Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration

Biomaterials. 2016 Oct;104:168-81. doi: 10.1016/j.biomaterials.2016.06.001. Epub 2016 Jun 29.

Abstract

The rapid and effective bone regeneration of large non-healing defects remains challenging. Bioactive proteins, such as bone morphogenetic protein (BMP)-2, are proved their osteoinductivity, but their clinical use is currently limited to collagen as biomaterial. Being able to deliver BMP-2 from any other biomaterial would broaden its clinical use. This work presents a novel means for repairing a critical size volumetric bone femoral defect in the rat by combining a osteoinductive surface coating (2D) to a polymeric scaffold (3D hollow tube) made of commercially-available PLGA. Using a polyelectrolyte film as BMP-2 carrier, we tune the amount of BMP-2 loaded in and released from the polyelectrolyte film coating over a large extent by controlling the film crosslinking level and initial concentration of BMP-2 in solution. Using microcomputed tomography and quantitative analysis of the regenerated bone growth kinetics, we show that the amount of newly formed bone and kinetics can be modulated: an effective and fast repair was obtained in 1-2 weeks in the best conditions, including complete defect bridging, formation of vascularized and mineralized bone tissue. Histological staining and high-resolution computed tomography revealed the presence of bone regeneration inside and around the tube with spatially distinct organization for trabecular-like and cortical bones. The amount of cortical bone and its thickness increased with the BMP-2 dose. In view of the recent developments in additive manufacturing techniques, this surface-coating technology may be applied in combination with various types of polymeric or metallic scaffolds to offer new perspectives of bone regeneration in personalized medicine.

Keywords: Biomedical engineering; Bone morphogenetic proteins; Functional coatings; Orthopedic materials; Tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Regeneration / drug effects*
  • Bone Regeneration / physiology
  • Delayed-Action Preparations / administration & dosage*
  • Delayed-Action Preparations / chemistry
  • Female
  • Femoral Fractures / physiopathology*
  • Femoral Fractures / therapy*
  • Fracture Healing / drug effects
  • Fracture Healing / physiology
  • Rats
  • Rats, Wistar
  • Surface Properties
  • Tissue Scaffolds*
  • Treatment Outcome

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Delayed-Action Preparations