Effectiveness of collagen and fibrin sealant in repairing articular cartilage damage in rabbits

Abstract

BACKGROUND: Articular cartilage is primarily composed of collagen. Using collagen as a scaffold material, combined with autologous bone marrow mesenchymal stem cells for in situ repair, has become a new method for treating articular cartilage damage. OBJECTIVE: To evaluate the effectiveness of collagen combined with fibrin sealant in repairing articular cartilage defects in rabbits. METHODS: Forty-eight New Zealand rabbits were used. Full-thickness cartilage defects of 4.5 mm in diameter and 3 mm in depth were created on the trochlear surface of the medial femoral condyle of the left hind limbs. The rabbits were randomly divided into four groups: microfracture group (n=12) underwent microfracture surgery. Collagen group (n=12) underwent microfracture surgery followed by injection of domestically produced collagen into the cartilage defect. CartiRegen group (n=12) underwent microfracture surgery followed by injection of a mixture of imported collagen and fibrin sealant into the cartilage defect. Experimental group (n=12) underwent microfracture surgery followed by injection of a mixture of domestically produced collagen and fibrin sealant into the cartilage defect. At 12 and 24 weeks post-surgery, knee joint MRI examinations were performed, and the knee joint cartilage repair tissue was subjected to hematoxylin-eosin, toluidine blue, safranin O-fast green staining, type II collagen immunohistochemical staining, ICRS scoring, and Mankin scoring. The compression modulus and hardness of the repaired cartilage were measured at 24 weeks. RESULTS AND CONCLUSION: MRI examination showed that at 24 weeks, the microfracture group had almost complete filling of the cartilage defect, but poor integration with surrounding normal cartilage; the collagen group had almost complete filling and basically complete integration with slight differences; the CartiRegen and experimental groups had complete filling and no obvious differences in integration and surface with surrounding healthy cartilage. Histological staining showed that the microfracture group had light and uneven staining with poor cartilage morphology; the collagen group had relatively uniform staining, smooth repair surface, basically integrated with surrounding normal cartilage, but with fissures; the CartiRegen and experimental groups had uniform staining, smooth surface, dense tissue, good integration with surrounding tissue, and good filling. The ICRS and Mankin scores at 24 weeks were lower in the CartiRegen and experimental groups than in the microfracture and collagen groups (P < 0.05). The hardness of the repaired cartilage at 24 weeks was greater in the collagen, CartiRegen, and experimental groups than in the microfracture group (P < 0.05). These results indicate that collagen combined with fibrin sealant and microfracture has good repair effects on cartilage damage.

1. Introduction

Osteoarthritis, also known as degenerative arthritis or proliferative arthritis [1], is a common chronic disabling disease that seriously affects the health and mobility of middle-aged and elderly people [2-3]. One of the main causes of osteoarthritis is articular cartilage damage. Due to the special physiological structure of articular cartilage, which lacks blood vessels and nerves [4], once damaged, it is almost impossible to self-repair. Therefore, the repair and regeneration of articular cartilage damage has always been a scientific and clinical challenge [5-6].

For articular cartilage damage, existing clinical treatments include microfracture, cartilage transplantation (autologous osteochondral transplantation and allogeneic osteochondral transplantation), and chondrocyte transplantation [7-8]. Microfracture involves drilling holes in the bone surface at the site of cartilage damage to allow bone marrow to flow out, forming a clot-like tissue on the damaged bone surface to promote cartilage repair. The newly formed cartilage is mostly fibrous cartilage [9-10]. This method is only suitable for patients with cartilage defects smaller than 2 cm2 [11-12], and the repair effect is highly correlated with the patient's age and body weight [13]. Microfracture has good short-term (2 years) repair effects, but long-term efficacy is poor because the repaired cartilage is mostly fibrocartilage with poor mechanical properties and is prone to secondary wear [13]. Cartilage transplantation involves surgically harvesting healthy articular cartilage from non-weight-bearing areas of the patient's own or allogeneic joints and implanting it into the damaged area [14], but this method has disadvantages such as limited cartilage sources, potential rejection reactions, and potential risk of viral transmission in allogeneic cartilage transplantation [15-16]. Chondrocyte transplantation involves extracting chondrocytes from the patient's own non-weight-bearing articular cartilage [17], culturing them in vitro, expanding them 10-20 times, and then injecting them into the cartilage defect area for local repair. This method can achieve good repair effects, but the surgery is complex, requires a second operation, and is costly; in addition, in vitro culture of chondrocytes has a dedifferentiation phenomenon [18-19]. Long-term in vitro culture leads to changes in cell phenotype, with significant differences in gene, protein expression, and phenotype compared to normal cartilage [20], and after implantation, it forms fibrocartilage [21-22].

Currently, there is a lack of a single surgical technique that can simultaneously achieve convenience and durable cartilage regeneration. The breakthrough in tissue engineering technology provides a new path for functional cartilage repair, such as matrix-induced autologous chondrocyte implantation and autologous matrix-induced chondrogenesis [23]. Biomaterials used for cartilage repair include natural materials and synthetic materials.