Rupture of the anterior cruciate ligament (ACL) is the most prevalent sports injury, amounting to approximately 200,000 per year in the United States alone and more than 100,000 ACL reconstructions (ACLR). The gold standard treatment utilises autologous tendon grafts with similar architectures and mechanical properties to the ACL, however, recovery is hampered by donor site morbidity, reduced strength and anterior knee pain. Decellularisation for ACLR predominantly focuses on whole tissue, although demonstrates non-specific degradation of ligament extracellular matrix (ECM) components with changes to the bulk mechanical response. Electrospun aligned fibre scaffolds with bio-resorbable polymers such as poly-ϵ-caprolactone (PCL) are popular for ligament tissue engineering (TE) as they mimic the anisotropic structure of the ACL, promoting elongated fibroblastic morphologies and neo-ligament ECM deposition. Developments in fabrication approaches have given rise to fibre crimping and the non-linear tensile response of bulk constructs which may better match biological strain transduction versus conventional straight fibres. Incorporating ACL-derived decellularised ECM (dECM) into electrospun fibre constructs is a novel TE concept which may offer ligament-specific cues for enhanced regeneration. This work aimed to develop a decellularisation protocol for the preparation of dECM from fresh porcine ACLs (FpACL) and fabrication of electrospun PCL-dECM hybrid fibre scaffolds for ACL TE. The DNA content of dECM was significantly reduced versus FpACLs, however, exhibited losses in structural ECM components such as collagen type I (COL I), confirmed with histological staining. Fibre diameter was significantly reduced with dECM, with COL I compositions reflecting the corresponding weight percentage. PCL:dECM scaffolds exhibited altered physical and chemical properties, and fibre crimp revealed a non-linear stress-strain response, although cell proliferation, morphology and ECM production was comparable versus controls. The novelty of fabricating crimped scaffolds may offer closer biomimicry of the ACL versus conventional TE constructs.
Date of Award | 6 Jan 2025 |
---|
Original language | English |
---|
Awarding Institution | - The University of Manchester
|
---|
Supervisor | Michael Mcnicholas (Supervisor), Julie Gough (Supervisor) & Jonny Blaker (Supervisor) |
---|
- Biomaterials
- Decellularisation
- Musculoskeletal
- Tissue Engineering
- Anterior Cruciate Ligament
- Electrospinning
Incorporating Decellularised Anterior Cruciate Ligament Extracellular Matrix into Electrospun Ligament Scaffolds
Williams, D. (Author). 6 Jan 2025
Student thesis: Phd