Abstract
Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG-fibrinogen hydrogel. Once engineered to express placental-derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in vivo survival and maturation of newly formed myofibres. When the graft was implanted underneath the skin on the surface of the tibialis anterior, mature and aligned myofibres formed within several weeks as a complete and functional extra muscle. Moreover, replacing the ablated tibialis anterior with PEG-fibrinogen-embedded mesoangioblasts also resulted in an artificial muscle very similar to a normal tibialis anterior. This strategy opens the possibility for patient-specific muscle creation for a large number of pathological conditions involving muscle tissue wasting.
Highlights
Tissue engineering aims to create a microenvironment similar to the one where organogenesis took place
We looked for an innovative strategy exploiting a biomaterial able to promote myogenic cell differentiation in vivo so that angiogenesis and innervation may occur during muscle fibre formation and maturation
A photopolymerizable hydrogel based upon polyethyleneglycol (PEG) and fibrinogen (PEG-fibrinogen: PF) (Almany & Seliktar, 2005; Fuoco et al, 2012; Seliktar, 2012) was combined with vesselassociated muscle progenitors, termed mesoangioblasts (Mabs), which are able to undergo robust myogenesis in vivo and in vitro
Summary
Tissue engineering aims to create a microenvironment similar to the one where organogenesis took place. Several other recent developments, using decellularized natural scaffold to repair massive muscle injury, exploit host stem cells regenerative capabilities The latter approach has shown only partial integration with damaged muscle and limited vascularization and innervation at the interface between the artificial and the host muscle (Corona et al, 2012; Sicari et al, 2012). This method still needs optimization, especially in terms of supporting blood vessel and nerves for artificial tissue survival and function. We looked for an innovative strategy exploiting a biomaterial able to promote myogenic cell differentiation in vivo so that angiogenesis and innervation may occur during muscle fibre formation and maturation
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