Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Stabile 4-58, Rochester, MN 55905, USA.
Acta Biomater. 2020 Apr 15;107:115-128. doi: 10.1016/j.actbio.2020.03.003. Epub 2020 Mar 7.
Chronic venous disease (CVD) is the most common reported chronic condition in the United States, affecting more than 25 million Americans. Regardless of its high occurrence, current therapeutic options are far from ideal due to their palliative nature. For best treatment outcomes, challenging cases of chronic venous insufficiency (CVI) are treated by repair or replacement of venous valves. Regrettably, the success of venous valve transplant is dependent on the availability of autologous venous valves and hindered by the possibility of donor site complications and increased patient morbidity. Therefore, the use of alternative tissue sources to provide off-the-shelf venous valve replacements has potential to be extremely beneficial to the field of CVI. This manuscript demonstrates the capability of producing off-the-shelf fully functional venous valved extracellular matrix (ECM) scaffold conduits from bovine saphenous vein (SV), using an antigen removal (AR) method. AR ECM scaffolds maintained native SV structure-function relationships and associated venous valves function. Conversely, SDS decellularization caused significant changes to the collagen and elastin macromolecular structures, resulting in collagen fibril merging, elimination of fibril crimp, amalgaming collagen fibers and fragmentation of the inner elastic lamina. ECM changes induced by SDS decellularization resulted in significant venous valve dysfunction. Venous valved conduits generated using the AR approach have potential to serve as off-the-shelf venous valve replacements for CVI. STATEMENT OF SIGNIFICANCE: Retention of the structure and composition of extracellular matrix (ECM) proteins within xenogeneic scaffolds for tissue engineering is of crucial importance, due to the undeniable effect ECM proteins can impose on repopulating cells and function of the resultant biomaterial. This manuscript demonstrates that alteration or elimination of ECM proteins via commonly utilized decellularization approach results in complete disruption of venous valve function. Conversely, retention of the delicate ECM structure and composition of native venous tissue, using an antigen removal tissue processing method, results in preservation of native venous valve function.
慢性静脉疾病（CVD）是美国最常见的慢性疾病，影响了超过 2500 万美国人。尽管其发病率很高，但由于其姑息性，目前的治疗选择远不理想。为了获得最佳的治疗效果，对于慢性静脉功能不全（CVI）的挑战性病例，通过修复或置换静脉瓣膜进行治疗。遗憾的是，静脉瓣膜移植的成功取决于自体静脉瓣膜的可用性，并受到供体部位并发症和患者发病率增加的可能性的阻碍。因此，使用替代组织来源提供即用型静脉瓣膜替代物有可能对 CVI 领域极为有益。本文展示了使用抗原去除（AR）方法从牛隐静脉（SV）生产即用型完全功能性静脉带瓣细胞外基质（ECM）支架导管的能力。AR ECM 支架保留了天然 SV 的结构-功能关系和相关静脉瓣膜功能。相反，SDS 去细胞化导致胶原和弹性蛋白大分子结构发生显著变化，导致胶原纤维融合、消除原纤维卷曲、胶原纤维融合和内弹性层碎裂。SDS 去细胞化引起的 ECM 变化导致静脉瓣膜功能显著丧失。使用 AR 方法生成的带瓣静脉导管有可能作为 CVI 的即用型静脉瓣膜替代物。
对于组织工程学来说，异种支架内细胞外基质（ECM）蛋白的结构和组成的保留至关重要，因为 ECM 蛋白对再殖细胞和生物材料功能的影响是不可否认的。本文表明，通过常用的去细胞化方法改变或消除 ECM 蛋白会导致静脉瓣膜功能完全丧失。相反，使用抗原去除组织处理方法保留天然静脉组织的精细 ECM 结构和组成，可保持天然静脉瓣膜功能。
