Department of Pediatrics, University of Colorado, Aurora, Colorado, USA.
Department of Bioengineering, University of Colorado, Aurora, Colorado, USA.
J Biomed Mater Res A. 2022 Mar;110(3):652-658. doi: 10.1002/jbm.a.37317. Epub 2021 Sep 30.
The continued development of minimally invasive therapeutic implants, such as injectable hydrogels, necessitates the concurrent advancement of methods to best assess their biocompatibility via functional outcomes in vivo. Biomaterial implants have been studied to treat kidney disease; however, assessment of biocompatibility has been limited to biomarker and histological assessments. Techniques now exist to measure kidney function serially in vivo in murine studies via transcutaneous measurements of glomerular filtration rate (tGFR). In this study, adult male and female wild-type BalbC mice underwent right unilateral nephrectomy. The remaining solitary left kidney was allowed 4 weeks to recover via compensatory hypertrophy, after which subcapsular injection of either saline or shear-thinning hyaluronic acid hydrogel was performed. Serial tGFR measurements before and after treatment were used to assess the effect of hydrogel injection on kidney filtration. Urine and serum biomarkers of kidney function, and kidney histology were also quantified. Hydrogel injection did not affect kidney function, as assessed by tGFR. Results were in agreement with standard metrics of serum and urine biomarkers of injury as well as histological assessment of inflammation. The model developed provides a direct functional assessment of implant compatibility for the treatment of kidney disease and impact on kidney function.
微创治疗植入物（如可注射水凝胶）的不断发展，需要同时推进通过体内功能结果来最佳评估其生物相容性的方法。生物材料植入物已被研究用于治疗肾脏疾病；然而，生物相容性的评估仅限于生物标志物和组织学评估。现在存在通过经皮测量肾小球滤过率（tGFR）在体内对小鼠研究中进行连续的肾功能测量的技术。在这项研究中，成年雄性和雌性野生型 BalbC 小鼠接受右侧单侧肾切除术。剩余的孤立左肾通过代偿性肥大允许恢复 4 周，然后在肾被膜下注射盐水或剪切稀化透明质酸水凝胶。在治疗前后进行的系列 tGFR 测量用于评估水凝胶注射对肾脏过滤的影响。还定量了尿液和血清肾功能生物标志物以及肾脏组织学。水凝胶注射对 tGFR 评估的肾功能没有影响。结果与损伤的血清和尿液生物标志物的标准指标以及炎症的组织学评估一致。所开发的模型为治疗肾脏疾病和对肾功能的影响的植入物相容性提供了直接的功能评估。
