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A Platform Technology for Concurrent 3D Printing of Decellularized Matrices and Polycaprolactone for Regeneration in Homogenous and Heterogeneous Tissues

Gruber, Stacey M. S.
http://orcid.org/0000-0002-2501-1211
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595850037389807

Abstract Details

2020, PhD, University of Cincinnati, Engineering and Applied Science: Biomedical Engineering.
3D printing can produce promising patient-specific scaffolds. However, traditional bioprinted samples are less capable of bearing loads. In contrast, thermoplastics offer superior mechanical integrity, but not bioactivity. These limitations become particularly important for structural and/or anisotropic tissues that need different properties and protein compositions distributed throughout the constructs. One pathology with these requirements is large osteochondral injury, which manifests in severe joint pain and osteoarthritis. Scaffolds for osteochondral injury must provide backbones for cartilage and bone layers that are strong enough to withstand in vivo forces. Another example is long-segment tracheal reconstruction. Tissue-engineered tracheal scaffolds must endure plural forces, allow flexibility during respiration, and provide for a cartilage phase and mucosal phase. Bearing these clinical issues in mind, this dissertation sought to design and manufacture bioinspired constructs for these two distinct applications, theorizing that they may be resolved with a singular 3D printing technology capable of producing depth- and height-dependent architectures, mechanical properties, and biological compositions. In this work, a major technological advancement was achieved when decellularized matrix (DM) was directly incorporated within polycaprolactone scaffolds via encapsulation in protective polylactic acid microspheres. Using the new technique, scaffolds were fabricated with articular cartilage derived DM and a 3D geometry designed for cartilage repair. When the scaffolds were seeded with mesenchymal stem cells and cultured in basal media, the cells self-assembled into biomimetic aggregates, deposited more collagen and glycosaminoglycans, and expressed higher levels of chondral markers than scaffolds without DM and/or scaffolds cultured in chondrogenic induction media. Subsequently, scaffolds of different geometries, base polymers, and architectures were produced. Particularly, a hybrid framework composed of polycaprolactone and alginate gel was designed and validated for use in tracheal repair. All of the constructs released protein over time, replicated mechanical properties of the native tissues, and demonstrated high cytocompatibility. Here, a bioinspired, all-in-one manufacturing technique was developed that can easily create multiphasic 3D scaffolds for the repair of various tissues. The successful fabrication and low cytotoxicity of these composite scaffolds show the potential of the proposed system as a platform technology for tissue engineering, specifically for the repair of large osteochondral injuries and long-segment tracheal defects. Based on the flexibility of the production protocol and the ability to decellularize any organ type, this base technology may present a way to comprehensively treat other damaged tissue types and lead to improved outcomes for patients requiring size-matched, mechanically sound implants across the board.
Chia-Ying Lin, Ph.D. (Committee Chair)
Greg Harris, Ph.D. (Committee Member)
Jing-Huei Lee, Ph.D. (Committee Member)
Stacey Schutte, Ph.D. (Committee Member)
Patrick Whitlock, MD (Committee Member)
108 p.
Biomedical Research
3D printing; Tissue engineering; Biofabrication; Osteochondral injury; Tracheal reconstruction; Bioinspiration

Recommended Citations

Citations

  • Gruber, S. M. S. (2020). A Platform Technology for Concurrent 3D Printing of Decellularized Matrices and Polycaprolactone for Regeneration in Homogenous and Heterogeneous Tissues [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595850037389807

    APA Style (7th edition)

  • Gruber, Stacey. A Platform Technology for Concurrent 3D Printing of Decellularized Matrices and Polycaprolactone for Regeneration in Homogenous and Heterogeneous Tissues. 2020. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595850037389807.

    MLA Style (8th edition)

  • Gruber, Stacey. "A Platform Technology for Concurrent 3D Printing of Decellularized Matrices and Polycaprolactone for Regeneration in Homogenous and Heterogeneous Tissues." Doctoral dissertation, University of Cincinnati, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595850037389807

    Chicago Manual of Style (17th edition)

ucin1595850037389807
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This open access ETD is published by University of Cincinnati and OhioLINK.