Methods for host cell homing and dental pulp regeneration

Abstract

Hydrogel-based scaffolds useful for promoting pulp cell growth and biosynthesis, regulating pulp cell migration and morphology, or both as well as methods for their production and use are provided.

1 . A hydrogel-based scaffold for dental pulp formation, said scaffold comprising a biosynthetic hydrogel of polymer and fibrinogen, wherein fibrinogen is present at a concentration sufficient for promoting pulp cell growth and biosynthesis, regulating pulp cell migration and morphology, or both. 
     
     
         2 . The hydrogel-based scaffold of  claim 1  wherein the polymer comprises polyethylene glycol. 
     
     
         3 . The hydrogel-based scaffold of  claim 1  which comprises an intact fibrinogen or a fibrinogen fragment. 
     
     
         4 . The hydrogel-based scaffold of  claim 2  further comprising 0 to 40 mg/ml PEG-diacrylate. 
     
     
         5 . The hydrogel-based scaffold of  claim 4  comprising 10 to 20 mg/ml of PEG-diacrylate to form PEG-fibrinogen monomers. 
     
     
         6 . The hydrogel-based scaffold of  claim 5  further comprising additional PEG-diacrylate from 1.7% to 3.2% w/v. 
     
     
         7 . The hydrogel-based scaffold of  claim 1  which is injectable. 
     
     
         8 . (canceled) 
     
     
         9 . The hydrogel-based scaffold of  claim 1  which solidifies in vivo. 
     
     
         10 . The hydrogel-based scaffold of  claim 1  which solidifies in vivo with non-toxic components. 
     
     
         11 . The hydrogel-based scaffold of  claim 1  wherein the fibrinogen concentration is at least 5 to 10 mg/ml. 
     
     
         12 . The hydrogel-based scaffold of  claim 1  wherein the fibrinogen concentration is at least 8 mg/ml. 
     
     
         13 . (canceled) 
     
     
         14 . The hydrogel-based scaffold of  claim 1  further comprising an antibiotic. 
     
     
         15 . The hydrogel-based scaffold of  claim 1  further comprising stem cells for tooth pulp repair and regeneration and/or dental pulp cells and/or endothelial cells. 
     
     
         16 . A method of promoting pulp cell growth and biosynthesis in a hydrogel-based scaffold, said method comprising modulating fibrinogen concentration, crosslinker content and/or PEG-diacrylate:fibrinogen ratio in the hydrogel-based scaffold. 
     
     
         17 . The method of  claim 16  wherein the fibrinogen concentration is increased to at least 5-10 mg/ml. 
     
     
         18 . The method of  claim 16  wherein the fibrinogen concentration is increased to at least 8 mg/ml. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 16  wherein additional PEG-diacrylate content is from 1.7% to 3.2% w/v. 
     
     
         21 . A method of regulating cell infiltration into, migration and morphology within a hydrogel-based scaffold, said method comprising modulating fibrinogen concentration, crosslinker content and/or PEG-diacrylate:fibrinogen ratio in the hydrogel-based scaffold. 
     
     
         22 . The method of  claim 21  wherein the fibrinogen concentration is increased to at least 5-10 mg/ml. 
     
     
         23 . The method of  claim 21  wherein the fibrinogen concentration is increased to at least  8  mg/ml. 
     
     
         24 . (canceled) 
     
     
         25 . The method of  claim 21  wherein additional PEG-diacrylate content is from 1.7% to 3.2% w/v. 
     
     
         26 . An in vitro method for differentiation and expansion of stem tells into dental pulp cells, said method comprising culturing stem cells on the hydrogel-based scaffold of  claim 1 . 
     
     
         27 . A method for promoting tooth vitality in a subject in need thereof, said method comprising injecting, implanting or molding the hydrogel-based scaffold of  claim 1  into a tooth of the subject. 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled)