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Integrated regeneration of myotendinous junction by immunoregulatory and anti-oxidative scaffold loaded with stem cells and recombinant Klotho protein

ABSTRACT: Myotendinous junction (MTJ) injury cannot be repaired efficiently due to the complex composition of two tissues with distinct biological structures and mechanical properties. Previous studies designed tissue engineering scaffolds with two or more materials to mimick the distinct mechanical properties of muscle and tendon, which was a difficult and time-consuming process. Herein, we developed an integrated SilMA-PLGA scaffold incorporated with Klotho protein and bone marrow mesenchymal stem cells (BMSCs) to regulate the pathological microenvironment and tissue-resident cells for the regeneration of MTJ. The photo-crosslinked porous silk-based hydrogel (SilMA) on the 3D-printed PLGA scaffold (SM-PA) enhanced the secretory activity of BMSCs, which ensured the biological functions of macrophages, tendon stem/progenitor cells (TSPCs) and myoblasts. Besides, the incorporation of Klotho protein endowed the SM-PA scaffold with anti-oxidative and immunomodulatory properties. In an MTJ injury model of rats, this composite hydrogel scaffold (Klo/BM@SM-PA) efficiently increased the survival of transplanted BMSCs in the early post-implantation period, and presented successful MTJ regeneration capacity as evidenced by histology and immunohistochemistry evaluation. The in vivo proteomics analysis provided additional verification that the Klo/BM@SM-PA could regulate the tissue microenvironment and promote tissue regeneration

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Wei Zhang

PROVIDER: PXD049378 | iProX | Tue Feb 13 00:00:00 GMT 2024

REPOSITORIES: iProX

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