Commentary on “Sterilization and Cross-Linking Combined with Ultraviolet Irradiation and Low-Energy Electron Irradiation Procedure: New Perspectives for Bovine Pericardial Implants in Cardiac Surgery”Funding None.
22 August 2019
07 January 2020
12 April 2020 (online)
The use of xenograft tissues for the replacement or augmentation of defective native tissue is widespread in surgical practice (e.g., heart valves, vascular patches, breast reconstruction, hernia). The optimal tissue to use in each clinical situation and the technique used to process the xenograft so that it is remodeled appropriately to deliver the best possible performance and outcomes for patients remain a source of intense debate. While collagen matrices could not convince in standard hernia repair due to slow integration and vascularization, the results seem to be much more favorable in cardiac surgery. This is probably due to different mechanical demands as well as the continuous perfusion of relatively small implants in the blood circulation.
The clinical challenges associated with glutaraldehyde cross-linking collagenous tissue such as calcification and poor biocompatibility led to its abandonment in some surgical spheres (e.g., hernia mesh, bulking agents for fecal and urinary incontinence) long ago. The authors have elegantly described their new technique of sterilization and cross-linking combined with UV irradiation and low-energy electron irradiation (SULEEI) as a novel strategy to conserve collagenous tissues (in this case bovine pericardium) without the need for glutaraldehyde. Alternative strategies for tissue processing such as SULEEI have the potential to offer better performance in vivo and hence better patient outcomes.
We know that when xenograft biomaterials are implanted into the human body that they undergo a process of remodeling that is governed by a delicate balance of collagenase activity and neocollagen deposition. All tissue processing, including cross-linking, exerts an effect both quantitatively and qualitatively on remodeling that can impact the performance of the xenograft implant. What has yet to be characterized fully is how these differences in performance impact the clinical situation. What is desirable in one clinical context (e.g., stiffness or tensile strength in hernia repair) may not be advantageous in another (e.g., heart valve replacement). Bearing this in mind, it is an extremely difficult task to interpret laboratory tests of novel biomaterials such as SULEEI-processed bovine pericardium. What constitutes the optimum biological scenario in terms of remodeling of the collagen matrix is likely to vary according to the tissue being replaced or augmented and the context in which it is used.
The authors present a series of standard laboratory tests of bovine pericardium subjected to SULEEI processing that have been extensively reported for biomaterials previously.  The SULEEI-processed pericardium performs well against commercially available alternative xenografts. The tests are, however, relatively static and fail to replicate the repetitive stress/strain scenario that would be encountered in vivo. This is important as substantial physicomechanical differences between biomaterials appear with exposure to collagenase activity and with repetitive loading. Of note in these tests, the SULEEI-processed pericardium appears to be substantially degraded by collagenase when compared with commercially available patches that have been cross-linked by alternative means. This degree of degradation and the consequent significant (>50%) loss of tissue weight may be disadvantageous clinically for arterial patches used in an infected wound (where synthetic materials would be contraindicated). It is plausible that faster remodeling, which follows faster degradation achieved with SULEEI procedure, is not beneficial here for the given reasons and that the seemingly worrisome features of glutaraldehyde cross-linking serve a hidden purpose in heart valve replacement.
In conclusion, the authors emphasize the importance of investigating further the impact of cross-linking procedures of collagen xenografts on physicomechanical and pathomorphological outcomes in general and specifically in valve replacement surgery. As often, clinical benefits and possible adverse effects are difficult to assess, and better insight needs to be obtained from preclinical studies to appreciate fully the translational value of work like this one.
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