Pathogenesis of post surgical adhesions and prevention using a novel fibrin sealant

Abstract

Post surgical adhesions (PSAs) are an inevitable outcome of surgery and their presence leads to pathogeneses and significant economic impact.

The studies within this thesis utilised standard and reproducible abrasion models, in rabbits, pigs and rats, to investigate the formation and maturation of PSAs with strict quantitative analyses. These studies have shown that the development of PSAs is a series of complex, multi-factorial processes. PSA development can be classified into two stages: (i) PSA modelling occurring up to/including 16 hours post injury characterised by the inflammatory response and fibrin deposition and maturation; and (ii) PSA remodelling occurring from 16 hours onwards and characterised by tissue repair, collagen deposition and maturation and chemical mediation by TGF-P.

Treatment with VivostatTM System Derived (novel) Fibrin Sealant significantly reduced the formation of PSAs with mean PSA reduction of 80% for the rabbit uterine horn abrasion model, from 3 separate studies; 83% for the pig stomach/colon/caecum abrasion model, from 2 separate studies; 80% for the rat caecum abrasion model. This is significantly better than other fibrin sealants investigated in this thesis.

PSA prevention with novel fibrin sealant demonstrated a similar pattern to PSA development, with two stages of development evident: (i) tissue generation modelling occurring up to/including 16 hours post injury characterised by the inflammatory response and fibrin deposition and maturation; and (ii) tissue generation remodelling occurring from 16 hours onwards and characterised by tissue repair, collagen deposition and maturation and chemical mediation by TGF-P. However the extent and subsequent time taken for these changes to occur was significantly reduced.

The prevention of PSAs and alterations of wound healing by novel fibrin sealant is most probably due to the sealant acting as a haemostat, as well as a physical barrier. Thus preventing fibrinous and subsequent fibrous PSA formation.