Morphological study of the capsular organization around tissue expanders coated with N-carboxybutyl chitosan G. Biagini, A. Pugnaloni, A_ Damadei, A. Bertani,A. Belligolli, V. Bicchiega R. Muzzarelli Facolt2 di Madicina a Chirurgia, lJniversit2 di Ancona, t-60 100 Ancona, Italy /Received 7 July 1989: revised 18 September 1989; accepted 18 October 1989) and zyxwvutsrqponmlkjihgfedcb Expanders coated with Ill-carboxybutyl chitosan were inserted into surgical wounds in the dorsal skin of rabbits and the formation of capsular tissue was studied by scanning electron microscopy and transmission electron microscopy. Ill-carboxybutyl chitosan. in the course of the capsular organization, favours and potentiates the correct proliferation and organization of the tissue, rather than sustaining reactive processes leading to scar formation. N-carboxybutyl chitosan stimulates physiologically the tissue repair process and favours angiogenesis, whilst depressing fibrogenesis to a certain extent. Applications are envisaged in the treatment of wounds and in plastic surgery. Keywords: Chitosan. tissue regeneration. angiogenesis Collagen undergoes synthetic and degradative processes that are particularly rapid in young subjects. Protein turnover has been recognized to be important where rapid tissue alteration becomes necessary’-3. An anomalous deposition of connective tissue takes place, however, when the dynamic equilibrium between synthesis and breakdown is altered, leading to fibrosis4. Fibrosis is a ubiquitous, aspecific and disordered increase of collagen5. Chronic inflammation processes give rise first to fibroplasia by activating macrophages and lymphocytes, then to fibrosis, as a repairing phenomenon4,6. The fibrous capsule formed after implanting a tissue expander under the skin is an aspect of such reparative process around an expanding foreign body7,s. Under these conditions, the connective tissue cellular components essential in the organization of the collagen lattice determine this structure by exerting orientated traction forcesg, lo. This work was undertaken to investigate the organiz- ation of the capsular structure formed as a consequence of the presence of an expanding foreign body coated with N-carboxybutyl chitosan. We have already reported that N-carboxyalkyl chitosans promote and sustain the regular reconstruction of the stromal tissue network. Being amphoteric polymers of N-acetylglucosamine, N-carboxyalkyl chitosans are chemically similar to glycosaminoglycans. The latter are known to be involved in tissue organization as morphogenetic factors”. N-carboxyalkyl chitosans were found to be Correspondence to Professor R. Muzzarelli. 0 1991 Butterworth-Heinemann Ltd. 0142-9612/91/030287-05 biologically similar to glycosaminoglycans and their inductive and stimulatory activity on connective tissue rebuilding was demonstrated”. Because N-carboxyalkyl chitosans are considered primers on which a normal tissue architecture is organized, it was expected that this class of chitosans would influence thecapsulartissueformation around an expanding body. MATERIALS AND METHODS N-carhoxybutyl chitosan N-carboxybutyl chitosan, M, 7 10 000 was prepared from crustacean chitin. It was purified from salts by extensive dialysis against distilled water (membrane cutoff 15 000) and freeze-dried. Just before use, a weighed amount of N- carboxybutyl chitosan was dissolved in water at 3% ratio to yield a gel that was spread on the Silastic expanders’*. Animals Experiments were done on four groups of California rabbits (15-I 8 wk old, 2.5-2.7 kg). The dorsal skin was incised (6 cm) and expandors (Silastic, 5 cm diameter), provided with subcutaneous filling valves, were inserted into the wounds. Expanders coated with N-carboxybutyl chitosan were implanted in two groups of rabbits. The edges of the wounds were immediately sutured and saline (10 ml) was injected into the expander. Further amounts of saline were Riomaterials 199 1, Vol 12 April 287