Benghuzzi H, England B
University of Mississippi Medical Center, Jackson, MS 39216, USA.
Biomed Sci Instrum. 2001;37:275-80.
The objective of this study was to analyze the fibrous tissue surrounding dihydrotestosterone (DHT loaded HA devices implanted subcutaneously (S/C) in adult castrated rams. The microcrystals of HA were prepared by following standard laboratory procedure. Housing, surgical implantation and bleeding procedure of all rams used in this study was conducted according to the NIH guideline and approval of UCUCA. A total of 11 rams were castrated by elastrator rings within a week after birth. At 7 months of age the animals were randomly divided into three groups. Group 1 rams (n = 4) were not treated and served as the control group. Rams in group 2 (n = 3) were implanted s.c. with two HA capsules (80 mg DHT/capsule). Each ram (n = 3) in group 3 was implanted with two empty HA capsules and served as a sham group. All animals were housed together throughout this study and water, high quality hay and grain were given ad libitum. The sterilized ceramics were inserted S/C through a single incision using standard aseptic surgical techniques. Gross, radiographic and histological examinations of the site of implantation did not show any untoward reactions during the entire investigation. Histopathological evaluation have revealed that all HA implants were encapsulated with hyaline fibrous tissue at the end of two weeks, and the degree of encapsulation increased with time. Results collected from this investigation showed that the passage of DHT through HA capsules started within 3 days after implantation. Furthermore, sustained delivery of DHT by means of HA devices at levels ranging between 1.4-3.3 ng/ml imposed continuous negative feedback on post-castration rise in serum LH and FSH secretion. Representative retrieved implants showed slight degradation of the implant (27% +/- 38) and increased erosion at the sharp edges with time was observed. Light and electron microscopic evaluation demonstrated that at the end of four weeks postimplantation, a well developed granulation tissue is seen surrounding the implants. The thin developing fibrous capsule infiltrated with macrophages and numerous small and large capillaries were observed. A well-developed fibrous capsule formed at 6 months postimplantation. Four different layers were observed: (i) the HA tissue layer contains macrophages, some mononuclear leukocytes, and fibroblasts indicative of the chronic inflammatory responses, (ii) the fibrous capsule layer is composed of longitudinally oriented fibroblasts and mature collagen fibers, (iii) the vascularization layer contains numerous large and small capillaries, and (iii) the outer side of the fibrous capsule predominately composed of adipose tissue. Data obtained from this study suggest that lack of vascularization at the immediate HA tissue layer and the fibrous capsule layer may function to retard the rapid release of DHT from the HA implants. This retardation of DHT release from HA implants by the formation of fibrous capsule is needed to compensate for the macropores formed during the biodegradation of the implants.
本研究的目的是分析成年去势公羊皮下植入二氢睾酮（DHT）负载透明质酸（HA）装置周围的纤维组织。HA微晶通过标准实验室程序制备。本研究中使用的所有公羊的饲养、手术植入和出血程序均按照美国国立卫生研究院（NIH）指南并经乌干达基督教大学动物使用与护理委员会（UCUCA）批准进行。总共11只公羊在出生后一周内用去势环进行去势。在7个月大时，将动物随机分为三组。第1组公羊（n = 4）不进行处理，作为对照组。第2组公羊（n = 3）皮下植入两个HA胶囊（80 mg DHT/胶囊）。第3组中的每只公羊（n = 3）植入两个空HA胶囊，作为假手术组。在整个研究过程中，所有动物一起饲养，并随意提供水、优质干草和谷物。使用标准无菌手术技术通过单个切口将消毒后的陶瓷皮下插入。在整个研究期间，植入部位的大体、影像学和组织学检查均未显示任何不良反应。组织病理学评估显示，所有HA植入物在两周结束时均被透明纤维组织包裹，并且包裹程度随时间增加。本研究收集的结果表明，DHT在植入后3天内开始通过HA胶囊。此外，通过HA装置以1.4 - 3.3 ng/ml的水平持续递送DHT对去势后血清促黄体生成素（LH）和促卵泡生成素（FSH）分泌的升高施加了持续的负反馈。取出的代表性植入物显示植入物有轻微降解（27% +/- 38），并且随着时间的推移，尖锐边缘处的侵蚀增加。光镜和电镜评估表明，植入后四周结束时，植入物周围可见发育良好的肉芽组织。观察到薄的正在形成的纤维囊浸润有巨噬细胞和许多大小不一的毛细血管。植入后6个月形成了发育良好的纤维囊。观察到四个不同的层：（i）HA组织层含有巨噬细胞、一些单核白细胞和成纤维细胞，表明存在慢性炎症反应，（ii）纤维囊层由纵向排列的成纤维细胞和成熟胶原纤维组成，（iii）血管化层含有许多大小不一的毛细血管，以及（iii）纤维囊外侧主要由脂肪组织组成。本研究获得的数据表明，HA组织层和纤维囊层紧邻处缺乏血管化可能起到延缓DHT从HA植入物中快速释放的作用。通过形成纤维囊来延缓DHT从HA植入物中的释放是为了补偿植入物生物降解过程中形成的大孔。
