PMID- 30835895
OWN - NLM
STAT- MEDLINE
DCOM- 20191220
LR  - 20191220
IS  - 1554-527X (Electronic)
IS  - 0736-0266 (Linking)
VI  - 37
IP  - 4
DP  - 2019 Apr
TI  - VEGF-loaded mineral-coated microparticles improve bone repair and are associated 
      with increased expression of epo and RUNX-2 in murine non-unions.
PG  - 821-831
LID - 10.1002/jor.24267 [doi]
AB  - A poor vascular supply of the fracture gap is a key factor for the development of 
      atrophic non-unions. Mineral-coated microparticles (MCM) represent a 
      sophisticated carrier system for the delivery of vascular endothelial growth 
      factor (VEGF). Hence, we investigated whether VEGF-loaded MCM improve bone repair 
      in non-unions. For this purpose, we analyzed binding and release kinetics of MCM 
      for VEGF in vitro. Moreover, we applied VEGF-loaded or -unloaded MCM in a murine 
      non-union model in vivo and studied the process of bone healing by means of 
      biomechanical, radiological, histomorphometric, and Western blot techniques. 
      MCM-free non-unions served as controls. The binding efficiency of MCM for VEGF 
      was 46 +/- 3% and the release profile revealed an initial minor burst release 
      followed by a sustained release over a 50-day study period, thus, mimicking the 
      physiological expression profile of VEGF during bone healing. In vivo, bone 
      defects treated with VEGF-loaded MCM exhibited a higher bending stiffness, a 
      higher fraction of bone volume/tissue volume and a larger callus area on days 14 
      and 70 when compared to the other groups. Western blot analyses on day 14 
      revealed a higher expression of VEGF, erythropoietin (EPO), and runt-related 
      transcription factor 2, but not of EPO-receptor in bone defects treated with 
      VEGF-loaded MCM. These findings demonstrate that the use of MCM for VEGF delivery 
      shows great potential due to the ability to maintain protein stability and 
      functionality in vivo. Moreover, the application of VEGF-loaded MCM represent a 
      promising strategy for the treatment of non-unions. (c) 2019 Orthopaedic Research 
      Society. Published by Wiley Periodicals, Inc. J Orthop Res.
CI  - (c) 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
FAU - Orth, Marcel
AU  - Orth M
AD  - Department of Trauma, Hand and Reconstructive Surgery, Saarland University, 
      Homburg, Germany.
AD  - Institute for Clinical and Experimental Surgery, Saarland University, Homburg, 
      Germany.
FAU - Shenar, Amira K
AU  - Shenar AK
AD  - Department of Trauma, Hand and Reconstructive Surgery, Saarland University, 
      Homburg, Germany.
AD  - Institute for Clinical and Experimental Surgery, Saarland University, Homburg, 
      Germany.
FAU - Scheuer, Claudia
AU  - Scheuer C
AD  - Institute for Clinical and Experimental Surgery, Saarland University, Homburg, 
      Germany.
FAU - Braun, Benedikt J
AU  - Braun BJ
AUID- ORCID: 0000-0001-7575-0568
AD  - Department of Trauma, Hand and Reconstructive Surgery, Saarland University, 
      Homburg, Germany.
FAU - Herath, Steven C
AU  - Herath SC
AD  - Department of Trauma, Hand and Reconstructive Surgery, Saarland University, 
      Homburg, Germany.
FAU - Holstein, Jorg H
AU  - Holstein JH
AD  - Department of Trauma, Hand and Reconstructive Surgery, Saarland University, 
      Homburg, Germany.
AD  - Institute for Clinical and Experimental Surgery, Saarland University, Homburg, 
      Germany.
FAU - Histing, Tina
AU  - Histing T
AD  - Department of Trauma, Hand and Reconstructive Surgery, Saarland University, 
      Homburg, Germany.
AD  - Institute for Clinical and Experimental Surgery, Saarland University, Homburg, 
      Germany.
FAU - Yu, Xiaohua
AU  - Yu X
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, 
      Wisconsin.
FAU - Murphy, William L
AU  - Murphy WL
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, 
      Wisconsin.
FAU - Pohlemann, Tim
AU  - Pohlemann T
AD  - Department of Trauma, Hand and Reconstructive Surgery, Saarland University, 
      Homburg, Germany.
FAU - Laschke, Matthias W
AU  - Laschke MW
AD  - Institute for Clinical and Experimental Surgery, Saarland University, Homburg, 
      Germany.
FAU - Menger, Michael D
AU  - Menger MD
AD  - Institute for Clinical and Experimental Surgery, Saarland University, Homburg, 
      Germany.
LA  - eng
GR  - AOTrauma Foundation Germany/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190328
PL  - United States
TA  - J Orthop Res
JT  - Journal of orthopaedic research : official publication of the Orthopaedic 
      Research Society
JID - 8404726
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Drug Carriers)
RN  - 0 (Runx2 protein, mouse)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
MH  - Animals
MH  - Core Binding Factor Alpha 1 Subunit/metabolism
MH  - *Drug Carriers
MH  - Drug Evaluation, Preclinical
MH  - Erythropoietin/metabolism
MH  - Fracture Healing/*drug effects
MH  - Fractures, Ununited/*drug therapy/metabolism
MH  - Mice
MH  - Vascular Endothelial Growth Factor A/*administration & dosage
OTO - NOTNLM
OT  - VEGF
OT  - bone healing
OT  - mineral coated microparticles
OT  - non-union
EDAT- 2019/03/06 06:00
MHDA- 2019/12/21 06:00
CRDT- 2019/03/06 06:00
PHST- 2018/09/19 00:00 [received]
PHST- 2019/02/12 00:00 [accepted]
PHST- 2019/03/06 06:00 [pubmed]
PHST- 2019/12/21 06:00 [medline]
PHST- 2019/03/06 06:00 [entrez]
AID - 10.1002/jor.24267 [doi]
PST - ppublish
SO  - J Orthop Res. 2019 Apr;37(4):821-831. doi: 10.1002/jor.24267. Epub 2019 Mar 28.