Prevention of adhesions post-abdominal surgery: Assessing the safety and efficacy of Chitogel with Deferiprone in a rat model

Introduction: Adhesions are often considered to be an inevitable consequence of abdominal and pelvic surgery, jeopardizing the medium and long-term success of these procedures. Numerous strategies have been tested to reduce adhesion formation, however, to date, no surgical or medical therapeutic approaches have been successful in its prevention. This study demonstrates the safety and efficacy of Chitogel with Deferiprone and/or antibacterial Gallium Protoporphyrin in different concentrations in preventing adhesion formation after abdominal surgery. Materials and Methods: DS: 112 adult (8-10 week old) male Wistar albino rats were subjected to midline laparotomy and caecal abrasion, with 48 rats having an additional enterotomy and suturing. Kaolin (0.005g/ml) was applied to further accelerate adhesion formation. The abrasion model rats were randomized to receive saline, Chitogel, or Chitogel plus Deferiprone (5, 10 or 20 mM), together with Gallium Protoporphyrin (250μg/mL). The abrasion with enterotomy rats were randomised to receive saline, Chitogel or Chitogel with Deferiprone (1 or 5 mM). At day 21, rats were euthanised, and adhesions graded macroscopically and microscopically; the tensile strength of the repaired caecum was determined by an investigator blinded to the treatment groups. Results: Chitogel with Deferiprone 5 mM significantly reduced adhesion formation (p<0.01) when pathologically assessed in a rat abrasion model. Chitogel with Deferiprone 5 mM and 1 mM also significantly reduced adhesions (p<0.05) after abrasion with enterotomy. Def-Chitogel 1mM treatment did not weaken the enterotomy site with treated sites having significantly better tensile strength compared to control saline treated enterotomy rats. Conclusions: Chitogel with Deferiprone 1 mM constitutes an effective preventative anti-adhesion barrier after abdominal surgery in a rat model. Moreover, this therapeutic combination of agents is safe and does not weaken the healing of the sutured enterotomy site.Rajan Sundaresan Vediappan, Catherine Bennett, Clare Cooksley, John Finnie, Markus Trochsler, Ryan D. Quarrington, Claire F. Jones, Ahmed Bassiouni, Stephen Moratti, Alkis J. Psaltis, Guy Maddern, Sarah Vreugde, P.J. Wormal

A novel rat model to test intra-abdominal anti-adhesive therapy

Background: Adhesion formation after abdominal surgery is considered almost inevitable and a major cause of morbidity. Novel treatments have been proposed, however there is a lack of suitable small animal models for pre-clinical evaluation, mainly due to inconsistency in adhesion formation in positive control animals. Here, we propose a new rat model of abdominal adhesions using Kaolin as the adhesion-inducing agent at an optimized dosage for testing newer agents in respect to their anti-adhesive property. Materials and Methods: Twenty-five adult (8-10 week old) male Wistar albino rats underwent midline laparotomy and caecal abrasion and were randomized to receive topical applications of normal saline or different concentrations and volumes of a Kaolin-based formulation. At day 14 rats were humanely killed, and adhesions graded macroscopically by an investigator blinded to the treatment groups, using pre-determined adhesion scores and microscopically using histopathology. Results: Kaolin at 0.005 g/mL caused consistent adhesions without compromising rat viability. At higher doses significant morbidity and mortality was observed in the animals treated. Conclusions: Kaolin induced adhesion in a rat abdominal surgery model is reliable and can be safely used to test the efficacy of novel anti-adhesive formulations to prevent intra-abdominal adhesions.Rajan Sundaresan Vediappan, Catherine Bennett, Ahmed Bassiouni, Matthew Smith, John Finnie, Markus Trochsler ... et al

Prevention of peridural adhesions in spinal surgery: assessing safety and efficacy of Chitogel with Deferiprone in a sheep model

Introduction: Spinal laminectomy is a common procedure performed to relieve neural compression in patients suffering from myelopathy or radiculopathy. However, up to 40% of patients suffer from persistent post-operative pain and disability, a condition known as Failed Back Surgery Syndrome (FBSS). Excessive scarring in the surgical bed is implicated as a cause. Hydrogels have been proposed to prevent adhesion formation post-laminectomy; however, their efficacy has not been proven. This study uses Chitogel complexed with the iron chelator Deferiprone (Def) to prevent adhesion formation in a sheep laminectomy model. Material & methods: Fifteen Adult Merino sheep (Ovis Aries, 1–5 yrs old) underwent laminectomy at lumbar levels 1–5 and had hydrated aluminum silicate (kaolin) applied to promote adhesion formation. Subjects were randomised to receive at each laminectomy level no-treatment control, Chitogel, Chitogel with Def at 20 mM or 40 mM or Carboxy-methyl-cellulose and Polyethylene oxide (CMC/PEO) gel. The animals were recovered for 3 months post-surgery, followed by assessment with Magnetic Resonance Imaging (MRI) and histopathology of the spinal tissues for evaluating the presence and extent of adhesions. Results: MRI and Histology assessment indicated that Kaolin induced severe inflammation with adhesion formation. Chitogel with and without 20 mM Def decreased inflammation (p < 0.01) and trended to reduce adhesions (p < 0.1). Chitogel with Def 40 mM was not significantly dis-similar to CMC/PEO and did not reduce inflammation or adhesions compared to no-treatment control. Conclusion: Chitogel in combination with Def 20 mM is safe and effective in decreasing the inflammatory process and may possibly reduce post-operative adhesions following laminectomy.Rajan Sundaresan Vediappan, Annika Mascarenhas, Ann Nguyen-Hoang, Stephanie Anne Fong, Alistair Jukes, Katharina Richter, Ahmed Bassiouni, Sandy Patel, Steve Chryssidis, Sophia Otto, Stephen Moratti, Alkis James Psaltis, Sarah Vreugde, Peter-John Wormal