Spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect created in the femoral condyle using a novel double-network hydrogel

Masashi Yokota,Shin Onodera,Kazunobu Arakaki,Nobuto Kitamura,Takayuki Kurokawa,Jian-Ping Gong,Kazunori Yasuda

doi:10.1186/1471-2474-12-49

Abstract

BackgroundFunctional repair of articular osteochondral defects remains a major challenge not only in the field of knee surgery but also in tissue regeneration medicine. The purpose is to clarify whether the spontaneous hyaline cartilage regeneration can be induced in a large osteochondral defect created in the femoral condyle by means of implanting a novel double-network (DN) gel at the bottom of the defect.MethodsTwenty-five mature rabbits were used in this study. In the bilateral knees of each animal, we created an osteochondral defect having a diameter of 2.4-mm in the medial condyle. Then, in 21 rabbits, we implanted a DN gel plug into a right knee defect so that a vacant space of 1.5-mm depth (in Group I), 2.5-mm depth (in Group II), or 3.5-mm depth (in Group III) was left. In the left knee, we did not apply any treatment to the defect to obtain the control data. All the rabbits were sacrificed at 4 weeks, and the gross and histological evaluations were performed. The remaining 4 rabbits underwent the same treatment as used in Group II, and real-time PCR analysis was performed at 4 weeks.ResultsThe defect in Group II was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen. The Wayne's gross appearance and histology scores showed that Group II was significantly greater than Group I, III, and Control (p < 0.012). The relative expression level of type-2 collagen, aggrecan, and SOX9 mRNAs was significantly greater in Group II than in the control group (p < 0.023).ConclusionsThis study demonstrated that spontaneous hyaline cartilage regeneration can be induced in vivo in an osteochondral defect created in the femoral condyle by means of implanting the DN gel plug at the bottom of the defect so that an approximately 2-mm deep vacant space was intentionally left in the defect. This fact has prompted us to propose an innovative strategy without cell culture to repair osteochondral lesions in the femoral condyle.

Highlights

Functional repair of articular osteochondral defects remains a major challenge in the field of knee surgery and in tissue regeneration medicine
In our previous study validating the implant and its use in a large osteochondral defect created in the patellofemoral (PF) joint of the rabbit knee [20], we found that spontaneous hyaline cartilage regeneration occurred in vivo in the defect within 4 weeks after surgery when a poly-(2-Acrylamido-2-methylpropanesulfonic acid) (PAMPS)/PDMAAm DN gel plug was implanted at the bottom of the defect so that a 1.5 to 3.5-mm deep vacant space was intentionally left in the defect
The immunohistochemical observation showed that the type-2 collagen was abundantly expressed in the proteoglycan-rich tissue (Figure 3J). These findings showed that the hyaline cartilage tissue was regenerated in the defect of Group II

Summary

Introduction

Functional repair of articular osteochondral defects remains a major challenge in the field of knee surgery and in tissue regeneration medicine. The purpose is to clarify whether the spontaneous hyaline cartilage regeneration can be induced in a large osteochondral defect created in the femoral condyle by means of implanting a novel double-network (DN) gel at the bottom of the defect. We paid attention to the fact that sufficient fibrocartilage tissue can be regenerated in an osteochondral defect by creating many thin holes that penetrate the subchondral bone at the base of the defect in order to create bleeding from the bone marrow and subsequent clot formation ("Microfracture” technique). These induced mesenchymal stem cells have a high potential for cartilage regeneration [15]. We hypothesize that a bioactive elastic material implanted in a chondral defect can stimulate and support hyaline cartilage regeneration

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