Viscoelastic Behavior of Fibrin Scaffolds under Static and Cyclic Loading: Toward Optimized Mechanical Stimulation in Tendon Bioreactor

Abstract

Tendon tissue engineering (TE) offers a promising approach to tackle the weak healingcapacity of tendons. In this context, bioreactors play a key role, as they enable the application of controlled mechanical stimulation on the tendon constructs. The MagneTissuebioreactor, designed for ring-shaped scaffolds, is used to mechanically stimulate fibrinbased tendon constructs, which have been seeded with tendon progenitor cells. Cyclicand static stimulation protocols of the tendon constructs are evaluated to determine theimpact of loading inputs. However, the viscoelastic properties of the fibrin scaffolds usedas a scaffold biomaterial are poorly understood, which may influence mechanical inputtransmission.This thesis aims to characterize the viscoelastic properties of fibrin ring-shaped scaffoldsand assess whether mechanical protocols in the MagneTissue bioreactor can be adaptedaccordingly. Stress relaxation and creep tests were performed for 30 minutes under staticand cyclic loading conditions, replicating the bioreactor environment. A viscoelastic modelusing a generalized Maxwell formulation with Prony series was developed from the stressrelaxation data and used to predict the creep behavior of the fibrin scaffolds. Finally,micro-CT imaging assessed scaffold geometry.The results showed that under both static and cyclic loading, fibrin rings exhibited asignificant stress relaxation, approximately 20%. The relaxation profile could be dividedinto 2 phases: a quick relaxation within the first minute and a slower phase lasting approximately 15 minutes. The Prony series model effectively described the stress relaxationbehavior but failed to predict the creep response. This highlights the challenge of predicting a general viscoelastic behavior. The experimental results showed high variability,which did not correlate with ring geometry. Instead, batch-to-batch variability suggeststhat intrinsic scaffold properties are the main source. This variability in viscoelastic behavior should be considered when analyzing fibrin-based tendon constructs.Although the fibrin scaffolds in the MagneTissue bioreactor were the main focus of thisresearch, a more general statement was identified: in order to provide physiologicallymeaningful and reliable mechanical inputs, mechanical stimulation in tendon TE must beadapted to scaffold-specific behavior.