Mediating bone regeneration by means of drug eluting implants: From passive to smart strategies.

In addition to excellent biocompatibility and mechanical performance, the new generation of bone and craniofacial implants are expected to proactively contribute to the regeneration process and dynamically interact with the host tissue. To this end, integration and sustained delivery of therapeutic agents has become a rapidly expanding area. The incorporated active molecules can offer supplementary features including promoting oteoconduction and angiogenesis, impeding bacterial infection and modulating host body reaction. Major limitations of the current practices consist of low drug stability overtime, poor control of release profile and kinetics as well as complexity of finding clinically appropriate drug dosage. In consideration of the multifaceted cascade of bone regeneration process, this research is moving towards dual/multiple drug delivery, where precise control on simultaneous or sequential delivery, considering the possible synergetic interaction of the incorporated bioactive factors is of utmost importance. Herein, recent advancements in fabrication of synthetic load bearing implants equipped with various drug delivery systems are reviewed. Smart drug delivery solutions, newly developed to provide higher tempo-spatial control on the delivery of the pharmaceutical agents for targeted and stimuli responsive delivery are highlighted. The future trend of implants with bone drug delivery mechanisms and the most common challenges hindering commercialization and the bench to bedside progress of the developed technologies are covered.