Comportamiento reparativo de implantes de bioprótesis de colágeno crosslink "vs" no crosslink en situación intra y extraperitoneal

  1. Arteaga Peralta, Vladimir
Supervised by:
  1. Juan Manuel Bellón Caneiro Director
  2. Gemma Pascual González Co-director

Defence university: Universidad de Alcalá

Fecha de defensa: 09 December 2013

  1. Francisco Javier Burgos Revilla Chair
  2. Natalio García Honduvilla Secretary
  3. Javier Arias Díaz Committee member
  4. Damián García Olmo Committee member
  5. Felipe de la Cruz Vigo Committee member
  1. Cirugía, Ciencias Médicas y Sociales

Type: Thesis


The use of biomaterials both for tissue repair and as tissue substitutes has been constantly growing. The excellent biocompatibility of the biomaterials available to date has meant their practically generalized use for the treatment of certain diseases. In search for the ideal prosthetic device, the biomaterial industry has designed materials derived from live tissues that offer benefits over the use of autologous tissues and lack many of their disadvantages (longer surgery time and morbidity in the donor zone). Such biological prosthetic materials represent an important advance since some show essential features such as their degradation and complete elimination in the host organism. Synthetic or inert prostheses lack this characteristic; they persist over the host’s lifetime and sometimes give rise to inflammatory or foreign body reactions along with various postimplant complications. The gradual degradation of a bioprosthesis, or biomesh, will determine the formation in its place of a neotissue, which will in the long term completely replace the biomaterial. In ideal conditions, the goal is to achieve both the repair of the damaged site and the regeneration of an adequately organised tissue that favours angiogenesis and shows identical characteristics to those of the healthy tissue. To manufacture these biomaterials, collagen is used and this collagen has to be treated by lyophilization to eliminate its cell component and leave behind only the cell matrix. Following purification, no immune response should be produced and the inflammatory reaction should be minimal. The mechanical strength of a bioprosthesis will depend on the structure and the bonds of the collagen triple helix. In in vivo conditions, collagens are degraded by enzymes such as metalloproteases and even by microbes when there is bacterial contamination. Hence implants comprised of collagen fibres that are not strongly linked together tend to be rapidly absorbed and do not provide good tissue support. Ideally, bioprostheses should not undergo excessively rapid degradation and should remain stable until they gradually become incorporated in the host tissue. To achieve this, the bonds of the triple helix of collagen need to be effective. If this is not the case, the mechanical strength of the material will be compromised. A bioprosthesis thus acts as a support or scaffold to guide the tissue repair process. The success of repair will, in turn, depend on the balance between the processes of host tissue repair and implant degradation. For this purpose, some biomaterials are subjected to different processes that induce the formation of covalent bonds, or crosslinks, in the collagen molecule. This makes them more resistant to degradation by collagenases. To date no experimental study has been designed to examine in detail the degradation of an implanted bioprosthesis at the different interfaces and its replacement with new well‐organized host tissue. The present thesis was designed to examine the response to the implant of a biomesh (crosslinked versus non crosslinked) at the intra‐ or extraperitoneal interface. The peritoneal interface was selected since biomeshes are being used in current clinical practice to reconstruct the pelvic peritoneum following cancer surgery. The working hypothesis for this thesis was: Do biomeshes show different intraperitoneal and extraperitoneal behaviour to the laminar polymer meshes? Does the biodegradation process experienced by these biological materials differ at the different interfaces? These questions were experimentally addressed as described below. The animal used was the New Zealand White rabbit weighing around 3,200 g. The biomaterials tested were crosslinked (Permacol®, Collamend®) and non crosslinked (Surgisis®). As the control, we used a laminar ePTFE mesh (Preclude®). All implants were the same size (3x3 cm). For the intraperitoneal implants, the prosthetic materials were placed on the parietal peritoneum and fixed by placing four polypropylene sutures at the four corners. The extraperitoneal implants were fixed by running polypropylene suture over a partial defect created in the lateral wall of the abdomen. The fascia and outermost muscles were removed, leaving only the parietal peritoneal plane, over which the prosthetic material is placed. Intraperitoneal implant behaviour was followed by sequential laparoscopy performed at 3, 7 and 14 days postimplant. This enabled us to monitor adhesion formation in a single animal at these time points. The study ended 90 days after the implant of the different biomateriales. Extraperitoneal implants were examined at 14, 30 and 90 days. Both the intra‐ and extraperitoneal implants were subjected to morphological (light microscopy and scanning electron microscopy) and immunohistochemical analysis. Mechanical resistance measurements were made in the extraperitoneal implants. Adhesions to the intraperitoneal implants were similar for the crosslinked (Permacol® and Collamend®) and ePTFE meshes. The non crosslinked biomesh (Surgisis®) showed optimal behaviour in terms of avoiding adhesions due to its rapid biodegradation. The rate of seroma in the extraperitoneal implants was significant. This variable was greater for the crosslinked than the non crosslinked and control ePTFE implants. Tissue integration was similar in the crosslink prostheses. After 30 days, these implants showed the presence of cells and angiogenesis in their interior. In the Surgisis® meshes, cell ingrowth was easy due to their multilaminar structure. At 90 days postimplant, this biomesh had been practically absorbed. The ePTFE implant became encapsulated and showed an intense inflammatory reaction in the first two weeks after implant. The macrophage response was more intense for both the intra‐ and extraperitoneal crosslinked and polymer implants compared to Surgisis®. This behaviour was attributable to the biodegradation of the latter prosthesis. Hence, biodegradation was similar for the intra‐ and extraperitoneal crosslinked and non crosslinked biomeshes. The crosslinked biomeshes were not biodegraded whereas the non crosslinked meshes were reabsorbed but to a similar extent at the intraperitoneal and extraperitoneal interface. Finally, our mechanical strength tests indicated a gradual increase in resistance to traction from 14 to 90 days in all the extraperitoneal implants. In conclusion, the findings of this study indicate that: A) Crosslinked biological meshes implanted in an intraperitoneal position showed similar behaviour in terms of adhesion formation to laminar polymer ePTFE meshes. Adhesion formation to the non crosslinked biomesh was reduced due to the rapid and steady biodegradation of this mesh. B) When placed in an intraperitoneal position, both the biological (crosslinked) and polymer (PTFEe Preclude®) meshes were useful for tissue repair. C) In the extraperitoneal implants, host tissue incorporation was similar for the crosslinked biomeshes. The polymer prosthesis became encapsulated given its lack of pores. Surgisis® induced the generation of a neotissue including well‐structured collagen. Good mechanical strength at the repair site was observed in all the implants. D) The intra‐ or extraperitoneal location of the implant did not affect its biodegradation.