Injectable thermosensitive alginate/β-tricalcium phosphate/aspirin hydrogels for bone augmentation

J Biomed Mater Res B Appl Biomater. 2018 Jul;106(5):1739-1751. doi: 10.1002/jbm.b.33982. Epub 2017 Sep 9.

Abstract

In this study, an injectable and thermo-sensitive alginate/β-tricalcium phosphate hydrogel (TSAH/β-TCP) was prepared for aspirin release to a bone defect. Aspirin was dissolved into a mixture of poly(N-isopropylacrylamide) (PNIPAAm), an aminated alginate-g-PNIPAAm co-polymer, and β-TCP powders. Scanning electron microscopy showed that TSAH/β-TCP had an interconnected porous microstructure with a porosity of 86.78%. The cross-linked hydrogel released approximately 40% of the aspirin in the first 3 days and then slowly released the remainder. At a low concentration (≤100 μg/mL), aspirin did not promote cell proliferation, but enhanced the alkaline phosphatase activity, and osteocalcin (OCN) and collagen I expression of human bone marrow-derived mesenchymal stem cells. The TSAH/β-TCP/aspirin hydrogel was injected into the periosteum of the rat cranial bone, and its in vivo bone-forming ability was evaluated at 12 weeks. A bone morphogenetic protein 2 (BMP-2)-loaded TSAH/β-TCP hydrogel was injected as a control. Micro-computed tomography showed that the percentage of mineralized tissue in the TSAH/β-TCP/BMP-2 and TSAH/β-TCP/aspirin groups were similar and significantly higher than that in the TSAH/β-TCP group. Immunohistochemical staining showed considerable expression of OCN, especially in the TSAH/β-TCP/BMP-2 and TSAH/β-TCP/aspirin groups. These results suggest that the injectable TSAH/β-TCP/aspirin hydrogel has great potential for bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1739-1751, 2018.

Keywords: aspirin; bone regeneration; injectable hydrogel; β-TCP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / chemistry
  • Acrylic Resins / pharmacokinetics
  • Alginates* / chemistry
  • Alginates* / pharmacokinetics
  • Alginates* / pharmacology
  • Animals
  • Aspirin* / chemistry
  • Aspirin* / pharmacokinetics
  • Aspirin* / pharmacology
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Morphogenetic Protein 2 / pharmacokinetics
  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone Regeneration / drug effects*
  • Calcium Phosphates* / chemistry
  • Calcium Phosphates* / pharmacokinetics
  • Calcium Phosphates* / pharmacology
  • Humans
  • Hydrogels / chemistry
  • Hydrogels / pharmacokinetics
  • Hydrogels / pharmacology
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Skull* / injuries
  • Skull* / metabolism
  • Skull* / pathology
  • X-Ray Microtomography

Substances

  • Acrylic Resins
  • Alginates
  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Calcium Phosphates
  • Hydrogels
  • beta-tricalcium phosphate
  • poly-N-isopropylacrylamide
  • Aspirin