Development of bioabsorbable polymeric textile scaffolds for tissue engineering applications
Date
2023-12-18Embargo Date
2024-12-15
Author
Caronna, Flavia
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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.