PMID- 17182096
OWN - NLM
STAT- MEDLINE
DCOM- 20070412
LR  - 20070126
IS  - 0142-9612 (Print)
IS  - 0142-9612 (Linking)
VI  - 28
IP  - 10
DP  - 2007 Apr
TI  - Analysis of ectopic and orthotopic bone formation in cell-based tissue-engineered 
      constructs in goats.
PG  - 1798-805
AB  - Despite decades of extensive research, the application of cell-based bone tissue 
      engineering in clinically relevant models remains challenging. To improve 
      effectiveness, a better understanding of how the technique should work is 
      crucial. In the current study, we investigated the onset time, rate, location and 
      direction of bone formation in ectopically and orthotopically implanted 
      clinically sized tissue-engineered constructs to gain insight the mechanism 
      behind it. Bone marrow stromal cells (BMSCs) were obtained from 10 goats, culture 
      expanded and cryopreserved. Porous biphasic calcium phosphate (BCP) disks of 
      17mmx6mm were per-operatively seeded with BMSCs or left empty. Both conditions 
      were implanted intramuscularly and in bilateral critical-sized iliac wing 
      defects. Fluorochromes were administered at 3, 5 and 7 weeks and samples were 
      retrieved after 9 weeks. Histology showed abundant and homogeneous bone formation 
      throughout the intramuscular BMSC samples and little bone in the controls. 
      Histomorphometry and measurements of the fluorochrome labels of the ectopical 
      BMSC samples indicated that osteogenesis started at the periphery and subsequent 
      osteoconduction filled the whole scaffold within 7 weeks. In the orthotopically 
      implanted disks, there was good integration with the surrounding bone, but 
      minimal bone in the center of the implants, in both conditions. Bone was only 
      derived from the interface with the surrounding bone, there was no early bone at 
      the surfaces in contact to soft tissue as was seen in the ectopical samples. 
      Apparently cell survival was minimal and insufficient for relevant additional 
      bone formation. However, the speed of integration with surrounding bone and 
      subsequent bone apposition on the BMSC-seeded orthotopic scaffolds were found to 
      be significantly enhanced, which may be relevant especially in challenging 
      environments.
FAU - Kruyt, Moyo C
AU  - Kruyt MC
AD  - Department of Orthopaedics, G05.228, University Medical Center Utrecht, P.O. Box 
      85500, 3508 GA Utrecht, The Netherlands. mkruyt@umcutrecht.nl
FAU - Dhert, Wouter J A
AU  - Dhert WJ
FAU - Oner, F Cumhur
AU  - Oner FC
FAU - van Blitterswijk, Clemens A
AU  - van Blitterswijk CA
FAU - Verbout, Abraham J
AU  - Verbout AJ
FAU - de Bruijn, Joost D
AU  - de Bruijn JD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061219
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Bone Substitutes)
SB  - IM
MH  - Animals
MH  - *Bone Substitutes
MH  - Cell Culture Techniques/methods
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Female
MH  - Goats
MH  - Hematopoietic Stem Cells/*cytology/*physiology
MH  - Osteoblasts/*cytology/*physiology
MH  - Osteogenesis/*physiology
MH  - Tissue Engineering/*methods
EDAT- 2006/12/22 09:00
MHDA- 2007/04/14 09:00
CRDT- 2006/12/22 09:00
PHST- 2006/10/05 00:00 [received]
PHST- 2006/11/29 00:00 [accepted]
PHST- 2006/12/22 09:00 [pubmed]
PHST- 2007/04/14 09:00 [medline]
PHST- 2006/12/22 09:00 [entrez]
AID - S0142-9612(06)01003-9 [pii]
AID - 10.1016/j.biomaterials.2006.11.038 [doi]
PST - ppublish
SO  - Biomaterials. 2007 Apr;28(10):1798-805. doi: 10.1016/j.biomaterials.2006.11.038. 
      Epub 2006 Dec 19.