Oxo-M and 4-PPBP induction of tenogenic differentiation of perivascular tendon stem cells

Abstract

Provided herein are compositions including oxotremorine (e.g., oxotremorine methiodide or Oxo-M) and 4-PPBP (e.g., 4-PPBP maleate). Also provided are methods of treating a connective tissue defect in a subject with oxotremorine and 4-PPBP. In addition, provided are scaffolds and methods of making same that include multiple fibers that include Oxo-M, 4-PPBP, and optionally icariin or kartogenin.

1 - 18 . (canceled) 
     
     
         19 . A composition comprising:
 a polymeric microfiber produced by 3D printing; and   a plurality of microspheres encapsulating at least one agent;   
       wherein the microspheres are distributed through the polymeric microfiber and wherein the at least one agent comprises Oxo-M, 4-PPBP, kartogenin or Icariin, or any combination thereof. 
     
     
         20 . The composition of  claim 19 , wherein the microspheres comprise at least a first group of microspheres and a second group of microspheres;
 the first group of microspheres and the second group of microspheres comprise at least one agent; and   the first group of microspheres and the second group of microspheres comprise at least one different agent.   
     
     
         21 . The composition of  claim 19 , wherein the polymeric microfiber comprises polycarprolactone (PCL). 
     
     
         22 . The composition of  claim 19 , further comprising a visualizing agent. 
     
     
         23 . The composition of  claim 22 , wherein visualization agent is detectable with near infrared imaging. 
     
     
         24 . The composition of claim of  claim 22 , wherein the visualizing agent is a quantum dot. 
     
     
         25 - 35 . (canceled)