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3D bioprinting of cartilage-mimetic implants for biological joint resurfacing
A major challenge in the field of tissue engineering and regenerative medicine is the development of effective therapies for treating large cartilage or osteochondral defects and ultimately regenerating whole osteoarthritic joints. The objective of this thesis was to 3D bioprint cell-laden biomaterials with biomimetic mechanical properties as implants for regenerating large osteochondral defects. To this end, a finite element modelling (FEM) strategy was first developed to design the 3D printed polycaprolactone (PCL) networks with user-defined mechanical properties. These PCL networks were then combined with an alginate-gelatin methacryloyl (gelMA) interpenetrating network (IPN) hydrogel to develop 3D bioprinted constructs that were both mechanically functional and supportive of mesenchymal stromal cells (MSCs) chondrogenesis. When the IPN hydrogels were reinforced with a PCL network characterized by relatively high tension-compression nonlinearity, the resulting composites possessed equilibrium and dynamic properties matching or approaching those of native articular cartilage. In addition, when a co-culture of bone marrow-stromal cells (BMSCs) and chondrocytes (CCs) was encapsulated within the IPN hydrogel, the 3D bioprinted composite provided an environment conducive to robust chondrogenesis with little evidence of hypertrophy. The next stage of this thesis explored the use of 3D bioprinting to fabricate mechanically reinforced bi-layered constructs, consisting of spatially defined hyaline and hypertrophic cartilage-like layers for osteochondral tissue engineering. To engineer phenotypically stable articular cartilage in the chondral region two different approaches were explored: 1) a co-culture of BMSCs and CCs was loaded in an alginate-gelMA IPN bioink or 2) dynamic compression was applied to constructs containing only BMSCs. While both approaches showed promise, printing a co-culture of BMSCs and CCs was found to be a particularly effective approach for engineering phenotypically stable cartilage in the chondral layer of osteochondral constructs in vitro. Finally, a novel multiple-tool 3D bioprinting strategy was developed to engineer 'off-the-shelf' bi-layered implants designed to treat large osteochondral defects in goats or to resurface the whole glenohumeral joint in rabbits. BMSCs and/or specific growth factors were incorporated into each layer of the implant to promote chondrogenesis in the chondral layer and vascularization and osteogenesis in the osseous layer. Although significant changes are required to improve the in vivo outcomes, the concept of engineering spatially complex patterns of growth factors within bioprinted implants was demonstrated. To conclude, this thesis describes a novel multiple-tool biofabrication framework for engineering biological joint resurfacing implants. By integrating FEM and bioprinting technology it was possible to design cell-laden constructs with cartilage-mimetic biomechanical properties, and to spatially direct the formation of phenotypically stable articular cartilage and hypertrophic cartilage within bi-layered osteochondral constructs. This work lays the foundation for new tissue engineering strategies that could ultimately be used to provide new regenerative treatments for joint diseases such as osteoarthritis.
Keyword(s): 3D bioprinting; tissue engineering; articular cartilage; finite element modelling; biomimetic implants; in vivo models
Publication Date:
Type: Doctoral thesis
Peer-Reviewed: Yes
Language(s): English
Institution: Trinity College Dublin
Citation(s): SCHIPANI, ROSSANA, 3D bioprinting of cartilage-mimetic implants for biological joint resurfacing, Trinity College Dublin.School of Engineering, 2020
Publisher(s): Trinity College Dublin. School of Engineering. Discipline of Mechanical & Manuf. Eng
Supervisor(s): Kelly, Daniel
First Indexed: 2020-07-24 07:29:54 Last Updated: 2020-07-24 07:29:54