Osteogenic magnesium incorporated into PLGA/TCP porous scaffold by 3D printing for repairing challenging bone defect

Biomaterials. 2019 Mar;197:207-219. doi: 10.1016/j.biomaterials.2019.01.013. Epub 2019 Jan 7.

Abstract

Bone defect repair is a challenging clinical problem in musculoskeletal system, especially in orthopaedic disorders such as steroid associated osteonecrosis (SAON). Magnesium (Mg) as a biodegradable metal with properly mechanical properties has been investigating for a long history. In this study, Mg powder, poly (lactide-co-glycolide) (PLGA), β-tricalcium phosphate (β-TCP) were the elements to formulate a novel porous PLGA/TCP/Mg (PTM) scaffolds using low temperature rapid prototyping (LT-RP) technology. The physical characterization of PTM scaffold and Mg ions release were analyzed in vitro. The osteogenic and angiogenic properties of PTM scaffolds, as well as the biosafety after implantation were assessed in an established SAON rabbit model. Our results showed that the PTM scaffold possessed well-designed bio-mimic structure and improved mechanical properties. Findings of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and micro-computed tomography (micro CT)-based angiography indicated that PTM scaffold could increase blood perfusion and promote new vessel ingrowth at 4 weeks after surgery, meanwhile, a plenty of newly formed vessels with well-architective structure were observed at 8 weeks. Correspondingly, at 12 weeks after surgery, micro-CT, histological and mechanical properties analysis showed that PTM could significant enhance new bone formation and strengthen newly formed bone mechanical properties. The mean bone volume in PTM group was 56.3% greater than that in PT group. Biosafety assessments from 0 to 12 weeks after implantation did not induce increase in serum Mg ions concentration, and immune response, liver and kidney function parameters were all at normal level. These findings suggested that the PTM scaffold had both osteogenic and angiogenic abilities which were synergistic effect in enhancing new bone formation and strengthen newly formed bone quality in SAON. In summary, PTM scaffolds are promising composite biomaterials for repairing challenging bone defect that would have great potential for its clinical translation.

Keywords: Angiogenesis; Biosafety; Osteogenesis; PLGA/TCP/Mg (PTM); Steroid associated osteonecrosis (SAON).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / therapeutic use
  • Calcium Phosphates / chemistry*
  • Calcium Phosphates / therapeutic use
  • Femur / blood supply
  • Femur / injuries
  • Femur / physiology
  • Magnesium / chemistry*
  • Magnesium / therapeutic use
  • Male
  • Osteogenesis*
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer / therapeutic use
  • Porosity
  • Printing, Three-Dimensional
  • Rabbits
  • Tissue Scaffolds / chemistry*

Substances

  • Biocompatible Materials
  • Calcium Phosphates
  • beta-tricalcium phosphate
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Magnesium