Injectable citrate-based polyurethane-urea as a tug-of-war-inspired bioactive self-expansive and planar-fixing screw augmented bone-tendon healing

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.

Anti-oxidant anti-inflammatory and antibacterial tannin-crosslinked citrate-based mussel-inspired bioadhesives facilitate scarless wound healing

The revolutionary role of tissue adhesives in wound closure,tissue sealing,and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing.In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators(exemplified by sodium periodate and silver nitrate),herein,the natural polyphenolic compound tannic acid(TA)was used to achieve near instantaneous(<25s),hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant,anti-inflammatory,and antimicrobial activities(3A-TCMBAs).The resulting materials were self-healing and possessed low swelling ratios(<60%)as well as considerable mechanical strength(up to~1.0 MPa),elasticity(elongation~2700%),and adhesion(up to 40 kPa).The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability,favorable cytocompatibility and cell migration,as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli(>90%bacterial death upon near-infrared(NIR)irradiation).In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs+NIR treatment could promote wound closure and collagen deposition and improve the collagen Ⅰ/Ⅲ ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines.Further,phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation&remodeling of the extracellular matrix(ECM)in the late stage(supported by phased CD31(platelet endothelial cell adhesion molecule-1)PDGF(platelet-derived growth factor)and VEGF(vascular endothelial growth factor)expression as well as elevated matrix metalloprotein-9(MMP-9)expression on day 21),resulting in scarless wound healing.The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant,new class of bioadhesive.