Development of anisotropic MeTro/GelMA and PVA cryogels for tendon regeneration

Abstract

Inferior healing and the peritendinous adhesions after tendon injury can cause pain, restricted mobility, and an increased risk of re-rupture. To accelerate functional tendon healing and prevent peritendinous adhesion formation, components of a tissue-engineered core-shell tendon graft have been developed, consisting of an anti-adhesive polyvinyl alcohol (PVA) cryogel as the shell and a bioactive MeTro/GelMA (MG) cryogel as the core.

PVA cryogels were fabricated using unidirectional freeze-thaw (DFT) cycles, followed by lyophilisation. The optimal mechanical properties were found after three DFT cycles, yielding a 5 wt% PVA cryogel with an ultimate tensile strength of 0.6 MPa, a Young’s modulus of 0.2 MPa, and a strain of failure of 288 %. In vitro studies showed that PVA cryogels did not support the attachment of fibroblasts or immune cells. When used as a circumferential wrap around surgically repaired rat Achilles tendons, they reduced peritendinous adhesions in 2 of 3 cases.

MG cryogels were fabricated using two DFT cycles, photocrosslinked, and lyophilised, resulting in aligned microchannels. They exhibited a Young’s modulus of 643 kPa, an ultimate tensile strength of 136 kPa and a strain at failure of 32 %. In vitro studies showed increased fibroblast attachment and proliferation. For in vivo studies, MG cryogels were surface-functionalised with tropoelastin (TE) or insulin-like growth factor (IGF-1). Following implantation into window defects created in a rat patellar tendon, the functionalised MG cryogels supported cell infiltration and collagen deposition. At 8 weeks, the repaired tendons treated with MG/TE and MG/IGF-1 achieved 97% and 83% of the failure load of the native tendon, respectively. Overall, the compartmentalised scaffold design shows promise for enhancing tendon healing and preventing adhesions, marking a significant advancement in biomaterials for clinical tendon regeneration.