E8002 Reduces Adhesion Formation and Improves Joint Mobility in a Rat Model of Knee Arthrofibrosis

Abstract

Knee arthrofibrosis is a common complication of knee surgery, caused by excessive scar tissue, which results in functional disability. However, no curative treatment has been established. E8002 is an anti-adhesion material that contains L-ascorbic acid, an antioxidant. We aimed to evaluate the efficacy of E8002 for the prevention of knee arthrofibrosis in a rat model, comprising injury to the surface of the femur and quadriceps muscle 1 cm proximal to the patella. Sixteen male, 8-week-old Sprague Dawley rats were studied: in the Adhesion group, haemorrhagic injury was induced to the quadriceps and bone, and in the E8002 group, an adhesion-preventing film was implanted between the quadriceps and femur after injury. Six weeks following injury, the restriction of knee flexion owing to fibrotic scarring had not worsened in the E8002 group but had worsened in the Adhesion group. The area of fibrotic scarring was smaller in the E8002 group than in the Adhesion group (p < 0.05). In addition, the numbers of fibroblasts (p < 0.05) and myofibroblasts (p < 0.01) in the fibrotic scar were lower in the E8002 group. Thus, E8002 reduces myofibroblast proliferation and fibrotic scar formation and improves the range of motion of the joint in a model of knee injury.

Establishments and Evaluations of Post‐Operative Adhesion Animal Models

“…As adhesions gradually form in the knee joint, this angle can gradually increase, up to about 8° in 6 weeks. [ 30 ]…”

“…When sampling tissue, the two injured parts that produce adhesions and their encapsulated adherent tissue are often removed together, then dehydrated, embedded, and sectioned. Some adhesions happen around bone tissue, such as spinal adhesions [ 95 ] and intra‐articular cavity adhesions, [ 30 ] so decalcification of the tissue is required. The inflammatory condition, degree of fibrosis, and area of adhesions are often observed with the help of H&E and Masson staining.…”

“…grafted PP membranes in a pericardial defect repair, which were seen to form fibrous chains of varying degrees on the visceral layer. [ 61 ] Also, the production of inflammatory cells and collagen fibers can be seen in the pathological staining images of IUA [ 28 ] (Figure 9e), spinal adhesions [ 95 ] (Figure 9f), tendon adhesions [ 74 ] (Figure 9g), and intra‐articular adhesions [ 30 ] (Figure 9h).…”

“…As adhesions gradually form in the knee joint, this angle can gradually increase, up to about 8°in 6 weeks. [30] When visualizing the adhesion site, an assessment of the adhesion fraction is required. There are many adhesion scoring criteria in the current study, which can be broadly divided into two aspects, one being assessed by comparing the manner and strength of separation of adherent tissue.…”

“…[ 26 ] This can be used to build models including abdominal adhesions, [ 27 ] uterine adhesions, [ 28 ] cardiac adhesions, [ 5 ] epidural adhesions, [ 29 ] tendon adhesions, [ 6 ] and joint adhesions. [ 30 ] On the other hand, when characterizing animal adhesion models, it is generally necessary to evaluate the animal from macrostructure to microstructure. This means from organs to tissue structures, to proteins and RNA.…”