构建骨组织工程支架中应用的3D打印技术

背景：3D打印技术自20世纪末出现以来逐渐应用在医学领域已成为一种趋势。近年来3D打印技术被广泛用于骨组织工程支架材料的成型,并取得了一些令人惊喜的成果。 目的：文章从骨组织工程支架基本概念、3D打印的基本原理和流程、3D打印应用于构造支架的要求以及不同的粉末材料等方面进行阐述,分析其优势与目前存在的局限性,并对未来3D打印在骨组织工程支架中的应用进行展望。 方法：第一作者应用计算机检索1990年1月至2015年2月MEDLINE数据库、Science Direct全文数据库、中国期刊全文数据库、维普中文期刊网等有关3D打印技术在构建骨组织工程支架中应用的文章,检索词“3D打印,组织工程学,快速成型技术,支架,材料”,排除重复性研究。文章共检索到52篇相关文献,其中33篇文献符合纳入标准。 结果与结论：3D打印技术具有高精度、构建速度快、可按需制造实现个性化定制等优势。3D打印应用于骨组织工程支架构建时,所用的粉末或黏合剂需具备一定的条件,如流动性、稳定性与可湿性等。用于打印的粉末材料可分为人工合成多聚体、天然高分子聚合物、生物陶瓷及它们的混合物。不同粉末材料的粉末各自优缺点不同,且最终成型效果也不尽相同。3D打印技术也存在一些包括费用昂贵、不易大规模生产等方面的局限性。但尽管如此,3D打印的临床应用前景一片光明。 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     

3D打印骨组织工程支架的制备技术

近年来，随着3D打印技术的飞速发展，人们开始通过3D打印技术去不断完善适合不同需求的定制骨组织工程支架。由于组织工程制造的支架是需要植入生物体内的，这就对支架有着极为严苛的要求。3D打印技术作为一种新兴制备骨组织工程支架的技术，其最大的优点是可以依照需求来定制个性化形状、结构，良好的宏微观结构、润湿性、机械强度和细胞反应的新型骨组织工程支架。本文回顾了2014―2019年间对骨组织工程支架的研究，对3D打印骨组织工程支架进行了总结，并且介绍了在多功能骨组织工程支架设计与制作中的理念与研究。     

3D打印胶原/壳聚糖支架改善大鼠脊髓损伤后神经功能恢复

文题释义：壳聚糖：为一种天然多糖,是虾蟹等低等动物外壳的重要成分,具有一定的机械强度,并且具有良好的生物相容性和抗菌性,在生物工程领域具有较好的应用前景。 3D生物打印：是组织工程中最重要的技术之一。目前常用的三维生物打印方法包括喷墨打印、挤压生物打印和激光生物打印,选择好合适的材料后,在计算机指导下根据所选择的生物材料和细胞类型逐层准确地打印出所设计的结构。 背景：3D打印技术可以根据需求制备出满足脊髓植入形状、大小和表面形态要求的生物支架。 目的：观察3D打印胶原/壳聚糖支架对脊髓损伤大鼠神经功能恢复的影响。 方法：将胶原和壳聚糖按2∶1的质量比混合,采用冷冻干燥法制备普通胶原/壳聚糖支架,采用3D打印机制备3D打印胶原/壳聚糖支架,分别测量两种支架的孔隙率和弹性模量,电镜观察支架形态。将神经干细胞分别与3D打印胶原/壳聚糖支架、普通胶原/壳聚糖支架共培养,进行扫描电镜观察与CCK-8检测。将40只雌性SD大鼠(由中国人民解放军医学科学院军事科学院提供)随机分成4组：假手术组、脊髓损伤组、普通胶    原/壳聚糖支架组和3D打印胶原/壳聚糖支架组,后3组制作脊髓全横断损伤模型,普通胶原/壳聚糖支架组和3D打印胶原/壳聚糖支架组损伤处填充对应的支架材料,术后相应时间点进行后肢功能BBB评分、斜坡实验、神经电生理检测与磁共振平扫。实验方案经天津市神经创伤重点实验室伦理委员会批准。 结果与结论：①扫描电镜显示,3D打印胶原/壳聚糖支架具有互连的多孔结构,普通胶原/壳聚糖支架内部结构紊乱;②神经干细胞在3D打印胶原/壳聚糖支架表面生长良好,完全伸展,且3D打印胶原/壳聚糖支架表面神经干细胞的活性显著高于普通胶原/壳聚糖支架组(P < 0.05);③3D打印胶原/壳聚糖支架的孔隙率与弹性模量均高于普通胶原/壳聚糖支架组(P < 0.05);④3D打印胶原/壳聚糖支架组术后3-8周的BBB评分高于脊髓损伤组、普通胶原/壳聚糖支架组(P < 0.05),术后4,6,8周的斜坡实验角度大于脊髓损伤组、普通胶原/壳聚糖支架组(P < 0.05);⑤3D打印胶原/壳聚糖支架组术后8周的运动诱发电位振幅、体感诱发电位振幅大于脊髓损伤组与普通胶原/壳聚糖支架组(P < 0.05),运动诱发电位潜伏期、体感诱发电位潜伏期短于脊髓损伤组与普通胶原/壳聚糖支架组(P < 0.05);⑥磁共振平扫显示与脊髓损伤组及普通胶原/壳聚糖支架组比较,3D打印胶原/壳聚糖支架组损伤处具有较好的连续性与较多的神经纤维束通过;⑦结果表明,3D打印胶原/壳聚糖支架可促进脊髓损伤大鼠神经功能的修复。 ORCID: 0000-0001-5771-8222(史新宇) 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     

3D打印骨组织工程支架的研究与应用

背景：虽然应用传统方法制作骨组织工程支架取得一定成就,但在支架的三维结构、力学强度、支架个性化方面不太满意,通过3D打印技术制作支架的方法有望改变这些不足。 目的：对3D打印技术制作骨组织工程支架作一综述,对支架的未来优化进行展望。 方法：应用计算机检索PubMed和谷歌学术数据库中,2008至2015年关于3D打印技术制作骨组织工程支架的文章。纳入包含骨组织工程支架结构设计、材料及通过不同3D打印技术制作的支架性能研究文章,排除观点重复和陈旧的文章,最后对37篇文献进行归纳总结。 结果与结论：目前可用作骨组织工程支架制作的3D打印技术有熔融层积成型、立体平版印刷、选区激光烧结及3DP技术。3D打印技术制作的骨组织工程支架在力学、结构、个性化方面有其独特优势,但该技术仍有很多问题需要解决,比如原材料的问题、不同3D打印技术的不足问题及3D打印机器的改进问题等。相信在未来多学科的共同合作下,可以制作出适合于临床的骨组织工程支架,造福于人类。  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     

改性3D打印钛支架对脂肪间充质干细胞成骨分化的影响北大核心

背景:3D打印钛支架克服了传统钛支架内部结构可控性差及外形不匹配等缺陷,但由于钛的生物惰性较大,使其在植入体内后难以与周围组织快速稳定地结合。目的:采用喷砂酸蚀和阳极氧化方法改性3D打印钛支架表面,观察其对脂肪间充质干细胞黏附、增殖和成骨分化能力的影响。方法:采用喷砂酸蚀联合阳极氧化方法在3D打印钛支架表面构建微纳米多孔结构,扫描电镜观察其表面特征。将第3代大鼠脂肪间充质干细胞分别接种于3D打印钛支架组(A组)、3D打印钛支架+成骨诱导液(B组)、改性3D打印钛支架(C组)上,通过细胞骨架与CCK-8实验检测细胞的黏附和增殖能力,碱性磷酸酶与茜素红染色观察细胞的成骨分化能力,实时定量PCR分析细胞成骨相关基因的表达,免疫荧光染色观察细胞骨钙素与骨桥蛋白的表达。结果与结论:①扫描电镜下可见,改性后的3D打印钛支架表面出现微米及亚微米级凹坑和沟槽,内部有直径为70-100 nm的纳米级孔隙,孔隙之间相互连通;②共聚焦显微镜下可见,A、B组细胞伪足及触角较少,尚未铺展;C组细胞完全铺展在材料表面,可见大量明显的细胞伪足和触角,紧密附着于材料表面;CCK-8实验显示,改性3D打印钛支架可促进脂肪间充质干细胞的增殖;③碱性磷酸酶与茜素红染色显示,B、C组碱细胞性磷酸酶活性与矿化水平高于A组(P<0.05);④B、C组细胞骨钙素、RUNX2、碱性磷酸酶及Ⅰ型胶原mRNA表达均高于A组(P<0.05),骨桥蛋白与骨钙素蛋白表达均高于A组(P<0.05);⑤结果表明,喷砂酸蚀联合阳极氧化改性3D打印钛支架具有良好的生物相容性,可促进脂肪间充质干细胞的黏附、增殖和成骨分化。     

M3D:面向3D打印的医学图像重建平台

本研究旨在构建面向3D打印的医学图像3D重建平台,实现医学影像数据的目标分割、3D重建与3D打印所需区域裁剪与输出功能。该软件平台采用Qt设计用户界面,调用ITK、VTK类库处理医学影像数据。软件平台实现了医学影像数据的输入输出及处理、分割与3D重建等功能;在3D打印模型输出前,可实现对感兴趣区域的截取。以肘关节为例,利用该平台可实现模型重建,截取区域输出STL文件并完成3D打印。结果表明,该软件平台操作简单、界面简洁,可以从医学影像数据中重建得到3D模型,并进行3D打印,具有重要的临床应用价值。     

基于同轴细胞打印双网络生物墨水优化及类血管支架的打印

文题释义：双网络生物墨水：生物墨水是指可以用于生物3D打印机的材料,具有类似细胞外基质的理化性质,可用于制造与人体器官相似的组织。双网络生物墨水内部具有两种交联网络,能使体外构建的组织具有良好的机械性能,适用于不同的应用场景。 同轴细胞打印：生物3D打印也叫细胞打印,是指操控细胞生物墨水体外构建活性组织的过程。同轴细胞打印是生物3D打印的延伸和发展,通过结合多层同轴针头可以直接快速制备含有内部连通网络的组织工程支架。 背景：细胞体外培养情况下无法在远离营养物质200 μm以上的区域存活,血管网络构建对组织工程领域厚组织和器官再生至关重要,同轴细胞打印为体外构建类血管通道提供了一种新的方式。 目的：优化生物墨水的同轴细胞打印性能,制备具有类血管结构的组织工程支架。 方法：通过间歇式巴氏灭菌制备无菌海藻酸钠溶液,冷冻保存;以脱胶蚕丝为原料制备无菌丝素蛋白冻干粉,密封保存;将丝素蛋白冻干粉加入解冻的海藻酸钠溶液中,再加入人脐静脉内皮细胞,作为生物墨水;将生物3D打印机的外轴连接生物墨水,内轴连接交联剂,同轴打印类血管支架材料,进行光学相干层析成像扫描、扫描电镜观察;拉伸测试海藻酸钠与丝素蛋白/海藻酸钠同轴打印环形试件(不含细胞)的弹性模量。采用冷冻保存7 d的海藻酸钠溶液与人脐静脉内皮细胞制作同轴打印支架,冷冻保存7 d的海藻酸钠溶液、人脐静脉内皮细胞与密封保存6个月的丝素蛋白冻干粉制作同轴打印支架,培养24 h后死活染色观察细胞存活率。设计打印串联与并联结构的类血管支架,培养1,3,7,10,14 d后检测细胞增殖情况。 结果与结论：①光学相干层析成像扫描显示,该混合生物墨水最高打印高度为9层,整体厚度约为4.4 mm;扫描电镜显示,类血管支架的中空纤维丝外壁呈无规则条状卷曲,存在微米级内部连通孔隙结构,中空纤维丝内壁具有更致密的孔隙结构;②丝素蛋白/海藻酸钠同轴打印环形试件的弹性模量大于单纯海藻酸钠同轴打印环形试件(P < 0.05);③采用保存7 d海藻酸钠溶液制作的支架细胞存活率为(86.7±3.4)%,加入丝素蛋白冻干粉支架的细胞存活率为(98.1±1.2)%,说明冷冻保存7 d的海藻酸钠溶液未染菌,丝素蛋白的保质期可达6个月;④并联结构类血管支架培养7,10,14 d的细胞增殖活性高于串联结构的类血管支架(P < 0.05);⑤结果表明,实验制备的类血管支架材料具有良好的生物相容性与机械性能。 ORCID: 0000-0002-5556-6672(张一帆) 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     

热处理技术对3D打印钛合金试件机械性能的影响

背景:近年来,增材制造(又称3D打印)逐渐成为制作可摘局部义齿钛合金支架的主流方式。热处理作为改善3D打印钛合金支架机械性能的重要方法而成为目前的关注热点。目的:总结目前应用于3D打印钛合金试件的主要热处理技术(包括退火处理、固溶时效处理、热等静压处理及其他热处理)以及这些热处理技术对3D打印钛合金试件机械性能、微观结构的影响,为改进可摘局部义齿钛合金支架的热处理技术提供理论依据。方法:采用计算机检索中国知网、PubMed和ScienceDirect数据库中有关3D打印钛合金热处理试件的文献资料,检索时限为2012-2023年,根据纳入和排除标准,最终选取61篇文献进行综述分析。结果与结论:(1)使用常规退火技术处理3D打印钛合金试件,使其在500-900℃下保持2-4 h,能有效增加3D打印钛合金试件的延伸率。(2)固溶时效处理相较于常规退火技术更复杂,固溶时效处理后的钛合金试件在屈服强度方面表现突出,并且有更好的耐腐蚀性;但固溶时效处理后的3D打印钛合金试件在延伸性方面没有优势。(3)热等静压处理可以减少3D打印钛合金试件的内部缺陷,可明显增加3D打印钛合金试件延伸率,并增加其疲劳...     

3D打印PLCL/PLLA复合材料支架的体外降解性能研究

目的探讨左旋聚乳酸(PLLA)与聚-L-丙交酯-己内酯(PLCL)的复合对PLCL的三维(3D)打印性能及其打印支架降解性能的影响。方法采用共混手段制备了系列不同比例的PLCL(100%、90%、80%、70%、60%、50%)为基质相、PLLA(10%、20%、30%、40%、50%、100%)为分散相的复合材料;利用熔融沉积成型(FDM)3D打印技术,制备不同比例、不同填充率(40%、50%、60%、70%)的PLCL/PLLA无边框3D多孔支架;通过支架宏/微观结构的观察及其体外加速降解实验,考察复合材料3D打印性能及其支架的降解性能。结果在研究条件下,复合材料均可打印成孔隙贯通的多孔支架,复合材料的孔径随填充率的增加而缩小,由40%时733μm缩小为70%时200μm。相对于单纯PLCL,复合PLLA更有利于支架结构成型。降解实验显示:PLCL支架降解较快,70%填充率打印支架60 d时降解达到88.58%,而PLLA的加入可以减慢支架降解速率;降解过程中,所有支架都较好地保持了原有结构的完整性,无明显断裂或崩解,但PLCL支架整体结构缩小、孔径增大明显,而复合PLLA明显改善了支架缩小和孔径增大的现象;微观形貌变化显示,PLCL支架表面在降解过程中出现了大量微孔结构,而PLCL/PLLA复合材料支架表面出现了微孔结构和微裂缝结构。结论复合PLLA不仅改善了PLCL的3D打印性能,而且也改变了复合材料支架的降解性能;通过改变PLCL和PLLA的比例及3D打印填充率,可以调控支架的孔径、孔隙率及降解速率,为多种组织、器官的工程化构建提供可选择的支架材料。     

3D打印生物墨水在组织修复与再生医学中的应用

背景：通过选用合适的生物墨水，3D打印技术可用以制造人体组织和器官的代替物，并在人体内发挥作用。近些年来3D打印技术发展迅速，在再生医学中有着巨大的应用潜力。目的：介绍3D打印用生物墨水的类型，并综述生物墨水的分类、应用、优缺点及未来愿景。方法：以“3D printing,Biological ink,Tissue engineering,hydrogel,Synthetic material,Cytoactive factor,3D打印、生物墨水、组织工程”为检索词，运用计算机检索2000-2022年以来发表在PubMed、CNKI数据库中的相关文献，最终纳入83篇进行综述。结果与结论：在过去的几十年里，生物3D打印技术发展迅速，在组织工程和生物医学等各个领域都受到了极大的关注。相对于传统生物支架制造方法在功能性及结构方面受到的限制，3D打印可以更好地模拟生物组织复杂的结构，并且具有合适的力学、流变学和生物学特性。生物墨水是3D打印中必不可少的一部分，通过生物材料制备的生物墨水，经打印后产生的生物支架在组织修复和再生医学等方面有着巨大的科研潜力及临床意义，其材料的研究本身也越来越受到...     

Ornamenting 3D printed scaffolds with cell-laid extracellular matrix for bone tissue regeneration

3D printing technique is the most sophisticated technique to produce scaffolds with tailorable physical properties. But, these scaffolds often suffer from limited biological functionality as they are typically made from synthetic materials. Cell-laid mineralized ECM was shown to be potential for improving the cellular responses and drive osteogenesis of stem cells. Here, we intend to improve the biological functionality of 3D-printed synthetic scaffolds by ornamenting them with cell-laid mineralized extracellular matrix (ECM) that mimics a bony microenvironment. We developed bone graft substitutes by using 3D printed scaffolds made from a composite of polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) and mineralized ECM laid by human nasal inferior turbinate tissue-derived mesenchymal stromal cells (hTMSCs). A rotary flask bioreactor was used to culture hTMSCs on the scaffolds to foster formation of mineralized ECM. A freeze/thaw cycle in hypotonic buffer was used to efficiently decellularize (97% DNA reduction) the ECM-ornamented scaffolds while preserving its main organic and inorganic components. The ECM-ornamented 3D printed scaffolds supported osteoblastic differentiation of newly-seeded hTMSCs by upregulating four typical osteoblastic genes (4-fold higher RUNX2; 3-fold higher ALP; 4-fold higher osteocalcin; and 4-fold higher osteopontin) and increasing calcium deposition compared to bare 3D printed scaffolds. In vivo, in ectopic and orthotopic models in rats, ECM-ornamented scaffolds induced greater bone formation than that of bare scaffolds. These results suggest a valuable method to produce ECM-ornamented 3D printed scaffolds as off-the-shelf bone graft substitutes that combine tunable physical properties with physiological presentation of biological signals.     

3D printing of composite calcium phosphate and collagen scaffolds for bone regeneration

Low temperature 3D printing of calcium phosphate scaffolds holds great promise for fabricating synthetic bone graft substitutes with enhanced performance over traditional techniques. Many design parameters, such as the binder solution properties, have yet to be optimized to ensure maximal biocompatibility and osteoconductivity with sufficient mechanical properties. This study tailored the phosphoric acid-based binder solution concentration to 8.75 wt% to maximize cytocompatibility and mechanical strength, with a supplementation of Tween 80 to improve printing. To further enhance the formulation, collagen was dissolved into the binder solution to fabricate collagen-calcium phosphate composites. Reducing the viscosity and surface tension through a physiologic heat treatment and Tween 80, respectively, enabled reliable thermal inkjet printing of the collagen solutions. Supplementing the binder solution with 1–2 wt% collagen significantly improved maximum flexural strength and cell viability. To assess the bone healing performance, we implanted 3D printed scaffolds into a critically sized murine femoral defect for 9 weeks. The implants were confirmed to be osteoconductive, with new bone growth incorporating the degrading scaffold materials. In conclusion, this study demonstrates optimization of material parameters for 3D printed calcium phosphate scaffolds and enhancement of material properties by volumetric collagen incorporation via inkjet printing.     

3D打印β-TCP/HA/PLA骨移植支架材料的研究

目的 制备个性化的3D打印骨移植支架修复材料,以满足骨缺损患者的需求.方法 运用计算机软件CAD设计出三维木堆结构的模型图,通过三维气浮运动平台,使用3D打印方法模拟出三维木堆结构的复合β-磷酸三钙(β-TCP)、羟基磷灰石(HA)和聚乳酸(PLA)材料的支架.再对支架材料进行抽真空热处理,X射线能谱仪检测其氯仿残留量,扫描电镜观察支架材料的表面形貌,最后用噻唑蓝(MTT)法检测支架材料对人SV40转染成骨细胞hFOB1.19的毒性.结果 当打印浆料的挤出气压在137.9～413.7kPa内,可打印出β-TCP/HA/PLA三维骨移植支架材料.成型后的三维骨移植支架材料经90℃保温抽真空处理及150℃热处理后能消除其中的氯仿;材料表面粗糙,拥有表面细孔和内部连通的微孔;其同hFOB1.19细胞共培养7d,细胞毒性等级为0级.结论 本研究制备的3D打印β-TCP/HA/PLA骨移植支架材料表面粗糙而具有通孔,利于成骨细胞的培养,且骨诱导作用明显,体现出3D打印在制备骨移植多孔材料上拥有很大的优势和发展前景.     

3D打印钛合金孔隙支架骨长入影响因素的分析

BACKGROUND: With the development of three-dimensional (3D) printing technology, 3D printed porous titanium scaffolds as bone substitutes have become a research hotspot. OBJECTIVE: To introduce and discuss the effects of each parameter of 3D printed porous titanium scaffolds on bone ingrowth, and to sum out the optimal parameters for bone ingrowth. METHODS: The first author retrieved PubMed, Springerlink and Medline databases with “three-dimensional (3D) printing, scaffold, titanium, bone ingrowth” as keywords for relevant articles published from 2006 to 2016. 125 articles were retrieved initially, and finally 42 eligible articles were included for analysis. RESULTS AND CONCLUSION: Pore size, porosity, pore structures and surface modifications of 3D printed porous titanium scaffolds all make effects on bone ingrowth or osteoblasts in scaffolds. Scaffolds with appropriate pore size and porosity can promote the vascularization and provide adequate nutrition and oxygen supplement, to ensure high cell viability. Regulations of cell performances, such as cell attachment, proliferation and differentiation, are also affected by pore structures and nano-scale surface modification. Herein, a detailed combination of the parameters, as mentioned above, can create a better porous scaffold for better bone ingrowth. Hence, the high-stability interface between bone and scaffolds may be obtained through the parameter adjustment.     

Novel processing of iron–manganese alloy-based biomaterials by inkjet 3-D printing

The present work provides an assessment of 3-D printed iron–manganese biodegradable scaffolds as a bone scaffold material. Iron-based alloys have been investigated due to their high strength and ability to slowly corrode. Current fabrications of Fe-based materials generate raw material which must be machined into their desired form. By using inkjet 3-D printing, a technique which generates complex, customizable parts from powders mechanically milled Fe–30Mn (wt.%) powder was directly processed into scaffolds. The 3-D printed parts maintained an open porosity of 36.3% and formed a mixed phase alloy of martensitic ε and austenitic γ phases. Electrochemical corrosion tests showed the 3-D printed Fe–Mn to desirably corrode significantly more rapidly than pure iron. The scaffolds exhibited similar tensile mechanical properties to natural bone, which may reduce the risk of stress shielding. Cell viability testing of MC3T3-E1 pre-osteoblast cells seeded directly onto the Fe–Mn scaffolds using the live/dead assay and with cells cultured in the presence of the scaffolds’ degradation products demonstrated good in vitro cytocompatibility compared to tissue culture plastic. Cell infiltration into the open pores of the 3-D printed scaffolds was also observed. Based on this preliminary study, we believe that 3-D printed Fe–Mn alloy is a promising material for craniofacial biomaterial applications, and represents an opportunity for other biodegradable metals to be fabricated using this unique method.     

3D printing algorithm of anisotropic biological scaffold with oxidized nanocellulose and gelatin

Abstract

Tissue scaffolds need to have anisotropic mechanical properties and a porous structure to meet the needs of different tissues and organs. This report presents results of a study on an especially-designed 3D printing method with oxidized nanocellulose and gelatin, analyzes the servo principle of pneumatic condensing extrusion 3D printer, and proposes a hexagonal algorithm. For the purpose of this study, a printing process file was written by G code, physical and mechanical performance of the 3D scaffolds was evaluated with Solidworks simulation, the porous structure and pressure-pull performance of the printed 3D scaffolds was observed by SEM, and experiments were conducted to measure their bio-compatibility. The study draws the conclusion that scaffolds thus printed have a highly porous structure and anisotropic mechanical properties.     

Three-dimensional printing of porous ceramic scaffolds for bone tissue engineering

This article reports a new process chain for custom-made three-dimensional (3D) porous ceramic scaffolds for bone replacement with fully interconnected channel network for the repair of osseous defects from trauma or disease. Rapid prototyping and especially 3D printing is well suited to generate complex-shaped porous ceramic matrices directly from powder materials. Anatomical information obtained from a patient can be used to design the implant for a target defect. In the 3D printing technique, a box filled with ceramic powder is printed with a polymer-based binder solution layer by layer. Powder is bonded in wetted regions. Unglued powder can be removed and a ceramic green body remains. We use a modified hydroxyapatite (HA) powder for the fabrication of 3D printed scaffolds due to the safety of HA as biocompatible implantable material and efficacy for bone regeneration. The printed ceramic green bodies are consolidated at a temperature of 1250 degrees C in a high temperature furnace in ambient air. The polymeric binder is pyrolysed during sintering. The resulting scaffolds can be used in tissue engineering of bone implants using patient-derived cells that are seeded onto the scaffolds.This article describes the process chain, beginning from data preparation to 3D printing tests and finally sintering of the scaffold. Prototypes were successfully manufactured and characterized. It was demonstrated that it is possible to manufacture parts with inner channels with a dimension down to 450 microm and wall structures with a thickness down to 330 microm. The mechanical strength of dense test parts is up to 22 MPa.     

New depowdering-friendly designs for three-dimensional printing of calcium phosphate bone substitutes

Powder-based three-dimensional printing (3DP) is a versatile method that allows creating synthetic calcium phosphate (CaP) scaffolds of complex shapes and structures. However, one major drawback is the difficulty of removing all remnants of loose powder from the printed scaffolds, the so-called depowdering step. In this study, a new design approach was proposed to solve this problem. Specifically, the design of the printed scaffolds consisted of a cage with windows large enough to enable depowdering while still trapping loose fillers placed inside the cage. To demonstrate the potential of this new approach, two filler geometries were used: sandglass and cheese segment. The distance between the fillers was varied and they were either glued to the cage or free to move after successful depowdering. Depowdering efficiency was quantified by microstructural morphometry. The results showed that the use of mobile fillers significantly improved depowdering. Based on this study, large 3DP scaffolds can be realized, which might be a step towards a broader clinical use of 3D printed CaP scaffolds.     

Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration

In this study, we fabricated strontium-containing mesoporous bioactive glass (Sr-MBG) scaffolds with controlled architecture and enhanced mechanical strength using a three-dimensional (3-D) printing technique. The study showed that Sr-MBG scaffolds had uniform interconnected macropores and high porosity, and their compressive strength was ∼170 times that of polyurethane foam templated MBG scaffolds. The physicochemical and biological properties of Sr-MBG scaffolds were evaluated by ion dissolution, apatite-forming ability and proliferation, alkaline phosphatase activity, osteogenic expression and extracelluar matrix mineralization of osteoblast-like cells MC3T3-E1. The results showed that Sr-MBG scaffolds exhibited a slower ion dissolution rate and more significant potential to stabilize the pH environment with increasing Sr substitution. Importantly, Sr-MBG scaffolds possessed good apatite-forming ability, and stimulated osteoblast cells’ proliferation and differentiation. Using dexamethasone as a model drug, Sr-MBG scaffolds also showed a sustained drug delivery property for use in local drug delivery therapy, due to their mesoporous structure. Therefore, the 3-D printed Sr-MBG scaffolds combined the advantages of Sr-MBG such as good bone-forming bioactivity, controlled ion release and drug delivery and enhanced mechanical strength, and had potential application in bone regeneration.