Preparation and Evaluation of a Hyaluronate-collagen Film for Preventing Post-surgical Adhesion

J Int Med Res 2005;33(1):68-76
Preparation and Evaluation of a Hyaluronate-collagen Film for Preventing Post-surgical Adhesions -W Tsai1, J-F Fang2, C-L Yang3, J-H Chen4, L-T Su5, S-H Jan61,3,4,5,6Biomedical Engineering Centre, Industrial Technology Research Centre, Hsin-Chu, Taiwan; 2Division of Trauma and Emergency Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan


Post-surgical adhesion occurs when fibrous strands of scar tissue form, leading to the abnormal joining of anatomical structures. Patients undergoing abdominal surgery are at risk of the complications associated with intraperitoneal adhesions. Hyaluronic acid (HA) is a biocompatible, biodegradable and non-toxic natural polymer, which is gain­ing popularity as a barrier agent for preventing post-surgical adhesions. As HA is water-soluble and rapidly degraded in vivo, chemical modification is required to pro­duce a non-soluble sheet that might be used to prevent tissue adhesion. We develop­ed a range of biocompatible cross-linked HA-collagen composites and then evalu­ated them in a rat model of post-surgical adhesion. The results showed that cross-linked HA-collagen was almost totally resistant to hyaluronidase digestion. HA-collagen membranes induced minimal tissue reactions and were bioresorbed with­in 14 days post-surgery. These results suggest that cross-linked HA-collagen mem­brane may be a valuable anti-adhesion material to prevent post-surgical intra­peritoneal adhesion.KEY WORDS: HYALURONIC ACID; COLLAGEN; ANTI-ADHESION; BIORESORPTION
Introduction
Adhesions are abnormal attachments that form between tissues or organs after surgery or as a result of local inflammation. The incidence of intraperitoneal adhesions follow­ing surgical operations is 40 – 70%.1 The mechanism of post-operative tissue adhesion is not fully understood, but peritoneal trauma, ischaemia and some foreign bodies have been recognized for many years as being able to stimulate adhesion.1,2 Post-surgical abdominal ad­hesion is associated with numerous complications, such as bowel obstruction, difficult re-operation and female infertility.
There has been a large volume of work published on the prevention of post-operative adhesion.3 The majority of studies concluded that the best method to prevent adhesion is to minimize peritoneal trauma during operations. In addition to an improvement in surgical technique, there has also been a steady flow of publications on animal experiments reporting the effects of various methods of preventing intra­peritoneal adhesion. The main approach has been to apply a barrier at the early stages of wound healing to separate serosal surfaces and decrease adhesion formation.4,5 The mechanical barriers, which have been composed of a variety of materials, have reduced post-surgical adhesions in several clinical trials and in an animal model.6 – 8
Hyaluronic acid (HA) is a naturally occurring linear polysaccharide found in connective tissue, synovial fluid, the umbilical cord and the vitreous humor; it is used extensively in ophthalmic surgery. Experi­mental work done by Ghellai et al.9 suggested that the HA membrane functions as a physical barrier by temporarily separat­ing serosal tissue during the post-operative healing phase, thus preventing adhesion formation. Urman et al.10 studied the effect of HA on intraperitoneal adhesions using a rat model with uterine horn injury and found that pre-treatment with HA decreased the number of post-operative adhesions. Mast et al.11 demonstrated that the increased concentrations of HA found in fetal wounds, but not in adult wounds, resulted in scarless wound healing. These results confirm that exogenous HA has anti-adhesive properties as well as having a beneficial effect on wound healing.
We aimed to develop a biocompatible 1-ethyl-3-(3-dimethylaminopropyl) carbo­diimide hydrochloride (EDC)-cross-linked HA-collagen composite and to evaluate its effect on post-surgical intraperitoneal adhesion in rats.
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