Table 5.

Effects of hyaluronan (hyaluronic acid) and hylans on cartilage

Effect	Reference	Experimental model/treatment/endpoints	MW-dependent
Suppressed cartilage degeneration	Shimizu et al., 1998 [18]	Rabbit ACL transection; HA (five weekly injections) or crosslinked HA (three weekly injections) 4 weeks PS; observations 9 weeks PS	Yes
	Listrat et al., 1997 [10]	Clinical study of OA patient (n = 36; 1 year); three weekly HA injections every 3 months; arthroscopic evaluation 1 year from study start	N/A
Prevented cartilage damage	Ghosh et al., 1995 [53]	Ovine meniscectomy; HA (five weekly injections) given 16 weeks PS; joint articular cartilage histologically graded 5 weeks after last injection	N/A
Prevented cartilage damage; maintained normal morphology	Schiavinato et al., 1989 [20]	Pond-Nuki canine OA model; HA given 1–7 weeks PS or 7–17 weeks PS; observations 7, 13, and 17 weeks PS	N/A
Preserved cartilage histology and smoothness	Yoshimi et al., 1994 [102]	Rabbit ACL resection; HA (various MWs) injections one week PS weekly until assessments were made (6 or 12 weeks)	Yes
	Sakakibara et al., 1994 [103]	Rabbits immobilized at the onset of HA administration; HA (various MWs) twice/week for 5 weeks; observations 1–6 weeks after immobilization	Yes
	Fu et al., 2001 [94]	Immobilization-induced cartilage degradation in rabbits; six weekly injections of HA with remobilization; assessments 1 week after the last injection	Yes
Improved superficial cartilage layer and synovial membrane morphology; reduced synovial thickness and inflammation	Frizziero et al., 1998 [104]	Clinical study of OA patients (n = 40); HA (five weekly injections); cartilage and synovial biopsies and arthroscopy performed at baseline and 6 months after first injection	N/A
Improved synovium structure and synoviocyte morphology; reduced inflammatory cells in the synovium	Pasquali Ronchetti et al., 2001 [105]	Clinical study of patients with primary and secondary OA (n = 99); HA (five weekly injections) or MP (three weekly injections); synovial biopsies 2–3 weeks pretreatment and 6 months post-treatment	N/A
Improved superficial cartilage compactness and thickness; increased chondrocyte density (HA better results than MP for most parameters); improved chondrocyte morphology	Guidolin et al., 2001 [106]	Clinical study of OA patients (n = 24); HA (five weekly injections) or MP (three weekly injections); biopsies taken 6 months from treatment initiation	N/A
Prevented cartilage damage; maintained cartilage thickness, area, and smoothness	Yoshioka et al., 1997 [19]	Rabbit ACL transection; HA given 4 weeks PS; assessed femoral condyles 9 weeks after surgery	N/A
Prevented cartilage damage; maintained cartilage thickness, area, smoothness, and surface uniformity	Shimizu et al., 1998 [95]	Rabbit ACL transection; HA given 4 weeks PS; assessed femoral condyles 21 weeks after surgery	N/A
Maintained cartilage smoothness; prevented deep fissures and cracks in the cartilage surface	Wenz et al., 2000 [101]	Severe and resect canine ACL (Pond-Nuki); HA (five weekly injections) given 3, 6, or 12 weeks PS; assessed patella and patella/knee 5 weeks after last injection	N/A
Enhanced meniscal regeneration; inhibited cartilage deterioration	Kobayashi et al., 2000 [96]	Rabbit partial meniscectomy; HA (five weekly injections) 1 week PS; assessed meniscus and tibial cartilage 6 months PS	N/A
Reduced disease severity	Marshall et al., 2000 [99]	Canine OA models; hylan G-F 20 (three weekly injections) given 2 months PS; assessed 6 months after treatment	N/A
Accelerated migration of synovial cells; enhanced migration of chondrocytes when coincubated with bFGF	Maniwa et al., 2001 [107]	Rabbit synovial cells and chondrocytes incubated with HA, bFGF, HA + bFGF	N/A

ACL, anterior cruciate ligament; bFGF, basic fibroblastic growth factor; HA, hyaluronan (hyaluronic acid); MP, methylprednisolone; MW, molecular weight; OA, osteoarthritis; PS, postsurgery.