$2 billion [217]. Without a sufficient healing response, cartilage lesions eventually degenerate to
osteoarthritis, which has much greater associated costs (in excess of $65 billion [218]) as discussed
in the next section.
Osteoarthritis is a significant problem in the US, especially with the aging population, as it poses
great costs both financially and to the patients quality of life. According to the National Health and
Nutrition Examination Survey I (NHANES I), 12.1% of the US population ages 25-74 years had
clinically defined OA of some joint [219]. With the aging population, the incidences of OA have
increased from an estimated 21 million in 1995 to nearly 27 million a decade later [220]. Broken
down by age,surveys show that in the US, over a fifth of the population over 45 and almost half over 65
develop OA [221]. OA is clinically divided into two types: primary (cases with no known cause) and
secondary (cases with identifiable cause).Known as post-traumatic OA,a majority of secondary OA is
attributable to traumatic joint injury that may have occurred years previously [222224]. Mechanical
injuries, such as those that happen during motor vehicle collisions, falls, and sports injuries, have
been implicated in the development of post-traumatic OA, though the precise pathophysiology
is not yet fully understood [225227]. Diagnosis of OA via radiographic evidence (based on the
presence of osteophytes) shows that the incidence of OA in people over the age of 45 is 27.8% in
the knees and 27.0% in the hips [220]. Symptomatic OA manifests itself as frequent pain in a joint
and radiographic evidence of OA in the same joint. It is important to note, though that the pain
may not be from the arthritis seen in the joint [220]. In addition to costs associated with treating
the articular surface, other medical comorbidities observed with OA and rheumatoid arthritis (RA)
contribute significantly to the costs of disease management [228].
While replacement cartilage for OA will address a significant clinical problem, tissue engi-
neering may be used to repair focal defects before such lesions manifest themselves into OA. The
aforementioned statistics on cartilage defects indicate that the majority are observed on the patella or
the medial femoral condyle [165,229]. The altered biomechanical environment resulting from ACL
transection has long been used as a model to induce osteoarthritis. Contributive to the degeneration
is the increased knee-abduction moment post-ACL transection [230]. Meniscus injuries have been
linked to osteoarthritis and meniscectomy has been linked to both increased prevalence and severity
of cartilage injuries [231]. An established experimental method to induce OA via meniscectomy has
shown that the patellar cartilage is adversely affected within three months in an ovine model [232].
Clinical studies of patients with meniscectomy have shown that, after twenty one years, mild ra-
diographic changes were found in 71% of the knees, while more advanced changes were seen in
48% [233].
As described above, causes of OA have been categorized into primary and secondary. Trauma
was first linked to OA by Hunter in 1743 [234]. Athletes with a history of joint injury have higher
incidence of OA than their peers [235]. ACL injury causes immediate changes in biomechanics [236
238], which may lead to OA [239,240]. For instance, the quadriceps and surrounding muscles of

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