ABSTRACT
In the field of tissue engineering, the extracellular matrix (ECM) is considered an important element for promoting neural regeneration after spinal cord injury (SCI). Dental pulp stem cells (DPSCs), mesenchymal stem cells that originate from the neural crest, are easy to harvest and culture in vitro, express a variety of neurotrophic factors (NTFs) and deposit a large amount of ECM, making them a good choice for stem cell- or ECM-based treatment of SCI. In the present study, decellularized extracellular matrix (dECM) derived from DPSC sheets is used for the treatment of SCI. Optimization experiments reveal that incubating DPSC sheets with 1% Triton X-100 for 5 min is the best procedure for preparing DPSC dECM. It is found that DPSC dECM promotes nerve repair and regeneration after SCI and restores hindlimb motor function in rats. Mechanistically, DPSC dECM facilitates the migration and neural differentiation of neural stem cells, as well as M2 polarization of microglia, and inhibits the formation of glial scars. This study suggests that the use of DPSC dECM is a potential strategy for the treatment of SCI.
ABSTRACT
Inspired by tug-of-war, a game-changing bone-tendon fixation paradigm was developed. Specifically, injectable citrate-based bioactive self-expansive and planar-fixing screw (iCSP-Scr) consisting of reactive isocyanate (NCO) terminalized citrate-based polyurethane, proanthocyanidin modified hydroxyapatite (HAp) and water (with/without porogen) was developed and administrated in the bone-tendon gap. Instead of the "point to point" tendon fixation by traditional interface screws, along with the moisture-induced crosslinking and expansion of iCSP-Scr within the confined space of the irregularly shaped bone-tendon gap, the tendon graft was evenly squeezed into the bone tunnel in a "surface to surface" manner to realize strong and stable bone-tendon fixation via physical expansion, mechanical interlocking and chemical bonding (between -NCO and the -NH2, -SH groups on bone matrix). The optimized iCSP-Scr exhibited rapid crosslinking, moderate expansion rate, high porosity after crosslinking, as well as tunable elasticity and toughness. The iCSP-Scr possessed favorable biodegradability, biocompatibility, and osteoinductivity derived from citrate, PC and HAp, it was able to promote osteogenesis and new bone growth inward of bone tunnel thus further enhanced the bone/iCSP-Scr mechanical interlock, ultimately leading to stronger tendon fixation (pull-out force 106.15 ± 23.15 N) comparing to titanium screws (93.76 ± 17.89 N) after 14 weeks' ACL reconstruction in a rabbit model. The iCSP-Scr not only can be used as a self-expansive screw facilitating bone-tendon healing, but also can be expanded into other osteogenic application scenarios.