Department of Cardiovascular Surgery, University Hospital Duesseldorf, Germany.
Xenotransplantation. 2012 Sep-Oct;19(5):286-97. doi: 10.1111/j.1399-3089.2012.00719.x.
Today, bovine pericardium (BP) is extensively investigated as a biomaterial for the generation of various bioimplants. But despite the commercial distribution, and the development of methods either to remove (decellularization) or to mask (chemical cross-linking, for example by glutaraldehyde [GA] treatment) the xenogeneic antigen epitopes, yet questions around the immunogenic reactivity of BP remain. The aim of this study is the comparison of crucial tissue characteristics, that is, biomechanical properties, the presence of αGal epitopes, and residual DNA in acellular vs. GA-fixed BP.
Bovine pericardium was either cross-linked with 0.6% GA or decellularized according to two common protocols using either sodium dodecyl sulfate (SDS) and desoxycholic acid (DCA) or trypsin and ethylenediaminetetraacetic acid (EDTA). The resulting extracellular matrix was prone to one-dimensional tensile testing. The tissue content for αGal was evaluated by immunoblotting, and residual DNA was determined by a commercial assay. Untreated BP served as control.
In contrast to previous reports, we found a pronounced decrease in the elastic modulus (E-Modulus) for common GA treatment and overall smaller values for the elastic moduli after decellularization (P < 0.05). In parallel, we observed an overall increased ultimate elongation of acellular and cross-linked BP, although ultimate stress values did not significantly differ. SDS/DCA decellularized BP revealed a dramatic reduction in the DNA content and an almost complete removal of αGal epitopes, whereas the trypsin/EDTA protocol retained a residual DNA content of almost 50% and with a great trail of αGal signal. GA-treated tissue had a remarkable content of DNA and αGal.
Although chemically fixated BP is clinically still in wide use, for example, for biological heart valve engineering, our results suggest that an improved biomaterial preparation may be provided by appropriate decellularization. SDS/DCA decellularized BP shows similar biomechanical characteristics as GA treatment, paired with reduced potential immunogenic reactivity. Furthermore, decellularized BP holds the potential of cellular repopulation in vivo or in vitro, to enable an endogenous regenerative capacity in contrast to the toxic effects of GA fixing.
如今,牛心包(BP)作为各种生物植入物的生物材料得到了广泛的研究。尽管已经商业化,并且开发了去除(去细胞)或掩盖(例如通过戊二醛[GA]处理进行化学交联)异种抗原表位的方法,但BP 的免疫反应性问题仍然存在。本研究的目的是比较脱细胞与 GA 固定 BP 在组织学特征方面的差异,即生物力学特性、αGal 表位的存在和残留 DNA。
牛心包分别用 0.6%GA 交联或根据两种常用方案脱细胞,分别使用十二烷基硫酸钠(SDS)和去氧胆酸(DCA)或胰蛋白酶和乙二胺四乙酸(EDTA)。所得细胞外基质进行一维拉伸试验。通过免疫印迹评估组织中αGal 的含量,通过商业测定法测定残留 DNA。未处理的 BP 作为对照。
与之前的报道相反,我们发现 GA 处理后的弹性模量(E-Modulus)明显降低,而去细胞化后的弹性模量总体较小(P < 0.05)。同时,我们观察到脱细胞和交联 BP 的整体伸长率增加,尽管极限应力值没有显著差异。SDS/DCA 脱细胞 BP 显示 DNA 含量大幅减少,αGal 表位几乎完全去除,而胰蛋白酶/EDTA 方案保留了近 50%的残留 DNA 含量,并且αGal 信号痕迹明显。GA 处理的组织具有大量的 DNA 和αGal。
尽管化学固定的 BP 在临床上仍被广泛应用,例如用于生物心脏瓣膜工程,但我们的结果表明,适当的去细胞化可以提供更好的生物材料准备。SDS/DCA 脱细胞 BP 具有与 GA 处理相似的生物力学特性,但潜在免疫反应性降低。此外,脱细胞 BP 具有体内或体外细胞再殖的潜力,与 GA 固定的毒性作用相反,可实现内源性再生能力。