Gelatin-Modified Bone Substitute with Bioactive Molecules Enhance Cellular Interactions and Bone Regeneration

ACS Appl Mater Interfaces. 2016 May 4;8(17):10775-87. doi: 10.1021/acsami.6b02145. Epub 2016 Apr 25.

Abstract

In this work, we have synthesized injectable bone cement incorporated with gelatin to enhance cellular interaction. Human osteosarcoma Saos-2 cells derived bone morphogenetic proteins (BMP's) and a bisphosphonate (zoledronic acid (0.2 mM)) were also incorporated to cement. In vitro studies conducted using Saos-2 demonstrated enhanced cell proliferation on gelatin (0.2%w/v) cement. The differentiation of C2C12 mouse myoblast cells into bone forming cells showed 6-fold increase in ALP levels on gelatin cement. Polymerase chain reaction (PCR) for bone biomarkers showed osteoinductive potential of gelatin cement. We investigated efficacy for local delivery of these bioactive molecules in enhancing bone substitution qualities of bone cements by implanting in 3.5 mm critical size defect in tibial metaphysis of wistar rats. The rats were sacrificed after 12 weeks and 16 weeks post implantation. X-ray, micro-CT, histology, and histomorphometry analysis were performed to check bone healing. The cement materials slowly resorbed from the defect site leaving HAP creating porous matrix providing surface for bone formation. The materials showed high biocompatibility and initial bridging was observed in all the animals but maximum bone formation was observed in animals implanted with cement incorporated with zoledronic acid followed by cement with BMP's compared to other groups.

Keywords: biomimetic; bisphosphonates; calcium sulfate; hydroxyapatite; osteoblasts; osteoinductivity; osteopromotive.

MeSH terms

  • Animals
  • Bone Cements
  • Bone Regeneration*
  • Bone Substitutes
  • Calcium Phosphates
  • Gelatin
  • Humans
  • Mice
  • Osteogenesis
  • Rats

Substances

  • Bone Cements
  • Bone Substitutes
  • Calcium Phosphates
  • Gelatin