engineering.

    PubMed

    Geris, Liesbet; Gerisch, Alf; Schugart, Richard C

    2010-12-01

    The processes of wound healing and bone regeneration and problems in tissue engineering have been an active area for mathematical modeling in the last decade. Here we review a selection of recent models which aim at deriving strategies for improved healing. In wound healing, the models have particularly focused on the inflammatory response in order to improve the healing of chronic wound. For bone regeneration, the mathematical models have been applied to design optimal and new treatment strategies for normal and specific cases of impaired fracture healing. For the field of tissue engineering, we focus on mathematical models that analyze the interplay between cells and their biochemical cues within the scaffold to ensure optimal nutrient transport and maximal tissue production. Finally, we briefly comment on numerical issues arising from simulations of these mathematical models.

  16. Nanotopography-guided tissue engineering and regenerative medicine.

    PubMed

    Kim, Hong Nam; Jiao, Alex; Hwang, Nathaniel S; Kim, Min Sung; Kang, Do Hyun; Kim, Deok-Ho; Suh, Kahp-Yang

    2013-04-01

    Human tissues are intricate ensembles of multiple cell types embedded in complex and well-defined structures of the extracellular matrix (ECM). The organization of ECM is frequently hierarchical from nano to macro, with many proteins forming large scale structures with feature sizes up to several hundred microns. Inspired from these natural designs of ECM, nanotopography-guided approaches have been increasingly investigated for the last several decades. Results demonstrate that the nanotopography itself can activate tissue-specific function in vitro as well as promote tissue regeneration in vivo upon transplantation. In this review, we provide an extensive analysis of recent efforts to mimic functional nanostructures in vitro for improved tissue engineering and regeneration of injured and damaged tissues. We first characterize the role of various nanostructures in human tissues with respect to each tissue-specific function. Then, we describe various fabrication methods in terms of patterning principles and material characteristics. Finally, we summarize the applications of nanotopography to various tissues, which are classified into four types depending on their functions: protective, mechano-sensitive, electro-active, and shear stress-sensitive tissues. Some limitations and future challenges are briefly discussed at the end.

  17. Relevance and safety of telomerase for human tissue engineering

    PubMed Central

    Klinger, Rebecca Y.; Blum, Juliana L.; Hearn, Bevin; Lebow, Benjamin; Niklason, Laura E.

    2006-01-01

    Tissue engineering holds the promise of replacing damaged or diseased tissues and organs. The use of autologous donor cells is often not feasible because of the limited replicative lifespan of cells, particularly those derived from elderly patients. Proliferative arrest can be overcome by the ectopic expression of telomerase via human telomerase reverse transcriptase (hTERT) gene transfection. To study the efficacy and safety of this potentially valuable technology, we used differentiated vascular smooth muscle cells (SMC) and vascular tissue engineering as a model system. Although we previously demonstrated that vessels engineered with telomerase-expressing SMC had improved mechanics over those grown with control cells, it is critical to assess the phenotypic impact of telomerase expression in donor cells, because telomerase up-regulation is observed in >95% of human malignancies. To study the impact of telomerase in tissue engineering, expression of hTERT was retrovirally induced in SMC from eight elderly patients and one young donor. In hTERT SMC, significant lifespan extension beyond that of control was achieved without population doubling time acceleration. Karyotype changes were seen in both control and hTERT SMC but were not clonal nor representative of cancerous change. hTERT cells also failed to show evidence of neoplastic transformation in functional assays of tumorigenicity. In addition, the impact of donor age on cellular behavior, particularly the synthetic capability of SMC, was not affected by hTERT expression. Hence, this tissue engineering model system highlights the impact of donor age on cellular synthetic function that appears to be independent of lifespan extension by hTERT. PMID:16477025

  18. Transient Hypoxia Improves Matrix Properties in Tissue Engineered Cartilage

    PubMed Central

    Yodmuang, Supansa; Gadjanski, Ivana; Chao, Pen-hsiu Grace; Vunjak-Novakovic, Gordana

    2014-01-01

    Adult articular cartilage is a hypoxic tissue, with oxygen tension ranging from <10% at the cartilage surface to <1% in the deepest layers. In addition to spatial gradients, cartilage development is also associated with temporal changes in oxygen tension. However, a vast majority of cartilage tissue engineering protocols involves cultivation of chondrocytes or their progenitors under ambient oxygen concentration (21% O2), that is, significantly above physiological levels in either developing or adult cartilage. Our study was designed to test the hypothesis that transient hypoxia followed by normoxic conditions results in improved quality of engineered cartilaginous ECM. To this end, we systematically compared the effects of normoxia (21% O2 for 28 days), hypoxia (5% O2 for 28 days) and transient hypoxia—reoxygenation (5% O2 for 7 days and 21% O2 for 21 days) on the matrix composition and expression of the chondrogenic genes in cartilage constructs engineered in vitro. We demonstrated that reoxygenation had the most effect on the expression of cartilaginous genes including COL2A1, ACAN, and SOX9 and increased tissue concentrations of amounts of glycosaminoglycans and type II collagen. The equilibrium Young’s moduli of tissues grown under transient hypoxia (510.01 ± 28.15 kPa) and under normoxic conditions (417.60 ± 68.46 kPa) were significantly higher than those measured under hypoxic conditions (279.61 ± 20.52 kPa). These data suggest that the cultivation protocols utilizing transient hypoxia with reoxygenation have high potential for efficient cartilage tissue engineering, but need further optimization in order to achieve higher mechanical functionality of engineered constructs. PMID:23203946

  19. Artificial corneas versus donor corneas for repeat corneal transplants

    PubMed Central

    Akpek, Esen K; Alkharashi, Majed; Hwang, Frank S; Ng, Sueko M; Lindsley, Kristina

    2014-01-01

    Background Individuals who have failed one or more full thickness penetrating keratoplasties (PKs) may be offered repeat corneal surgery using an artificial or donor cornea. An artificial or prosthetic cornea is known as a keratoprosthesis. Both donor and artificial corneal transplantations involve removal of the diseased and opaque recipient cornea (or the previously failed cornea) and replacement with another donor or prosthetic cornea. Objectives To assess the effectiveness of artificial versus donor corneas in individuals who have had one or more failed donor corneal transplantations. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2013, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 November 2013. Selection criteria Two review authors independently assessed reports from the electronic searches to identify randomized controlled trials (RCTs) or controlled clinical trials (CCTs). We resolved discrepancies by discussion or consultation with a third review author. Data collection and analysis For discussion purposes, we assessed findings from observational cohort studies and non-comparative case series. No data synthesis was performed. Main results We did not identify any RCTs or CCTs comparing artificial corneas with donor corneas for repeat corneal transplantations. Authors

  20. Vascular tissue engineering by computer-aided laser micromachining.

    PubMed

    Doraiswamy, Anand; Narayan, Roger J

    2010-04-28

    Many conventional technologies for fabricating tissue engineering scaffolds are not suitable for fabricating scaffolds with patient-specific attributes. For example, many conventional technologies for fabricating tissue engineering scaffolds do not provide control over overall scaffold geometry or over cell position within the scaffold. In this study, the use of computer-aided laser micromachining to create scaffolds for vascular tissue networks was investigated. Computer-aided laser micromachining was used to construct patterned surfaces in agarose or in silicon, which were used for differential adherence and growth of cells into vascular tissue networks. Concentric three-ring structures were fabricated on agarose hydrogel substrates, in which the inner ring contained human aortic endothelial cells, the middle ring contained HA587 human elastin and the outer ring contained human aortic vascular smooth muscle cells. Basement membrane matrix containing vascular endothelial growth factor and heparin was to promote proliferation of human aortic endothelial cells within the vascular tissue networks. Computer-aided laser micromachining provides a unique approach to fabricate small-diameter blood vessels for bypass surgery as well as other artificial tissues with complex geometries.

  1. Nuclear morphology and deformation in engineered cardiac myocytes and tissues.

    PubMed

    Bray, Mark-Anthony P; Adams, William J; Geisse, Nicholas A; Feinberg, Adam W; Sheehy, Sean P; Parker, Kevin K

    2010-07-01

    Cardiac tissue engineering requires finely-tuned manipulation of the extracellular matrix (ECM) microenvironment to optimize internal myocardial organization. The myocyte nucleus is mechanically connected to the cell membrane via cytoskeletal elements, making it a target for the cellular response to perturbation of the ECM. However, the role of ECM spatial configuration and myocyte shape on nuclear location and morphology is unknown. In this study, printed ECM proteins were used to configure the geometry of cultured neonatal rat ventricular myocytes. Engineered one- and two-dimensional tissue constructs and single myocyte islands were assayed using live fluorescence imaging to examine nuclear position, morphology and motion as a function of the imposed ECM geometry during diastolic relaxation and systolic contraction. Image analysis showed that anisotropic tissue constructs cultured on microfabricated ECM lines possessed a high degree of nuclear alignment similar to that found in vivo; nuclei in isotropic tissues were polymorphic in shape with an apparently random orientation. Nuclear eccentricity was also increased for the anisotropic tissues, suggesting that intracellular forces deform the nucleus as the cell is spatially confined. During systole, nuclei experienced increasing spatial confinement in magnitude and direction of displacement as tissue anisotropy increased, yielding anisotropic deformation. Thus, the nature of nuclear displacement and deformation during systole appears to rely on a combination of the passive myofibril spatial organization and the active stress fields induced by contraction. Such findings have implications in understanding the genomic consequences and functional response of cardiac myocytes to their ECM surroundings under conditions of disease.

  2. Nonsteady State Oxygen Transport in Engineered Tissue: Implications for Design

    PubMed Central

    Ehsan, Seema M.

    2013-01-01

    Engineered tissue constructs are limited in size, and thus clinical relevance, when diffusion is the primary mode of oxygen transport. Understanding the extent of oxygen diffusion and cellular consumption is necessary for the design of engineered tissues, particularly those intended for implantation into hypoxic wound sites. This study presents a combined experimental and computation model to predict design constraints for cellularized fibrin tissues subjected to a step change in the oxygen concentration to simulate transplantation. Nonsteady state analysis of oxygen diffusion and consumption was used to estimate the diffusion coefficient of oxygen (mean±SD, 1.7×10−9±8.4×10−11 m2/s) in fibrin hydrogels as well as the Michaelis-Menten parameters, Vmax (1.3×10−17±9.2×10−19 mol·cell−1·s−1), and Km (8.0×10−3±3.5×0−3 mol/m3), of normal human lung fibroblasts. Nondimensionalization of the governing diffusion-reaction equation enabled the creation of a single dimensionless parameter, the Thiele modulus (φ), which encompasses the combined effects of oxygen diffusion, consumption, and tissue dimensions. Tissue thickness is the design parameter with the most pronounced influence on the distribution of oxygen within the system. Additionally, tissues designed such that φ<1 achieve a near spatially uniform and adequate oxygen concentration following the step change. Understanding and optimizing the Thiele modulus will improve the design of engineered tissue implants. PMID:23350630

  3. Portable light transmission measuring system for preserved corneas

    PubMed Central

    Ventura, Liliane; de Jesus, Gabriel Torres; de Oliveira, Gunter Camilo Dablas; Sousa, Sidney JF

    2005-01-01

    Background The authors have developed a small portable device for the objective measurement of the transparency of corneas stored in preservative medium, for use by eye banks in evaluation prior to transplantation. Methods The optical system consists of a white light, lenses, and pinholes that collimate the white light beams and illuminate the cornea in its preservative medium, and an optical filter (400–700 nm) that selects the range of the wavelength of interest. A sensor detects the light that passes through the cornea, and the average corneal transparency is displayed. In order to obtain only the tissue transparency, an electronic circuit was built to detect a baseline input of the preservative medium prior to the measurement of corneal transparency. The operation of the system involves three steps: adjusting the "0 %" transmittance of the instrument, determining the "100 %" transmittance of the system, and finally measuring the transparency of the preserved cornea inside the storage medium. Results Fifty selected corneas were evaluated. Each cornea was submitted to three evaluation methods: subjective classification of transparency through a slit lamp, quantification of the transmittance of light using a corneal spectrophotometer previously developed, and measurement of transparency with the portable device. Conclusion By comparing the three methods and using the expertise of eye bank trained personnel, a table for quantifying corneal transparency with the new device has been developed. The correlation factor between the corneal spectrophotometer and the new device is 0,99813, leading to a system that is able to standardize transparency measurements of preserved corneas, which is currently done subjectively. PMID:16372912

  4. Creating tissues from textiles: scalable nonwoven manufacturing techniques for fabrication of tissue engineering scaffolds.

    PubMed

    Tuin, S A; Pourdeyhimi, B; Loboa, E G

    2016-02-23

    Electrospun nonwovens have been used extensively for tissue engineering applications due to their inherent similarities with respect to fibre size and morphology to that of native extracellular matrix (ECM). However, fabrication of large scaffold constructs is time consuming, may require harsh organic solvents, and often results in mechanical properties inferior to the tissue being treated. In order to translate nonwoven based tissue engineering scaffold strategies to clinical use, a high throughput, repeatable, scalable, and economic manufacturing process is needed. We suggest that nonwoven industry standard high throughput manufacturing techniques (meltblowing, spunbond, and carding) can meet this need. In this study, meltblown, spunbond and carded poly(lactic acid) (PLA) nonwovens were evaluated as tissue engineering scaffolds using human adipose derived stem cells (hASC) and compared to electrospun nonwovens. Scaffolds were seeded with hASC and viability, proliferation, and differentiation were evaluated over the course of 3 weeks. We found that nonwovens manufactured via these industry standard, commercially relevant manufacturing techniques were capable of supporting hASC attachment, proliferation, and both adipogenic and osteogenic differentiation of hASC, making them promising candidates for commercialization and translation of nonwoven scaffold based tissue engineering strategies.

  5. Engineered skeletal muscle tissue networks with controllable architecture

    PubMed Central

    Bian, Weining; Bursac, Nenad

    2009-01-01

    The engineering of functional skeletal muscle tissue substitutes holds promise for the treatment of various muscular diseases and injuries. However, no tissue fabrication technology currently exists for the generation of a relatively large and thick bioartificial muscle made of densely packed, uniformly aligned, and differentiated myofibers. In this study, we describe a versatile cell/hydrogel micromolding approach where polydimethylsiloxane (PDMS) molds containing an array of elongated posts were used to fabricate relatively large neonatal rat skeletal muscle tissue networks with reproducible and controllable architecture. By combining cell-mediated fibrin gel compaction and precise microfabrication of mold dimensions including the length and height of the PDMS posts, we were able to simultaneously support high cell viability, guide cell alignment along the microfabricated tissue pores, and reproducibly control the overall tissue porosity, size, and thickness. The interconnected muscle bundles within the porous tissue networks were composed of densely packed, aligned, and highly differentiated myofibers. The formed myofibers expressed myogenin, developed abundant cross-striations, and generated spontaneous tissue contractions at the macroscopic spatial scale. The proliferation of non-muscle cells was significantly reduced compared to monolayer cultures. The more complex muscle tissue architectures were fabricated by controlling the spatial distribution and direction of the PDMS posts. PMID:19070360

  6. The Ets Transcription Factor EHF as a Regulator of Cornea Epithelial Cell Identity*

    PubMed Central

    Stephens, Denise N.; Klein, Rachel Herndon; Salmans, Michael L.; Gordon, William; Ho, Hsiang; Andersen, Bogi

    2013-01-01

    The cornea is the clear, outermost portion of the eye composed of three layers: an epithelium that provides a protective barrier while allowing transmission of light into the eye, a collagen-rich stroma, and an endothelium monolayer. How cornea development and aging is controlled is poorly understood. Here we characterize the mouse cornea transcriptome from early embryogenesis through aging and compare it with transcriptomes of other epithelial tissues, identifying cornea-enriched genes, pathways, and transcriptional regulators. Additionally, we profiled cornea epithelium and stroma, defining genes enriched in these layers. Over 10,000 genes are differentially regulated in the mouse cornea across the time course, showing dynamic expression during development and modest expression changes in fewer genes during aging. A striking transition time point for gene expression between postnatal days 14 and 28 corresponds with completion of cornea development at the transcriptional level. Clustering classifies co-expressed, and potentially co-regulated, genes into biologically informative categories, including groups that exhibit epithelial or stromal enriched expression. Based on these findings, and through loss of function studies and ChIP-seq, we show that the Ets transcription factor EHF promotes cornea epithelial fate through complementary gene activating and repressing activities. Furthermore, we identify potential interactions between EHF, KLF4, and KLF5 in promoting cornea epithelial differentiation. These data provide insights into the mechanisms underlying epithelial development and aging, identifying EHF as a regulator of cornea epithelial identity and pointing to interactions between Ets and KLF factors in promoting epithelial fate. Furthermore, this comprehensive gene expression data set for the cornea is a powerful tool for discovery of novel cornea regulators and pathways. PMID:24142692

  7. Advancements in electrospinning of polymeric nanofibrous scaffolds for tissue engineering.

    PubMed

    Ingavle, Ganesh C; Leach, J Kent

    2014-08-01

    Polymeric nanofibers have potential as tissue engineering scaffolds, as they mimic the nanoscale properties and structural characteristics of native extracellular matrix (ECM). Nanofibers composed of natural and synthetic polymers, biomimetic composites, ceramics, and metals have been fabricated by electrospinning for various tissue engineering applications. The inherent advantages of electrospinning nanofibers include the generation of substrata with high surface area-to-volume ratios, the capacity to precisely control material and mechanical properties, and a tendency for cellular in-growth due to interconnectivity within the pores. Furthermore, the electrospinning process affords the opportunity to engineer scaffolds with micro- to nanoscale topography similar to the natural ECM. This review describes the fundamental aspects of the electrospinning process when applied to spinnable natural and synthetic polymers; particularly, those parameters that influence fiber geometry, morphology, mesh porosity, and scaffold mechanical properties. We describe cellular responses to fiber morphology achieved by varying processing parameters and highlight successful applications of electrospun nanofibrous scaffolds when used to tissue engineer bone, skin, and vascular grafts.

  8. Mechanical stimulation improves tissue-engineered human skeletal muscle.

    PubMed

    Powell, Courtney A; Smiley, Beth L; Mills, John; Vandenburgh, Herman H

    2002-11-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  9. Mechanical stimulation improves tissue-engineered human skeletal muscle

    NASA Technical Reports Server (NTRS)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  10. Osteochondral Interface Tissue Engineering Using Macroscopic Gradients of Bioactive Signals

    PubMed Central

    Dormer, Nathan H.; Singh, Milind; Wang, Limin; Berkland, Cory J.; Detamore, Michael S.

    2013-01-01

    Continuous gradients exist at osteochondral interfaces, which may be engineered by applying spatially patterned gradients of biological cues. In the present study, a protein-loaded microsphere-based scaffold fabrication strategy was applied to achieve spatially and temporally controlled delivery of bioactive signals in three-dimensional (3D) tissue engineering scaffolds. Bone morphogenetic protein-2 and transforming growth factor-β1-loaded poly(d,llactic- co-glycolic acid) microspheres were utilized with a gradient scaffold fabrication technology to produce microsphere-based scaffolds containing opposing gradients of these signals. Constructs were then seeded with human bone marrow stromal cells (hBMSCs) or human umbilical cord mesenchymal stromal cells (hUCMSCs), and osteochondral tissue regeneration was assessed in gradient scaffolds and compared to multiple control groups. Following a 6-week cell culture, the gradient scaffolds produced regionalized extracellular matrix, and outperformed the blank control scaffolds in cell number, glycosaminoglycan production, collagen content, alkaline phosphatase activity, and in some instances, gene expression of major osteogenic and chondrogenic markers. These results suggest that engineered signal gradients may be beneficial for osteochondral tissue engineering. PMID:20379780

  11. Design and analysis of tissue engineering scaffolds that mimic soft tissue mechanical anisotropy.

    PubMed

    Courtney, Todd; Sacks, Michael S; Stankus, John; Guan, Jianjun; Wagner, William R

    2006-07-01

    Tissue engineered constructs must exhibit tissue-like functional properties, including mechanical behavior comparable to the native tissues they are intended to replace. Moreover, the ability to reversibly undergo large strains can help to promote and guide tissue growth. Electrospun poly (ester urethane) ureas (ES-PEUU) are elastomeric and allow for the control of fiber diameter, porosity, and degradation rate. ES-PEUU scaffolds can be fabricated to have a well-aligned fiber network, which is important for applications involving mechanically anisotropic soft tissues. We have developed ES-PEUU scaffolds under variable speed conditions and modeled the effects of fiber orientation on the macro-mechanical properties of the scaffold. To illustrate the ability to simulate native tissue mechanical behavior, we demonstrated that the high velocity spun scaffolds exhibited highly anisotropic mechanical properties closely resembling the native pulmonary heart valve leaflet. Moreover, use of the present fiber-level structural constitutive model allows for the determination of electrospinning conditions to tailor ES-PEUU scaffolds for specific soft tissue applications. The results of this study will help to provide the basis for rationally designed mechanically anisotropic soft tissue engineered implants.

  12. Advancing biomaterials of human origin for tissue engineering

    PubMed Central

    Chen, Fa-Ming; Liu, Xiaohua

    2015-01-01

    Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for

  13. Porous magnesium-based scaffolds for tissue engineering.

    PubMed

    Yazdimamaghani, Mostafa; Razavi, Mehdi; Vashaee, Daryoosh; Moharamzadeh, Keyvan; Boccaccini, Aldo R; Tayebi, Lobat

    2017-02-01

    Significant amount of research efforts have been dedicated to the development of scaffolds for tissue engineering. Although at present most of the studies are focused on non-load bearing scaffolds, many scaffolds have also been investigated for hard tissue repair. In particular, metallic scaffolds are being studied for hard tissue engineering due to their suitable mechanical properties. Several biocompatible metallic materials such as stainless steels, cobalt alloys, titanium alloys, tantalum, nitinol and magnesium alloys have been commonly employed as implants in orthopedic and dental treatments. They are often used to replace and regenerate the damaged bones or to provide structural support for healing bone defects. Among the common metallic biomaterials, magnesium (Mg) and a number of its alloys are effective because of their mechanical properties close to those of human bone, their natural ionic content that may have important functional roles in physiological systems, and their in vivo biodegradation characteristics in body fluids. Due to such collective properties, Mg based alloys can be employed as biocompatible, bioactive, and biodegradable scaffolds for load-bearing applications. Recently, porous Mg and Mg alloys have been specially suggested as metallic scaffolds for bone tissue engineering. With further optimization of the fabrication techniques, porous Mg is expected to make a promising hard substitute scaffold. The present review covers research conducted on the fabrication techniques, surface modifications, properties and biological characteristics of Mg alloys based scaffolds. Furthermore, the potential applications, challenges and future trends of such degradable metallic scaffolds are discussed in detail.

  14. Conductive polymers: towards a smart biomaterial for tissue engineering.

    PubMed

    Balint, Richard; Cassidy, Nigel J; Cartmell, Sarah H

    2014-06-01

    Developing stimulus-responsive biomaterials with easy-to-tailor properties is a highly desired goal of the tissue engineering community. A novel type of electroactive biomaterial, the conductive polymer, promises to become one such material. Conductive polymers are already used in fuel cells, computer displays and microsurgical tools, and are now finding applications in the field of biomaterials. These versatile polymers can be synthesised alone, as hydrogels, combined into composites or electrospun into microfibres. They can be created to be biocompatible and biodegradable. Their physical properties can easily be optimized for a specific application through binding biologically important molecules into the polymer using one of the many available methods for their functionalization. Their conductive nature allows cells or tissue cultured upon them to be stimulated, the polymers' own physical properties to be influenced post-synthesis and the drugs bound in them released, through the application of an electrical signal. It is thus little wonder that these polymers are becoming very important materials for biosensors, neural implants, drug delivery devices and tissue engineering scaffolds. Focusing mainly on polypyrrole, polyaniline and poly(3,4-ethylenedioxythiophene), we review conductive polymers from the perspective of tissue engineering. The basic properties of conductive polymers, their chemical and electrochemical synthesis, the phenomena underlying their conductivity and the ways to tailor their properties (functionalization, composites, etc.) are discussed.

  15. Polymeric scaffolds in tissue engineering: a literature review.

    PubMed

    Jafari, Maissa; Paknejad, Zahrasadat; Rad, Maryam Rezai; Motamedian, Saeed Reza; Eghbal, Mohammad Jafar; Nadjmi, Nasser; Khojasteh, Arash

    2017-02-01

    The tissue engineering scaffold acts as an extracellular matrix that interacts to the cells prior to forming new tissues. The chemical and structural characteristics of scaffolds are major concerns in fabricating of ideal three-dimensional structure for tissue engineering applications. The polymer scaffolds used for tissue engineering should possess proper architecture and mechanical properties in addition to supporting cell adhesion, proliferation, and differentiation. Much research has been done on the topic of polymeric scaffold properties such as surface topographic features (roughness and hydrophilicity) and scaffold microstructures (pore size, porosity, pore interconnectivity, and pore and fiber architectures) that influence the cell-scaffold interactions. In this review, efforts were given to evaluate the effect of both chemical and structural characteristics of scaffolds on cell behaviors such as adhesion, proliferation, migration, and differentiation. This review would provide the fundamental information which would be beneficial for scaffold design in future. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 431-459, 2017.

  16. Tissue-Engineered Autologous Grafts for Facial Bone Reconstruction

    PubMed Central

    Bhumiratana, Sarindr; Bernhard, Jonathan C.; Alfi, David M.; Yeager, Keith; Eton, Ryan E.; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M.; Lopez, Mandi J.; Eisig, Sidney B.; Vunjak-Novakovic, Gordana

    2016-01-01

    Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665

  17. Stem Cell-Based Tissue-Engineered Laryngeal Replacement.

    PubMed

    Ansari, Tahera; Lange, Peggy; Southgate, Aaron; Greco, Karin; Carvalho, Carla; Partington, Leanne; Bullock, Anthony; MacNeil, Sheila; Lowdell, Mark W; Sibbons, Paul D; Birchall, Martin A

    2017-02-01

    Patients with laryngeal disorders may have severe morbidity relating to swallowing, vocalization, and respiratory function, for which conventional therapies are suboptimal. A tissue-engineered approach would aim to restore the vocal folds and maintain respiratory function while limiting the extent of scarring in the regenerated tissue. Under Good Laboratory Practice conditions, we decellularized porcine larynges, using detergents and enzymes under negative pressure to produce an acellular scaffold comprising cartilage, muscle, and mucosa. To assess safety and functionality before clinical trials, a decellularized hemilarynx seeded with human bone marrow-derived mesenchymal stem cells and a tissue-engineered oral mucosal sheet was implanted orthotopically into six pigs. The seeded grafts were left in situ for 6 months and assessed using computed tomography imaging, bronchoscopy, and mucosal brushings, together with vocal recording and histological analysis on explantation. The graft caused no adverse respiratory function, nor did it impact swallowing or vocalization. Rudimentary vocal folds covered by contiguous epithelium were easily identifiable. In conclusion, the proposed tissue-engineered approach represents a viable alternative treatment for laryngeal defects. Stem Cells Translational Medicine 2017;6:677-687.

  18. Immunobiology of Fibrin-Based Engineered Heart Tissue

    PubMed Central

    Conradi, Lenard; Schmidt, Stephanie; Neofytou, Evgenios; Deuse, Tobias; Peters, Laura; Eder, Alexandra; Hua, Xiaoqin; Hansen, Arne; Robbins, Robert C.; Beygui, Ramin E.; Reichenspurner, Hermann; Eschenhagen, Thomas

    2015-01-01

    Different tissue-engineering approaches have been developed to induce and promote cardiac regeneration; however, the impact of the immune system and its responses to the various scaffold components of the engineered grafts remains unclear. Fibrin-based engineered heart tissue (EHT) was generated from neonatal Lewis (Lew) rat heart cells and transplanted onto the left ventricular surface of three different rat strains: syngeneic Lew, allogeneic Brown Norway, and immunodeficient Rowett Nude rats. Interferon spot frequency assay results showed similar degrees of systemic immune activation in the syngeneic and allogeneic groups, whereas no systemic immune response was detectable in the immunodeficient group (p < .001 vs. syngeneic and allogeneic). Histological analysis revealed much higher local infiltration of CD3- and CD68-positive cells in syngeneic and allogeneic rats than in immunodeficient animals. Enzyme-linked immunospot and immunofluorescence experiments revealed matrix-directed TH1-based rejection in syngeneic recipients without collateral impairment of heart cell survival. Bioluminescence imaging was used for in vivo longitudinal monitoring of transplanted luciferase-positive EHT constructs. Survival was documented in syngeneic and immunodeficient recipients for a period of up to 110 days after transplant, whereas in the allogeneic setting, graft survival was limited to only 14 ± 1 days. EHT strategies using autologous cells are promising approaches for cardiac repair applications. Although fibrin-based scaffold components elicited an immune response in our studies, syngeneic cells carried in the EHT were relatively unaffected. Significance An initial insight into immunological consequences after transplantation of engineered heart tissue was gained through this study. Most important, this study was able to demonstrate cell survival despite rejection of matrix components. Generation of syngeneic human engineered heart tissue, possibly using human induced

  19. 3D printing of functional biomaterials for tissue engineering.

    PubMed

    Zhu, Wei; Ma, Xuanyi; Gou, Maling; Mei, Deqing; Zhang, Kang; Chen, Shaochen

    2016-08-01

    3D printing is emerging as a powerful tool for tissue engineering by enabling 3D cell culture within complex 3D biomimetic architectures. This review discusses the prevailing 3D printing techniques and their most recent applications in building tissue constructs. The work associated with relatively well-known inkjet and extrusion-based bioprinting is presented with the latest advances in the fields. Emphasis is put on introducing two relatively new light-assisted bioprinting techniques, including digital light processing (DLP)-based bioprinting and laser based two photon polymerization (TPP) bioprinting. 3D bioprinting of vasculature network is particularly discussed for its foremost significance in maintaining tissue viability and promoting functional maturation. Limitations to current bioprinting approaches, as well as future directions of bioprinting functional tissues are also discussed.

  20. Importance of dual delivery systems for bone tissue engineering.

    PubMed

    Farokhi, Mehdi; Mottaghitalab, Fatemeh; Shokrgozar, Mohammad Ali; Ou, Keng-Liang; Mao, Chuanbin; Hosseinkhani, Hossein

    2016-03-10

    Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering.

  1. Today Prospects for Tissue Engineering Therapeutic Approach in Dentistry

    PubMed Central

    Bossù, Maurizio; Pacifici, Andrea; Carbone, Daniele; Tenore, Gianluca; Ierardo, Gaetano; Pacifici, Luciano; Polimeni, Antonella

    2014-01-01

    In dental practice there is an increasing need for predictable therapeutic protocols able to regenerate tissues that, due to inflammatory or traumatic events, may suffer from loss of their function. One of the topics arising major interest in the research applied to regenerative medicine is represented by tissue engineering and, in particular, by stem cells. The study of stem cells in dentistry over the years has shown an exponential increase in literature. Adult mesenchymal stem cells have recently been isolated and characterized from tooth-related tissues and they might represent, in the near future, a new gold standard in the regeneration of all oral tissues. The aim of our review is to provide an overview on the topic reporting the current knowledge for each class of dental stem cells and to identify their potential clinical applications as therapeutic tool in various branches of dentistry. PMID:25379516

  2. Today prospects for tissue engineering therapeutic approach in dentistry.

    PubMed

    Bossù, Maurizio; Pacifici, Andrea; Carbone, Daniele; Tenore, Gianluca; Ierardo, Gaetano; Pacifici, Luciano; Polimeni, Antonella

    2014-01-01

    In dental practice there is an increasing need for predictable therapeutic protocols able to regenerate tissues that, due to inflammatory or traumatic events, may suffer from loss of their function. One of the topics arising major interest in the research applied to regenerative medicine is represented by tissue engineering and, in particular, by stem cells. The study of stem cells in dentistry over the years has shown an exponential increase in literature. Adult mesenchymal stem cells have recently been isolated and characterized from tooth-related tissues and they might represent, in the near future, a new gold standard in the regeneration of all oral tissues. The aim of our review is to provide an overview on the topic reporting the current knowledge for each class of dental stem cells and to identify their potential clinical applications as therapeutic tool in various branches of dentistry.

  3. Tissue Engineering Using Transfected Growth-Factor Genes

    NASA Technical Reports Server (NTRS)

    Madry, Henning; Langer, Robert S.; Freed, Lisa E.; Trippel, Stephen; Vunjak-Novakovic, Gordana

    2005-01-01

    A method of growing bioengineered tissues includes, as a major component, the use of mammalian cells that have been transfected with genes for secretion of regulator and growth-factor substances. In a typical application, one either seeds the cells onto an artificial matrix made of a synthetic or natural biocompatible material, or else one cultures the cells until they secrete a desired amount of an extracellular matrix. If such a bioengineered tissue construct is to be used for surgical replacement of injured tissue, then the cells should preferably be the patient s own cells or, if not, at least cells matched to the patient s cells according to a human-leucocyteantigen (HLA) test. The bioengineered tissue construct is typically implanted in the patient's injured natural tissue, wherein the growth-factor genes enhance metabolic functions that promote the in vitro development of functional tissue constructs and their integration with native tissues. If the matrix is biodegradable, then one of the results of metabolism could be absorption of the matrix and replacement of the matrix with tissue formed at least partly by the transfected cells. The method was developed for articular chondrocytes but can (at least in principle) be extended to a variety of cell types and biocompatible matrix materials, including ones that have been exploited in prior tissue-engineering methods. Examples of cell types include chondrocytes, hepatocytes, islet cells, nerve cells, muscle cells, other organ cells, bone- and cartilage-forming cells, epithelial and endothelial cells, connective- tissue stem cells, mesodermal stem cells, and cells of the liver and the pancreas. Cells can be obtained from cell-line cultures, biopsies, and tissue banks. Genes, molecules, or nucleic acids that secrete factors that influence the growth of cells, the production of extracellular matrix material, and other cell functions can be inserted in cells by any of a variety of standard transfection techniques.

  4. Micro-/nano-engineered cellular responses for soft tissue engineering and biomedical applications.

    PubMed

    Tay, Chor Yong; Irvine, Scott Alexander; Boey, Freddy Y C; Tan, Lay Poh; Venkatraman, Subbu

    2011-05-23

    The development of biomedical devices and reconstruction of functional ex vivo tissues often requires the need to fabricate biomimetic surfaces with features of sub-micrometer precision. This can be achieved with the advancements in micro-/nano-engineering techniques, allowing researchers to manipulate a plethora of cellular behaviors at the cell-biomaterial interface. Systematic studies conducted on these 2D engineered surfaces have unraveled numerous novel findings that can potentially be integrated as part of the design consideration for future 2D and 3D biomaterials and will no doubt greatly benefit tissue engineering. In this review, recent developments detailing the use of micro-/nano-engineering techniques to direct cellular orientation and function pertinent to soft tissue engineering will be highlighted. Particularly, this article aims to provide valuable insights into distinctive cell interactions and reactions to controlled surfaces, which can be exploited to understand the mechanisms of cell growth on micro-/nano-engineered interfaces, and to harness this knowledge to optimize the performance of 3D artificial soft tissue grafts and biomedical applications.

  5. Spatiotemporal Tracking of Cells in Tissue Engineered Cardiac Organoids

    PubMed Central

    Iyer, Rohin K.; Chui, Jane; Radisic, Milica

    2009-01-01

    Cardiac tissue engineering aims to create myocardial patches for repair of defective or damaged native heart muscle. The inclusion of non-myocytes in engineered cardiac tissues has been shown to improve the properties of cardiac tissue compared to tissues engineered from enriched populations of myocytes alone. While attempts to mix non-myocytes (fibroblasts, endothelial cells) with cardiomyocytes have been made, very little is understood about how the tissue properties are affected by varying the respective ratios of the three cell types and how these cells assemble into functional tissues with time. The goal of this study was to investigate the effects of modulating the ratios of the three cell types as well as to spatially and temporally track cardiac tri-cultures of cells. Primary neonatal cardiac fibroblasts and D4T endothelial cells were incubated in 5µM of CellTracker™ Green dye and CellTracker™ Red dye respectively while neonatal cardiomyocytes were labeled with 20µg/mL of DAPI. The non-myocytes were seeded either sequentially (Pre-culture) or simultaneously (Tri-culture) in Matrigel-coated microchannels and allowed to form organoids, as in our previous studies. We also varied the seeding percentage of cardiomyocytes while keeping the total cell number constant in an attempt to improve the functional properties of the organoids. Organoids were imaged on days 1 and 4. Endothelial cells were seen to aggregate into clusters when Simultaneously Tri-cultured with myocytes and fibroblasts, while Pre-cultures contained elongated cells. Functional properties of organoids were improved by increasing the seeding percentage of enriched cardiomyocytes from 40% to 80%. PMID:19235264

  6. Clinical transplantation of individualized recipient serum-adapted cornea reduces the risk of graft rejection after keratoplasty.

    PubMed

    Thanos, Solon; Gatzioufas, Zissis; Schallenberg, Maurice; König, Simone; Meyer-Rüsenberg, Hans-Werner; Busse, Holger

    2013-01-01

    Corneal diseases cause severe visual impairment that necessitates corneal transplantation and frequently repetitive procedures due to graft rejection. We tested the hypothesis that exposure of donor corneas to recipient serum-derived factors during eye banking triggers a preoperative adaptation that is beneficial for postoperative tolerance. Donor corneas were incubated in a medium containing human serum (HS) obtained in each case from the prospective graft recipient in order to individually expose the donor cornea to the recipient's serum. All recipient serum-adapted corneas (RSACs) fulfilled the clinical criteria required by the national law and were transplanted successfully. The postoperative ophthalmological examination extended up to 8 years. All RSACs were tolerated by their recipients and did not cause postoperative complications and no rejection. Proteomic analysis of corneas cultivated in culture medium containing either fetal calf serum (FCS) that is routinely used for cornea banking or HS revealed different patterns of proteins. HS-cultured corneas showed a greater proteomic similarity with native human corneas than did the FCS-cultured corneas, indicating a differential nutrification of the cultured corneal tissue by HS-derived factors. The clinical results show for the first time that postoperative complications such as tissue intolerance and graft rejection might be managed if the corneal tissue is individually adapted to the recipient's serum trophic factors. This new donor tissue treatment procedure offers incontrovertible advantages and could be adapted for low-risk eyes as well as other transplantable tissues.

  7. Preliminary results of non-contact THz imaging of cornea

    NASA Astrophysics Data System (ADS)

    Sung, Shijun; Garritano, James; Bajwa, Neha; Deng, Sophie; Hubschman, Jean-Pierre; Grundfest, Warren S.; Taylor, Zachary D.

    2015-03-01

    This paper presents a novel THz optical design that allows the acquisition of THz reflectivity maps of in vivo cornea without the need for a field flattening window and preliminary imaging results of in vivo rabbit cornea. The system's intended use is to sense small changes in corneal tissue water content (CTWC) that can be precursors for a host of diseases and pathologies. Unique beam optics allows the scanning of a curved surface at normal incidence while keeping the source detector and target stationary. Basic system design principles are discussed and image sets of spherical calibration targets and corneal phantom models are presented. The presented design will enable, for the first time, non-contact THz imaging of animal and human cornea.

  8. Nanoceramics on osteoblast proliferation and differentiation in bone tissue engineering.

    PubMed

    S, Sai Nievethitha; N, Subhapradha; D, Saravanan; N, Selvamurugan; Tsai, Wei-Bor; N, Srinivasan; R, Murugesan; A, Moorthi

    2017-05-01

    Bone, a highly dynamic connective tissue, consist of a bioorganic phase comprising osteogenic cells and proteins which lies over an inorganic phase predominantly made of CaPO4 (biological apatite). Injury to bone can be due to mechanical, metabolic or inflammatory agents also owing pathological conditions like fractures, osteomyelitis, osteolysis or cysts may arise in enameloid, chondroid, cementum, or chondroid bone which forms the intermediate tissues of the body. Bone tissue engineering (BTE) applies bioactive scaffolds, host cells and osteogenic signals for restoring damaged or diseased tissues. Various bioceramics used in BTE can be bioactive (like glass ceramics and hydroxyapatite bioactive glass), bioresorbable (like tricalcium phosphates) or bioinert (like zirconia and alumina). Limiting the size of these materials to nano-scale has resulted in a higher surface area to volume ratio thereby improving multi-functionality, solubility, surface catalytic activity, high heat and electrical conductivity. Nanoceramics have been found to induce osteoconduction, osteointegration, osteogenesis and osteoinduction. The present review aims at summarizing the interactions of nanoceramics and osteoblast/stem cells for promoting the proliferation and differentiation of the osteoblast cells by nanoceramics as superior bone substitutes in bone tissue engineering applications.

  9. Optically Controlled Oscillators in an Engineered Bioelectric Tissue

    NASA Astrophysics Data System (ADS)

    McNamara, Harold M.; Zhang, Hongkang; Werley, Christopher A.; Cohen, Adam E.

    2016-07-01

    Complex electrical dynamics in excitable tissues occur throughout biology, but the roles of individual ion channels can be difficult to determine due to the complex nonlinear interactions in native tissue. Here, we ask whether we can engineer a tissue capable of basic information storage and processing, where all functional components are known and well understood. We develop a cell line with four transgenic components: two to enable collective propagation of electrical waves and two to enable optical perturbation and optical readout of membrane potential. We pattern the cell growth to define simple cellular ring oscillators that run stably for >2 h (˜104 cycles ) and that can store data encoded in the direction of electrical circulation. Using patterned optogenetic stimulation, we probe the biophysical attributes of this synthetic excitable tissue in detail, including dispersion relations, curvature-dependent wave front propagation, electrotonic coupling, and boundary effects. We then apply the biophysical characterization to develop an optically reconfigurable bioelectric oscillator. These results demonstrate the feasibility of engineering bioelectric tissues capable of complex information processing with optical input and output.

  10. Matrices and Scaffolds for DNA Delivery in Tissue Engineering

    PubMed Central

    De Laporte, Laura; Shea, Lonnie D.

    2007-01-01

    Regenerative medicine aims to create functional tissue replacements, typically through creating a controlled environment that promotes and directs the differentiation of stem or progenitor cells, either endogenous or transplanted. Scaffolds serve a central role in many strategies by providing the means to control the local environment. Gene delivery from the scaffold represents a versatile approach to manipulating the local environment for directing cell function. Research at the interface of biomaterials, gene therapy, and drug delivery has identified several design parameters for the vector and the biomaterial scaffold that must be satisfied. Progress has been made towards achieving gene delivery within a tissue engineering scaffold, though the design principles for the materials and vectors that produce efficient delivery require further development. Nevertheless, these advances in obtaining transgene expression with the scaffold have created opportunities to develop greater control of either delivery or expression and to identify the best practices for promoting tissue formation. Strategies to achieve controlled localized expression within the tissue engineering scaffold will have broad application to the regeneration of many tissues, with great promise for clinical therapies. PMID:17512630

  11. Practical aspects of cardiac tissue engineering with electrical stimulation.

    PubMed

    Cannizzaro, Christopher; Tandon, Nina; Figallo, Elisa; Park, Hyoungshin; Gerecht, Sharon; Radisic, Milica; Elvassore, Nicola; Vunjak-Novakovic, Gordana

    2007-01-01

    Heart disease is a leading cause of death in western society. Despite the success of heart transplantation, a chronic shortage of donor organs, along with the associated immunological complications of this approach, demands that alternative treatments be found. One such option is to repair, rather than replace, the heart with engineered cardiac tissue. Multiple studies have shown that to attain functional tissue, assembly signaling cues must be recapitulated in vitro. In their native environment, cardiomyocytes are directed to beat in synchrony by propagation of pacing current through the tissue. Recently, we have shown that electrical stimulation directs neonatal cardiomyocytes to assemble into native-like tissue in vitro. This chapter provides detailed methods we have employed in taking this "biomimetic" approach. After an initial discussion on how electric field stimulation can influence cell behavior, we examine the practical aspects of cardiac tissue engineering with electrical stimulation, such as electrode selection and cell seeding protocols, and conclude with what we feel are the remaining challenges to be overcome.

  12. Electroactive 3D materials for cardiac tissue engineering

    NASA Astrophysics Data System (ADS)

    Gelmi, Amy; Zhang, Jiabin; Cieslar-Pobuda, Artur; Ljunngren, Monika K.; Los, Marek Jan; Rafat, Mehrdad; Jager, Edwin W. H.

    2015-04-01

    By-pass surgery and heart transplantation are traditionally used to restore the heart's functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

  13. Tissue engineering in urology: where are we going?

    PubMed

    Metwalli, Adam R; Colvert, James R; Kropp, Bradley P

    2003-04-01

    Tissue engineering in urology is a broad term used to describe the development of alternative tissue sources for diseased or dysfunctional native urologic tissue. This article reviews the recently published techniques involving synthetic and natural biodegradable matrices alone, known as "unseeded" scaffolds, and the latest data on "seeded" scaffolds, which are impregnated with cultured cells from urologic organs. Recent discoveries in reporter gene labeling of urologic tissue are discussed as a new method to identify and track the fates of these transplanted cells in vivo. This article also investigates how these bioengineering techniques are applied to synthetic and natural scaffolds, such as polyglycolic acid and porcine small intestine submucosa, to increase bladder capacity, repair urethral strictures, and replace corporal plaques in Peyronie's disease. Furthermore, recently published reports that these materials have been seeded with chondrocytes to create corporal rods for penile prostheses and stents for ureteral and urethral stricture disease are discussed. With these latest developments as a foundation, the future directions of tissue engineering in urology are presented.

  14. Tissue engineering and regenerative medicine: history, progress, and challenges.

    PubMed

    Berthiaume, François; Maguire, Timothy J; Yarmush, Martin L

    2011-01-01

    The past three decades have seen the emergence of an endeavor called tissue engineering and regenerative medicine in which scientists, engineers, and physicians apply tools from a variety of fields to construct biological substitutes that can mimic tissues for diagnostic and research purposes and can replace (or help regenerate) diseased and injured tissues. A significant portion of this effort has been translated to actual therapies, especially in the areas of skin replacement and, to a lesser extent, cartilage repair. A good amount of thoughtful work has also yielded prototypes of other tissue substitutes such as nerve conduits, blood vessels, liver, and even heart. Forward movement to clinical product, however, has been slow. Another offshoot of these efforts has been the incorporation of some new exciting technologies (e.g., microfabrication, 3D printing) that may enable future breakthroughs. In this review we highlight the modest beginnings of the field and then describe three application examples that are in various stages of development, ranging from relatively mature (skin) to ongoing proof-of-concept (cartilage) to early stage (liver). We then discuss some of the major issues that limit the development of complex tissues, some of which are fundamentals-based, whereas others stem from the needs of the end users.

  15. Silk fibroin-based scaffolds for tissue engineering

    NASA Astrophysics Data System (ADS)

    Li, Zi-Heng; Ji, Shi-Chen; Wang, Ya-Zhen; Shen, Xing-Can; Liang, Hong

    2013-09-01

    Silk fibroin (SF) from the Bombyx mori silkworm exhibits attractive potential applications as biomechanical materials, due to its unique mechanical and biological properties. This review outlines the structure and properties of SF, including of its biocompatibility and biodegradability. It highlights recent researches on the fabrication of various SF-based composites scaffolds that are promising for tissue engineering applications, and discusses synthetic methods of various SF-based composites scaffolds and valuable approaches for controlling cell behaviors to promote the tissue repair. The function of extracellular matrices and their interaction with cells are also reviewed here.

  16. Functionalized synthetic biodegradable polymer scaffolds for tissue engineering.

    PubMed

    Liu, Xiaohua; Holzwarth, Jeremy M; Ma, Peter X

    2012-07-01

    Scaffolds (artificial ECMs) play a pivotal role in the process of regenerating tissues in 3D. Biodegradable synthetic polymers are the most widely used scaffolding materials. However, synthetic polymers usually lack the biological cues found in the natural extracellular matrix. Significant efforts have been made to synthesize biodegradable polymers with functional groups that are used to couple bioactive agents. Presenting bioactive agents on scaffolding surfaces is the most efficient way to elicit desired cell/material interactions. This paper reviews recent advancements in the development of functionalized biodegradable polymer scaffolds for tissue engineering, emphasizing the syntheses of functional biodegradable polymers, and surface modification of polymeric scaffolds.

  17. Impact of decellularization on porcine myocardium as scaffold for tissue engineered heart tissue.

    PubMed

    Ye, Xiaofeng; Wang, Haozhe; Gong, Wenhui; Li, Shen; Li, Haiqing; Wang, Zhe; Zhao, Qiang

    2016-04-01

    Decellularized myocardium has been proposed to construct tissue engineered heart tissue, providing the advantage of natural extracellular architecture. Various decellularization protocols have been developed, but the impact of individual decellularization reagent in the protocol remains unclear. The aim of this study is to evaluate the structural impact of three commonly used decellularization reagents on the porcine myocardium. We decellularized porcine heart tissue with trypsin, Triton X-100 or SDS, and analyzed the morphological characteristics of the remaining tissue by SEM, AFM and two-photon LSM. We further recellularized the scaffold with rat myocardial fibroblasts and cardiomyocytes separately. According to the H&E staining and DNA quantification, SDS decellularized more efficiently in comparison to the other two reagents. Moreover, we found distinct surface microarchitecture differences among groups. The changed structure of tissue might result in varied proliferation myocardial fibroblasts and biophysical performance of the engineered heart tissue. This study demonstrated that the microstructure of decellularized porcine heart tissue vary with decellularization agents. Compared to trypsin and Triton X-100, SDS not only decellularized more efficiently but also preserved the biocompatible microstructure of ECM for recellularization.

  18. Cell-based vascularization strategies for skin tissue engineering.

    PubMed

    Hendrickx, Benoit; Vranckx, Jan J; Luttun, Aernout

    2011-02-01

    Providing a blood-vascular network to promote survival and integration of cells in thick dermal substitutes for application in full-thickness wounds is essential for the successful outcome of skin tissue engineering. Nevertheless, promoting vascularization also represents a critical bottleneck in today's skin tissue engineering practice. Several cell types have been considered and tested, mostly in preclinical studies, to increase vascularization. When the clinical situation allows delayed reconstruction of the defect, an autologous approach is preferable, whereas in acute cases allogeneic therapy is needed. In both cases, the cells should be harvested with minimal donor-site morbidity and should be available in large amounts and safe in terms of tumor formation and transmission of animal diseases. Here, we outline the different mechanisms of cell-based vascularization and subsequently elaborate in more detail on the candidate cell types and their pros and cons in terms of clinical application and regulation of the wound healing process.

  19. Fabrication and application of nanofibrous scaffolds in tissue engineering.

    PubMed

    Li, Wan-Ju; Tuan, Rocky S

    2009-03-01

    Nanofibers fabricated by electrospinning are morphological mimics of fibrous components of the native extracellular matrix, making nanofibrous scaffolds ideal for three-dimensional cell culture and tissue engineering applications. Although electrospinning is not a conventional technique in cell biology, the experimental setup may be constructed in a relatively straightforward manner, and the procedure can be carried out by individuals with limited engineering experience. Here, we detail a protocol for electrospinning of nanofibers and provide relevant specific details concerning the optimization of fiber formation (Basic Protocol 1). The protocol also includes conditions required for preparing biodegradable polymer solutions for the fabrication of nonwoven and aligned nanofibrous scaffolds suitable for various cell/tissue applications. In addition, information on effective cell loading into nanofibrous scaffolds and cellular constructs grown in a bioreactor is provided (Basic Protocol 2). Instructions for building the electrospinning apparatus are also included (see the Support Protocol).

  20. Tissue engineering of autologous heart valves: a focused update.

    PubMed

    Le Huu, Alice; Shum-Tim, Dominique

    2014-01-01

    The prevalence of valvular heart disease is expected to increase in the coming decades, with an associated rise in valve-related surgeries. Current options for valve prostheses remain limited, essentially confined to mechanical or biological valves. Neither selection provides an optimal balance between structural integrity and associated morbidity. Mechanical valves offer exceptional durability coupled with a considerable risk of thrombogenesis. Conversely, a biological prosthesis affords freedom from anticoagulation, but with a truncated valve lifespan. Tissue-engineered heart valves have been touted as a solution to this dilemma, by offering an immunopriviledged prosthesis combined with resistance from degeneration and the potential to grow. Although the reality of commercially available tissue-engineered heart valves remains distant, this article will highlight the cellular and clinical advancements in recent years.

  1. Towards autotrophic tissue engineering: Photosynthetic gene therapy for regeneration.

    PubMed

    Chávez, Myra Noemi; Schenck, Thilo Ludwig; Hopfner, Ursula; Centeno-Cerdas, Carolina; Somlai-Schweiger, Ian; Schwarz, Christian; Machens, Hans-Günther; Heikenwalder, Mathias; Bono, María Rosa; Allende, Miguel L; Nickelsen, Jörg; Egaña, José Tomás

    2016-01-01

    The use of artificial tissues in regenerative medicine is limited due to hypoxia. As a strategy to overcome this drawback, we have shown that photosynthetic biomaterials can produce and provide oxygen independently of blood perfusion by generating chimeric animal-plant tissues during dermal regeneration. In this work, we demonstrate the safety and efficacy of photosynthetic biomaterials in vivo after engraftment in a fully immunocompetent mouse skin defect model. Further, we show that it is also possible to genetically engineer such photosynthetic scaffolds to deliver other key molecules in addition to oxygen. As a proof-of-concept, biomaterials were loaded with gene modified microalgae expressing the angiogenic recombinant protein VEGF. Survival of the algae, growth factor delivery and regenerative potential were evaluated in vitro and in vivo. This work proposes the use of photosynthetic gene therapy in regenerative medicine and provides scientific evidence for the use of engineered microalgae as an alternative to deliver recombinant molecules for gene therapy.

  2. Patterning methods for polymers in cell and tissue engineering.

    PubMed

    Kim, Hong Nam; Kang, Do-Hyun; Kim, Min Sung; Jiao, Alex; Kim, Deok-Ho; Suh, Kahp-Yang

    2012-06-01

    Polymers provide a versatile platform for mimicking various aspects of physiological extracellular matrix properties such as chemical composition, rigidity, and topography for use in cell and tissue engineering applications. In this review, we provide a brief overview of patterning methods of various polymers with a particular focus on biocompatibility and processability. The materials highlighted here are widely used polymers including thermally curable polydimethyl siloxane, ultraviolet-curable polyurethane acrylate and polyethylene glycol, thermo-sensitive poly(N-isopropylacrylamide) and thermoplastic and conductive polymers. We also discuss how micro- and nanofabricated polymeric substrates of tunable elastic modulus can be used to engineer cell and tissue structure and function. Such synergistic effect of topography and rigidity of polymers may be able to contribute to constructing more physiologically relevant microenvironment.

  3. Genetically modified cells in regenerative medicine and tissue engineering.

    PubMed

    Sheyn, Dima; Mizrahi, Olga; Benjamin, Shimon; Gazit, Zulma; Pelled, Gadi; Gazit, Dan

    2010-06-15

    Regenerative medicine appears to take as its patron, the Titan Prometheus, whose liver was able to regenerate daily, as the field attempts to restore lost, damaged, or aging cells and tissues. The tremendous technological progress achieved during the last decade in gene transfer methods and imaging techniques, as well as recent increases in our knowledge of cell biology, have opened new horizons in the field of regenerative medicine. Genetically engineered cells are a tool for tissue engineering and regenerative medicine, albeit a tool whose development is fraught with difficulties. Gene-and-cell therapy offers solutions to severe problems faced by modern medicine, but several impediments obstruct the path of such treatments as they move from the laboratory toward the clinical setting. In this review we provide an overview of recent advances in the gene-and-cell therapy approach and discuss the main hurdles and bottlenecks of this approach on its path to clinical trials and prospective clinical practice.

  4. Functional attachment of soft tissues to bone: development, healing, and tissue engineering.

    PubMed

    Lu, Helen H; Thomopoulos, Stavros

    2013-01-01

    Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue-to-bone interface, and concludes with a summary of challenges and future directions.

  5. Nanostructured polymer scaffolds for tissue engineering and regenerative medicine.

    PubMed

    Smith, I O; Liu, X H; Smith, L A; Ma, P X

    2009-01-01

    The structural features of tissue engineering scaffolds affect cell response and must be engineered to support cell adhesion, proliferation and differentiation. The scaffold acts as an interim synthetic extracellular matrix (ECM) that cells interact with prior to forming a new tissue. In this review, bone tissue engineering is used as the primary example for the sake of brevity. We focus on nanofibrous scaffolds and the incorporation of other components including other nanofeatures into the scaffold structure