A Pilot Study of Seamless Regeneration of Bone and Cartilage in Knee Joint Regeneration Using Honeycomb TCP.

Kiyofumi Takabatake,May Wathone Oo,Hotaka Kawai,Keisuke Nakano,Hitoshi Nagatsuka,Hidetsugu Tsujigiwa,Takayuki Furumatsu,Aki Yoshida

doi:10.3390/ma14237225

Kiyofumi Takabatake, May Wathone Oo + Show 6 more

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https://doi.org/10.3390/ma14237225

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Abstract

The knee joint is a continuous structure of bone and cartilage tissue, making it difficult to regenerate using artificial biomaterials. In a previous study, we succeeded in developing honeycomb tricalcium phosphate (TCP), which has through-and-through holes and is able to provide the optimum microenvironment for hard tissue regeneration. We demonstrated that TCP with 300 μm pore diameters (300TCP) induced vigorous bone formation, and that TCP with 75 μm pore diameters (75TCP) induced cartilage formation. In the present study, we regenerated a knee joint defect using honeycomb TCP. 75TCP and 300TCP were loaded with transforming growth factor (TGF)-β alone or bone morphogenic protein (BMP)-2+TGF-β with or without Matrigel and transplanted into knee joint defect model rabbits. 75TCP showed no bone or cartilage tissue formation in any of the groups with TGF-β alone and BMP-2+TGF-β with/without Matrigel. However, for 300TCP and BMP-2+TGF-β with or without Matrigel, vigorous bone tissue formation was observed in the TCP holes, and cartilage tissue formation in the TCP surface layer was continuous with the existing cartilage. The cartilage area in the TCP surface was larger in the group without Matrigel (with BMP-2+TGF-β) than in the group with Matrigel (with BMP-2+TGF-β). Therefore, honeycomb TCP can induce the seamless regeneration of bone and cartilage in a knee joint.

Highlights

In recent years, artificial biomaterials have been used for reconstruction after surgical resection of tumors and for bone tissue defects caused by trauma
For 75TCP, Matrigel remained in the tricalcium phosphate (TCP) pores, and no bone tissue formation was observed in the pores with Matrigel only (Figure 2A,B), bone morphogenic protein (BMP)-2 with Matrigel (Figure 2C,D), and transforming growth factor (TGF)-β+BMP-2 with Matrigel (Figure 2E,F)
A small amount of cartilage tissue formation was observed at the knee joint side of TCP for Matrigel only and for TGF-β+BMP-2 with Matrigel groups

Summary

Introduction

Artificial biomaterials have been used for reconstruction after surgical resection of tumors and for bone tissue defects caused by trauma. A variety of artificial biomaterials having high biocompatibility such as hydroxyapatite (HA), calcium, and β-tricalcium phosphate (β-TCP) have already been clinically applied for bone tissue regeneration [1,2,3,4,5]. Bone tissue regeneration using artificial biomaterials has been reported in various studies and clinically applied, and these have been further developed and used clinically with new composite materials, such as hydroxyapatite and collagen composites [6,7,8]. Brittberg et al developed an autologous cultured chondrocyte transplantation method [9], and recently cartilage tissue regeneration by cell transplantation using bone marrow mesenchymal stem cells and synovial cells, as well as cartilage regeneration research using iPS cells, has progressed [10,11,12,13,14]. Cartilage tissue regeneration is easy because cartilage tissue does not require the introduction of blood vessels and does not require an environment in which multiple cell types work together like internal organs

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