A Pyk2 inhibitor incorporated into a PEGDA-gelatin hydrogel promotes osteoblast activity and mineral deposition

Sumana Posritong, Regina Flores Chavez, T.M. Gabriel Chu, Angela Bruzzaniti

Research output: Contribution to journalArticle

Abstract

Pyk2 is a non-receptor tyrosine kinase that belongs to the family of focal adhesion kinases. Studies from our laboratory and others demonstrated that mice lacking the Pyk2 gene (Ptk2B) have high bone mass, which was due to increased osteoblast activity, as well as decreased osteoclast activity. It was previously reported that a chemical inhibitor that targets both Pyk2 and its homolog FAK, led to increased bone formation in ovariectomized rats. In the current study, we developed a hydrogel containing poly(ethylene glycol) diacrylate (PEGDA) and gelatin which was curable by visible-light and was suitable for the delivery of small molecules, including a Pyk2-targeted chemical inhibitor. We characterized several critical properties of the hydrogel, including viscosity, gelation time, swelling, degradation, and drug release behavior. We found that a hydrogel composed of PEGDA1000 plus 10% gelatin (P1000:G10) exhibited Bingham fluid behavior that can resist free flowing before in situ polymerization, making it suitable for use as an injectable carrier in open wound applications. The P1000:G10 hydrogel was cytocompatible and displayed a more delayed drug release behavior than other hydrogels we tested. Importantly, the Pyk2-inhibitor-hydrogel retained its inhibitory activity against the Pyk2 tyrosine kinase, and promoted osteoblast activity and mineral deposition in vitro. Overall, our findings suggest that a Pyk2-inhibitor based hydrogel may be suitable for the treatment of craniofacial and appendicular skeletal defects and targeted bone regeneration.

Original languageEnglish (US)
Article number025015
JournalBiomedical Materials (Bristol)
Volume14
Issue number2
DOIs
StatePublished - Mar 1 2019

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Hydrogel
Osteoblasts
Gelatin
Hydrogels
Polyethylene glycols
Minerals
Bone
Protein-Tyrosine Kinases
Focal Adhesion Protein-Tyrosine Kinases
Gelation
Pharmaceutical Preparations
Swelling
poly(ethylene glycol)diacrylate
Rats
Genes
Polymerization
Viscosity
Adhesion
Degradation
Defects

Keywords

  • alkaline phosphatase
  • bone formation
  • bone regeneration
  • mineralization
  • osteoblast
  • tyrosine kinase

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Biomedical Engineering

Cite this

A Pyk2 inhibitor incorporated into a PEGDA-gelatin hydrogel promotes osteoblast activity and mineral deposition. / Posritong, Sumana; Flores Chavez, Regina; Chu, T.M. Gabriel; Bruzzaniti, Angela.

In: Biomedical Materials (Bristol), Vol. 14, No. 2, 025015, 01.03.2019.

Research output: Contribution to journalArticle

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