For many applications, tissue engineering strategies are increasingly moving from an in vitro to an in situ-driven approach. This innovative strategy employs readily-available, resorbable scaffolds, designed to induce endogenous tissue regeneration directly in situ. Therein, one of the main challenges is the regeneration of functional new tissue, rather than fibrotic scar tissue, for which harnessing and directing the host immune system is paramount. In this concise review, we address the most important recent findings with respect to immunomodulatory strategies, considering both the scaffold-dependent factors (e.g. material composition, microstructure) and scaffold-independent, patient-specific factors (e.g. age, comorbidities). Moreover, we reflect on the necessity of adequate models to truly grasp a fundamental understanding of the immunological processes underlying regeneration in a clinically relevant context.
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