In vivo tissue integration and healing stiffness of woven collagen meshes: comparison to porcine dermis and polypropylene.

Abstract

Event Abstract Back to Event In vivo tissue integration and healing stiffness of woven collagen meshes: comparison to porcine dermis and polypropylene. Katherine J. Chapin1, Ahmad Khalifa2, James M. Anderson3, Yuri Novitsky4, Adonis Hijaz2 and Ozan Akkus1, 5 1 Case Western Reserve University, Biomedical Engineering, United States 2 University Hospitals, Department of Urology, United States 3 Case Western Reserve University, Department of Pathology, United States 4 University Hospitals, Department of General Surgery, United States 5 Case Western Reserve University, Mechanical and Aerospace Engineering, United States Introduction: Shortcomings of modern sling materials used to manage stress urinary incontinence (SUI) underscore the need for an absorbable material that bio-integrates and matches stiffness of surrounding tissues[1]. Our group has developed an electrocompaction method for creating pure macroporous woven collagen meshes that are mechanically robust and induce de novo collagen production in vitro[2]. The aim of this study was to compare the tissue integration and remodeled stiffness of woven collagen meshes versus typical sling materials in an in vivo model to evaluate their potential application as a sling material. Methods: Electrochemically aligned collagen (ELAC) threads were made as previously described, cross-linked using genipin (Wako) or a combination of 1-ethyl-3-(3-dimethylaminopropyl carboiimide) and N-hydroxy succinimide (EDC-NHS, Sigma) and woven into scaffolds (Fig. 1)[2],[3]. Decellularized porcine dermis (Xenmatrix™, Davol) and monofilament polypropylene mesh (Prolene™, Ethicon) were included as typical sling materials for comparison. Scaffolds for mechanical testing and tissue integration were implanted subcutaneously (dorsal and ventral respectively) in female Sprague Dawley rats. Mechanical testing samples were tested in tension until failure (10 mm/min) at baseline, 2 months, and 5 months along with native vaginal tissue and rectus fascia to act as reference points. Tissue integration samples were processed at 2 weeks, 2 months, and 5 months, then scored for granulation tissue, foreign body response, and fibrous encapsulation (Table 1). The Kruskal-Walis test for group wise comparisons and the Mann-Whitney test for pair-wise comparisons were employed for statistical analysis (α = 0.05). Results and Discussion: Tissue integration and fibrous encapsulation were robust in Prolene, although there was no significant change in stiffness over time (Fig. 2). Modulus values for Xenmatrix were significantly greater than native tissue at baseline and at 2 months (p= 0.004, p= 0.004), but the stiffness fell about 10-fold at 5 months. Xenmatrix incited fibrous encapsulation, however, tissue integration was poor. EDC-NHS scaffolds also fell in stiffness from baseline, such they could not be recovered for testing at 5 months. The outcome is likely driven by poor fibrous encapsulation, leading to early resorption. Genipin scaffolds showed excellent tissue integration and fibrous encapsulation. Such host response is reflected in the increase in stiffness between 2 and 5 months; remodeled tissue halted the decline in material properties. Conclusion: The woven framework of collagen meshes provided ample porosity for rapid and thorough cellularization in vivo, an advantage over porcine dermis. The longer term presence of collagen meshes was defined by crosslinking formulations, such that genipin cross-linked scaffolds maintained the overall stiffness beyond 2 months. Thus, genipin crosslinked collagen meshes hold potential as a new biomaterial to treat SUI.