Biomedical Engineering Reference
In-Depth Information
22 CHAPTER 2. CARTILAGE AGINGAND PATHOLOGY
2.3.3 REPAIR RESPONSESTOCARTILAGE INJURY
Cellular responses to osteochondral defects are complex due to the involvement of cells both from the
articular cartilage and elsewhere. For cartilage microfractures and chondral defects, the dense matrix
keeps other cell types out of the repair response. Radiolabeling and other techniques have shown
chondrocyte proliferation and matrix synthesis occurring for about two weeks post-injury [
207
,
208
].
However, before the defect is filled, this anabolic activity ceases and the matrix is left unprepared for
the continued rigors of daily use, leading to eventual degeneration as described previously [
209
,
210
].
With osteochondral defects, the repair process extends greatly beyond two weeks. The sub-
chondral vasculature delivers progenitor cells that are much more swift and active than chondrocytes,
dominating the healing process. Blood from the bone forms a fibrin clot, which contains platelets
that secrete factors to recruit mesenchymal stem cells from the bone. In the two weeks following
injury, MSCs proliferate and differentiate. Repair continues beyond two weeks as differentiated cells
produce collagen type II and collagen type I. By six to eight weeks, the defect is filled [
174
,
211
,
212
].
From here on, matrix production slowly shifts from collagen type II to collagen I such that by the end
of one year the repair tissue consists of both hyaline cartilage and fibrocartilage [
207
,
210
,
211
]. Since
the fibrocartilage does not possess sufficient mechanical properties for sustained function, continued
matrix degeneration via fibrillation [
213
], GAG loss [
214
], chondrocyte death and proliferation,
and development of deep fissures are observed beyond the first year [
174
,
210
]. Repair responses
from both chondrocytes or other cells are also seen with immature cartilage where calcification has
yet to be completed and where vasculature still exists close to the articulating surface. However, it
has been shown that cartilage defects do not heal even in immature animals [
208
,
209
]. Whereas it
has been proposed that “non-critical” defects (under 3-9 mm in diameter, depending on the animal
model) can heal [
215
], the repair tissue is again fibrocartilage, which eventually degenerates, leading
to osteoarthritis.
2.3.4 COSTS OF ARTICULAR CARTILAGE INJURIES
In a retrospective cross-sectional study, the follow up costs for the first five years following arthroscopy
and treatment for 1,708 Germans between 1997 and 2001 was quantified. The treatments in-
cluded mostly debridement/cartilage shaving, with abrasion arthroplasty, chondroplasty/laser chon-
droplasty, and microfracture or subchondral drilling performed at roughly the same frequency. Au-
tologous chondrocyte implantation, osteochondral allografts, and autografts were also observed,
though much less frequently. Not included in the study were cases that were grade 4 according to
the Outerbridge classification system, osteoarthritic (Fairbanks greater than grade 3), or consisting
of bacterial infections or tumors. Cumulative costs associated with loss of productivity were found
to be almost four times that of the direct costs, with those who had prior operative history on the
knee spending roughly double [
216
]. Another source of traumatic injuries posing significant costs
is combat trauma. Based on queries to the Department of Defense Medical Metrics (M2) database
for the hospital admissions and billing data between October 2001 and January 2005 for injuries
sustained in Iraq and Afghanistan, estimates to the cost of combat-related joint injuries to approach
