Healing of articular cartilage defects treated with a novel drug-releasing rod-type implant after microfracture surgery

J Control Release. 2008 Aug 7;129(3):187-91. doi: 10.1016/j.jconrel.2008.04.003. Epub 2008 Apr 18.

Abstract

Microfracture therapy is a widely used technique for the repair of articular cartilage defects because it can be readily performed arthroscopically. However, the regenerated cartilage after microfracture surgery clearly differs from normal articular cartilage. This suggests that the clinical outcome of patients undergoing microfracture therapy could be improved. Dehydroepiandrosterone sulfate (DHEA-S) is known to protect against articular cartilage loss. Therefore, in an effort to achieve cartilage regeneration of high efficacy, we manufactured a DHEA-S-releasing rod-type implant for implantation into the holes produced by microfracture surgery. The polymeric rod-type implant was made of biodegradable poly (D, L-lactide-co-glycolide) (PLGA) and beta-tricalcium phosphate to enable controlled release of DHEA-S. The implant was dip-coated with a dilute PLGA solution to prevent the burst release of DHEA-S. The rod-type implant was sufficiently stiff to permit implantation into the holes made by microfracture. DHEA-S was released from the implant for more than four weeks. Furthermore, eight weeks after implantation into rabbit knees, the implants dramatically enhanced cartilage regeneration compared to control. Moreover, the degradation of the implant over the eight weeks from implantation into the knee did not induce any adverse effects. Therefore, this polymeric rod-type implant does not only provide an improvement in microfracture surgery, but also has great potential as a new formulation for drug delivery.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthroplasty, Subchondral*
  • Buffers
  • Calcium Phosphates / chemistry
  • Cartilage, Articular / injuries
  • Cartilage, Articular / pathology
  • Cartilage, Articular / surgery*
  • Cartilage, Articular / ultrastructure
  • Chloroform / chemistry
  • Coloring Agents / metabolism
  • Compressive Strength
  • Dehydroepiandrosterone Sulfate / chemistry
  • Dehydroepiandrosterone Sulfate / metabolism
  • Drug Implants / chemistry
  • Drug Implants / metabolism
  • Drug Implants / pharmacology*
  • Hydrogen-Ion Concentration
  • Lactic Acid / chemistry
  • Methylene Chloride / chemistry
  • Molecular Weight
  • Phenazines / metabolism
  • Phosphates / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Powders
  • Prostheses and Implants
  • Rabbits
  • Solvents / chemistry
  • Temperature
  • Time Factors
  • Viscosity
  • Wound Healing / drug effects*

Substances

  • Buffers
  • Calcium Phosphates
  • Coloring Agents
  • Drug Implants
  • Phenazines
  • Phosphates
  • Powders
  • Solvents
  • beta-tricalcium phosphate
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Dehydroepiandrosterone Sulfate
  • Methylene Chloride
  • Chloroform
  • safranine T