Karnik Tanvi, Dempsey Sandi G, Jerram Micheal J, Nagarajan Arun, Rajam Ravindra, May Barnaby C H, Miller Christopher H
Aroa Biosurgery, 2 Kingsford Smith Place, PO Box 107111, Auckland Airport, Auckland, 2150 New Zealand.
Biomater Res. 2019 Feb 22;23:6. doi: 10.1186/s40824-019-0155-0. eCollection 2019.
Antimicrobial technologies, including silver-containing medical devices, are increasingly utilized in clinical regimens to mitigate risks of microbial colonization. Silver-functionalized resorbable biomaterials for use in wound management and tissue regeneration applications have a narrow therapeutic index where antimicrobial effectiveness may be outweighed by adverse cytotoxicity. We examined the effects of ionic silver functionalization of an extracellular matrix (ECM) biomaterial derived from ovine forestomach (OFM-Ag) in terms of material properties, antimicrobial effectiveness and cytotoxicity profile.
Material properties of OFM-Ag were assessed by via biochemical analysis, microscopy, atomic absorption spectroscopy (AAS) and differential scanning calorimetry. The silver release profile of OFM-Ag was profiled by AAS and antimicrobial effectiveness testing utilized to determine the minimum effective concentration of silver in OFM-Ag in addition to the antimicrobial spectrum and wear time. Biofilm prevention properties of OFM-Ag in comparison to silver containing collagen dressing materials was quantified via in vitro crystal violet assay using a polymicrobial model. Toxicity of ionic silver, OFM-Ag and silver containing collagen dressing materials was assessed toward mammalian fibroblasts using elution cytoxicity testing.
OFM-Ag retained the native ECM compositional and structural characteristic of non-silver functionalized ECM material while imparting broad spectrum antimicrobial effectiveness toward 11 clinically relevant microbial species including fungi and drug resistant strains, maintaining effectiveness over a wear time duration of 7-days. OFM-Ag demonstrated significant prevention of polymicrobial biofilm formation compared to non-antimicrobial and silver-containing collagen dressing materials. Where silver-containing collagen dressing materials exhibited cytotoxic effects toward mammalian fibroblasts, OFM-Ag was determined to be non-cytotoxic, silver elution studies indicated sustained retention of silver in OFM-Ag as a possible mechanism for the attenuated cytotoxicity.
This work demonstrates ECM biomaterials may be functionalized with silver to favourably shift the balance between detrimental cytotoxic potential and beneficial antimicrobial effects, while preserving the ECM structure and function of utility in tissue regeneration applications.
包括含银医疗器械在内的抗菌技术在临床治疗方案中越来越多地被用于降低微生物定植风险。用于伤口管理和组织再生应用的银功能化可吸收生物材料的治疗指数较窄，其抗菌效果可能会被不良的细胞毒性所抵消。我们研究了源自绵羊前胃的细胞外基质（ECM）生物材料（OFM-Ag）的离子银功能化在材料特性、抗菌效果和细胞毒性方面的影响。
通过生化分析、显微镜检查、原子吸收光谱法（AAS）和差示扫描量热法评估OFM-Ag的材料特性。通过AAS分析OFM-Ag的银释放曲线，并进行抗菌效果测试，以确定OFM-Ag中银的最低有效浓度以及抗菌谱和磨损时间。使用多微生物模型通过体外结晶紫试验对OFM-Ag与含银胶原蛋白敷料材料相比的生物膜预防特性进行定量。使用洗脱细胞毒性试验评估离子银、OFM-Ag和含银胶原蛋白敷料材料对哺乳动物成纤维细胞的毒性。
OFM-Ag保留了非银功能化ECM材料的天然ECM组成和结构特征，同时对包括真菌和耐药菌株在内的11种临床相关微生物具有广谱抗菌效果，在7天的磨损时间内保持有效性。与非抗菌和含银胶原蛋白敷料材料相比，OFM-Ag对多微生物生物膜形成具有显著的预防作用。含银胶原蛋白敷料材料对哺乳动物成纤维细胞表现出细胞毒性作用，而OFM-Ag被确定为无细胞毒性，银洗脱研究表明银在OFM-Ag中持续保留可能是细胞毒性减弱的机制。
这项工作表明，ECM生物材料可以用银进行功能化，以有利地改变有害细胞毒性潜力和有益抗菌效果之间的平衡，同时保留ECM在组织再生应用中的结构和功能。
