Skeletal muscle tissue engineering(SMTE)has recently emerged to address major clinical challenges such as volumetric muscle loss(VML).Here,we report a rotary wet-spinning(RoWS)biofabrication technique for producing hu...Skeletal muscle tissue engineering(SMTE)has recently emerged to address major clinical challenges such as volumetric muscle loss(VML).Here,we report a rotary wet-spinning(RoWS)biofabrication technique for producing human myo-substitutes with biomimetic architectures and functions.Here,we demonstrate how the proposed technique may be used to establish a welltailored,anisotropic microenvironment that promotes myogenic differentiation of human skeletal muscle–derived pericytes(hPeri).Using high-resolutionmass spectrometry–based proteomics with the integration of literature-derived signaling networks,we uncovered that(i)a 3D biomimetic matrix environment(PEG-fibrinogen)confers a less mitogenic microenvironment compared to standard 2D cultures,favoring the formation of contractile-competent bundles of pericyte-derived myotubes in an anchoring-independent 3D state and(ii)the RoWS method promotes an upregulation of muscle matrix structural protein besides increasing contractile machinery proteins with respect to 3D bulk cultures.Finally,in vivo investigations demonstrate that the 3D-biofabricated myo-substitute is fully compatible with the host ablated muscular tissue,exhibiting myo-substitute engraftment andmuscle regeneration in a mousemodel of VML.Overall,the results show that RoWS offers a superior capability for controlling themyogenic differentiation process on a macroscale and,with future refining,may have the potential to be translated into clinical practice.展开更多
基金supported by AFM-Telethon(23551)Fondazione Telethon(TMPGMFU22TT)+2 种基金Muscular Dystrophy Association(MDA 968551)National Science Centre Poland(NCN)within SONATA BIS 12(project no.2022/46/E/ST8/00284)Ministero dell’Istruzione,dell’Universita e della Ricerca(PRIN funding scheme no.201742SBXA_004 and 2022F37JRF).
文摘Skeletal muscle tissue engineering(SMTE)has recently emerged to address major clinical challenges such as volumetric muscle loss(VML).Here,we report a rotary wet-spinning(RoWS)biofabrication technique for producing human myo-substitutes with biomimetic architectures and functions.Here,we demonstrate how the proposed technique may be used to establish a welltailored,anisotropic microenvironment that promotes myogenic differentiation of human skeletal muscle–derived pericytes(hPeri).Using high-resolutionmass spectrometry–based proteomics with the integration of literature-derived signaling networks,we uncovered that(i)a 3D biomimetic matrix environment(PEG-fibrinogen)confers a less mitogenic microenvironment compared to standard 2D cultures,favoring the formation of contractile-competent bundles of pericyte-derived myotubes in an anchoring-independent 3D state and(ii)the RoWS method promotes an upregulation of muscle matrix structural protein besides increasing contractile machinery proteins with respect to 3D bulk cultures.Finally,in vivo investigations demonstrate that the 3D-biofabricated myo-substitute is fully compatible with the host ablated muscular tissue,exhibiting myo-substitute engraftment andmuscle regeneration in a mousemodel of VML.Overall,the results show that RoWS offers a superior capability for controlling themyogenic differentiation process on a macroscale and,with future refining,may have the potential to be translated into clinical practice.
