PMID- 34885527
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211214
IS  - 1996-1944 (Print)
IS  - 1996-1944 (Electronic)
IS  - 1996-1944 (Linking)
VI  - 14
IP  - 23
DP  - 2021 Dec 1
TI  - The Granule Size Mediates the In Vivo Foreign Body Response and the Integration 
      Behavior of Bone Substitutes.
LID - 10.3390/ma14237372 [doi]
LID - 7372
AB  - The physicochemical properties of synthetically produced bone substitute 
      materials (BSM) have a major impact on biocompatibility. This affects bony tissue 
      integration, osteoconduction, as well as the degradation pattern and the 
      correlated inflammatory tissue responses including macrophages and multinucleated 
      giant cells (MNGCs). Thus, influencing factors such as size, special surface 
      morphologies, porosity, and interconnectivity have been the subject of extensive 
      research. In the present publication, the influence of the granule size of three 
      identically manufactured bone substitute granules based on the technology of 
      hydroxyapatite (HA)-forming calcium phosphate cements were investigated, which 
      includes the inflammatory response in the surrounding tissue and especially the 
      induction of MNGCs (as a parameter of the material degradation). For the in vivo 
      study, granules of three different size ranges (small = 0.355-0.5 mm; medium = 
      0.5-1 mm; big = 1-2 mm) were implanted in the subcutaneous connective tissue of 
      45 male BALB/c mice. At 10, 30, and 60 days post implantationem, the materials 
      were explanted and histologically processed. The defect areas were initially 
      examined histopathologically. Furthermore, pro- and anti-inflammatory macrophages 
      were quantified histomorphometrically after their immunohistochemical detection. 
      The number of MNGCs was quantified as well using a histomorphometrical approach. 
      The results showed a granule size-dependent integration behavior. The surrounding 
      granulation tissue has passivated in the groups of the two bigger granules at 60 
      days post implantationem including a fibrotic encapsulation, while a granulation 
      tissue was still present in the group of the small granules indicating an ongoing 
      cell-based degradation process. The histomorphometrical analysis showed that the 
      number of proinflammatory macrophages was significantly increased in the small 
      granules at 60 days post implantationem. Similarly, a significant increase of 
      MNGCs was detected in this group at 30 and 60 days post implantationem. Based on 
      these data, it can be concluded that the integration and/or degradation behavior 
      of synthetic bone substitutes can be influenced by granule size.
FAU - Abels, Manuel
AU  - Abels M
AD  - BerlinAnalytix GmbH, 12109 Berlin, Germany.
FAU - Alkildani, Said
AU  - Alkildani S
AD  - BerlinAnalytix GmbH, 12109 Berlin, Germany.
FAU - Prohl, Annica
AU  - Prohl A
AUID- ORCID: 0000-0001-7251-7621
AD  - BerlinAnalytix GmbH, 12109 Berlin, Germany.
AD  - Clinic and Policlinic for Dermatology and Venereology, University Medical Center 
      Rostock, 18057 Rostock, Germany.
FAU - Xiong, Xin
AU  - Xiong X
AUID- ORCID: 0000-0003-0902-7886
AD  - NMI Natural and Medical Sciences Institute, University of Tubingen, 72770 
      Reutlingen, Germany.
FAU - Krastev, Rumen
AU  - Krastev R
AUID- ORCID: 0000-0002-1890-0707
AD  - Faculty of Applied Chemistry, Reutlingen University, 72762 Reutlingen, Germany.
FAU - Korzinskas, Tadas
AU  - Korzinskas T
AD  - Bokstu Odontologijos Klinika, 92125 Klaipeda, Lithuania.
FAU - Stojanovic, Sanja
AU  - Stojanovic S
AD  - Department for Cell and Tissue Engineering, Faculty of Medicine, University of 
      Nis, 18000 Nis, Serbia.
AD  - Department of Biology and Human Genetics, Faculty of Medicine, University of Nis, 
      18000 Nis, Serbia.
FAU - Jung, Ole
AU  - Jung O
AD  - Clinic and Policlinic for Dermatology and Venereology, University Medical Center 
      Rostock, 18057 Rostock, Germany.
FAU - Najman, Stevo
AU  - Najman S
AUID- ORCID: 0000-0002-2411-9802
AD  - Department for Cell and Tissue Engineering, Faculty of Medicine, University of 
      Nis, 18000 Nis, Serbia.
AD  - Department of Biology and Human Genetics, Faculty of Medicine, University of Nis, 
      18000 Nis, Serbia.
FAU - Barbeck, Mike
AU  - Barbeck M
AUID- ORCID: 0000-0002-3001-1347
AD  - Department of Ceramic Materials, Chair of Advanced Ceramic Materials, Institute 
      for Materials Science and Technologies, Technical University of Berlin, 10623 
      Berlin, Germany.
LA  - eng
PT  - Journal Article
DEP - 20211201
PL  - Switzerland
TA  - Materials (Basel)
JT  - Materials (Basel, Switzerland)
JID - 101555929
PMC - PMC8658545
OTO - NOTNLM
OT  - bone regeneration
OT  - bone substitute
OT  - granule size
OT  - histomorphometry
OT  - in vivo
OT  - inflammation
OT  - macrophages
OT  - multinucleated giant cells (MNGCs)
COIS- The authors declare no conflict of interest.
EDAT- 2021/12/11 06:00
MHDA- 2021/12/11 06:01
PMCR- 2021/12/01
CRDT- 2021/12/10 01:07
PHST- 2021/10/22 00:00 [received]
PHST- 2021/11/28 00:00 [revised]
PHST- 2021/11/29 00:00 [accepted]
PHST- 2021/12/10 01:07 [entrez]
PHST- 2021/12/11 06:00 [pubmed]
PHST- 2021/12/11 06:01 [medline]
PHST- 2021/12/01 00:00 [pmc-release]
AID - ma14237372 [pii]
AID - materials-14-07372 [pii]
AID - 10.3390/ma14237372 [doi]
PST - epublish
SO  - Materials (Basel). 2021 Dec 1;14(23):7372. doi: 10.3390/ma14237372.