Citric acid-derived in situ crosslinkable biodegradable polymers for cell delivery

Biomaterials. 2010 Dec;31(34):9092-105. doi: 10.1016/j.biomaterials.2010.08.022. Epub 2010 Aug 30.

Abstract

Herein, we report a first citric acid (CA)-derived in situ crosslinkable biodegradable polymer, poly(ethylene glycol) maleate citrate (PEGMC). The synthesis of PEGMC could be carried out via a one-pot polycondensation reaction without using organic solvents or catalysts. PEGMC could be in situ crosslinked into elastomeric PPEGMC hydrogels. The performance of hydrogels in terms of swelling, degradation, and mechanical properties were highly dependent on the molar ratio of monomers, crosslinker concentration, and crosslinking mechanism used in the synthesis process. Cyclic conditioning tests showed that PPEGMC hydrogels could be compressed up to 75% strain without permanent deformation and with negligible hysteresis. Water-soluble PEGMC demonstrated excellent cytocompatibilty in vitro. The degradation products of PPEGMC also showed minimal cytotoxicity in vitro. Animal studies in rats clearly demonstrated the excellent injectability of PEGMC and degradability of the in situ-formed PPEGMC. PPEGMC elicited minimal inflammation in the early stages post-injection and was completely degraded within 30 days in rats. In conclusion, the development of CA-derived injectable biodegradable PEGMC presents numerous opportunities for material innovation and offers excellent candidate materials for in situ tissue engineering and drug delivery applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry*
  • Cattle
  • Cell Count
  • Cell Death
  • Citric Acid / chemical synthesis
  • Citric Acid / chemistry*
  • Cross-Linking Reagents / chemistry*
  • Drug Delivery Systems*
  • Female
  • Fibroblasts / cytology
  • Foreign-Body Reaction / pathology
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry
  • Implants, Experimental
  • Macrophages / cytology
  • Magnetic Resonance Spectroscopy
  • Mechanical Phenomena
  • Mice
  • Microscopy, Electron, Scanning
  • NIH 3T3 Cells
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Serum Albumin, Bovine / metabolism
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Biocompatible Materials
  • Cross-Linking Reagents
  • Hydrogels
  • Serum Albumin, Bovine
  • Citric Acid
  • Polyethylene Glycols