In vitro tissue-engineered scaffolds toward tendon tissue repair and regeneration.

Dominguez Falcon, Noelia (2020) In vitro tissue-engineered scaffolds toward tendon tissue repair and regeneration. Doctoral thesis, University of East Anglia.

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Each year, 30 million musculoskeletal disorders are reported in the UK. It is estimated that more than half of these disorders are related to tendon tissue injuries. Moreover, it is anticipated that the number of injuries is set to increase, due to an ageing population and the prevalence of active lifestyles. As a result, there is a concern that musculoskeletal-related injuries will become an even greater burden on the healthcare system. The current treatment strategy for tendinopathies involves surgery procedures and often results in inferior tissue healing due to the slow healing mechanism from tendons. Therefore, there is a pressing need to develop effective therapies that can restore the damaged tissue to the normal functioning state.

The aim of this thesis is the generation of a novel tendon therapy in the form of a 3D printed synthetic tendon scaffold. These 3D scaffolds are developed with aligned structures and mechanical properties similar to native tendon tissue. The scaffolds were combined with cultured Adipose-Derived Stem Cells (ADSCs) in serum-free conditions in order to study their alignment, creating a relevant platform for the study of tendon regeneration and repair.

Herein, novel serum-free in vitro culture systems were developed for the differentiation of ADSCs toward a tendon-like phenotype, using the tenogenic Growth Factors (GFs) Bone Morphogenetic Protein 12 (BMP-12) and Transforming Growth Factor-β1 (TGF-β1). The ADSCs response was characterised by Real Time quantitative Polymerase Chain Reaction (RT-qPCR), Immunocytochemistry (ICC), and Western Blotting (WB).

The scaffold was designed with adjustable mechanical properties and compared to rat tendon models. For this purpose, a library of adjustable photopolymerisable resins was created and characterised by Thermogravimetric Analysis, Differential Scanning Calorimetry, Fourier-Transform Infrared Spectroscopy (FT-IR) and uniaxial cyclic loading. A suitable material selected from this library was then used for the 3D printing of high-resolution aligned scaffolds. The alignment of ADSCs was investigated with Live/Dead fluorescent staining in serum-free conditions.

Taken together, the combination of the mentioned approaches provided a candidate tendon tissue- engineered scaffold. It is anticipated that this scaffold could be suitable as an implant or as a platform for the study of tendon pathologies and future therapies for tendon regeneration and repair.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Chris White
Date Deposited: 13 Apr 2021 15:21
Last Modified: 13 Apr 2021 15:21

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