CN113289063A - 一种软组织修复生物材料及其制备方法 - Google Patents

一种软组织修复生物材料及其制备方法 Download PDF

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CN113289063A
CN113289063A CN202110585270.3A CN202110585270A CN113289063A CN 113289063 A CN113289063 A CN 113289063A CN 202110585270 A CN202110585270 A CN 202110585270A CN 113289063 A CN113289063 A CN 113289063A
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tissue repair
soft tissue
small intestine
collagen
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阚鹏
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Jiangyin Peoples Hospital
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Abstract

本发明公开了一种软组织修复生物材料，所述生物材料的制备方法包括：制得I型胶原蛋白醋酸溶液，制备小肠黏膜下层组织，制备小肠黏膜下层组织粉末，制得小肠黏膜下层脱细胞基质裂解物溶液，制得初次冻干支架和制备所述软组织修复生物材料。本发明可以同时实现该合成材料结构、力学性质的可调性，为软组织修复提供能够诱导组织修复同时满足临床对材料性质个性化需求的材料。

Description

一种软组织修复生物材料及其制备方法
技术领域
本发明涉及医学工程技术领域，尤其是涉及一种软组织修复生物材料及其制备方法。
背景技术
创伤导致的软组织撕裂和缺失、手术导致的器官和组织缺损、烧伤和烫伤导致的皮肤和皮下组织坏死是一类严重危害人体健康的重大疾病。由于器官和组织移植的供体来源缺乏和手术费用高昂，此类疾病的救治十分苦难。随着生物医学的快速发展，生物材料在组织缺损修复和再生的领域显示了优良应用前景，主要通过对损伤组织微环境的调控促进组织修复。
近20年来，组织修复生物材料的研究及其相关临床技术的发展明显加速。在软组织修复领域，出现了以胶原蛋白为基质的合成支架材料，例如，PELNAC人工真皮和Integra真皮再生模板以及我国自主研发的兰度人工真皮等，上述合成材料已通过药监部门批准，被批准用于深度创面、瘢痕整形、慢性创面等适应症的救治；此外，还有一类材料引起了广泛关注，即脱细胞基质类生物材料，这类材料是异体、异种组织经组织前处理、脱细胞处理、消毒处理得到的低核酸残留的支架或膜材料。例如小肠黏膜下层基质是一猪小肠为原料制备的高分子材料，目前被用于急慢性创面、腹壁修复、跟腱等软组织的修复。
但是，上述材料存在生物活性缺乏、材料结构和力学性质难以控制等不足。首先，由于组织来源差异造成制备过程和参数变异毒高，脱细胞真皮基质类生物材料的质量不稳定，各生产批次之间可能存在质量差别，进而影响其作为组织修复的应用效果，并可能造成二次手术等严重后果。其次，动物组织来源的脱细胞基质材料，其结构和力学性质无法控制，相比合成类生物材料，无法有效地满足临床治疗的针对性需求。因此，以丝素蛋白、胶原蛋白、壳聚糖等为基质的合成类支架材料在材料结构设计、性能调控方面显示了很强的优越性。但是，合成类支架材料由于缺乏主动诱导组织修复的活性，例如细胞趋化和活性的功能、促血管新生功能和炎症反应调控功能等，其临床应用效果有限，特别是对于严重软组组缺损的修复，需联合外源性生长因子、负压封闭引流的药物或临床技术，以达到组织修复的目的。
发明内容
针对现有技术存在的上述问题，本发明申请人提供了一种软组织修复生物材料及其制备方法。本发明可以同时实现该合成材料结构、力学性质的可调性，为软组织修复提供能够诱导组织修复同时满足临床对材料性质个性化需求的材料。
本发明的技术方案如下：
一种软组织修复生物材料，所述生物材料的制备方法包括如下步骤：
(1)用醋酸溶液溶解I型胶原蛋白，制得I型胶原蛋白醋酸溶液；
(2)取10-18cm健康成年猪近端空肠，除去多余结缔组织和肠内残留杂质，之后盐水脱细胞，脱除肠上皮细胞；之后通过机械刮擦、水合方法，除去浆膜、平滑肌组织，获得小肠黏膜下层组织；
(3)将步骤(2)制得的小肠黏膜下层组织放置过氧乙酸和乙醇的混合溶液中浸泡2h，之后PBS润洗15min，2次；无菌水润洗15min，2次；冷冻，使用液氮冷冻粉碎机粉碎成为颗粒，过40目筛，制得小肠黏膜下层组织粉末；
(4)将1g步骤(3)制得的小肠黏膜下层组织粉末和100mg的胃蛋白酶加入20～100ml 0.01M盐酸溶液中，25℃室温下恒速搅拌10～72h，得到粘性溶液，即小肠黏膜下层脱细胞基质裂解物的混合液；离心力为5000g下除去粘性溶液中的不溶物后，通过干燥除水法测定溶液中的溶质含量；之后，在冰浴条件下，向所得溶液中滴加2～10ml的0.1N NaOH溶液至溶液pH变为7.4；然后，加入2.2～11.1ml 0.1M的PBS，制得小肠黏膜下层脱细胞基质裂解物溶液；
(5)将5～10份胶原蛋白溶液与0.5～5份小肠黏膜下层脱细胞基质裂解物溶液和0～10份纯水，用匀浆机匀浆后，在离心力为1500g下离心3min，除去溶液中的气泡；
(6)将离心处理的溶液转移至聚四氟乙烯槽中，在37℃条件下孵育0.5～24h，使胶原蛋白和裂解物分子发生不同强度的组装，之后在真空冷冻干燥机中冷冻干燥，制得初次冻干支架；
(7)将初次冻干支架放于直径30cm、抽真空的干燥器隔板之上，干燥器底部放置装有20ml戊二醛溶液、直径为6cm的培养板，室温下反应1～24h，然后，将支架浸泡于超纯水中过夜，经二次冻干和环氧乙烷灭菌得到最终的支架，即所述软组织修复生物材料。
步骤(1)中，醋酸的浓度为0.5M；I型胶原蛋白与醋酸的质量体积比为0.5～2％。
步骤(2)中，盐水脱细胞的方法为：将组织在4℃冰箱放置0.5～10h，然后再用1.0N的氯化钠盐水浸泡1h-24h。
步骤(3)中，氧乙酸和乙醇的混合溶液中过氧乙酸的体积分数为0.1％，乙醇的体积分数为4％；PBS的pH为7.2～7.4；
步骤(5)中，匀浆的条件为在1000～5000rad/s的速度下匀浆1～10min。
步骤(6)中，聚四氟乙烯槽的深度为2mm；真空冷冻干燥条件为：隔板原位冷冻温度-60℃，冷阱温度-55℃、真空度3～5Pa，时间18h。
步骤(7)中，戊二醛溶液的质量浓度为1～25％；环氧乙烷灭菌温度为55～65℃，相对湿度为30％～60％。
本发明有益的技术效果在于：
本发明基于合成支架材料的可加工性，通过材料制备工艺和参数的调节，能够实现材料性能的优化和调节。
本发明胶原蛋白是一种生物相容性良好的天然高分子，其分子结构中含有GFOGER肽段，能够促进细胞的黏附，并且胶原蛋白含有自由氨基和羧基，能够与其他蛋白和多糖物质如小肠黏膜下层脱细胞基质裂解物，发生化学交联从而获得具有一定体内稳定性和可降解性的组织修复材料。
本发明通过将小肠黏膜下层脱细胞基质裂解化，并将相应产物及其所含生物活性成分与I型胶原蛋白有效地混合，实现了一种复合多孔支架的构建。通过I型胶原蛋白和小肠黏膜下层脱细胞基质裂解物充分混合，可以是活性成分均匀地分布于支架之中，并且通过戊二醛交联的固定方式，本发明实现了对小肠黏膜下层脱细胞基质裂解物活性成分的缓慢释放，本发明缓慢释放PDGF-BB生长因子的性能，累积释放时间达到5～10天，10天后逐渐进入平台期，累积释放浓度达3000pg/mg。本发明的优越性还在于，通过调节I型胶原蛋白和小肠黏膜下层脱细胞基质裂解物的初始浓度和质量比、戊二醛的浓度和交联时间，能够在很宽的范围内调控本发明所涉及组织修复材料的孔径和降解速度，实现了结构的调控。
本发明采用真空冷冻干燥处理获得胶原蛋白/小肠黏膜下层脱细胞基质裂解物组织修复生物材料，能够材料在干态下保持其多孔结构和力学特性。
附图说明
图1为埋植14d时，实施例1所得软组织修复生物材料的组织化学染色结果；
图2为埋植14d时，纯胶原蛋白支架的组织化学染色结果；
图3为Transwell实验中，实施例1所得软组织修复生物材料浸提液作用的NIH-3T3小鼠趋化；
图4为Transwell实验中，胶原蛋白浸提液诱导的NIH-3T3小鼠趋化；
图5为实施例1所得软组织修复生物材料的SEM图片；
图6为实施例2所得软组织修复生物材料的SEM图片。
具体实施方式
下面结合附图和实施例，对本发明进行具体描述。
实施例1
一种软组织修复生物材料，其制备方法包括如下步骤：
(1)用0.5M醋酸溶液溶解I型胶原蛋白，制得1w/v％的I型胶原蛋白醋酸溶液；
(2)取10cm健康成年猪近端空肠，除去多余结缔组织和肠内残留杂质，之后将组织在4℃冰箱放置10h，然后再用1.0N的氯化钠盐水浸泡6h，脱除肠上皮细胞；之后通过机械刮擦、水合方法，除去浆膜、平滑肌组织，获得小肠黏膜下层组织；
(3)将步骤(2)制得的小肠黏膜下层组织放置过氧乙酸和乙醇的混合溶液中(氧乙酸的体积分数为0.1％，乙醇的体积分数为4％)浸泡2h，之后PBS(pH7.2)润洗15min，2次；无菌水润洗15min，2次；冷冻，使用液氮冷冻粉碎机粉碎成为颗粒，过40目筛，制得小肠黏膜下层组织粉末；
(4)将1g步骤(3)制得的小肠黏膜下层组织粉末和100mg的胃蛋白酶加入50ml0.01M盐酸溶液中，25℃室温下恒速搅拌72h，得到粘性溶液，即小肠黏膜下层脱细胞基质裂解物的混合液；离心力为5000g下除去粘性溶液中的不溶物后，通过干燥除水法测定溶液中的溶质含量；之后，在冰浴条件下，向所得溶液中滴加5ml的0.1N NaOH溶液至溶液pH变为7.4；然后，加入5.5ml 0.1M的PBS，制得小肠黏膜下层脱细胞基质裂解物溶液；
(5)将10份胶原蛋白溶液与4份小肠黏膜下层脱细胞基质裂解物溶液和5份纯水，用匀浆机在1000rad/s的速度下匀浆5min后，在离心力为1500g下离心3min，除去溶液中的气泡；
(6)将离心处理的溶液转移至深度为2mm的聚四氟乙烯槽中，在37℃条件下孵育12h，使胶原蛋白和裂解物分子发生不同强度的组装，之后在真空冷冻干燥机中冷冻干燥，制得初次冻干支架；真空冷冻干燥条件为：隔板原位冷冻温度-60℃，冷阱温度-55℃、真空度3～5Pa，时间18h；
(7)将初次冻干支架放于直径30cm、抽真空的干燥器隔板之上，干燥器底部放置装有20ml质量浓度为5％的戊二醛溶液、直径为6cm的培养板，室温下反应24h，然后，将支架浸泡于超纯水中过夜，经二次冻干和环氧乙烷灭菌(灭菌温度为55℃，相对湿度为30％)得到最终的支架，即所述软组织修复生物材料。
实施例2
一种软组织修复生物材料，其制备方法包括如下步骤：
(1)用0.5M醋酸溶液溶解I型胶原蛋白，制得1w/v％的I型胶原蛋白醋酸溶液；
(2)取10cm健康成年猪近端空肠，除去多余结缔组织和肠内残留杂质，之后将组织在4℃冰箱放置6h，然后再用1.0N的氯化钠盐水浸泡12h，脱除肠上皮细胞；之后通过机械刮擦、水合方法，除去浆膜、平滑肌组织，获得小肠黏膜下层组织；
(3)将步骤(2)制得的小肠黏膜下层组织放置过氧乙酸和乙醇的混合溶液中(氧乙酸的体积分数为0.1％，乙醇的体积分数为4％)浸泡2h，之后PBS(pH7.4)润洗15min，2次；无菌水润洗15min，2次；冷冻，使用液氮冷冻粉碎机粉碎成为颗粒，过40目筛，制得小肠黏膜下层组织粉末；
(4)将1g步骤(3)制得的小肠黏膜下层组织粉末和100mg的胃蛋白酶加入100ml0.01M盐酸溶液中，25℃室温下恒速搅拌24h，得到粘性溶液，即小肠黏膜下层脱细胞基质裂解物的混合液；离心力为5000g下除去粘性溶液中的不溶物后，通过干燥除水法测定溶液中的溶质含量；之后，在冰浴条件下，向所得溶液中滴加10ml的0.1N NaOH溶液至溶液pH变为7.4；然后，加入11.1ml0.1M的PBS，制得小肠黏膜下层脱细胞基质裂解物溶液；
(5)将5份胶原蛋白溶液与2份小肠黏膜下层脱细胞基质裂解物溶液和8份纯水，用匀浆机在5000rad/s的速度下匀浆10min后，在离心力为1500g下离心3min，除去溶液中的气泡；
(6)将离心处理的溶液转移至深度为2mm的聚四氟乙烯槽中，在37℃条件下孵育24h，使胶原蛋白和裂解物分子发生不同强度的组装，之后在真空冷冻干燥机中冷冻干燥，制得初次冻干支架；真空冷冻干燥条件为：隔板原位冷冻温度-60℃，冷阱温度-55℃、真空度3～5Pa，时间18h；
(7)将初次冻干支架放于直径30cm、抽真空的干燥器隔板之上，干燥器底部放置装有20ml质量浓度为5％的戊二醛溶液、直径为6cm的培养板，室温下反应1～24h，然后，将支架浸泡于超纯水中过夜，经二次冻干和环氧乙烷灭菌(灭菌温度为65℃，相对湿度为40％)得到最终的支架，即所述软组织修复生物材料。
实施例3
一种软组织修复生物材料，其制备方法包括如下步骤：
(1)用0.5M醋酸溶液溶解I型胶原蛋白，制得1w/v％的I型胶原蛋白醋酸溶液；
(2)取10cm健康成年猪近端空肠，除去多余结缔组织和肠内残留杂质，之后将组织在4℃冰箱放置6h，然后再用1.0N的氯化钠盐水浸泡12h，脱除肠上皮细胞；之后通过机械刮擦、水合方法，除去浆膜、平滑肌组织，获得小肠黏膜下层组织；
(3)将步骤(2)制得的小肠黏膜下层组织放置过氧乙酸和乙醇的混合溶液中(氧乙酸的体积分数为0.1％，乙醇的体积分数为4％)浸泡2h，之后PBS(pH7.4)润洗15min，2次；无菌水润洗15min，2次；冷冻，使用液氮冷冻粉碎机粉碎成为颗粒，过40目筛，制得小肠黏膜下层组织粉末；
(4)将1g步骤(3)制得的小肠黏膜下层组织粉末和100mg的胃蛋白酶加入100ml0.01M盐酸溶液中，25℃室温下恒速搅拌24h，得到粘性溶液，即小肠黏膜下层脱细胞基质裂解物的混合液；离心力为5000g下除去粘性溶液中的不溶物后，通过干燥除水法测定溶液中的溶质含量；之后，在冰浴条件下，向所得溶液中滴加10ml的0.1N NaOH溶液至溶液pH变为7.4；然后，加入11.1ml0.1M的PBS，制得小肠黏膜下层脱细胞基质裂解物溶液；
(5)将5份胶原蛋白溶液与2份小肠黏膜下层脱细胞基质裂解物溶液和8份纯水，用匀浆机在3000rad/s的速度下匀浆8min后，在离心力为1500g下离心3min，除去溶液中的气泡；
(6)将离心处理的溶液转移至深度为2mm的聚四氟乙烯槽中，在37℃条件下孵育24h，使胶原蛋白和裂解物分子发生不同强度的组装，之后在真空冷冻干燥机中冷冻干燥，制得初次冻干支架；真空冷冻干燥条件为：隔板原位冷冻温度-60℃，冷阱温度-55℃、真空度3～5Pa，时间18h；
(7)将初次冻干支架放于直径30cm、抽真空的干燥器隔板之上，干燥器底部放置装有20ml质量浓度为20％的戊二醛溶液、直径为6cm的培养板，室温下反应14h，然后，将支架浸泡于超纯水中过夜，经二次冻干和环氧乙烷灭菌(灭菌温度为60℃，相对湿度为60％)得到最终的支架，即所述软组织修复生物材料。
对比例1
(1)用0.5M的醋酸溶液溶解I型胶原蛋白(2％，w/v)，在离心力为1500g下离心3min，除去溶液中的气泡；
(2)将所得溶液转移至聚四氟乙烯槽中，溶液的厚度为2mm，在真空冷冻干燥机中冷冻干燥，真空冷冻干燥条件为：隔板原位冷冻温度-60℃，冷阱温度-55℃、真空度3～5Pa，时间18h；
(3)将初次冻干支架放于直径30cm、抽真空的干燥器隔板之上，干燥器底部放置装有20ml的(5％)戊二醛溶液、直径为6cm的培养板，室温下反应3h，然后，将支架浸泡于超纯水中过夜，经二次冻干和环氧乙烷灭菌得到最终的支架。
测试例：
(1)将实施例1-3制得的生物材料切割为5×5×2mm3的长方体，称重后放入5ml的离心管底部，加入3ml释放液(％0.1牛血清白蛋白、0.1％NaN3的PBS溶液)，测试支架材料累积释放PDGF-BB的性能，测试结果如表1所示。
表1
项目 实施例1 实施例2 实施例3 对比例1
累积释放时间(天) 10 7 7 —
累积释放浓度(ng/ml) 4.26 1.17 0.96 低于最低检测限
(2)通过SEM测试材料的微观形貌已经通过压汞仪测试材料的孔径，测试结果如图5、6和表2所示。
表2
项目 实施例1 实施例2 实施例3 对比例1
形貌 多孔 多孔 多孔 多孔
平均孔径(μm) 139 514 472 695
SEM和压汞仪测试结果表明，实施例1所得支架材料的平均孔径范围为50～300微米(图5)，明显低于实施例2所得支架材料(400～800微米)(图6)。原因在于：浓度的改变使冷冻过程中冰晶形成的形状和大小发生改变，在隔板原位冷冻温度-60℃的条件下，胶原蛋白和裂解液总浓度为2.5mg/ml的溶液形成的冰晶平均直径为30～80微米，而总浓度为1mg/ml的溶液形成冰晶平均直径为150～500微米。冰晶的大小与冷冻干燥后支架的孔径呈正相关性。因此通过调节溶液的浓度，实现了对于材料结构的调控。
(3)通过小鼠皮下埋植模型观察材料对内生性细胞迁移进入支架影响。将实施例1和对比例1的材料剪裁为直径为5mm、厚度为1.5mm支架，植入小鼠背部皮肤肉膜和筋膜之间的口袋。通过H&E染色观察内源性细胞长入支架的情况。结果见图1(实施例1)和图2(对比例2)。
由图可以看出，小鼠背部皮肤肉膜下埋植3天后，内源性细胞开始长入支架；相比埋植3天，埋植14天后支架中均出现更多细胞，实施例1材料中的细胞较对比例1材料中的细胞分布更为密集，并且，大量细胞出现在实施例1材料远离肉膜-材料界面的材料内部区域，而仅有少量细胞出现在对比例1的相应区域。
(4)通过Transwell实验观察真皮成纤维细胞和微血管内皮细胞在实施例1及对比例1所得材料对NIH-3T3成纤维细胞趋化影响。NIH-3T3成纤维细胞的接种密度为2×104/cm2，结果见图3和图4。
由图可以看出，通过匀浆作用，小肠黏膜下层脱细胞基质裂解物的成分均匀的分散在胶原蛋白网络中，PDGF-BB活性分子能够从支架中逐渐释放，累积释放时间最常达到了7天。理论上，与支架中的糖胺聚糖、collagen IV等分子的特异性结合，加上高分子网络对分子的屏障作用，使活性分子能缓慢从支架中释放，从而发挥持久的细胞趋化作用。

Claims (7)

1.一种软组织修复生物材料，其特征在于，所述生物材料的制备方法包括如下步骤：
(1)用醋酸溶液溶解I型胶原蛋白，制得I型胶原蛋白醋酸溶液；
(2)取10-18cm健康成年猪近端空肠，除去多余结缔组织和肠内残留杂质，之后盐水脱细胞，脱除肠上皮细胞；之后通过机械刮擦、水合方法，除去浆膜、平滑肌组织，获得小肠黏膜下层组织；
(3)将步骤(2)制得的小肠黏膜下层组织放置过氧乙酸和乙醇的混合溶液中浸泡2h，之后PBS润洗15min，2次；无菌水润洗15min，2次；冷冻，使用液氮冷冻粉碎机粉碎成为颗粒，过40目筛，制得小肠黏膜下层组织粉末；
(4)将1g步骤(3)制得的小肠黏膜下层组织粉末和100mg的胃蛋白酶加入20～100ml0.01M盐酸溶液中，25℃室温下恒速搅拌10～72h，得到粘性溶液，即小肠黏膜下层脱细胞基质裂解物的混合液；离心力为5000g下除去粘性溶液中的不溶物后，通过干燥除水法测定溶液中的溶质含量；之后，在冰浴条件下，向所得溶液中滴加2～10ml的0.1N NaOH溶液至溶液pH变为7.4；然后，加入2.2～11.1ml 0.1M的PBS，制得小肠黏膜下层脱细胞基质裂解物溶液；
(5)将5～10份胶原蛋白溶液与0.5～5份小肠黏膜下层脱细胞基质裂解物溶液和0～10份纯水，用匀浆机匀浆后，在离心力为1500g下离心3min，除去溶液中的气泡；
(6)将离心处理的溶液转移至聚四氟乙烯槽中，在37℃条件下孵育0.5～24h，使胶原蛋白和裂解物分子发生不同强度的组装，之后在真空冷冻干燥机中冷冻干燥，制得初次冻干支架；
(7)将初次冻干支架放于直径30cm、抽真空的干燥器隔板之上，干燥器底部放置装有20ml戊二醛溶液、直径为6cm的培养板，室温下反应1～24h，然后，将支架浸泡于超纯水中过夜，经二次冻干和环氧乙烷灭菌得到最终的支架，即所述软组织修复生物材料。
2.根据权利要求1所述的软组织修复生物材料，其特征在于，步骤(1)中，醋酸的浓度为0.5M；I型胶原蛋白与醋酸的质量体积比为0.5～2％。
3.根据权利要求1所述的软组织修复生物材料，其特征在于，步骤(2)中，盐水脱细胞的方法为：将组织在4℃冰箱放置0.5～10h，然后再用1.0N的氯化钠盐水浸泡1h-24h。
4.根据权利要求1所述的软组织修复生物材料，其特征在于，步骤(3)中，氧乙酸和乙醇的混合溶液中过氧乙酸的体积分数为0.1％，乙醇的体积分数为4％；PBS的pH为7.2～7.4。
5.根据权利要求1所述的软组织修复生物材料，其特征在于，步骤(5)中，匀浆的条件为在1000～5000rad/s的速度下匀浆1～10min。
6.根据权利要求1所述的软组织修复生物材料，其特征在于，步骤(6)中，聚四氟乙烯槽的深度为2mm；真空冷冻干燥条件为：隔板原位冷冻温度-60℃，冷阱温度-55℃、真空度3～5Pa，时间18h。
7.根据权利要求1所述的软组织修复生物材料，其特征在于，步骤(7)中，戊二醛溶液的质量浓度为1～25％；环氧乙烷灭菌温度为55～65℃，相对湿度为30％～60％。
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114540267A (zh) * 2022-01-27 2022-05-27 广东省农业科学院动物科学研究所 一种关于仔猪肠黏膜的不同浓度胶原蛋白网络体外制备方法
WO2023231195A1 (zh) * 2022-05-31 2023-12-07 南开大学 一种脱细胞基质组织纸的制备方法及应用
CN117797172A (zh) * 2024-02-28 2024-04-02 合肥启色生物科技有限公司 一种抗炎、止血、促愈合的组合体的制备方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003002168A1 (en) * 2001-06-29 2003-01-09 Cook Biotech Incorporated Porous sponge matrix medical devices and methods
GB0722984D0 (en) * 2003-08-25 2008-01-30 Cook Biotech Inc Graft materials containing bioactive substances, and methods for their manufacture
CN104307046A (zh) * 2014-10-27 2015-01-28 王黎明 一种可注射骨髓间充质干细胞外基质/琼脂糖复合水凝胶及其制备方法和应用
CN105169483A (zh) * 2015-10-20 2015-12-23 中山大学 一种脱细胞基质凝胶的制备方法及其脱细胞基质凝胶
CN105999410A (zh) * 2016-05-05 2016-10-12 广州昕生医学材料有限公司 脱细胞组织基质复合材料及其制备方法
CN106729984A (zh) * 2016-12-22 2017-05-31 青岛琛蓝海洋生物工程有限公司 一种鱼胶原蛋白修复海绵及其制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003002168A1 (en) * 2001-06-29 2003-01-09 Cook Biotech Incorporated Porous sponge matrix medical devices and methods
GB0722984D0 (en) * 2003-08-25 2008-01-30 Cook Biotech Inc Graft materials containing bioactive substances, and methods for their manufacture
CN104307046A (zh) * 2014-10-27 2015-01-28 王黎明 一种可注射骨髓间充质干细胞外基质/琼脂糖复合水凝胶及其制备方法和应用
CN105169483A (zh) * 2015-10-20 2015-12-23 中山大学 一种脱细胞基质凝胶的制备方法及其脱细胞基质凝胶
CN105999410A (zh) * 2016-05-05 2016-10-12 广州昕生医学材料有限公司 脱细胞组织基质复合材料及其制备方法
CN106729984A (zh) * 2016-12-22 2017-05-31 青岛琛蓝海洋生物工程有限公司 一种鱼胶原蛋白修复海绵及其制备方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
RISHENG ZHONG ET AL: ""Novel Biodegradable Antimicrobial Composite Scaffold by Coating Type I Collagen Scaffold with Pepsin-Degraded SIS Extraction"", 《IOP CONFERENCE SERIES: MATERIALS SCIENCE AND ENGINEERING》 *
孙慧哲等: ""猪小肠黏膜下层海绵的构建与细胞黏附性观察"", 《中国组织工程研究》 *
许洁等: "大鼠子宫去细胞支架及其细胞外基质凝胶的制备", 《生物医学工程学杂志》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114540267A (zh) * 2022-01-27 2022-05-27 广东省农业科学院动物科学研究所 一种关于仔猪肠黏膜的不同浓度胶原蛋白网络体外制备方法
WO2023231195A1 (zh) * 2022-05-31 2023-12-07 南开大学 一种脱细胞基质组织纸的制备方法及应用
CN117797172A (zh) * 2024-02-28 2024-04-02 合肥启色生物科技有限公司 一种抗炎、止血、促愈合的组合体的制备方法
CN117797172B (zh) * 2024-02-28 2024-05-14 合肥启色生物科技有限公司 一种抗炎、止血、促愈合的组合体的制备方法

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