人类细胞真皮基质的血管化:非人灵长类动物模型比较研究

IF 3.5 3区 医学 Q3 CELL & TISSUE ENGINEERING
Victoria Stefanelli, Jared Lombardi, Joselito Ferrer, Maryellen Gardocki-Sandor
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引用次数: 0

摘要

在非人灵长类动物腹壁修复模型中,通过评估宿主免疫反应、血管生成和与宿主组织的结合情况,对四种人类无细胞真皮基质(hADM)进行了鉴定。和 FlexHD™(乙醇处理过的 hADM [EtOH-hADM])分别植入非人灵长类动物的腹壁桥接缺损处(n=3 只动物/时间点,N=36 只动物)。在植入后 1、3 和 6 个月时,对每个 hADM 的活检组织进行免疫组织化学和组织学评估,以评估血管形成(苏木精和伊红 [H&E]、CD31、α 平滑肌肌动蛋白 [αSMA]、胶原蛋白 IV)、炎症/免疫反应(H&E、CD3、CD20、CD68)和胶原周转(H&E、基质金属蛋白酶-9 [MMP-9])。不同的 hADM 在 1 个月时的 MMP-9 免疫标记相似;但是,hADM-FD 和 EtOH-hADM 的 MMP-9 免疫阳性总平均面积约为 16%,比 hADM-FD 和 EtOH-hADM 高。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Vascularization of Human Acellular Dermal Matrices: A Comparative Study in a Nonhuman Primate Model.

Four human acellular dermal matrices (hADMs) were characterized in a nonhuman primate abdominal wall repair model by evaluating host immune response, vascularization, and incorporation into host tissues. AlloDerm™ (electron beam-sterilized hADM [e-hADM]), AlloMax™ (gamma beam-sterilized hADM, freeze-dried [g-hADM-FD]), DermaMatrix™ (hADM, freeze-dried [hADM-FD]), and FlexHD™ (ethanol-treated hADM [EtOH-hADM]) were each implanted in an abdominal wall-bridging defect in nonhuman primates (n = 3 animals/time point, n = 36 animals). Immunohistochemical and histological assessments were conducted on biopsies from each hADM at 1-, 3-, and 6-months postimplantation to assess vascularization (hematoxylin and eosin [H&E], CD31, alpha smooth muscle actin [αSMA], collagen IV), inflammatory/immune response (H&E, CD3, CD20, CD68), and collagen turnover (H&E, matrix metalloproteinase-9 [MMP-9]). MMP-9 immunolabeling was similar among different hADMs at 1 month; however, hADM-FD and EtOH-hADM showed higher total mean MMP-9-immunopositive areas at approximately 16% compared with <1% for e-hADM and g-hADM at 6 months postimplantation. Cells that stained positively for CD68, CD3, and CD20 were generally higher for hADM-FD and EtOH-hADM compared with other hADMs. The mean CD31-immunopositive area, CD31 vessel density, CD31 vessel diameter, and collagen IV-immunopositive area increased over time. Among all the hADM types, e-hADM had the highest mean (±standard deviation [SD]) CD31-immunopositive area at 1.54% ± 1.01%, vessel density at 7.86 × 10-5 ± 3.96 × 10-5 vessels/µm2, and collagen IV-immunopositive area at 2.55% ± 0.73% 1-month postimplantation. The pattern of αSMA immunolabeling varied among the hADMs. Histology showed that overall inflammation was mild at 1 month. Overall fibroblast repopulation and collagen remodeling increased over time from 1 to 6 months postimplantation. Fibroblast infiltration was minimal to mild at 1 month, with e-hADM showing the highest mean (±SD) score at 2.00 ± 0.00 compared with other hADMs. Only hADM-FD was not completely replaced by neotissue formation at 6 months postimplantation. All hADMs promoted vascularization, cell infiltration, and incorporation into host tissue, which were associated with acute inflammation and immune responses, within a 6-month period. A trend toward relatively enhanced early vascularization in e-hADM compared with other hADMs was observed. Immunogenic responses among the hADMs in the present study showed a slight distinction toward more quiescent terminally sterilized hADMs (e-hADM, g-hADM-FD) versus aseptically processed hADMs (EtOH-hADM, hADM-FD).

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来源期刊
Tissue Engineering Part A
Tissue Engineering Part A Chemical Engineering-Bioengineering
CiteScore
9.20
自引率
2.40%
发文量
163
审稿时长
3 months
期刊介绍: Tissue Engineering is the preeminent, biomedical journal advancing the field with cutting-edge research and applications that repair or regenerate portions or whole tissues. This multidisciplinary journal brings together the principles of engineering and life sciences in the creation of artificial tissues and regenerative medicine. Tissue Engineering is divided into three parts, providing a central forum for groundbreaking scientific research and developments of clinical applications from leading experts in the field that will enable the functional replacement of tissues.
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