A non-cellular root canal filler comprises a tetrahydroisoquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate of the compound or the salt, and a dental tissue regeneration promotion kit comprises a pretreatment agent comprising a serine protease, and the non-cellular root canal filler.

Dermal fillers are provided, particularly hyaluronic acid-based dermal fillers containing additives, for example, unstable additives, the dermal fillers being provided in an anhydrous state for extended shelf life.

Matrix metalloproteases (MMPs) play many important roles in normal and pathological remodeling processes including atherothrombotic disease, inflammation, angiogenesis and cancer. This invention relates to the activation of protease-activated receptor-1 (PAR-1) by endogenous platelet MMP-1 collagenase on the surface of platelets. Exposure of platelets to fibrillar collagen converts the surface-bound pro-MMP-1 zymogen to active MMP-1, which promotes aggregation through PAR-1. MMP-1 is shown to cleave the PAR-1 extracellular domain at a novel site, which then strongly activates Rho-GTP signaling pathways, cell shape change and motility, and MAPK signaling. Blockade of MMP-PAR1 suppresses thrombogenesis under arterial flow conditions and inhibited thrombosis in animals. These studies provide a link between matrix-dependent activation of metalloproteases and platelet-G protein signaling and identify MMP-1/PAR-1 as a new target for the treatment and prevention of arterial thrombosis and other thrombotic diseases.

Oral cavity wound healing occurs in an environment that sustains ongoing physical trauma and is rich in bacteria. Patients undergoing cleft palate repair have a high degree of wound healing complications, such as oronasal fistula (ONF) formation. Following hard palate injury, ONF was created that demonstrated little change in pro-regenerative monocytes LY6C.sup.lo monocytes; however, there were increased M2 macrophages observed. Delivery of FTY720 nanofiber scaffolds following hard palate injury prevented ONF formation, allowed complete wound healing and was associated with increased LY6C.sup.lo monocytes and pro-regenerative M2 macrophages. Evaluation of interleukin gene expression revealed reduction in pro-inflammatory IL1 and IL6 and increased expression of pro-regenerative IL10 with FTY720 nanofiber delivery. The ability of FTY720 scaffolds to increase LY6C.sup.lo monocytes, increase M2 macrophages and alter the interleukin expression during hard palate mucosal healing demonstrates the ability of a FTY720-based autotherapy to improve oral cavity wound healing.

Systems and methods to eliminate or reduce the foreign body response (FBR) that occurs when a medical device is implanted into a patient. The FBR causes a chronic inflammatory response that leads to the encapsulation of a medical device by a fibrous capsule. Macrophages have been discovered to become persistent as a result of the implanted biomaterial which occurs by an up-regulation in cFLIP. This persistence of macrophages appears to be the primary driver of the FBR. Re-sensitizing macrophages to apoptosis using a small molecule inhibitor (e.g., YM155) of cFLIP will abrogate the formation of the fibrous capsule in the FBR.

Oral cavity wound healing occurs in an environment that sustains ongoing physical trauma and is rich in bacteria. Patients undergoing cleft palate repair have a high degree of wound healing complications, such as oronasal fistula (ONF) formation. Following hard palate injury, ONF was created that demonstrated little change in pro-regenerative monocytes LY6C.sup.lo monocytes; however, there were increased M2 macrophages observed. Delivery of FTY720 nanofiber scaffolds following hard palate injury prevented ONF formation, allowed complete wound healing and was associated with increased LY6C.sup.lo monocytes and pro-regenerative M2 macrophages. Evaluation of interleukin gene expression revealed reduction in pro-inflammatory IL1 and IL6 and increased expression of pro-regenerative IL10 with FTY720 nanofiber delivery. The ability of FTY720 scaffolds to increase LY6C.sup.lo monocytes, increase M2 macrophages and alter the interleukin expression during hard palate mucosal healing demonstrates the ability of a FTY720-based autotherapy to improve oral cavity wound healing.

A bone graft composition comprising a calcium phosphate putty is provided. A method of repairing a bone defect in a patient by applying the bone graft composition is also provided.