Local administration of aspirin with β-tricalcium phosphate/poly-lactic-co-glycolic acid (β-TCP/PLGA) could enhance osteoporotic bone regeneration

J Bone Miner Metab. 2019 Nov;37(6):1026-1035. doi: 10.1007/s00774-019-01008-w. Epub 2019 May 10.

Abstract

Composite materials β-tricalcium phosphate (β-TCP) and poly-lactic-co-glycolic acid (PLGA) have achieved stable bone regeneration without cell transplantation in previous studies. Recent research shows that aspirin (ASP) has great potential in promoting bone regeneration. The objective of the present study was to incorporate PLGA into β-TCP combined with a lower single-dose local administration of ASP to enhance its in vivo biodegradation and bone tissue growth. After the creation of a rodent critical-sized femoral metaphyseal bone defect, PLGA -modified β-TCP (TP) was prepared by mixing sieved granules of β-TCP and PLGA (50:50, v/v) for medical use, then TP with dripped 50 µg/0.1 ml and 100 µg/0.1 ml aspirin solution was implanted into the defect of OVX rats until death at 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, biomechanics and real time RT-PCR. The results of our study show that a single-dose local administration of ASP combined with the local usage of TP can increase the healing of defects in OVX rats. Single-dose local administration of aspirin can improve the transcription of genes involved in the regulation of bone formation and vascularization in the defect area, and inhibits osteoclast activity. Furthermore, treatments with a higher single-dose local administration of ASP and TP showed a stronger effect on accelerating the local bone formation than while using a lower dose of ASP. The results from our study demonstrate that the combination of a single-dose local administration of ASP and β-TCP/PLGA had an additive effect on local bone formation in osteoporosis rats, and bone regeneration by PLGA/β-TCP/ASP occured in a dose-dependent manner.

Keywords: Aspirin; Osteoporotic bone defect; Poly-lactic-co-glycolic acid; Regeneration; β-Tricalcium phosphate.

MeSH terms

  • Animals
  • Aspirin / administration & dosage*
  • Aspirin / pharmacology
  • Aspirin / therapeutic use*
  • Biomarkers / metabolism
  • Biomechanical Phenomena
  • Bone Regeneration* / drug effects
  • Calcium Phosphates / administration & dosage*
  • Disease Models, Animal
  • Female
  • Femur / diagnostic imaging
  • Femur / drug effects
  • Neovascularization, Physiologic / drug effects
  • Osteogenesis / drug effects
  • Osteoporosis / diagnostic imaging
  • Osteoporosis / drug therapy*
  • Ovariectomy
  • Polylactic Acid-Polyglycolic Acid Copolymer / administration & dosage*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • X-Ray Microtomography

Substances

  • Biomarkers
  • Calcium Phosphates
  • RNA, Messenger
  • beta-tricalcium phosphate
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Aspirin