In vivo drug release behavior and osseointegration of a doxorubicin-loaded tissue-engineered scaffold

Abstract

Bone tissue-engineered scaffolds with therapeutic effects must meet the basic requirements as to support bone healing at the defect side and to release an effect drug within the therapeutic window. Here, a rapid prototyped PCL scaffold embedded with a chitosan/nanoclay/β-tricalcium phosphate composite (DESCLAYMR) loaded with the chemotherapeutic drug doxorubicin (DESCLAYMR_DOX) is proposed as a potential multifunctional medical application for patients who undergo bone tumor resection. We showed the DESCLAYMR_DOX scaffold released DOX locally in a sustained manner in mice without significantly increasing the plasma DOX concentrations. The evaluation of osseointegration in a porcine study showed increased mineralized bone formation, unmineralized collagen fibers and significantly higher alpha Smooth Muscle Actin (α-SMA) positive areas relative to the total investigated area (TA) in defects treated solely with the DESCLAYMR scaffold than in the DESCLAYMR_DOX; and alkaline phosphatase activity, α-SMA/TA and bone formation were higher in the DESCLAYMR loaded with 100 μg per scaffold DOX (DOX_low) than with 400 μg per scaffold DOX (DOX_high). Our results suggest that the DESCLAYMR_DOX can be a viable candidate as a multifunctional medical application by delivering the chemotherapeutic agent to target remaining tumor cells and facilitate bone formation.