Development of bioabsorbable polymeric textile scaffolds for tissue engineering applications
Caronna, Flavia
Caronna, Flavia
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Publication Date
2023-12-18
Type
Thesis
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Abstract
Critical-sized bone defects are defined as those that will not heal spontaneously within a patient’s lifetime. Tissue engineering aims to solve such problems by combining highly porous biomaterial scaffold with cells from the body and mechanobiological cues, to generate new functional tissue. Bioabsorbable polymers, such as poly(lactic acid) (PLA) and poly-4-hydroxybutyrate (P4HB), are very attractive for such applications, since they can support new tissue formation, and become replaced over time. PLA and P4HB feature a well established biocompatibility profile, suitable mechanical properties, and predictable degradation rate; furthermore, they can be processed using a wide variety of methods. However, polymers are sensitive to moisture and heat, and their properties are highly dependent on the processing conditions employed. Additionally, acidic by-products of polymer degradation can cause local inflammation and tissue necrosis. Textile technologies using natural or synthetic fibres, offer a wide range of scaffold designs and are readily scalable to large volumes of production, hence representing a promising manufacturing method of scaffold-based implants. Although bioabsorbable polymers are widely used for biomedical applications and the degradation rates of PLA based materials are well studied, the behaviour of PLA yarns or textiles is not well reported. To facilitate the design and optimization of bioabsorbable textile-based tissue engineering scaffolds, understanding the evolution of the molecular weight and mechanical properties of a degrading scaffold is necessary. Additionally, it is not clear how textile manufacturing processes impact yarn mechanical and degradation properties, which are of interest for cell scaffold interactions. In this thesis, 3D bioabsorbable PLA and P4HB spacer fabric scaffolds were fabricated by warp-knitting and their potential for tissue engineering was explored through in vitro characterization of physical, mechanical, and biological properties. In this context, PLA yarns properties were also investigated during in vitro accelerated degradation tests. The two warp-knitted spacer fabric scaffolds are proposed here as candidates for tissue engineering applications. Following this, the osteogenic potential of the manufactured PLA and P4HB warp-knitted spacer fabric scaffolds was investigated over 35 days of culture in vitro using osteogenic media, for applications in bone tissue engineering. Using MC3T3-E1 preosteoblasts, cell attachment, metabolic activity, proliferation, and differentiation on the scaffolds were investigated at different time points. It was found that the two scaffolds support cell attachment, proliferation, and differentiation, with limited calcium deposition. Observed differences in cell behaviour were linked to the physical and mechanical properties of the yarns employed for scaffold manufacturing. Finally, several strategies were investigated to optimize the properties of the manufactured PLA textile scaffold. The effect of heat setting treatments on yarn mechanical properties was investigated prior and during in vitro accelerated degradation. It was found that the heat setting process could be employed to tune scaffold properties at the yarn scale without influencing the material degradation rate. A computational model for semicrystalline polymer degradation was implemented in the commercial software Comsol Multiphysics. The degradation behaviour of the two morphologically different PLA yarns used (monofilament and multifilament yarns) was measured experimentally using gel permeation chromatography (GPC) during accelerated in vitro degradation and was compared with computational results. The simulated degradation behaviour of the yarns did not capture the experimental results, which showed different degradation behaviour for the two yarns (monofilament and multifilament yarn); this suggests that the model used is not able to capture all relevant phenomena involved in yarn degradation. The mechanical properties of a stack of PLA textile layers under monotonic and cyclic compression were also investigated, giving useful insights on practical use of the PLA warp-knitted spacer fabric textile for both biomedical and other applications. The present work shows the potential of spacer fabric scaffolds as a versatile and scalable scaffold fabrication technique, having the ability to create a microenvironment with appropriate physical, mechanical, and degradation properties for 3D tissue engineering. The research presented in this thesis contributes to further development of textile based bioabsorbable tissue engineering scaffolds.
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NUI Galway