Browsing by Subject "tissue engineering"

Now showing 1 - 7 of 7
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    Combined local delivery of tacrolimus and stem cells in hydrogel for enhancing peripheral nerve regeneration
    (Wiley, 2021-07) Saffari, Tiam M.; Chan, Katelyn; Saffari, Sara; Zuo, Kevin J.; McGovern, Renee M.; Reid, Joel M.; Borschel, Gregory H.; Shin, Alexander Y.; Medicine, School of Medicine
    The application of scaffold-based stem cell transplantation to enhance peripheral nerve regeneration has great potential. Recently, the neuroregenerative potential of tacrolimus (a U.S. Food and Drug Administration-approved immunosuppressant) has been explored. In this study, a fibrin gel-based drug delivery system for sustained and localized tacrolimus release was combined with rat adipose-derived mesenchymal stem cells (MSC) to investigate cell viability in vitro. Tacrolimus was encapsulated in poly(lactic-co-glycolic) acid (PLGA) microspheres and suspended in fibrin hydrogel, using concentrations of 0.01 and 100 ng/ml. Drug release over time was measured. MSCs were cultured in drug-released media collected at various days to mimic systemic exposure. MSCs were combined with (i) hydrogel only, (ii) empty PLGA microspheres in the hydrogel, (iii) 0.01, and (iv) 100 ng/ml of tacrolimus PLGA microspheres in the hydrogel. Stem cell presence and viability were evaluated. A sustained release of 100 ng/ml tacrolimus microspheres was observed for up to 35 days. Stem cell presence was confirmed and cell viability was observed up to 7 days, with no significant differences between groups. This study suggests that combined delivery of 100 ng/ml tacrolimus and MSCs in fibrin hydrogel does not result in cytotoxic effects and could be used to enhance peripheral nerve regeneration.
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    Comparison of Biomaterial-Dependent and -Independent Bioprinting Methods for Cardiovascular Medicine
    (Elsevier, 2017) Moldovan, Leni; Babbey, Clifford; Murphy, Michael; Moldovan, Nicanor I.; Department of Biomedical Engineering, School of Engineering and Technology
    There is an increasing need of human organs for transplantation, of alternatives to animal experimentation, and of better in vitro tissue models for drug testing. All these needs create unique opportunities for the development of novel and powerful tissue engineering methods, among which the 3D bioprinting is one of the most promising. However, after decades of incubation, ingenuous efforts, early success and much anticipation, biomaterial-dependent 3D bioprinting, although shows steady progress, is slow to deliver the expected clinical results. For this reason, alternative ‘scaffold-free’ 3D bioprinting methods are developing in parallel at an accelerated pace. In this opinion paper we discuss comparatively the two approaches, with specific examples drawn from the cardiovascular field. Moving the emphasis away from competition, we show that the two platforms have similar goals but evolve in complementary technological niches. We conclude that the biomaterial-dependent bioprinting is better suited for tasks requiring faster, larger, anatomically-true, cell-homogenous and matrix-rich constructs, while the scaffold-free biofabrication is more adequate for cell-heterogeneous, matrix-poor, complex and smaller constructs, but requiring longer preparation time.
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    Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing of Endothelial Cells Derived from Pluripotent Stem Cells
    (Elsevier, 2018-07-24) Smith, Quinton; Macklin, Bria; Chan, Xin Yi; Jones, Hannah; Trempel, Michelle; Yoder, Mervin C.; Gerecht, Sharon; Pediatrics, School of Medicine
    Summary The role of primary cilia in mechanosensation is essential in endothelial cell (EC) shear responsiveness. Here, we find that venous, capillary, and progenitor ECs respond to shear stress in vitro in a cilia-dependent manner. We then demonstrate that primary cilia assembly in human induced pluripotent stem cell (hiPSC)-derived ECs varies between different cell lines with marginal influence of differentiation protocol. hiPSC-derived ECs lacking cilia do not align to shear stress, lack stress fiber assembly, have uncoordinated migration during wound closure in vitro, and have aberrant calcium influx upon shear exposure. Transcriptional analysis reveals variation in regulatory genes involved in ciliogenesis among different hiPSC-derived ECs. Moreover, inhibition of histone deacetylase 6 (HDAC6) activity in hiPSC-ECs lacking cilia rescues cilia formation and restores mechanical sensing. Taken together, these results show the importance of primary cilia in hiPSC-EC mechano-responsiveness and its modulation through HDAC6 activity varies among hiPSC-ECs.
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    Facile Synthesis of Rapidly Degrading PEG-Based Thiol-Norbornene Hydrogels
    (American Chemical Society (ACS), 2021-02-09) Lin, Fang-Yi; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and Technology
    An alternate synthesis route was developed to prepare norbornene-functionalized poly(ethylene glycol) (PEG) from reacting multiarm PEG with carbic anhydride. The macromer, PEGNBCA, permits photo-cross-linking of thiol-norbornene hydrogels with kinetics comparable to conventional PEGNB macromer. In addition, PEGNBCA provides an additional carboxylate group for further conjugation with amine-bearing molecules. Interestingly, PEGNBCA thiol-norbornene hydrogels are highly susceptible to hydrolytic degradation through enhanced ester hydrolysis. The ester linkage is further weakened after the secondary conjugation, resulting in extremely rapid degradation of PEGNB hydrogels. More importantly, the degradation can be readily adjusted via tuning macromer compositions, with complete degradation time ranging from hours to weeks. The PEGNBCA hydrogels are also highly cytocompatible toward various cell types, providing opportunities for future applications in tissue engineering and advanced biofabrication.
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    Gene-enhanced tissue engineering for dental hard tissue regeneration: (I) dentin-pulp and periodontal regeneration
    (2006-05-15) Edwards, Paul C.; Mason, James M.
    Gene-based therapies for tissue regeneration involve delivering a specific gene to a target tissue with the goal of changing the phenotype or protein expression profile of the recipient cell; the ultimate goal being to form specific tissues required for regeneration. One of the principal advantages of this approach is that it provides for a sustained delivery of physiologic levels of the growth factor of interest. This manuscript will review the principals of gene-enhanced tissue engineering and the techniques of introducing DNA into cells. Part 2 will review recent advances in gene-based therapies for dental hard tissue regeneration, specifically as it pertains to dentin regeneration/pulp capping and periodontal regeneration.
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    Of balls, inks and cages: Hybrid biofabrication of 3D tissue analogs
    (2019) Moldovan, Nicanor I.; Moldovan, Leni; Raghunath, Michael; Biomedical Engineering, School of Engineering and Technology
    The overarching principle of three-dimensional (3D) bioprinting is the placing of cells or cell clusters in the 3D space to generate a cohesive tissue microarchitecture that comes close to in vivo characteristics. To achieve this goal, several technical solutions are available, generating considerable combinatorial bandwidth: (i) Support structures are generated first, and cells are seeded subsequently; (ii) alternatively, cells are delivered in a printing medium, so-called “bioink,” that contains them during the printing process and ensures shape fidelity of the generated structure; and (iii) a “scaffold-free” version of bioprinting, where only cells are used and the extracellular matrix is produced by the cells themselves, also recently entered a phase of accelerated development and successful applications. However, the scaffold-free approaches may still benefit from secondary incorporation of scaffolding materials, thus expanding their versatility. Reversibly, the bioink-based bioprinting could also be improved by adopting some of the principles and practices of scaffold-free biofabrication. Collectively, we anticipate that combinations of these complementary methods in a “hybrid” approach, rather than their development in separate technological niches, will largely increase their efficiency and applicability in tissue engineering.
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    The tissue diagnostic instrument
    (2009-05) Hansma, Paul; Yu, Hongmei; Schultz, David; Rodriguez, Azucena; Yurtsev, Eugene A.; Orr, Jessica; Tang, Simon; Miller, Jon; Wallace, Joseph M.; Zok, Frank; Li, Cheng; Souza, Richard; Proctor, Alexander; Brimer, Davis; Nogues-Solan, Xavier; Mellbovsky, Leonardo; Peña, M Jesus; Diez-Ferrer, Oriol; Mathews, Phillip; Randall, Connor; Kuo, Alfred; Chen, Carol; Peters, Mathilde; Kohn, David; Buckley, Jenni; Li, Xiaojuan; Pruitt, Lisa; Diez-Perez, Adolfo; Alliston, Tamara; Weaver, Valerie; Lotz, Jeffrey
    Tissuemechanical properties reflect extracellular matrix composition and organization, and as such, their changes can be a signature of disease. Examples of such diseases include intervertebral disk degeneration, cancer, atherosclerosis, osteoarthritis, osteoporosis, and tooth decay. Here we introduce the tissue diagnostic instrument (TDI), a device designed to probe the mechanical properties of normal and diseased soft and hard tissues not only in the laboratory but also in patients. The TDI can distinguish between the nucleus and the annulus of spinal disks, between young and degenerated cartilage, and between normal and cancerous mammary glands. It can quantify the elastic modulus and hardness of the wet dentin left in a cavity after excavation. It can perform an indentation test of bone tissue, quantifying the indentation depth increase and other mechanical parameters. With local anesthesia and disposable, sterile, probe assemblies, there has been neither pain nor complications in tests on patients. We anticipate that this unique device will facilitate research on many tissue systems in living organisms, including plants, leading to new insights into disease mechanisms and methods for their early detection.