Computational modeling of endogenous tissue restoration in biodegradable implants: Bridging scaffold degradation and neo-tissue adaptation.

Biodegradable polymeric scaffolds produced by electrospinning offer an innovative alternative to conventional implants made from animal or synthetic materials. By promoting endogenous tissue restoration (ETR), these scaffolds solve problems such as limited durability, calcification, and thromboembolic complications. The concept of ETR is based on the idea that a biodegradable scaffold provides temporary structural support until it is gradually replaced by the body's own tissue through natural regeneration processes. This study investigates the underlying processes following implantation by introducing a computational modeling framework for ETR. Specifically, we focused on the gradual formation of neo-tissue that leads to the functional restoration of the degraded vessel wall. Our model focuses on implementing growth and remodeling to predict the in vivo evolution of ETR as well as the long-term behavior of a biodegradable conduit implant. This is accomplished by coupling the homogenized constrained mixture theory with a plasticity framework. The combination of both allowed us to model scaffold degradation and neo-tissue formation within the porous scaffold. A global sensitivity analysis was performed to assess the influence of uncertain model inputs and their interactions on the ETR process, thereby identifying the most influential parameters to reduce subsequent calibration effort. The computational model was then calibrated using 6-months data from an animal study in which biodegradable conduits were implanted into the carotid arteries of three sheep. Through a parallel twelve-month follow-up in three additional animals, we could subsequently assess the model's predictive capabilities. This study demonstrates the efficacy of the proposed ETR modeling framework in predicting the long-term outcomes of biodegradable conduit implants. By comparing the evolution of scaffold and neo-tissue mass densities and the inner diameter of the conduit over time, the framework provides a valuable tool to accelerate implant development and demonstrates how research can be translated into practical applications.