Biomedical Engineering Reference
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This mechanism characterizes CC-chemokines that are producing antagonists
for the receptors that will inhibit signaling pathways, following MMP processing
[ 126 ]. It appears that chemokines CCL-2, 5, 7, 8, and 13 are more efficiently and
frequently activated by MMP-1 and -3. CXC chemokines show variable response
following cleavage by MMPs. Some chemokines are resistant to MMP process-
ing (CXCL1, -2 and -3) while others are processed by multiple MMPs (CXCL5,
-12 and interleukin-8). Human CXCL8 [ 35 ] is processed by MMP-8 and -9 and
induce their activation. CXCL5 (LIX) chemokine [ 66 ] is processed by MMP 1,
2, 8, 9, and 13. This chemokine processing determines an increase of its activity
that promotes an accelerated recruitment of the inflammatory cells. CXCL12
(SDF1) chemokine is also processed by multiple MMPs (1, 2, 3, 9, 13, 14) and
its processing induces a decrease of the chemokine activity [ 42 ] . From all MMPs,
it appears that MMP-1, -3, and -9 are the most potent agents for modulating
chemokine signaling activity.
Other MMPs (disintegrins) are able to cleave CXCL16 at cell surface, allow-
ing binding to specific receptor and regulating the T-cell activity in wound repair
[ 2, 36, 111 ]. MMPs are also required to define chemotactic gradient. MMP-7
represents a key factor for regulating transepithelial neutrophils migration.
Injured epithelial cells are expressing CXCL1 that bind to heparan-sulfate gly-
cosaminoglycan chains and to syndecan-1, thus generating a chemical gradient
required for activated neutrophils. In the absence of MMP-7, neutrophils are not
migrating anymore and are sequestrated into intercellular space. MMPs and dis-
integrins ADAM's ( A Disintegrin And Metalloproteinase ) play an important role
in diapedesis [ 61 ]. ADAM-28 is expressed by lymphocytes in the peripheral
blood and is located as membrane coupled secreted enzymes [ 50 ] . It may bind
the selectin glycoprotein at lymphocyte surface thus activating P-selectin bind-
ing on endothelial cells. MMPs are able to cleave occludins from tight junctions
and VE-cadherins (vascular endothelial) from adhesion junctions, being involved
in endothelial permeability [ 96 ]. Inflammation represents a main step in wound
healing and in tissue early response to implant. Peri-implant reactivity following
biomaterial implantation into soft tissues involves the follow-up for inflammatory
reactions, necrosis, granuloma presence dystrophy or calcification reactions
around implanted tissue [ 5 ]. These reactions are induced and depend on the germ
contamination of the implanted materials. Inflammatory reaction is notable from
2 to 4 weeks, being usually moderate and limited to a very thin area around the
implant, regardless the biomaterial physical properties. Between 4 and 12 weeks
the fibrous capsule shows two separate areas: a layer of inflammatory cells with
a moderate inflammatory response more reduced than the previous interval and a
fibrous area formed by a collagen network and fibroblasts. After 26 weeks, only
a thin fibrous capsule remains, where macrophages and inflammatory cells are
missing. We can describe new formed capillaries between the fibrous capsule and
the surrounding tissues [ 72 ] .
Our group has performed various biomaterials testing in vivo by subcutaneous
rat implantation followed by analysis of peri-implant tissues in order to detect
inflammatory processes and their consequences. Following some collagenated
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