Is cellulose sponge degradable or stable as implantation material? An in vivo subcutaneous study in the rat

Abstract

The long-term behaviour of cellulose sponge implants, 10×10×5 mm in size, and tissue reactions in and around them were examined in the subcutaneous tissue of the rat from 1 to 60 weeks after implantation. The cellulose sponge used was filled up with connective tissue 4 to 8 weeks after implantation. Histologically, moderate foreign body tissue reaction inside the implant, the appearance of cracks and fissures, spotty colouration, and softening of the pore walls were observed up to 16 weeks after implantation. Later, the foreign body reaction inside the sponge became milder, the spotty colouration disappeared and micropores enlarged in the viscose cellulose matrix. Histomorphometrically, the cross-sectional area of the implants and the size of the pore wall fragments decreased, and the number of pore wall fragments increased significantly. The cellulose sponge used can be regarded as a slowly degradable implantation material. However, the time needed for the total disappearance of the cellulose sponge from subcutaneous tissue is longer than the 60 weeks.

Introduction

Cellulose is a naturally occurring, linear homopolymer of glucose (C₆H₁₀O₅)_n. It is insoluble in water and degradable in nature by microbial and fungal enzymes. The disappearance of cellulose in animal and human tissues is considered to be limited, if it occurs at all, because of the absence of hydrolases that attack the β(1–4) linkage. Physical transformation of higher ordered structures of cellulose may modulate its degradation as well as its tissue response [1].

High purity cellulose sponge for biomedical purposes has an open cell structure, characterised by thin pore walls with one or more interpore openings and good overall homogeneity. Additionally, the sponge has elasticity, a property of reversible compression and expansion without damage to the internal structure, thus providing a free entry for the cells to inner parts of the sponge [2]. Calcification of fibrous tissue does not occur, and the sponge shows negative staining properties with routine histological stains [3].

The number of invading cells and the production of granulation tissue depend on the internal structure, size and shape of the cellulose sponge. The minimal pore size required for tissue growth into a porous implant is 50 μm [4]. However, in cellulose sponges with an average pore size of approximately 250 μm and more, synthesis of granulation tissue decreased [5]. The sponges with lower cellulose content and smaller size were invaded by more cells and filled up with connective tissue more rapidly than those with higher cellulose content and bigger size [6]. Thin sponges were filled with granulation tissue earlier than the thick ones with the same volume [4], [7]. The porous cellulose materials have been shown to have biocompatibility with bone tissue [8] and hepatocytes [9].

The cellulose sponge has established clinical use. It is an essential part of the Cellstick^® device for wound healing research in humans [2], [10]. It has been used to stimulate granulation tissue in the wound base after deep burns and traumatic injuries [11], [12].

Subcutaneous implantation of the cellulose sponge has been a well-documented method to study granulation tissue formation since the early 1960s [13], [14], [15], [16], [17]. It has been used as control material in biocompatibility testing [18]. Little attention has, however, been focused on the long-term effects and fate of cellulose sponge implants. The use of the cellulose sponge as a permanently implanted matrix in tissue engineering requires more information on this aspect. Therefore, the present study was designed to examine the long-term consequences of events in the subcutaneously implanted cellulose sponge itself and the tissue reactions in and around it.