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Nanofiber matrix formulations for the delivery of Exendin-4 for tendon regeneration: In vitro and in vivo assessment

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Bioactive Materials 2023年第7期25卷 42-60页

作者： Sama Abdulmalik Jack Gallo Jonathan Nip Sara Katebifar Michael Arul amir lebaschi Lucas N.Munch Jenna M.Bartly Shilpa Choudhary Ivo Kalajzic Yeshavanth Kumar Banasavadi-Siddegowdae Syam P.Nukavarapu Sangamesh G.Kumbar Department of Orthopedic Surgery University of Connecticut HealthFarmingtonCTUSA Department of Biomedical Engineering University of ConnecticutStorrsCTUSA Department of Materials Science and Engineering University of ConnecticutStorrsCTUSA Department of Physiology and Neurobiology University of ConnecticutStorrsCTUSA Department of Immunology Center on AgingUniversity of Connecticut HealthFarmingtonCTUSA Department of Reconstructive Sciences University of Connecticut HealthFarmingtonCTUSA Surgical Neurology Branch National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMDUSA

Tendon and ligament injuries are the most common musculoskeletal injuries,which not only impact the quality of life but result in a massive economic *** interventions for tendon/ligament injuries utilize biological and/or engineered grafts to reconstruct damaged tissue,but these have *** matrices confer superior physicochemical properties over biological grafts but lack desirable bioactivity to promote tissue *** incorporating drugs can enhance bioactivity,large matrix surface areas and hydrophobicity can lead to uncontrolled burst release and/or incomplete release due to *** overcome these limitations,we evaluated the delivery of a peptide growth factor(exendin-4;Ex-4)using an enhanced nanofiber matrix in a tendon injury *** overcome drug surface binding due to matrix hydrophobicity of poly(caprolactone)(PCL)-which would be expected to enhance cell-material interactions-we blended PCL and cellulose acetate(CA)and electrospun nanofiber matrices with fiber diameters ranging from 600 to 1000 *** avoid burst release and protect the drug,we encapsulated Ex-4 in the open lumen of halloysite nanotubes(HNTs),sealed the HNT tube endings with a polymer blend,and mixed Ex-4-loaded HNTs into the polymer mixture before *** reduced burst release from~75%to~40%,but did not alter matrix morphology,fiber diameter,or tensile *** evaluated the bioactivity of the Ex-4 nanofiber formulation by culturing human mesenchymal stem cells(hMSCs)on matrix surfaces for 21 days and measuring tenogenic differentiation,compared with nanofiber matrices in basal media ***,we observed that Ex-4 nanofiber matrices accelerated the hMSC proliferation rate and elevated levels of sulfated glycosaminoglycan,tendon-related genes(Scx,Mkx,and Tnmd),and ECM-related genes(Col-Ⅰ,Col-Ⅲ,and Dcn),compared to *** then assessed the safety and efficacy of Ex-4 nanofiber matrices in a full-thickness rat Achilles tendon

关键词： Nanofiber matrix formulation Protein delivery Soft tissue regeneration Halloysite nanotubes

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