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· DOS Abstracts
In vivo drug release behavior and osseointegration of
a doxorubicin-loaded tissue-engineered scaffold
Ming Sun, Muwan Chen, Miao Wang, Jakob Hansen, Anette Anette Baatrup,
Frederik Dagnaes-Hansen, Jan Rölfing, Jonas Jensen, Helle Lysdahl, Mogens
Johannsen, Dang Le, Jørgen Kjems, Cody Bünger
Orthopaedic Research Lab , Aarhus University Hospital; Interdisciplinary Nanoscience
Center (iNANO), Aarhus University; Orthopaedic Research Lab , Aarhus University
Hospital; Department of Forensic Medicine, Aarhus University; Orthopaedic Research Lab
, Aarhus University Hospital; Department of Biomedicine, Aarhus University; Orthopaedic
Research Lab , Aarhus University Hospital; Orthopaedic Research Lab , Aarhus University
Hospital; Orthopaedic Research Lab , Aarhus University Hospital; Department of Forensic
Medicine, Aarhus University; Orthopaedic Research Lab , Aarhus University Hospital;
Interdisciplinary Nanoscience Center (iNANO), Aarhus University; Orthopaedic Research
Lab , Aarhus University Hospital
Background:
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.
Purpose / Aim of Study:
Here, a rapid prototyped PCL scaffold embedded with chi-
tosan/nanoclay/
β
-tricalcium phosphate composite (DESCLAYMR) loaded with chemo-
therapeutic drug doxorubicin (DESCLAYMR _DOX) is proposed as a potential multifunc-
tional medical application for patients who undergo bone tumor resection.
Materials and Methods:
In this study, we have set up two animal models: 1) mouse
model was used to investigate the in vivo release behavior of DOX from the DESCLAYMR
scaffold. Local release behavior in treated area was obtained using an in vivo imaging
system (IVIS) and systemic pharmacokinetics were analyzed by UHPLC- MS/MS. 2) Pig
model was employed to investigate the bone biocompatibility of the DESCLAYMR scaf-
fold loaded with or without DOX.
Findings / Results:
We showed the DESCLAYMR_DOX scaffold released DOX locally in
a sustained manner in mice without significantly increasing the plasma DOX concentra-
tions. The evaluation of osseointegration in a porcine study showed increased mineral-
ized bone formation, unmineralized collagen fibers and significantly higher alpha Smooth
Muscle Actin (
α
- SMA) positive areas relative to 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/scaffold DOX (DOX_low) than with 400 μg/scaffold DOX (DOX_
high).
Conclusions:
Our results suggest that the DESCLAYMR_DOX can be a viable candidate
as a multifunctional medical application by delivering the chemotherapeutic agent to tar-
get remaining tumor cells and facilitate bone formation.
No conflicts of interest reported
1.