中国组织工程研究

中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (10): 1562-1567.doi: 10.12307/2024.371

• 功能性生物材料Functional biomaterials • 上一篇    下一篇

3D打印多功能敷料治疗放创复合伤

焦文成1，2，代  晶3，严文锐2，4，沈锦涛2，胡静璐2，5，金义光2，4，杜丽娜1，2，4，5   

  1. 1河北大学，河北省保定市  071002；2中国人民解放军军事医学研究院辐射医学研究所，北京市  100850；3中国人民解放军西部战区总医院，四川省成都市  610083；4广东药科大学，广东省广州市  510006；5河南大学，河南省开封市  475004
  • 收稿日期:2023-04-14 接受日期:2023-06-06 出版日期:2024-04-08 发布日期:2023-08-19
  • 通讯作者: 杜丽娜，博士，研究员，河北大学，河北省保定市 071002；中国人民解放军军事医学研究院辐射医学研究所，北京市 100850；广东药科大学，广东省广州市 510006；河南大学，河南省开封市 475004
  • 作者简介:焦文成，男，1997年生，安徽省亳州市人，汉族，硕士，主要从事新型经皮给药系统研究。

3D-printed multifunctional wound dressing for combined radiation and wound injury

Jiao Wencheng1, 2, Dai Jing3, Yan Wenrui2, 4, Shen Jintao2, Hu Jinglu2, 5, Jin Yiguang2, 4, Du Lina1, 2, 4, 5   

  1. 1Hebei University, Baoding 071002, Hebei Province, China; 2Beijing Institute of Radiation Medicine, Beijing 100850, China; 3General Hospital of Western War Zone, Chengdu 610083, Sichuan Province, China; 4Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong Province, China; 5Henan University, Kaifeng 475004, Henan Province, China
  • Received:2023-04-14 Accepted:2023-06-06 Online:2024-04-08 Published:2023-08-19
  • Contact: Du Lina, PhD, Researcher, Hebei University, Baoding 071002, Hebei Province, China; Beijing Institute of Radiation Medicine, Beijing 100850, China; Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong Province, China; Henan University, Kaifeng 475004, Henan Province, China
  • About author:Jiao Wencheng, Master, Hebei University, Baoding 071002, Hebei Province, China; Beijing Institute of Radiation Medicine, Beijing 100850, China

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摘要：


文题释义：

3D打印：是一种将数字模型文件分层处理、逐层添加材料并逐层叠加，最终获得实物的快速成型技术。3D打印工艺分为3个步骤：首先是数据处理，即对模型进行处理；其次是材料选择，将处理后的数据通过逐层叠加的方式制作实物；最后是成型处理，即将所选的材料逐层添加到实体模型中。在打印过程中，电脑会根据扫描获得的三维数据来控制激光发生器、喷头和材料，从而将模型分层、切片并逐层打印出来。                                                                                      
放创复合伤：是由辐射损伤复合机械损伤引起的皮肤损伤，主要表现为辐射破坏了修复机制，导致创面愈合延迟或经久不愈，易反复发作。此外，辐射还会导致皮肤表面产生大量自由基，细胞因子与生长因子表达降低，而相关凋亡基因表达增高，受照皮肤局部成纤维细胞数量减少、形态受损、功能下降、肉芽组织生长缓慢等。


背景：放创复合伤主要发生在肿瘤放疗和核辐射事故患者中，由于辐射破坏修复机制导致伤口愈合延迟或延长，目前仍缺乏有效的治疗策略。

目的：针对放创复合伤的多种临床症状，制备抗菌、加速愈合和局部麻醉的多功能敷料。
方法：以左氧氟沙星、丝素蛋白和盐酸利多卡因为原料，应用3D生物打印技术制备多功能创面敷料。①将多功能敷料分别放置于表面涂有金黄色葡萄球菌、大肠杆菌与铜绿假单胞菌的固定培养板上，37 ℃孵育过夜，检测抑菌圈直径。②将40只昆明种小鼠随机分单纯创伤组、放创模型组、治疗组、阳性药组，每组10只。放创模型组、治疗组、阳性药组小鼠全身接受60Co γ射线照射，辐射1 h后，在4组小鼠背部各制作1个直径1 cm的全层皮肤缺损创面，单纯创伤组、放创模型组创面涂抹生理盐水，阳性药组创面涂抹三乙醇胺乳膏，治疗组创面覆盖多功能敷料，每隔1 d更换敷料或换药，连续治疗14 d。创面造模后3，7，14 d，检测创面愈合率与血清白细胞介素6水平；创面造模后14 d，获取创面处皮肤组织，进行苏木精-伊红、Masson染色及细胞角蛋白14免疫组化染色。

结果与结论：①3D打印多功能创面敷料具有良好的抗菌活性，对金黄色葡萄球菌、大肠杆菌与铜绿假单胞菌的抑菌圈直径分别为(4.15±0.09)，(4.18±0.23)，(4.35±0.13) cm。②随着造模时间的延长，小鼠创面逐渐愈合，治疗组、阳性药组造模后3，7，14 d的创面愈合率均高于放创模型组(P < 0.01，P < 0.001)，并且治疗组创面愈合率高于阳性药组。随着造模时间的延长，小鼠血清白细胞介素水平呈先升高后降低的趋势，治疗组造模后3，7，14 d的血清白细胞介素水平均低于放创模型组。苏木精-伊红、Masson染色显示，单纯创伤组肉芽肿组织可见炎性细胞浸润，真皮层胶原纤维排列致密；放创模型组表皮层和真皮层正常结构被破坏，可见炎性细胞浸润；治疗组可见正常皮肤黏膜组织，表皮层排列规则紧密，汗腺、毛囊和真皮层胶原纤维排列整齐规则；阳性药组表皮层排列规则紧密，汗腺、毛囊和真皮层胶原纤维排列整齐规则。细胞角蛋白14免疫组化染色显示，治疗组表皮组织厚度低于其他3组(P < 0.01，P < 0.001)。③结果表明，3D打印多功能敷料具有局部麻醉、抗感染、促愈合多重功能。

https://orcid.org/0009-0003-9507-8360(焦文成)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 3D打印, 放创复合伤, 创面愈合, 多功能敷料, 敷料, 丝素蛋白

Abstract: BACKGROUND: Combined radiation and wound injury appeared mainly in patients with tumor radiotherapy and nuclear radiation accidents. The radiation destroys the repair mechanism, resulting in delayed or prolonged wound healing. It still lacks an effective therapeutic strategy currently. 
OBJECTIVE: To prepare multifunctional wound dressings based on the multiple clinical symptoms of combined radiation and wound injury, which are designed to be antibacteria, promoted healing and analgesics. 
METHODS: Using levofloxacin, fibroin and lidocaine hydrochloride as raw materials, 3D bioprinting technology was applied to prepare the multifunctional wound dressing. (1) The multifunctional dressing was placed on a fixed culture plate coated with Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, and incubated at 37 °C overnight to detect the diameter of the antibacterial zone. (2) 40 Kunming mice were randomly divided into trauma group, radiation and trauma model group, treatment group and positive drug group, with 10 mice in each group. Mice in the radiation and trauma model group, treatment group and positive drug group were irradiated by 60Co gamma rays. After 1 hour of radiation, a full-layer skin defect wound with a diameter of 1 cm was made on the back of each mouse in the four groups. Normal saline was applied to the wounds of the trauma group and the radiation and trauma model group. Trethanolamine cream was applied to the wounds of the positive drug group. Multifunctional dressing was applied to the wounds of the treatment group. The dressing was changed every 2 days, and the treatment was continued for 14 days. Wound healing rate and serum interleukin-6 level were measured at 3, 7 and 14 days after wound modeling. 14 days after the wound modeling, the skin tissue of the wound was obtained and received hematoxylin-eosin staining, Masson staining and cytokeratin-14 immunohistochemical staining. 
RESULTS AND CONCLUSION: (1) 3D-printed multifunctional wound dressing had good antibacterial activity. The antibacterial zone diameters against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were (4.15±0.09), (4.18±0.23) and (4.35±0.13) cm, respectively. (2) With the extension of modeling time, the wound healed gradually. The wound healing rate of the treatment group and the positive drug group was higher than that of the radiation and trauma model group at 3, 7 and 14 days after modeling (P < 0.01, P < 0.001). The wound healing rate of the treatment group was higher than that of the positive drug group. With the extension of modeling time, the serum interleukin level of mice increased first and then decreased. The serum interleukin level in the treatment group at 3, 7 and 14 days after modeling was lower than that in the radiation and trauma model group. Hematoxylin-eosin staining and Masson staining exhibited that inflammatory cells infiltrated the granuloma tissue in the trauma group, and the dermal collagen fibers were densely arranged. The normal structure of epidermis and dermis was destroyed and inflammatory cells were infiltrated in the radiation and trauma model group. In the treatment group, normal skin mucosal tissue was observed, the epidermis was arranged closely, and the sweat glands, hair follicles and dermal collagen fibers were arranged regularly. In the positive drug group, the arrangement of epidermal layer was tight, and the arrangement of sweat glands, hair follicles and dermal collagen fibers was regular. Cytokeratin-14 immunohistochemical staining displayed that the epidermal tissue thickness in the treatment group was lower than that in the other three groups (P < 0.01, P < 0.001). (3) The results confirm that the 3D-printed multifunctional dressing has multiple functions of local anesthesia, anti-infection and promoting healing.

Key words: 3D printing, combined radiation and wound injury, wound healing, multifunctional dressing, dressing, fibroin

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