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Adhesion prevention, existing strategies in clinical practice
Strategies targeting the pathophysiological mechanisms involved in dysregulated serosal repair, such as the coagulation and inflammatory pathways, have also been trialed in an effort to prevent adhesion formation, including the inhibition of inflammation (27–30), prevention of fibrin formation and promotion of fibrinolysis (31–35), anti-angiogenesis (36,37) and tissue separation using hyaluronan-based membranes (38). During the past years, addition of surgical barriers – biologically derived meshes (e.g. Surgisis®, Permacol®, Alloderm®) – that provide anti-adhesive separation of denuded serosal tissues have proved beneficial but none completely prevent adhesion development in all patients (39,40). All of them, in common, are decellularized human or animal tissue, and act as a collagen scaffold for fibroblastic ingrowth and collagen deposition. The recent tendancy is to develop nanofibers, nanosheets or composite matrix to decrease the quantity of synthetic biomaterial (30,32,33) and reduce the side effects or to use natural hydrogels as chitosan, pullulan, and carboxymethyl cellulose (32,34,35). For example, Xia developed a biodegradable trilayered barrier membrane composed of sponge and electrospun layers offering hemostasis and antiadhesion features thanks to the biomaterials chosen. On one side, a poly-lactic-co-glycolic acid (PLGA) / polyethylene glycol (PEG) electrospun layer promoted the growth of epithelial cells, and exhibited inhibition on the adhesion and spread of FBs. On the other side, a chitosan sponge and glycerin tooked away the blood clots during the swelling and dissolution stages. With this strategy, on a rat model of cecum and parietal peritoneum abrasion, the author showed an effective reduction of the severity and the occurrence of adhesions (32). Up to know, none of theses recent strategies suppressed totally the formation of adhesion. Despite certain anti-adhesion effect, the limitations for clinical applications lie in the difficulty of treatment due to their lack of flexibility, loose contact with applied tissue; and need for suture fixation that can lead additional tissue damage. Morover, the disease itself (pelvic cancer, endometriosis) can induce adhesion. The prevention of tissue adhesion after surgery is still considered as a big challenge in clinical fields.
Adhesion formation process, reproducibility and efficiency
Various techniques have been reported to induce adhesion formation including thermal effect or burn, abrasion, sutures and mechanical excisions. In the first part of our review, we discuss these techniques as well as their relative efficiency and reproducibility. The effect of adding liquid such as serum, buffer, culture medium or blood will also be examined.
Thermal effect or burn
Burn can obtained by different electro-surgery methods the most widely used being bipolar and monopolar electro-coagulation. In bipolar electro-coagulation, the electrical current passes between two tips of a handpiece whereas in monopolar electro-coagulation, the electrical current passes from the handpiece to a ground plate, passing through the patient or the animal. The power (Watts) and the strengh (ranging from 0 to 6) inducing fulguration, section, coagulation or desiccation can be changed according to the need (Table 1) (85).
Histological assessment of postoperative peritoneal adhesions
During the second-look laparotomy, to determine whether postoperative adhesion existed, the tissue around the standard peritoneal lesion was excised completely, rinsed with isotonic solution, and fixed in a 4% formalin solution. All tissue specimens were embedded in paraffin, sectioned into 5-µm-thick slices, and stained with hematoxylin phloxine saffron (HPS) using standardized methods.
Table of contents :
Abstract
Abbreviations
1. Part 1: STATE OF THE ART
1.1. STATE OF THE ART OF MESOTHELIUM HISTOPHYSIOLOGY REPAIR AND ADHESION
FORMATION
1.1.1. Macroscopical description of the peritoneum
1.1.2. Microscopical description of the peritoneum
1.1.3. Functions of the peritoneum
1.1.4. Peritoneum healing
1.1.5. Adhesion formation
1.1.6. Clinical impact
1.1.7. Adhesion prevention, existing strategies in clinical practice
1.1.8. Adhesion prevention, potential strategies
1.2. STATE OF THE ART OF THE ANIMAL MODELS OF ADHESION
1.2.1. Introduction
1.2.2. Adhesion creation
1.2.3. Clinical relevancy
1.2.4. Adhesion assessment
1.2.5. Conclusions
OBJECTIVES OF THE PROJECT 36-37
2. Part 2: METHOD AND RESULTS OF THE PROJECT
2.1. CHAPTER 1: VALIDATION OF THE ANIMAL MODEL
2.1.1. Introduction
2.1.2. Method
2.1.3. Results and discussion
2.1.4. Conclusions
2.2. CHAPTER 2: CHOICE OF CELL SOURCE
2.2.1. Mesothelial cells (MCs)
2.2.1.1. Method
2.2.1.2. Results and discussion
2.2.1.3. Conclusions
2.2.1.4. Perspectives
2.2.2. Adipose stem cells (ASCs)
2.2.2.1. Method
2.2.2.2. Results and discussion
2.2.2.3. Conclusions
2.2.2.4. Perspectives
2.3. CHAPTER 3: COMPARISON BETWEEN CELL-THERAPY AND CELL-LADENED
SCAFFOLDS OR TISSUE-THERAPY
2.3.1. Introduction
2.3.2. Cell therapy using IP injection of MCs
2.3.2.1. Method
2.3.2.2. Results and discussion
2.3.2.3. Conclusions
2.3.3. Comparison between cell-sheet therapy and tissue therapy (peritoneal graft)
2.3.3.1. Introduction
2.3.3.2. Method
2.3.3.3. Experimental design and induction of standardized peritoneal lesion
2.3.3.3.1. Preparation and transplantation of autologous peritoneal graft
2.3.3.3.2. Preparation and implantation of bilayer cellsheet
2.3.3.4. Results
2.3.3.4.1. Macroscopic evaluation
2.3.3.4.2. Histological evaluation
2.3.4. Discussion
2.3.5. Conclusion
2.4. CHAPTER 4: CHOICE OF SCAFFOLD MATERIALS
2.4.1. Introduction
2.4.2. BD-Purastat® choice
2.4.3. BD-Purastat® dilution and gelation assays
2.4.4. Viability of in vitro encapsulated cells
2.4.5. In vivo transplantation of 0.5% BD-Purastat® into an animal model of adhesion
2.4.6. Conclusions
2.5. CHAPTER 5: IN VIVO APPLICATION OF CELL-LADENED BD-PURASTAT® GELS
2.5.1. Cell type comparisons
2.5.2. MC density comparison for MCs laden 0,5% BD-Purastat® applications
2.5.3. Discussion
2.5.4. Conclusions
2.5.5. Perspectives
3. Part 3: CONCLUSIONS and PERSPECTIVES
3.1. Conclusions
3.2. Perspectives
REFERENCES
