CN107261208A - 一种分层次负载药物角膜修复材料的制备方法 - Google Patents

一种分层次负载药物角膜修复材料的制备方法 Download PDF

Info

Publication number
CN107261208A
CN107261208A CN201710358432.3A CN201710358432A CN107261208A CN 107261208 A CN107261208 A CN 107261208A CN 201710358432 A CN201710358432 A CN 201710358432A CN 107261208 A CN107261208 A CN 107261208A
Authority
CN
China
Prior art keywords
preparation
repair material
cornea
derivative
cornea repair
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201710358432.3A
Other languages
English (en)
Inventor
任力
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guangzhou Pudao Lianxin Biotechnology Co ltd
Original Assignee
Guangzhou Pudao Lianxin Biotechnology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guangzhou Pudao Lianxin Biotechnology Co ltd filed Critical Guangzhou Pudao Lianxin Biotechnology Co ltd
Priority to CN201710358432.3A priority Critical patent/CN107261208A/zh
Publication of CN107261208A publication Critical patent/CN107261208A/zh
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/20—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222—Gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23—Carbohydrates
    • A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings
    • A61L2300/608—Coatings having two or more layers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea

Abstract

本发明公开了一种分层次负载药物角膜修复材料的制备方法，其包括以下步骤：1)将高分子材料加入溶剂中，配置高分子溶液；2)将高分子溶液干燥成膜；3)将药物溶液滴加在高分子膜表面，均匀平铺。本发明的制备过程工艺简单可行，重复性好，适合于新型功能化角膜修复材料大规模量产。

Description

一种分层次负载药物角膜修复材料的制备方法
技术领域
本发明采用先制备角膜修复材料后载药以及在制备角膜修复材料过程中载药的方法，涉及生物医学领域。
背景技术
角膜是位于眼球的前部和巩膜一起构成眼球的外壁，其质地透明，是屈光间质的重要组成部分，是保护眼睛免受外因素伤害的第一道防线。角膜内不含血管，营养主要依靠角膜缘血管网供给，代谢过程缓慢；所以一旦发生病变，修复难度大、时间长。角膜疾患是眼科的常见病和多发病，也是主要的致盲原因之一。我国因角膜病导致失明的患者约有1000万人以上，其中80％可以通过角膜移植术来复明，但由于供体有限，每年仅可以完成约5000例角膜移植手术；所以研究者们就开始致力于角膜替代物的研究来帮助角膜患者恢复视力。理想的人工角膜替代物应该是像天然角膜一样被植入后达到良好的修复效果，在体外重建角膜修复材料变成可能，这有可能是解决角膜供体缺乏的一种有效途径。然而细菌感染及炎症反应是导致角膜移植失败的主要原因之一，药物负载于人工角膜修复材料之中是一种可能的解决办法，不仅可以完成角膜损伤的修复还能免于炎症或诱变的影响，从而满足人工重建生物材料修复过程的需求。本发明分别采用直接角膜修复材料制备过程中分层次负载药物以满足角膜修复过程中的药物需求，相较于药物和高分子共混载药或先制备膜材料后载药的方式，分层次载药可以使药物分散更加均匀，可达到较好的持续释放效果；另外部分药物可与高分子之间产生相关化学键作用，使膜材料机械性能更好。
发明内容
本发明的目的在于：对角膜修复材料的设计与制备的基础上，进行载药技术优化，有效减少或抑制临床应用过程中细菌感染或炎症反应，并通过功能药物控释促进角膜损伤修复。本发明所采取的技术方案是：
一种分层次负载药物角膜修复材料的制备方法，包括如下步骤：
1)将高分子材料加入溶剂中，配置高分子溶液；
2)将高分子溶液干燥成膜；
3)将药物溶液滴加在高分子膜表面，均匀平铺。
优选的，高分子溶液的配置方法是：将高分子材料加入到溶剂中，搅拌速率100～800r/min机械搅拌4～48h。
优选的，高分子溶液中，高分子材料的质量百分数为1～30wt％。
优选的，高分子膜与滴加的药物质量比为1000：(5～100)。
优选的，高分子材料是胶原及其衍生物、丝素蛋白及其衍生物、壳聚糖及其衍生物、明胶及其衍生物、透明质酸及其衍生物，聚乙烯醇、聚乙二醇、聚乳酸、聚己内酯、聚甲基丙烯酸甲酯、聚亚胺酯或聚对苯二甲酸乙二醇酯中的至少一种。
优选的，溶剂是N，N-二甲基甲酰胺、四氢呋喃、二氯甲烷、氯仿、乙醇、六氟异丙醇、丙酮、醋酸、盐酸、硫酸中的至少一种。
优选的，滴加的药物为头孢唑啉、阿米卡星、万古霉素、克林霉素、头孢他啶、头孢曲松、妥布霉素、庆大霉素、普拉洛芬、氟比洛芬钠、阿昔洛韦、双氯芬酸钠、碘苷、玻璃酸钠中的至少一种。
优选的，角膜修复材料干燥方式限定为真空干燥，干燥温度为35～37℃。
本发明的有益效果是：本发明在特定温度下将功能性药物以分层次的载药方式负载于角膜修复材料，提供药物均匀负载和持续释放效果；达到修复和治疗为一体，优势互补，相互促进；最终实现具有合适结构与功能的角膜修复材料，为角膜损伤修复的深入研究提供理论基础和技术指导。
附图说明
图1真空干燥条件下得到的角膜修复材料(a)和自然干燥得到的角膜修复材料(b)。
图2分层次载药角膜修复材料(a)和直接共混载药角膜修复材料(b)的力学性能。
图3在35℃条件下制备角膜修复材料(a)和室温条件下制备角膜修复材料(b)的表面微观形貌。
图4在35℃条件下制备角膜修复材料(a)和室温条件下制备角膜修复材料(b)的表面细胞生长情况。
图5分层次载药角膜修复材料(a)和直接共混载药角膜修复材料(b)的动物实验修复情况。
具体实施方式
实施例1：
称取0.8g明胶，加入到80g盐酸溶液(1wt％)中，机械搅拌4h，搅拌速率800r/min，充分溶解制得1wt％(重量比)明胶溶液；将2mL明胶溶液注入模具中并平铺于底部，在环境温度为35℃的条件下，真空干燥2h后制得明胶膜。将万古霉素加入到去离子水中配制1mg/mL浓度的药物溶液，将0.5mL药物溶液滴加在干燥后的明胶膜表面并均匀平铺，放置于温度为35℃的条件下，真空干燥1h待药物完全浸润薄膜并干燥后，反复交替循环加入明胶溶液和药物溶液重复上述步骤。最终得到厚度为200μm的分层次负载药物角膜修复材料。相同的制备工艺和条件，干燥方法为室温自然干燥的角膜修复材料会产生较多的气泡，严重影响了透明度以及应用效果，如图1所示。
实施例2：
称取0.6g胶原，加入到60g弱醋酸溶液(1.5wt％)中，机械搅拌48h，搅拌速率100r/min；将2mL胶原溶液注入模具中并平铺于底部，在环境温度为37℃的条件下，真空干燥6h后制得胶原膜。将妥布霉素加入到去离子水中配制1mg/mL浓度的药物溶液，将0.5mL药物溶液滴加在干燥后的明胶膜表面并均匀平铺，放置于温度为37℃的条件下，真空干燥4h待药物完全浸润薄膜并干燥后，反复交替循环加入胶原溶液和药物溶液，重复上述步骤。最终得到厚度为400μm的分层次负载药物角膜修复材料。相同的制备条件和原料用量，由于妥布霉素药物与胶原分子链间的相互作用，直接将药物和胶原溶液共混制得的膜材料的力学强度低于分层次药物负载膜材料，如图2所示。
实施例3：
称取0.9g壳聚糖，加入到30g浓度为1wt％盐酸溶液中，机械搅拌4h，搅拌速率800r/min，充分溶解制得30wt％(重量比)壳聚糖溶液；将1.5mL胶原溶液注入模具中，在环境温度为35℃，真空干燥5h后制得壳聚糖膜。将头孢曲松加入到去离子水中配制1mg/ml浓度的药物溶液，将0.45ml药物溶液滴加在干燥后的壳聚糖膜表面并均匀平铺，放置于温度为35℃的条件下，真空干燥3h待药物完全浸润薄膜并干燥后，反复交替循环加入壳聚糖溶液和药物溶液，重复上述步骤；最终得到厚度为300μm的分层次负载药物角膜修复材料。温度过高情况下，部分药物容易失活，在人体正常温度(～37.3℃)范围内，与其他温度(如：室温)制备的膜材料相比，35～37℃温度范围得到的膜材料表面微观形貌较均匀平整(如图3)，角膜上皮细胞在35～37℃温度范围得到的膜材料表面的生长均匀，而在室温得到的膜材料表面细胞分布不均(如图4)。
实施例4：
称取0.5g胶原，加入到50g弱醋酸溶液(1.5wt％)中，机械搅拌48h，搅拌速率100r/min，将1.5mL胶原溶液注入模具中并平铺于底部，在环境温度为37℃的条件下，真空干燥4.5h后制得胶原膜。将头孢唑啉钠加入到去离子水中配制1mg/mL浓度的药物溶液，将0.5mL药物溶液滴加在干燥后的明胶膜表面并均匀平铺，放置于温度为37℃的条件下，真空干燥3.5h待药物完全浸润薄膜并干燥后，反复交替循环加入胶原溶液和药物溶液，重复上述步骤。最终得到厚度为350μm的分层次负载药物角膜修复材料。直接将等量药物混入到胶原溶液中，一步法直接浇筑制备相同厚度的负载药物角膜修复材料，由于高分子溶液具有一定的粘度，在一定程度上影响了药物的分散性，在动物实验进行到第七天出现了明显的炎症反应，而分层次自组装载药没有炎症反应发生(图5)。

Claims (8)

1.一种分层次负载药物角膜修复材料的制备方法，包括如下步骤：
1)将高分子材料加入溶剂中，配置高分子溶液；
2)将高分子溶液干燥成膜；
3)将药物溶液滴加在高分子膜表面，均匀平铺。
2.根据权利要求1所述的制备方法，其特征在于，高分子溶液的配置方法是：将高分子材料加入到溶剂中，搅拌速率100～800r/min机械搅拌4～48h。
3.根据权利要求1所述的制备方法，其特征在于，高分子溶液中，高分子材料的质量百分数为1～30wt％。
4.根据权利要求1所述的制备方法，其特征在于，高分子膜与滴加的药物质量比为1000：(5～100)。
5.根据权利要求1所述的制备方法，其特征在于，高分子材料是胶原及其衍生物、丝素蛋白及其衍生物、壳聚糖及其衍生物、明胶及其衍生物、透明质酸及其衍生物，聚乙烯醇、聚乙二醇、聚乳酸、聚己内酯、聚甲基丙烯酸甲酯、聚亚胺酯或聚对苯二甲酸乙二醇酯中的至少一种。
6.根据权利要求1所述的制备方法，其特征在于，所述的溶剂是N，N-二甲基甲酰胺、四氢呋喃、二氯甲烷、氯仿、乙醇、六氟异丙醇、丙酮、醋酸、盐酸、硫酸中的至少一种。
7.根据权利要求1所述的制备方法，其特征在于，所述药物为头孢唑啉、阿米卡星、万古霉素、克林霉素、头孢他啶、头孢曲松、妥布霉素、庆大霉素、普拉洛芬、氟比洛芬钠、阿昔洛韦、双氯芬酸钠、碘苷、玻璃酸钠中的至少一种。
8.根据权利要求1所述的制备方法，其特征在于，角膜修复材料干燥方式限定为真空干燥，干燥温度为35～37℃。
CN201710358432.3A 2017-05-19 2017-05-19 一种分层次负载药物角膜修复材料的制备方法 Pending CN107261208A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710358432.3A CN107261208A (zh) 2017-05-19 2017-05-19 一种分层次负载药物角膜修复材料的制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710358432.3A CN107261208A (zh) 2017-05-19 2017-05-19 一种分层次负载药物角膜修复材料的制备方法

Publications (1)

Publication Number Publication Date
CN107261208A true CN107261208A (zh) 2017-10-20

Family

ID=60065508

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710358432.3A Pending CN107261208A (zh) 2017-05-19 2017-05-19 一种分层次负载药物角膜修复材料的制备方法

Country Status (1)

Country Link
CN (1) CN107261208A (zh)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN2708893Y (zh) * 2003-12-23 2005-07-13 天津市医港医药科技发展有限公司 一种复合涂层膏药
CN1973911A (zh) * 2006-12-08 2007-06-06 华南理工大学 结构仿生的角膜组织工程支架的制备方法
CN103239762A (zh) * 2013-05-23 2013-08-14 中国海洋大学 一种甲壳素膜及其在眼科治疗中的应用
CN103272268A (zh) * 2013-05-16 2013-09-04 华南理工大学 一种抗菌角膜修复材料及其制备方法
CN104825425A (zh) * 2014-09-28 2015-08-12 青岛大学附属医院 含那他霉素-环糊精包合物的眼用缓释药膜及其应用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN2708893Y (zh) * 2003-12-23 2005-07-13 天津市医港医药科技发展有限公司 一种复合涂层膏药
CN1973911A (zh) * 2006-12-08 2007-06-06 华南理工大学 结构仿生的角膜组织工程支架的制备方法
CN103272268A (zh) * 2013-05-16 2013-09-04 华南理工大学 一种抗菌角膜修复材料及其制备方法
CN103239762A (zh) * 2013-05-23 2013-08-14 中国海洋大学 一种甲壳素膜及其在眼科治疗中的应用
CN104825425A (zh) * 2014-09-28 2015-08-12 青岛大学附属医院 含那他霉素-环糊精包合物的眼用缓释药膜及其应用

Similar Documents

Publication Publication Date Title
Zhang et al. 3D bioprinting for artificial cornea: Challenges and perspectives
Jian et al. 3D bioprinting of a biomimetic meniscal scaffold for application in tissue engineering
Warnke et al. Primordium of an artificial Bruch’s membrane made of nanofibers for engineering of retinal pigment epithelium cell monolayers
Kundu et al. Silk fibroin biomaterials for tissue regenerations
CN101522133B (zh) 可植入的光学系统，其开发和应用的方法
Tran et al. A review of the emerging role of silk for the treatment of the eye
US20230069580A1 (en) Chemically cross-linked hydrogel and its microspheres, preparation method and application
CN105536055B (zh) 一种形状记忆型高弹性活性纳米纤维支架及其应用
US10730928B2 (en) Biofabrication techniques for the implementation of intrinsic tissue geometries to an in vitro collagen hydrogel
Sun et al. Construction and evaluation of collagen-based corneal grafts using polycaprolactone to improve tension stress
Lace et al. Biomaterials for ocular reconstruction
Saiding et al. Abdominal wall hernia repair: From prosthetic meshes to smart materials
Liu et al. Challenges and opportunities of silk protein hydrogels in biomedical applications
Wang et al. Application of bioprinting in ophthalmology
Xia et al. Emerging polymeric biomaterials and manufacturing techniques in regenerative medicine
Crouch et al. Exploiting biomaterial approaches to manufacture an artificial trabecular meshwork: A progress report
CN110404110A (zh) 一种耐缝合的胶原基角膜再生修复材料及其制备方法
Garg et al. The emerging role of 3D-printing in ocular drug delivery: Challenges, current status, and future prospects
Sachdev IV et al. A review on techniques and biomaterials used in 3D bioprinting
Li et al. L-polylactic acid porous microspheres enhance the mechanical properties and in vivo stability of degummed silk/silk fibroin/gelatin scaffold
CN107261208A (zh) 一种分层次负载药物角膜修复材料的制备方法
CN107007879A (zh) 一种活性人工角膜及其制备方法
Lu et al. Porous hydrogel constructs based on methacrylated gelatin/polyethylene oxide for corneal stromal regeneration
Eshgh et al. Nanocelluloses for tissue engineering and biomedical scaffolds
Qu et al. PLLA-COI multilayer nanofiber membrane for anti-adhesion of the Achilles tendon

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20171020