CN110721346A - A kind of biological 3D printing ink and preparation method thereof - Google Patents
A kind of biological 3D printing ink and preparation method thereofDownload PDFInfo
- Publication number
- CN110721346A CN110721346ACN201911046255.0ACN201911046255ACN110721346ACN 110721346 ACN110721346 ACN 110721346ACN 201911046255 ACN201911046255 ACN 201911046255ACN 110721346 ACN110721346 ACN 110721346A
- Authority
- CN
- China
- Prior art keywords
- preparation
- gelatin
- cross
- sodium alginate
- biological
- 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.)
- Granted
Links
Images
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
- A61L27/52—Hydrogels or hydrocolloids
- 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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
- 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
- A61L27/56—Porous materials, e.g. foams or sponges
- 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
- A61L27/60—Materials for use in artificial skin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Dispersion Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Composite Materials (AREA)
- Materials Engineering (AREA)
- Materials For Medical Uses (AREA)
Abstract
Translated fromChinese
Description
Translated fromChinese技术领域technical field
本发明涉及医疗模型制造及应用领域，特别涉及一种生物3D打印墨水及其制备方法。The invention relates to the field of medical model manufacturing and application, in particular to a biological 3D printing ink and a preparation method thereof.
背景技术Background technique
皮肤是人体最大的器官，对维持人体内环境的稳态和机体的正常生理功能具有十分重要的作用，由于暴露于外界环境中，皮肤的破损、缺失时常发生，对于较小的皮肤缺损，机体可以通过自身代偿达到一定程度的完全再生，但是对于较大的创面来说，皮肤一般进行瘢痕修复，而对于更大的创面，皮肤的缺损常常延迟愈合或无法愈合，此种创面使患者的机体直接暴露于外界环境中，不仅无法维持机体的体液平衡，还使得患者暴露于高危的感染风险之下，因此及时的封闭创面就显得十分必要，以往，临床工作中常常采用无菌纱布进行创面覆盖，以起到隔绝细菌、保护创面的作用，最终的创面愈合还依赖于患者创面自身的愈合能力，而对于糖尿病患者和局部血运不良的患者，依靠自身的修复能力很难做到创面的封闭，因此，如何解决此类修复功能不足的创面成为临床工作中的一大难点。The skin is the largest organ of the human body and plays a very important role in maintaining the homeostasis of the internal environment of the human body and the normal physiological functions of the body. Due to exposure to the external environment, skin damage and loss often occur. A certain degree of complete regeneration can be achieved through self-compensation, but for larger wounds, the skin generally undergoes scar repair, while for larger wounds, skin defects often delay healing or fail to heal. The body is directly exposed to the external environment, which not only fails to maintain the body's fluid balance, but also exposes the patient to a high risk of infection. Therefore, it is very necessary to seal the wound in time. In the past, sterile gauze was often used in clinical work. Covering to isolate bacteria and protect the wound. The final wound healing also depends on the patient's own wound healing ability. For diabetic patients and patients with local poor blood supply, it is difficult to achieve wound healing by relying on their own repair ability. Therefore, how to solve such wounds with insufficient repair function has become a major difficulty in clinical work.
随着组织工程技术的日新月异，3D打印技术和载细胞水凝胶正逐渐成为人们关注的重点，理想的创面敷料应具备黏附创面、柔软、透气/透水、维持内环境稳态等基本特征，同时还能够形成保水层，此外，还应具备便于携带、使用的特性，而水凝胶因其能同时满足以上的要求，被广泛应用于生物敷料的研发中。With the rapid development of tissue engineering technology, 3D printing technology and cell-loaded hydrogels are gradually becoming the focus of attention. It can also form a water-retaining layer, and in addition, it should have the characteristics of being easy to carry and use, and hydrogels are widely used in the research and development of biological dressings because they can meet the above requirements at the same time.
与以往组织工程的种子细胞向支架材料迁移，并辅助以促进再生的微环境不同，载细胞生物墨水可以将生物材料、种子细胞以及再生微环境融为一体，极大的提高了组织工程皮肤在临床应用的可能，而在载细胞水凝胶的研制过程中，生物材料的选择应用以及适当地加入再生微环境是目前研究的重点，明胶因其出色的生物降解性、生物相容性、高细胞附着和增殖以及低免疫原性等被广泛应用于伤口敷料的研究中，在以往的研究中，明胶-海藻酸钠载细胞生物墨水不仅具有良好的生物相容性，还能提高细胞的迁移、增殖和分化的能力，然而在实际应用的过程中，明胶-海藻酸钠载细胞生物墨水的打印胶块硬度较低，导致质地较软，难以应用于动物的创面模型。Different from the microenvironment in which the seed cells migrate to the scaffold material in the previous tissue engineering and assist to promote regeneration, the cell-loaded bioink can integrate the biological material, the seed cells and the regenerative microenvironment, which greatly improves the performance of tissue-engineered skin. The possibility of clinical application, and in the development of cell-loaded hydrogels, the selection and application of biomaterials and the appropriate addition of regenerative microenvironment are the current research focus. Gelatin is due to its excellent biodegradability, biocompatibility, high Cell attachment and proliferation and low immunogenicity are widely used in wound dressing research. In previous studies, gelatin-sodium alginate cell-loaded bioink not only has good biocompatibility, but also improves cell migration. However, in the process of practical application, the printing gel block of gelatin-sodium alginate cell-loaded bioink has low hardness, resulting in a soft texture, which is difficult to apply to animal wound models.
发明内容SUMMARY OF THE INVENTION
为了解决以上技术问题，本发明提供了一种生物3D打印墨水及其制备方法，In order to solve the above technical problems, the present invention provides a biological 3D printing ink and a preparation method thereof,
本发明提供了一种应用于生物3D打印墨水的改性纳米生物玻璃粒子，该改性纳米生物玻璃粒子的制备方法如下：制备氢氧化钙饱和溶液，在氢氧化钙饱中加入二氧化硅纳米粒子悬液、离心、取沉淀；即得改性纳米生物玻璃粒子。The invention provides a modified nano bio-glass particle applied to biological 3D printing ink. The preparation method of the modified nano bio-glass particle is as follows: preparing a calcium hydroxide saturated solution, adding silica nano-particles into the calcium hydroxide saturated solution Particle suspension, centrifugation, and sedimentation; namely, the modified nano-biological glass particles are obtained.
本发明还提供了一种由改性纳米生物玻璃粒子和明胶-海藻酸钠复合水凝胶、交联剂制备的生物3D打印墨水，其中，改性纳米生物玻璃粒子、明胶-海藻酸钠复合水凝胶和交联剂的质量比为100-120:1-1:10-12The present invention also provides a biological 3D printing ink prepared from modified nano-biological glass particles, gelatin-sodium alginate composite hydrogel, and a cross-linking agent, wherein the modified nano-biological glass particles, gelatin-sodium alginate composite hydrogel, and The mass ratio of hydrogel and crosslinker is 100-120:1-1:10-12
本发明还提供了一种生物3D打印墨水的制备方法，该制备方法包括以下步骤：The present invention also provides a preparation method of biological 3D printing ink, and the preparation method comprises the following steps:
S1：改性纳米生物玻璃粒子的制备：制备氢氧化钙饱和溶液，在氢氧化钙饱中加入二氧化硅纳米粒子悬液、离心、取沉淀；即得改性纳米生物玻璃粒子；S1: Preparation of modified nano-biological glass particles: prepare a saturated solution of calcium hydroxide, add silica nanoparticle suspension to the saturated calcium hydroxide, centrifuge, and take the precipitate; namely, to obtain modified nano-biological glass particles;
S2：明胶-海藻酸钠复合水凝胶的制备：将明胶和海藻酸钠溶解于去离子水中溶解，再加入步骤S1制得的改性纳米生物玻璃粒子，搅拌均匀制得液态水凝胶，消毒、平衡，即得明胶-海藻酸钠复合水凝胶；S2: Preparation of gelatin-sodium alginate composite hydrogel: dissolve gelatin and sodium alginate in deionized water, then add the modified nano-bioglass particles obtained in step S1, and stir evenly to obtain a liquid hydrogel, Sterilize and balance to obtain gelatin-sodium alginate composite hydrogel;
S3：交联剂的制备：将氯化钙固体粉末溶解于去离子水中，制得氯化钙溶液，消毒灭菌，即得交联剂；S3: Preparation of cross-linking agent: dissolving calcium chloride solid powder in deionized water to obtain calcium chloride solution, sterilizing and sterilizing to obtain cross-linking agent;
S4：在明胶-海藻酸钠复合水凝胶中加入交联剂进行交联，即得生物3D打印墨水。S4: adding a cross-linking agent to the gelatin-sodium alginate composite hydrogel for cross-linking to obtain a bio-3D printing ink.
进一步地改进，步骤S1的制备氢氧化钙饱和溶液具体包括以下步骤：称量氢氧化钙固体粉末置于烧杯中，加入去离子水使氢氧化钙固体粉末在去离子水中的浓度为1.6-1.7g/L，用恒温磁力搅拌器搅拌12h以上，搅拌过程中将烧杯密封，搅拌结束后离心，弃沉淀，取上清，即得氢氧化钙饱和溶液。Further improvement, the preparation of calcium hydroxide saturated solution in step S1 specifically includes the following steps: weighing calcium hydroxide solid powder and placing it in a beaker, adding deionized water to make the concentration of calcium hydroxide solid powder in deionized water 1.6-1.7 g/L, stir with a constant temperature magnetic stirrer for more than 12 hours, seal the beaker during the stirring process, centrifuge after stirring, discard the precipitate, and take the supernatant to obtain a saturated calcium hydroxide solution.
进一步地改进，步骤S1中的在氢氧化钙饱中加入二氧化硅纳米粒子悬液、离心、取沉淀具体包括以下步骤：取氢氧化钙饱和溶液置于烧杯中，加入40wt％二氧化硅纳米粒子悬液，氢氧化钙饱和溶液与40wt％二氧化硅纳米粒子悬液的体积比为40:6-7，将烧杯置于恒温磁力搅拌器上搅拌，搅拌时间不少于72h，搅拌过程中保持烧杯为密封状态，搅拌后离心，取沉淀，加入去离子水洗涤，再离心，取沉淀，加水洗涤，如此往复洗涤三次，取沉淀。Further improvement, in step S1, adding silica nanoparticle suspension, centrifugation, and taking the precipitate into the saturated calcium hydroxide specifically include the following steps: taking the saturated calcium hydroxide solution and placing it in a beaker, adding 40wt% silica nanoparticle Particle suspension, the volume ratio of calcium hydroxide saturated solution and 40wt% silica nanoparticle suspension is 40:6-7, the beaker is placed on a constant temperature magnetic stirrer and stirred, and the stirring time is not less than 72h. During the stirring process Keep the beaker in a sealed state, centrifuge after stirring, take the precipitate, add deionized water to wash, centrifuge again, take the precipitate, add water to wash, and wash it back and forth three times to take the precipitate.
其中，离心速度为1500rpm，离心时间为5min。Among them, the centrifugation speed was 1500rpm, and the centrifugation time was 5min.
进一步地改进，步骤S2的明胶为A型明胶，来源于猪皮。Further improvement, the gelatin of step S2 is A-type gelatin, which is derived from pig skin.
进一步地改进，步骤S2的将明胶和海藻酸钠溶解于去离子水中溶解，再加入步骤S1制得的改性纳米生物玻璃粒子，搅拌均匀制得液态水凝胶具体为：称取明胶和海藻酸钠置于小烧杯中，加入去离子水，明胶在去离子水中的浓度为0.01g/ml，海藻酸钠在去离子水中的浓度为0.03g/ml，密封烧杯，在40℃±5条件下的水浴锅内溶解25-35min，加入步骤S1制得的改性纳米生物玻璃粒子，再次密封烧杯，使用恒温磁力搅拌器在40±5℃条件下搅拌1.5-2.5h，即得液态水凝胶。Further improvement, in step S2, the gelatin and sodium alginate are dissolved in deionized water to dissolve, and then the modified nano-biological glass particles obtained in step S1 are added, and the liquid hydrogel is prepared by stirring evenly. Specifically: Weighing gelatin and seaweed Place sodium in a small beaker, add deionized water, the concentration of gelatin in deionized water is 0.01g/ml, and the concentration of sodium alginate in deionized water is 0.03g/ml, seal the beaker, at 40℃±5 Dissolve in the water bath under the lower temperature for 25-35min, add the modified nano-bioglass particles obtained in step S1, seal the beaker again, and use a constant temperature magnetic stirrer to stir at 40±5℃ for 1.5-2.5h, that is, liquid water condensation is obtained. glue.
进一步地改进，步骤S2的消毒、平衡具体包括以下步骤：将液态水凝胶在70℃水浴条件下处理30min，再放置于4℃冷浴5min，重复3次，消毒完成后放室温条件下平衡1h，用封口膜密封后放置于4℃条件下保存。Further improvement, the disinfection and balancing of step S2 specifically includes the following steps: treating the liquid hydrogel in a 70°C water bath for 30 minutes, then placing it in a 4°C cold bath for 5 minutes, repeating 3 times, and equilibrating at room temperature after the disinfection is completed. 1h, sealed with parafilm and stored at 4°C.
进一步地改进，步骤S3的交联剂的制备具体包括以下步骤：称氯化钙固体粉末置于烧杯中，加入去离子水，每1000ml去离子水中添加25g氯化钙固体粉末，置于恒温磁力搅拌器搅拌25-35min，得到2.5％的氯化钙溶液，转移至耐高温玻璃瓶，高压锅高压消毒灭菌后密封，放4℃保存，即得交联剂。Further improvement, the preparation of the crosslinking agent in step S3 specifically includes the following steps: weigh the calcium chloride solid powder and place it in a beaker, add deionized water, add 25g calcium chloride solid powder per 1000ml of deionized water, and place it in a constant temperature magnetic force. Stir with a stirrer for 25-35min to obtain a 2.5% calcium chloride solution, transfer it to a high temperature resistant glass bottle, sterilize it in a high pressure cooker, seal it, and store it at 4°C to obtain a crosslinking agent.
进一步地改进，步骤S4的在明胶-海藻酸钠复合水凝胶中加入交联剂进行交联具体为：取交联剂滴加到3D打印块表面至交联剂完全覆盖打印块，交联10min后去除交联剂，用DMEM完全培养基冲洗一遍。To further improve, adding a cross-linking agent to the gelatin-sodium alginate composite hydrogel for cross-linking in step S4 is as follows: drop the cross-linking agent onto the surface of the 3D printing block until the cross-linking agent completely covers the printing block, and cross-link for 10 minutes. After removing the cross-linking agent, rinse once with DMEM complete medium.
本发明还提供了改性纳米生物玻璃粒子在制备力学性能、成胶性能良好、孔隙丰富和具有很好的载细胞潜能的生物3D打印墨水中的应用。The invention also provides the application of the modified nano-bioglass particles in preparing the biological 3D printing ink with good mechanical properties, good gel-forming properties, abundant pores and good cell-carrying potential.
本发明所提供的生物3D打印墨水的制备方法制备的生物3D打印墨水不仅力学性能显著提高且成胶性能良好、孔隙丰富，具有很好的载细胞潜能。此外，在载细胞实验中，该水凝胶还能保持完好的形态，具备优越的临床应用潜力。The biological 3D printing ink prepared by the preparation method of the biological 3D printing ink provided by the present invention not only has significantly improved mechanical properties, but also has good gel-forming properties, abundant pores, and good cell-carrying potential. In addition, in the cell loading experiment, the hydrogel can maintain the intact morphology, which has excellent clinical application potential.
附图说明Description of drawings
附图1.为改性前后的纳米生物玻璃粒子的外观图片，其中，A为改性前的纳米生物玻璃粒子的外观图片，B为改性纳米生物玻璃粒子的外观图片；
附图2.为改性纳米生物玻璃粒子加入到明胶、海藻酸钠水凝胶中，充分搅拌混匀后制得的液态水凝胶分别在室温和37℃条件下放置72h后的状态图；其中A是改性纳米生物玻璃粒子制得的液态水凝胶在37℃条件下放置72h后的状态图；B是未改性纳米生物玻璃粒子制得的液态水凝胶在37℃条件下放置72h后的状态图；C是改性纳米生物玻璃粒子制得的液态水凝胶在室温下放置72h后的状态图；D是未改性纳米生物玻璃粒子制得的液态水凝胶在室温下放置72h后的状态图；Accompanying drawing 2 is the state diagram of the liquid hydrogel obtained after the modified nano-biological glass particles are added to gelatin and sodium alginate hydrogel, and are placed at room temperature and 37° C. for 72 hours, respectively; Among them, A is the state diagram of the liquid hydrogel prepared from the modified nano-biological glass particles after being placed at 37 °C for 72 hours; B is the liquid hydrogel prepared by the unmodified nano-biological glass particles placed at 37 °C. The state diagram after 72h; C is the state diagram of the liquid hydrogel prepared by the modified nano-biological glass particles after being placed at room temperature for 72 hours; D is the liquid hydrogel prepared by the unmodified nano-biological glass particles at room temperature State diagram after 72h placement;
附图3.是将第三代小鼠成纤维细胞与凝胶混合后交联培养和培养三天后的形状图片，其中，A是实施例的水凝胶载细胞交联后的状态图；B是对照例的水凝胶载细胞交联后的状态图；C是实施例的水凝胶载细胞培养3天后的水凝胶的状态图；D是对照例的水凝胶载细胞培养3天后的水凝胶的状态图；Accompanying drawing 3. is the shape picture after the third generation mouse fibroblast is mixed with the gel and cross-linked and cultured for three days, wherein, A is the state diagram of the hydrogel-loaded cells of the embodiment after cross-linking; B is the state diagram of the hydrogel-loaded cells of the control example after cross-linking; C is the state diagram of the hydrogel of the embodiment after culturing the hydrogel-loaded cells for 3 days; D is the hydrogel-loaded cells of the control example after culturing for 3 days The state diagram of the hydrogel;
附图4.为试验例4的细胞存活率和细胞抑制率的柱状图；其中，BG为实施例，con为对照例。Fig. 4 is a bar graph of the cell survival rate and cell inhibition rate of Test Example 4; wherein, BG is an example, and con is a control example.
具体实施方式Detailed ways
下面结合实施例，对本发明进一步说明；下述实施例是说明性的，不是限定性的，不能以下述实施例来限定本发明的保护范围；本发明中所使用的设备，如无特殊规定，均为本领域内常用的设备；本发明中所使用的方法，如无特殊规定，均为本领域内常用的方法。The present invention is further described below in conjunction with the examples; the following examples are illustrative, not restrictive, and the protection scope of the present invention cannot be limited by the following examples; the equipment used in the present invention, unless otherwise specified, All are equipment commonly used in the field; the methods used in the present invention, unless otherwise specified, are all commonly used methods in the field.
实施例1Example 1
本实施例提供了一种改性纳米生物玻璃粒子，该改性纳米生物玻璃粒子由以下方法制备而成：称量1.65g氢氧化钙固体粉末置于烧杯中，加入1000ml去离子水后用恒温磁力搅拌器搅拌，搅拌速度为1500r/min，搅拌时间为12h，搅拌过程中将烧杯密封，搅拌结束后离心，弃沉淀，取上清，即得氢氧化钙饱和溶液，取400ml氢氧化钙饱和溶液置于烧杯中，加入67ml的40wt％二氧化硅纳米粒子悬液，将烧杯置于恒温磁力搅拌器上搅拌，搅拌时间为72h，搅拌速度为200r/min，搅拌过程中保持烧杯为密封状态，搅拌后离心5500rpm，10min，取沉淀，加入去离子水洗涤，再离心，取沉淀，加水洗涤，如此往复洗涤三次，取沉淀，即得改性纳米生物玻璃粒子。This embodiment provides a modified nano-biological glass particle. The modified nano-biological glass particle is prepared by the following method: Weighing 1.65g calcium hydroxide solid powder and placing it in a beaker, adding 1000ml deionized water, and using a constant temperature Stir with a magnetic stirrer, the stirring speed is 1500 r/min, and the stirring time is 12 h. During the stirring process, the beaker is sealed. After stirring, centrifuge, discard the precipitate, and take the supernatant to obtain a saturated calcium hydroxide solution. Take 400 ml of calcium hydroxide saturated The solution was placed in a beaker, 67ml of 40wt% silica nanoparticle suspension was added, and the beaker was stirred on a constant temperature magnetic stirrer. The stirring time was 72h, and the stirring speed was 200r/min. During the stirring process, the beaker was kept in a sealed state. , after stirring, centrifuge at 5500 rpm for 10 min, take the precipitate, add deionized water to wash, centrifuge again, take the precipitate, add water to wash, so repeat washing three times, take the precipitate to obtain modified nano-bioglass particles.
实施例2Example 2
本实施例提供了一种生物3D打印墨水的制备方法，该制备方法包括以下步骤：The present embodiment provides a preparation method of biological 3D printing ink, and the preparation method includes the following steps:
S1：称量1.65g氢氧化钙固体粉末置于烧杯中，加入1000ml去离子水后用恒温磁力搅拌器搅拌，搅拌速度为1500r/min，搅拌时间为12h，搅拌过程中将烧杯密封，搅拌结束后离心，弃沉淀，取上清，即得氢氧化钙饱和溶液，取400ml氢氧化钙饱和溶液置于烧杯中，加入67ml的40wt％二氧化硅纳米粒子悬液，将烧杯置于恒温磁力搅拌器上搅拌，搅拌时间为72h，搅拌速度为200r/min，搅拌过程中保持烧杯为密封状态，搅拌后离心5500rpm，10min，取沉淀，加入去离子水洗涤，再离心，取沉淀，加水洗涤，如此往复洗涤三次，取沉淀，即得改性纳米生物玻璃粒子；S1: Weigh 1.65g of calcium hydroxide solid powder into a beaker, add 1000ml of deionized water and stir with a constant temperature magnetic stirrer, the stirring speed is 1500r/min, the stirring time is 12h, the beaker is sealed during the stirring process, and the stirring is over After centrifugation, discard the precipitation, take the supernatant to obtain a saturated calcium hydroxide solution, take 400 ml of the saturated calcium hydroxide solution and place it in a beaker, add 67 ml of 40wt% silica nanoparticle suspension, and place the beaker in a constant temperature magnetic stirring Stir on the machine, the stirring time is 72h, the stirring speed is 200r/min, the beaker is kept in a sealed state during the stirring process, and after stirring, centrifuge at 5500rpm for 10min, take the precipitate, add deionized water to wash, centrifuge again, take the precipitate, add water to wash, Repeatedly washing in this way for three times, taking the precipitate to obtain the modified nano-biological glass particles;
S2：称取0.1g的A型明胶来源于猪皮和0.3g海藻酸钠置于小烧杯中，加入10ml去离子水，密封烧杯，在40℃条件下的水浴锅内溶解30min，加入步骤S1制得的改性纳米生物玻璃粒子，再次密封烧杯，使用恒温磁力搅拌器在40℃条件下搅拌2h，搅拌速度为200r/min，即得液态水凝胶，将液态水凝胶在70℃水浴条件下处理30min，再放置于4℃冷浴5min，重复3次，消毒完成后放室温条件下平衡1h，用封口膜密封后放置于4℃条件下保存，即得明胶-海藻酸钠复合水凝胶；S2: Weigh 0.1 g of Type A gelatin from pigskin and 0.3 g of sodium alginate into a small beaker, add 10 ml of deionized water, seal the beaker, dissolve in a water bath at 40°C for 30 minutes, and add step S1 The obtained modified nano-biological glass particles were sealed again in the beaker, and stirred at 40 °C for 2 h with a constant temperature magnetic stirrer, and the stirring speed was 200 r/min to obtain a liquid hydrogel, and the liquid hydrogel was placed in a 70 °C water bath. Treated for 30 minutes under conditions, then placed in a cold bath at 4 °C for 5 minutes, repeated 3 times, after disinfection was completed, placed at room temperature for 1 hour, sealed with parafilm, and then stored at 4 °C to obtain gelatin-sodium alginate composite water gel;
S3：称2.5g氯化钙固体粉末置于烧杯中，加入100ml去离子水，置于恒温磁力搅拌器搅拌30min，得到2.5％的氯化钙溶液，转移至耐高温玻璃瓶，高压锅高压消毒灭菌后密封，放4℃保存，即得交联剂；S3: Weigh 2.5g of calcium chloride solid powder into a beaker, add 100ml of deionized water, place it in a constant temperature magnetic stirrer and stir for 30min to obtain a 2.5% calcium chloride solution, transfer it to a high temperature resistant glass bottle, sterilize it in an autoclave After the bacteria, seal it and store it at 4°C to obtain the cross-linking agent;
S4：在明胶-海藻酸钠复合水凝胶中加入交联剂进行交联，即得生物3D打印墨水。S4: adding a cross-linking agent to the gelatin-sodium alginate composite hydrogel for cross-linking to obtain a bio-3D printing ink.
对照例1Comparative Example 1
本对照例提供了一种生物3D打印墨水的制备方法，该制备方法包括以下步骤：This comparative example provides a preparation method of biological 3D printing ink, and the preparation method includes the following steps:
S1：称取0.1g的A型明胶来源于猪皮和0.3g海藻酸钠置于小烧杯中，加入10ml去离子水，密封烧杯，在40℃条件下的水浴锅内溶解30min，再次密封烧杯，使用恒温磁力搅拌器在40,℃条件下搅拌2h，搅拌速度为200r/min，即得液态水凝胶，将液态水凝胶在70℃水浴条件下处理30min，再放置于4℃冷浴5min，重复3次，消毒完成后放室温条件下平衡1h，用封口膜密封后放置于4℃条件下保存，即得明胶-海藻酸钠复合水凝胶；S1: Weigh 0.1g of Type A gelatin from pigskin and 0.3g of sodium alginate into a small beaker, add 10ml of deionized water, seal the beaker, dissolve in a water bath at 40°C for 30min, and seal the beaker again , use a constant temperature magnetic stirrer to stir at 40, ℃ for 2h, and the stirring speed is 200r/min, that is, liquid hydrogel is obtained. The liquid hydrogel is treated in a 70 ℃ water bath for 30 minutes, and then placed in a 4 ℃ cold bath Repeat 3 times for 5 min, equilibrate at room temperature for 1 h after disinfection, seal with parafilm and store at 4°C to obtain gelatin-sodium alginate composite hydrogel;
S2：称2.5g氯化钙固体粉末置于烧杯中，加入100ml去离子水，置于恒温磁力搅拌器搅拌30min，得到2.5％的氯化钙溶液，转移至耐高温玻璃瓶，高压锅高压消毒灭菌后密封，放4℃保存，即得交联剂；S2: Weigh 2.5g of calcium chloride solid powder into a beaker, add 100ml of deionized water, place it in a constant temperature magnetic stirrer and stir for 30min to obtain a 2.5% calcium chloride solution, transfer it to a high temperature resistant glass bottle, sterilize it in an autoclave After the bacteria, seal it and store it at 4°C to obtain the cross-linking agent;
S3：取交联剂滴加到3D打印块表面至交联剂完全覆盖打印块，交联10min后去除交联剂，用DMEM完全培养基冲洗一遍，即得生物3D打印墨水。S3: Take the cross-linking agent and drip it onto the surface of the 3D printing block until the cross-linking agent completely covers the printing block, remove the cross-linking agent after 10 minutes of cross-linking, and rinse it with DMEM complete medium to obtain the biological 3D printing ink.
试验例1外观观察Test Example 1 Appearance Observation
取未改性的纳米玻璃粒子分散液(购买自sigma的试剂货号420816-1L)和实施例1制得的改性纳米生物玻璃粒子，观察其外观，结果见图1，可知，未经改性的纳米玻璃粒子分散液呈透明色，而本发明提供的改性纳米生物玻璃粒子呈乳白色。Take the unmodified nano-glass particle dispersion (reagent product number 420816-1L purchased from sigma) and the modified nano-biological glass particles obtained in Example 1, observe their appearance, the results are shown in Figure 1, it can be seen that the unmodified The nano-glass particle dispersion liquid is transparent, while the modified nano-biological glass particles provided by the present invention are milky white.
试验例2凝胶状态稳定性Test Example 2 Gel State Stability
分别将未改性的纳米生物玻璃粒子和改性纳米生物玻璃粒子加入到实施例2步骤S2制得的明胶-海藻酸钠复合水凝胶中，充分搅拌混匀后在40℃条件下放置72h，观察其是否出现沉淀，结果如图2所示，由图2可知，改性纳米生物玻璃粒子可与明胶和海藻酸钠维持稳定的凝胶状态。The unmodified nano-bioglass particles and the modified nano-bioglass particles were respectively added to the gelatin-sodium alginate composite hydrogel obtained in step S2 of Example 2, fully stirred and mixed, and then placed at 40 °C for 72 hours. , to observe whether there is precipitation, and the results are shown in Figure 2. It can be seen from Figure 2 that the modified nano-bioglass particles can maintain a stable gel state with gelatin and sodium alginate.
试验例3各组生物3D打印墨水与细胞培养后的状态测试Test Example 3 The state test of each group of biological 3D printing ink and cell culture
将实施例2和对照例1的生物3D打印墨水分别与第三代小鼠成纤维细胞混合后交联，放置于37℃，5％CO2细胞培养箱培养3天后，取出凝胶块，观察凝胶块状态，结果见图3，由图3可知，各组生物3D打印墨水与第三代小鼠成纤维细胞交联以及培养3天后均未出现溶解、分散现象，形状保持完好。The bio-3D printing inks of Example 2 and Control Example 1 were mixed with the third-generation mouse fibroblasts and then cross-linked, placed at 37°C, and incubated in a 5% CO2 cell incubator for 3 days. The results are shown in Figure 3. It can be seen from Figure 3 that the bio-3D printing inks in each group were cross-linked with the third-generation mouse fibroblasts and did not dissolve or disperse after 3 days of culture, and the shape remained intact.
试验例4细胞增殖/毒性实验Test Example 4 Cell proliferation/toxicity test
细胞增殖/毒性实验：取第三代小鼠成纤维细胞按每孔1×104细胞浓度接种到96孔板中，每孔加入DMEM完全培养基100ul，放细胞培养箱培养，培养条件为5％CO2、37℃，待细胞完全贴壁后，弃掉旧的培养基，重新加入新的DMEM完全培养基100ul，分别加入10ul将实施例2和对照例1的生物3D打印墨水(提前在37℃溶解)，左右轻微摇匀后继续放回细胞培养箱培养12h、24h、48h，接着向每孔加入10ul CCK-8溶液(购买自碧云天的试剂，货号C0038)，再将96孔板放回培养箱内孵育2h，培养条件为5％CO2、37℃，最后用酶标仪测定在450nm处的吸光度，测定并计算细胞存活率和对细胞的抑制率，结果见图4，由图4可知，共培12h时，对照例1的细胞存活率稍稍高于实施例2，24h、48h时，两组细胞存活率无明显差异，无论共培12h、24h还是48h，两组的细胞存活率均高于90％，表明本发明提供的生物3D打印墨水具有良好的生物相容性。Cell proliferation/toxicity experiment: The third-generation mouse fibroblasts were inoculated into a 96-well plate at a concentration of 1 × 104 cells per well, and 100 ul of DMEM complete medium was added to each well, and cultured in a cell incubator with a culture condition of 5 %CO2 , 37°C, after the cells are completely adherent, discard the old medium, re-add 100ul of new DMEM complete medium, and add 10ul of the biological 3D printing inks of Example 2 and Control Example 1 (in advance in Dissolve at 37°C), shake it slightly from side to side and continue to put it back into the cell incubator for 12h, 24h, and 48h, then add 10ul of CCK-8 solution (purchased from Biyuntian, product number C0038) to each well, and then add 96-well plate Put it back into the incubator and incubate for 2h, the culture conditions are 5% CO2 , 37°C, and finally measure the absorbance at 450nm with a microplate reader, measure and calculate the cell viability and the inhibition rate of the cells, the results are shown in Figure 4, by Figure 4 shows that when co-cultured for 12h, the cell viability of control example 1 was slightly higher than that of example 2, and at 24h and 48h, there was no significant difference in cell viability between the two groups. The survival rates are all higher than 90%, indicating that the bio-3D printing ink provided by the present invention has good biocompatibility.
试验例5热稳定性测量Test Example 5 Thermal Stability Measurement
将实施例2和对照例1制得的液态水凝胶分别放置于室温(25℃)、37℃及4℃条件下，观察两组液态水凝胶流动状态并记录两组液态水凝胶在室温(25℃)和37℃条件下的成胶时间，以及在37℃条件下的熔胶时间，每组做三个平行样，每隔5min观察一下，结果取平均值，试验结果见表1。The liquid hydrogels prepared in Example 2 and Comparative Example 1 were placed at room temperature (25 °C), 37 °C and 4 °C, respectively, and the flow states of the two groups of liquid hydrogels were observed and recorded. The gel time at room temperature (25°C) and 37°C, and the melt time at 37°C, three parallel samples were made for each group and observed every 5 minutes, and the results were averaged. The test results are shown in Table 1. .
表1.两组液态水凝胶的成胶时间和溶胶时间Table 1. Gel formation time and sol time of two groups of liquid hydrogels
由表1可以看出，本发明提供的方法制备的液态水凝胶的成胶时间和溶胶时间都较对照例的短，证明本发明提供的制备方法制备的生物3D打印墨水更加易于成型且易于溶解。It can be seen from Table 1 that the gel formation time and the sol time of the liquid hydrogel prepared by the method provided by the present invention are both shorter than those of the control example, which proves that the 3D bioprinting ink prepared by the preparation method provided by the present invention is easier to form and easy to use. dissolve.
试验例6杨氏模量测量Test Example 6 Young's modulus measurement
本试验例的杨氏模量测量均在实验室环境、室温下、空气湿度在30％环境内完成，将实施例2和对照例1制备的液态水凝胶放置于10ml的注射器内，实施例2和对照例1均做3个平行样，将各装有液态水凝胶的注射器放置于4℃冷浴2h，待液态水凝胶完全凝固后得到固态凝胶支架，用35ml 2.5％的CaCl2溶液交联凝胶支架，过夜14h，弃掉交联剂，测量交联后的凝胶支架的长、宽、高以便计算体积和表面积。测量完成后，将凝胶支架置于杨氏模量测定仪(Instron model 5567)上，运行速度设为5mm/min，测量各组生物3D打印墨水的杨氏模量，试验结果见表2。The Young's modulus measurements of this test example were all completed in a laboratory environment, at room temperature, and in an environment with an air humidity of 30%. The liquid hydrogels prepared in Example 2 and Comparative Example 1 were placed in a 10ml syringe. Example 2 and Comparative Example 1 were made three parallel samples, and each syringe filled with liquid hydrogel was placed in a 4°C cold bath for 2 h. After the liquid hydrogel was completely solidified, a solid gel scaffold was obtained, and 35 ml of 2.5% CaCl2. The gel scaffold was cross-linked with the solution overnight for 14 hours, the cross-linking agent was discarded, and the length, width and height of the cross-linked gel scaffold were measured in order to calculate the volume and surface area. After the measurement was completed, the gel holder was placed on a Young's modulus tester (Instron model 5567), and the running speed was set to 5 mm/min to measure the Young's modulus of each group of bio-3D printing inks. The test results are shown in Table 2.
表2.实施例和对照例的生物3D打印墨水杨氏模量测试结果Table 2. Test results of Young's modulus of bio-3D printing inks for Examples and Controls
由表2可知，本发明提供的生物3D打印墨水的杨氏模量胶未添加改性纳米生物玻璃粒子的对照组更大，硬度比对照组增加了一倍还要多，表明本发明提供的生物3D打印墨水的机械性能更好。As can be seen from Table 2, the control group in which the Young's modulus glue of the biological 3D printing ink provided by the present invention is not added with modified nano-bioglass particles is larger, and the hardness is more than doubled compared with the control group, indicating that the The mechanical properties of bio-3D printing inks are better.
试验例73孔隙率测量Test Example 73 Porosity Measurement
将实施例2和对照例1制备的液态水凝胶放置于10ml的注射器内，实施例和对照例均做3个平行样，将各装有液态水凝胶的注射器放置于4℃冷浴2h，待液态水凝胶完全凝固后得到固态凝胶支架，向每个固态凝胶支架中加入35ml的2.5％CaCl2交联剂交联过夜14h，第二天弃掉交联剂，将各凝胶支架放置于-20℃冷冻14h，再转移至冻干机上，设置冻干机参数，按程序冻干后得到冻干凝胶样品，每组准备相同的3个有刻度的试管，每管放入10ml无水乙醇，得到体积V1，将冻干凝胶样品放入无水乙醇中，在4℃条件下放置48h,待冻干凝胶全部吸液沉底后记录试管内总体积得到V 2，将吸液后冻干凝胶样品取出，并记录试管内的液体体积得到V 3，则凝胶孔隙率P(％)＝(V1-V3)/(V2-V1)*100％.计算各组生物3D打印墨水的凝胶孔隙率，结果见表3。The liquid hydrogels prepared in Example 2 and Comparative Example 1 were placed in a 10ml syringe, and three parallel samples were made for both the Example and the Comparative Example, and the syringes containing the liquid hydrogel were placed in a 4°C cold bath for 2h. After the liquid hydrogel is completely solidified, a solid gel scaffold is obtained, and 35 ml of 2.5% CaCl2 cross-linking agent is added to each solid gel scaffold to cross-link overnight for 14 hours. The cross-linking agent is discarded the next day, and each gel The stents were placed at -20°C and frozen for 14 hours, then transferred to a freeze dryer, set the parameters of the freeze dryer, and freeze-dried according to the program to obtain freeze-dried gel samples. Prepare the same 3 test tubes with the same scale for each group, and put in each tube. 10ml of absolute ethanol to obtain volume V1, put the freeze-dried gel sample into absolute ethanol, and place it at 4°C for 48 hours. After all the freeze-dried gel has absorbed liquid and settled to the bottom, record the total volume in the test tube to obtain V2, Take out the freeze-dried gel sample after suction, and record the liquid volume in the test tube to get V3, then the gel porosity P(%)=(V1-V3)/(V2-V1)*100%. Calculate each group The gel porosity of the bio-3D printing ink is shown in Table 3.
表3.实施例2和对照例1的生物3D打印墨水的孔隙率结果Table 3. Porosity results of bio-3D printing inks of Example 2 and Comparative Example 1
由表3可知，实施例2提供的生物3D打印墨水的孔隙率略低于对照例1，但二者均大于0.8，可允许细胞粘附和伸展。It can be seen from Table 3 that the porosity of the 3D bioprinting ink provided by Example 2 is slightly lower than that of Control Example 1, but both are greater than 0.8, which can allow cells to adhere and stretch.
最后应说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的精神和范围，其均应涵盖在本发明的权利要求范围当中。Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be Modifications or equivalent substitutions are made without departing from the spirit and scope of the technical solutions of the present invention, and they should all be included in the scope of the claims of the present invention.
Claims (10)
Translated fromChinesePriority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911046255.0ACN110721346B (en) | 2019-10-30 | 2019-10-30 | A kind of biological 3D printing ink and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911046255.0ACN110721346B (en) | 2019-10-30 | 2019-10-30 | A kind of biological 3D printing ink and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110721346Atrue CN110721346A (en) | 2020-01-24 |
| CN110721346B CN110721346B (en) | 2020-08-18 |
Family
ID=69222566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911046255.0AActiveCN110721346B (en) | 2019-10-30 | 2019-10-30 | A kind of biological 3D printing ink and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110721346B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111849888A (en)* | 2020-08-07 | 2020-10-30 | 中国人民解放军总医院 | Method for efficiently inducing mesenchymal stem cells to differentiate into sweat glands based on 3D bioprinting technology |
| CN113679887A (en)* | 2020-05-18 | 2021-11-23 | 中国科学院化学研究所 | Application of bioactive composite material in periodontal bone defect repair and/or periodontal bone regeneration |
| CN114870071A (en)* | 2022-04-29 | 2022-08-09 | 中国科学院上海硅酸盐研究所 | Silicon-based bioactive ink, natural inorganic silicon-based material flexible three-dimensional porous scaffold and application |
| CN114887116A (en)* | 2022-03-23 | 2022-08-12 | 广州医科大学附属口腔医院（广州医科大学羊城医院） | Mesenchymal stem cell extracellular matrix-loaded 3D printing bone defect repair support and preparation method thereof |
| CN115581806A (en)* | 2022-10-18 | 2023-01-10 | 上海交通大学医学院附属第九人民医院 | 3D printing biological scaffold capable of promoting regeneration of periodontal tissues and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012039592A1 (en)* | 2010-09-20 | 2012-03-29 | Universite Hassan Ii Mohammedia-Casablanca | Method for producing macroporous two-phase cement comprising bioglass and an apatite, said cement being bioactive, bioresorbable and suitable for biomedical use |
| CN107661540A (en)* | 2017-10-31 | 2018-02-06 | 华南理工大学 | A kind of method that high-strength hydroxylapatite chitosan SiO 2 hybrid support is prepared using 3D printing |
| CN110229352A (en)* | 2019-07-03 | 2019-09-13 | 上海大学 | A kind of preparation of compound hydrogel material and its compound rest Method of printing |
- 2019
- 2019-10-30CNCN201911046255.0Apatent/CN110721346B/enactiveActive
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012039592A1 (en)* | 2010-09-20 | 2012-03-29 | Universite Hassan Ii Mohammedia-Casablanca | Method for producing macroporous two-phase cement comprising bioglass and an apatite, said cement being bioactive, bioresorbable and suitable for biomedical use |
| CN107661540A (en)* | 2017-10-31 | 2018-02-06 | 华南理工大学 | A kind of method that high-strength hydroxylapatite chitosan SiO 2 hybrid support is prepared using 3D printing |
| CN110229352A (en)* | 2019-07-03 | 2019-09-13 | 上海大学 | A kind of preparation of compound hydrogel material and its compound rest Method of printing |
Non-Patent Citations (2)
| Title |
|---|
| QING LIN等: ""Preparation and characterization of novel alkali-activated nano silica cements for biomedical application", 《JOURNAL OF BIOMEDICAL MATERIALS RESEARCH》* |
| UDAY KIRAN ROOPAVATH等: "3D printable SiO2 nanoparticle ink for patient specific bone regeneration", 《RSC ADVANCES》* |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113679887A (en)* | 2020-05-18 | 2021-11-23 | 中国科学院化学研究所 | Application of bioactive composite material in periodontal bone defect repair and/or periodontal bone regeneration |
| CN111849888A (en)* | 2020-08-07 | 2020-10-30 | 中国人民解放军总医院 | Method for efficiently inducing mesenchymal stem cells to differentiate into sweat glands based on 3D bioprinting technology |
| CN114887116A (en)* | 2022-03-23 | 2022-08-12 | 广州医科大学附属口腔医院（广州医科大学羊城医院） | Mesenchymal stem cell extracellular matrix-loaded 3D printing bone defect repair support and preparation method thereof |
| CN114887116B (en)* | 2022-03-23 | 2023-04-07 | 广州医科大学附属口腔医院（广州医科大学羊城医院） | 3D printing bone defect repairing support loaded with mesenchymal stem cell extracellular matrix and preparation method thereof |
| WO2023179544A1 (en)* | 2022-03-23 | 2023-09-28 | 广州医科大学附属口腔医院（广州医科大学羊城医院） | 3d-printed bone defect repair scaffold loaded with mesenchymal stem cell extracellular matrixes and preparation method therefor |
| CN114870071A (en)* | 2022-04-29 | 2022-08-09 | 中国科学院上海硅酸盐研究所 | Silicon-based bioactive ink, natural inorganic silicon-based material flexible three-dimensional porous scaffold and application |
| CN114870071B (en)* | 2022-04-29 | 2023-08-04 | 中国科学院上海硅酸盐研究所 | Silicon-based bioactive ink, natural inorganic silicon-based material flexible three-dimensional porous support and application |
| CN115581806A (en)* | 2022-10-18 | 2023-01-10 | 上海交通大学医学院附属第九人民医院 | 3D printing biological scaffold capable of promoting regeneration of periodontal tissues and preparation method and application thereof |
| CN115581806B (en)* | 2022-10-18 | 2024-04-23 | 上海交通大学医学院附属第九人民医院 | 3D printing biological scaffold capable of promoting periodontal tissue regeneration and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110721346B (en) | 2020-08-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110721346B (en) | A kind of biological 3D printing ink and preparation method thereof | |
| Fu et al. | Skin tissue repair materials from bacterial cellulose by a multilayer fermentation method | |
| CN112675360B (en) | Preparation and application of a bilayer skin biomimetic hydrogel composite scaffold loaded with hADSCs | |
| ES2960795T3 (en) | Artificial dermis repair material and preparation method thereof | |
| CN110755408B (en) | Chitosan antibacterial microspheres capable of slowly releasing growth factors and preparation method and application thereof | |
| CN110200922A (en) | A kind of preparation method and application of gelatine microsphere | |
| CN118542968B (en) | Heterogeneous adhesive hydrogel and preparation method and application thereof | |
| CN113244178B (en) | Gellan gum composite drug-loaded microspheres with remote controllable drug release and preparation method and application thereof | |
| TWI400100B (en) | Medical equipment and manufacturing methods thereof | |
| CN101259292A (en) | A method for constructing tissue engineered blood vessels | |
| CN105935317B (en) | Plant percutaneous base station and preparation method thereof in a kind of surface carried medicine sustained-release jaw face | |
| CN104548201B (en) | A kind of corneal tissue repair material and preparation method thereof | |
| Gong et al. | Engineered composite dressing with exudate management capabilities for the process of entire wound healing | |
| CN115040685A (en) | Growth factor-entrapped antibacterial wound dressing and preparation method and application thereof | |
| CN106220874A (en) | The preparation method of composite aquogel and application, composite aquogel repair materials and preparation method thereof | |
| CN110339403B (en) | Spherical nano-hydroxyapatite/natural polymer biomimetic scaffold and preparation method | |
| CN114832149A (en) | Wound dressing based on stem cell micro-embedded composite hydrogel and preparation method thereof | |
| CN103467778A (en) | Bacterial cellulose/lecithin composite material as well as preparation method and application thereof | |
| CN116688234A (en) | Preparation of a composite stem cell active biomaterial and its application in artificial skin | |
| CN108084466A (en) | A kind of composite membrane that fluidized polymer is derived based on egg white and methacrylic acid and its application in terms of stem cell is cultivated | |
| CN110507852A (en) | A bone tissue repair material | |
| CN112755236A (en) | Antibacterial elastic composite medical dressing and preparation method thereof | |
| CN110903510A (en) | Preparation method of visible light copolymerization crosslinked porous mesh GelMA-dHAMMA hydrogel | |
| CN111467576B (en) | Artificial gallbladder wall synthetic material, preparation method and application thereof, and artificial gallbladder wall | |
| CN115737922B (en) | Molybdenum disulfide reinforced hybrid fiber bonding 3D printing bracket and preparation method and application thereof |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |