Journal of Prevention and Treatment for Stomatological Diseases
3D打印含镁聚己内酯支架修复大鼠颅骨缺损
1， 1， 1， 1， 1， 2， 2，
李筱叶 李强 戴卓 丁梦 董衡 董强生 白晶 牟永斌1
1. 南京（210008）； 2. 南京（211189）
南京大学医学院附属口腔医院，江苏 东南大学材料科学与工程学院，江苏3D打印含镁（Mg）聚己内酯（polycaprolactone，PCL）支架在大鼠颅骨缺损模型中的骨修复【摘要】 目的 评价
3D Mg PCL PCL支架为对照组，用扫描电镜（scanning效果。方法 通过 打印技术制备掺杂 微粒的 支架，以纯
electron microscopy，SEM）观察两种支架的表面形貌，用能谱分析仪（energy dispersive spectroscopy，EDS）分析表PCL⁃Mg面元素成分，并通过接触角仪和电子万能试验机对其材料学性能进行表征。此外，将 支架浸入磷酸
28 d SD盐缓冲液中，连续 检测镁离子的释放行为。本研究已通过单位伦理委员会审查批准。建立 大鼠颅骨
临界尺寸缺损模型，根据植入支架材料不同，15 SD 3组：PCL组、PCL⁃Mg
只 大鼠分为 组和对照组（未作处理），
5 4 8 micro⁃CT 8
每组 只。术后 周和 周进行 扫描检测分析，并在 周后获取颅骨缺损区样本及大鼠主要脏器进
3D Mg PCL支架孔径为（480 ± 25）μm，纤维直径为行组织学染色。结果 通过 打印技术制备掺杂 微粒的
（300 ± 25）μm，孔隙率约为66%。PCL⁃Mg Mg 1.0 At%，表明Mg微粒的成功掺杂。PCL⁃Mg
支架含 支架的接触
68.97° ± 1.39°，压缩模量为（57.37 ± 8.33）MPa，相较PCL
角为 支架显示出更好的润湿性和机械强度。在术后
4 ~ 8 PCL PCL⁃Mg
周的观察期内，与对照组及 组相比，在 组大鼠颅骨缺损区观察到最佳的新生骨形成，其骨再生指标新生骨体积、骨体积分数、骨表面积、骨表面积组织体积比、骨小梁厚度、骨小梁数和骨矿物密度均
显著优于对照组、PCL组。另外，H&E染色、Glodner VG PCL⁃Mg
染色和 染色结果显示 组诱导较多的矿化新生
H&E PCL⁃Mg
骨形成，同时主要脏器 染色提示良好的生物安全性。结论 支架能够促进骨缺损的修复，为颌面部骨缺损修复提供了新的支架材料选择，具有潜在的临床应用前景。
3D
【关键词】 骨缺损； 颅骨缺损； 骨再生； 骨组织工程； 支架； 打印； 聚己内酯； 镁；新生骨体积； 骨体积分数
R78 A 2096⁃1456（2024）04⁃0249⁃08
【中图分类号】 【文献标志码】 【文章编号】
微信公众号
. 3D打印含镁聚己内酯支架修复大鼠颅骨缺损[J]. 口腔疾病防治,【引用著录格式】 李筱叶，李强，戴卓，等
2024, 32(4): 249⁃256. doi:10.12016/j.issn.2096⁃1456.2024.04.002. 3D printed Mg⁃incorporated polycaprolactone scaffolds for repairing rat skull defects LI Xiaoye1, LI Qiang1,
DAI Zhuo1, DING Meng1, DONG Heng1, DONG Qiangsheng2, BAI Jing2, MOU Yongbin1. 1. Nanjing Stomatological
Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; 2. School of Materials Sci⁃ ence and Engineering, Southeast University, Nanjing 211189, China
Corresponding authors: MOU Yongbin, Email: yongbinmou@nju.edu.cn，Tel: 86 ⁃ 25 ⁃ 83620228; DONG Heng, Email: dongheng90@smail.nju.edu.cn，Tel：86⁃25⁃83620272
To evaluate the bone repair effect of 3D ⁃ printed magnesium (Mg) ⁃ loaded polycaprolactone
【Abstract】 Objective
(PCL) scaffolds in a rat skull defect model. PCL scaffolds mixed with Mg microparticles were prepared by
Methods
using 3D printing technology, as were pure PCL scaffolds. The surface morphologies of the two scaffolds were observed by scanning electron microscopy (SEM), and the surface elemental composition was analyzed via energy dispersive spec⁃ troscopy (EDS). The physical properties of the scaffolds were characterized through contact angle measurements and an
electronic universal testing machine. This study has been reviewed and approved by the Ethics Committee. A critical size defect model was established in the skull of 15 Sprague⁃Dawley (SD) rats, which were divided into the PCL group, PCL⁃Mg group, and untreated group, with 5 rats in each group. Micro⁃CT scanning was performed to detect and analyze skull defect healing at 4 and 8 weeks after surgery, and samples from the skull defect area and major organs of the rats were obtained for histological staining at 8 weeks after surgery. The scaffolds had a pore size of (480 ±
Results
25) μm, a fiber diameter of (300 ± 25) μm, and a porosity of approximately 66%. The PCL⁃Mg scaffolds contained 1.0 At% Mg, indicating successful incorporation of Mg microparticles. The contact angle of the PCL ⁃ Mg scaffolds was 68.97° ± 1.39° , indicating improved wettability compared to that of pure PCL scaffolds. Additionally, compared with that of pure PCL scaffolds, the compressive modulus of the PCL⁃Mg scaffolds was (57.37 ± 8.33) MPa, demonstrating en⁃ hanced strength. The PCL⁃Mg group exhibited the best bone formation behavior in the skull defect area compared with the control group and PCL group at 4 and 8 weeks after surgery. Moreover, quantitative parameters, such as bone vol⁃ ume (BV), bone volume/total volume (BV/TV), bone surface (BS), bone surface/total volume (BS/TV), trabecular thick⁃ ness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD), of skull defects were better than those in the other groups, indicating the best bone regeneration effect. H&E, Goldner, and VG staining revealed more mineralized new bone formation in the PCL⁃Mg group than in the other groups, and H&E staining of the major organs revealed good biosafety of the material. PCL⁃Mg scaffolds can promote the repair of bone defects and have clinical po⁃
Conclusion
tential as a new scaffold material for the repair of maxillofacial bone defects. bone defect; skull defect; bone regeneration; bone tissue engineering; scaffolds; 3D printing;
【Key words】
polycaprolactone; magnesium; bone volume; bone volume/total volume
J Prev Treat Stomatol Dis, 2024, 32(4): 249⁃256.
The authors declare no competing interests.
【Competing interests】
This study was supported by the National Natural Sciences Foundation of China (No. 82301104), the Jiangsu Provincial Key Research and Development Program (No. BE2020629) and the Nanjing Medical Science and Technique Develop⁃ ment Foundation (No. YKK22182).
颌面部骨缺损是指由感染、创伤，肿瘤、手术以及部分先天性疾病引起的骨质局部缺失，其在一定程度上限制了口腔种植手术的应用，因此如
何更好地修复骨缺损引起了许多学者的关注［1⁃2］。
bone tissue engineering，
基于支架的骨组织工程（
BTE）是促进骨再生修复的方法之一［3］。相对于自
体骨移植、同种异体骨移植和异种骨移植，其优势在于规避了免疫排斥、感染、移植骨供应有限等不
足［4⁃5］。BTE
支架是一种能在骨缺损部位为骨再生提供特定环境和三维空间、促进骨组织向内生长的生物材料。通过改善其几何形态、机械性能和生物学活性可以增强其骨修复效果。
酯（polycaprolactone，PCL
聚己内 ）是一种具有良好生物相容性的聚合物材料，其具备优异的生
FDA
物降解性和可修饰性能，已被 批准应用于临
床试验［6⁃8］。相对于天然聚合物，如胶原、壳聚糖、
海藻酸盐等，合成聚合物是经过严格设计且可大
规模合成的［9⁃10］。值得关注的是，PCL
由于其较低的熔点表现出极大的设计灵活性，辅以三维打印（3D print），可以定制具有个性化形状和孔径/孔隙
PCL支架［11］。然而，与天然聚合物相比，PCL
率的支架与细胞间的相互作用能力较弱，不具备骨诱
导功能［12］。镁（magnesium，Mg）元素天然存在于骨
Mg
组织中，缺乏 会导致骨骼脆性增加、骨再生延
Mg
迟、骨密度降低等［13⁃15］。因此，本课题组试想将
作为一种掺杂剂应用在骨组织工程中，其可以高
Mg
效率地提供 离子，以促进细胞黏附及增殖分化、增强骨再生和钙化。根据本课题组之前的研
3 wt% Mg
究［16
］，掺杂 微粒对比于其他掺杂比例
（1 wt%、5 wt%、7 wt%和 9 wt%），显示出最高的成
骨效率和良好的综合性能。因此，本实验拟构建
3 wt% Mg
大鼠颅骨缺损模型，缺损区植入掺杂 微
3D PCL PCL⁃Mg
粒的 打印 基支架，以评估 支架的骨修复能力，为骨组织工程提供新的潜在材料。
SCXK（沪）2018 ⁃ 0006］。3D
物合格证号［ 打印机
（FDM3000，Stratasys，美国）；场发射扫描电子显微镜（Sigma360，Zeiss，德国）；能谱分析仪（Ultra 55， Zeiss，德国）；接触角仪（One Attension，Biolin Scien⁃ tific，瑞典）；电子万能试验机（CMT4503，美特斯工
业系统有限公司，中国）；电感耦合等离子体质谱
仪（iCP 6500，Thermo，美国）；micro⁃CT（Hiscan XM，苏州海斯菲德信息科技有限公司，中国）；CT
三维
重建分析（Hiscan Reconstruct/Analyzer software V3.0，
苏州海斯菲德信息科技有限公司，中国）。
1.2 3D
支架材料的制备及表征
3D 3wt%
通过共混合 打印制备掺入 镁微粒
PCL PCL 200 ℃并保持
支架［16 ⁃ 17］。首先，加热
的 至
15 min，直至达到黏稠流动状态。Mg 3 wt%
微粒以
PCL 50 rpm/min
加入熔融 中。以 的速率搅拌熔融
Mg/PCL 160 min，使 Mg PCL
的 混合物 微粒在 基质
3D
中均匀分布。将凝固后的混合物装入 打印机，
3D 0°/90°
然后在 打印机的挤出腔中熔化，最后以
z轴逐层打印。3D 160 ℃，打印
沿 打印温度设定为
1.5 mm/s ，3D
机喷嘴移动速度为 打印的模型为
Ø13 mm × 4.3 mm
圆柱体（用于物理化学表征）或
Ø5 mm × 1.5 mm
圆柱体（用于动物实验）。
PCL PCL⁃Mg
通过扫描电子显微镜观察 及 支架的微观形貌，并计算孔径、纤维直径和孔隙率。使
用能谱分析仪（energy dispersive spectrometer，EDS） PCL⁃Mg
对 支架表面元素进行分析，以验证镁微粒的成功掺入。通过接触角计测量接触角，测试液
2 μL
体为 蒸馏水，待水滴在支架材料表面稳定后，记录并分析水滴切线与材料水平面夹角。室温
1 mm/min
下，支架材料使用电子万能试验机以 的
Mg
压缩速率测试压缩性能。此外，为了揭示 离子
3D PCL⁃Mg
的释放行为，将 打印的 支架浸泡在磷酸
缓冲盐溶液（phosphate buffer solution，PBS）中，溶液30 mL/cm2，使
体积与支架表面积之比设定为 用电
PBS
感耦合等离子体质谱法检测不同时间点 溶液
Mg2+
中的 含量。
1.3
实验分组
15 SD 3 5
只 大鼠，随机分为 组，每组 只：根据
PCL PCL⁃Mg
植入支架材料不同，分为 组和 组，未行治疗的作为对照组。本实验已获得南京大学实验
IACUC ⁃
动物福利伦理审查委员会批准（批号：
2003034）。
1.4
大鼠颅骨缺损模型构建
SD
大鼠行异氟烷吸入麻醉，麻醉产生效果后，
颅顶区备皮，消毒，铺无菌手术孔巾。沿颅顶做正
15 mm。解剖分离，暴露颅顶
中矢状全层切口，约区，于颅骨正中缝一侧顶骨区使用取骨环钻，在生
5 mm
理盐水冷却下制备出直径 圆形颅骨全层缺损，术中避免损伤硬脑膜和矢状窦。分别将各组支架材料植入缺损处，对照组不植入任何材料。
3 d
最后缝合封闭骨膜和头皮。术后 予以青霉素
4万单位/d，预防感染。
1.5 微型计算机断层扫描（micro⁃CT）及数据定量
分析
SD 4周、8
每组 大鼠吸入麻醉下，于术后 周分
micro⁃CT
别行活体 扫描，用于定量评估缺损部位新
生骨形成。扫描参数为：80 kV，100 μA，单次曝光50 ms，扫描分辨率25 μm，扫描角度间隔0.5
时间度，通过软件重建及分析定量颅骨缺损区域的新
生骨体积（bone volume，BV）、骨体积分数（bone vol⁃ ume/total volume，BV/TV bone surface，
）、骨表面积（
BS bone surface/total vol⁃
）、骨表面积组织体积比（
ume，BS/TV）、骨小梁厚度（trabecular thickness，Tb. Th trabecular separation/spacing，
）、骨小梁分离度（
Tb.Sp）、骨小梁数（trabecular number，Tb.N）和骨矿物密度（bone mineral density，BMD）。
1.6
组织学切片及安全性评价
8
术后 周，在戊巴比妥麻醉下用颈椎脱位法处死大鼠，获取颅骨术区样本，去除颅内容物及软组
4%
织，仅留颅顶骨及植入物，标本经 多聚甲醛固
定，10% 酸（EDTA）脱钙2
乙二胺四乙 周。经石蜡
包埋，切片，苏木素⁃伊红（H&E）染色、Goldner
染色
VG
或 染色，封片，干燥。采用光镜观察新生骨情况。为了研究支架材料的体内安全性，在植入支
8 H&E
架 周后，通过 染色切片对主要的组织器官（心、肝、脾、肺和肾）进行切片观察。
1.7
统计学分析
GraphPad Prism 10.0
统计分析使用 软件进
ANOVA
行。使用单因素方差分析（ ）评估组间差
Tukey
异，然后使用 多重比较检验。所有计量资料
± = 0.05。
均用均值 标准差表示，检验水准2 结 果2.1 3D
支架材料表征
PCL PCL⁃Mg
支架及 支架的宏观及微观形貌见
1a，均为多孔结构，孔径为（480 ± 25）μm，纤维
图
直径为（300 ± 25）μm，孔隙率约为66%。EDS
分析
1b），PCL⁃Mg Mg
结果显示（图 支架表面可见含 元
Mg 1.0 At%
素的凸起（ 含量为 ），表明成功掺入了
Mg 75.0 At%的C 23.7 At%的O
微粒；占 元素和 元素
PCL
为 的主要成分。基于水接触角对支架润湿性
1c），PCL 97.63°
的评估结果显示（图 的水接触角为
± 2.66°，PCL⁃Mg 68.97° ± 1.39°，相较
的水接触角为
PCL降低，具有统计学差异（P＜0.001），表明Mg
于微粒的掺杂增加了材料表面亲水性。机械性能测
1d），PCL ⁃ Mg
试结果显示（图 支架的压缩模量
（57.37 ± 8.33）MPa PCL 36.27 ± 1.65）
优于 支架（
MPa，差异具有统计学意义（P = 0.025）。Mg2+
的体
1e），在 28 d Mg2外释放行为结果显示（图 中 +被持续释放到浸泡溶液中。
2.2
不同材料支架对大鼠颅骨缺损的修复效果比较
2，对照
不同材料对颅骨缺损修复的效果见图4 8
组（无植入物）手术后 周和 周，骨缺损底部及边缘均未见新增阻射影，表明无明显骨再生现象；
PCL
组缺损底部形成少量不规则点状骨，缺损边缘出现少量不规则新生骨，空洞缺损略有缩小，缺损
区大部分未修复；PCL⁃Mg 4周
组中新生骨在手术后
8
即生长到支架中，且在手术 周后继续增长，在骨缺损上形成较厚的新骨组织层。
3，支架植入后4
新生骨定量分析结果见图 周，
PCL PCL ⁃ Mg BV/TV
对照组、 组和 组的 分别为
7.17% ± 0.44%、7.49% ± 0.67% 10.29 ± 1.28%
和 ，
BMD 1 680.91 ± 17.67）mg/cm3、（1 692.67 ±
分别为（
17.5）mg/cm3和（1 715.88 ± 6.48）mg/cm3 ；8
周后对照
组、PCL PCL ⁃ Mg BV/TV 7.90% ±
组和 组的 分别为
0.50%、9.53%±1.12%和13.51% ± 0.53%，BMD
分别为
（1 690.66 ± 13.85）mg/cm3、（1 715.65 ± 12.67）mg/cm3 a: macro⁃morphologies (scale bar=1 mm) and micro⁃morphologies (scale bar=500 μm) of PCL and PCL⁃Mg scaffolds. The scaffolds are porous and become grey with the addition of Mg micro⁃particles. As detected in micro⁃morphologies, the scaffolds display the pore size of (480 ± 25) μm, the fiber diameter of (300 ± 25) μm, and the scaffold porosity of about 66%. b: EDS analysis of Mg bulge on the scaffold surface. The PCL scaffolds are embedded with Mg micro ⁃ particles during the preparation process, in which Mg accounts for 1.0 At% . C and O are the main constituent elements of PCL with 75.0 At% and 23.7 At%, respectively. c: contact angle of the two kinds of scaffolds indicating better wettability of PCL⁃Mg scaffolds. d: a higher compressive modulus was obtained by PCL⁃Mg scaffolds with statistical differences. e: Mg ion of the PCL⁃Mg scaffolds is continuously released into PBS solution during 28 days. PCL: polycaprolactone. *: P＜0.05, ***: P＜0.001
Figure 1 Morphologies and characterization of the PCL and PCL⁃Mg scaffolds
1 PCL PCL⁃Mg
图 和 支架材料的形貌及材料学表征结果
Control group: untreated bone defect, there was little new bone formation at both the bottom and edge of the bone defect in the control group for 8 weeks, indicat⁃ ing no significant bone regeneration; PCL group: skull bone defect implanted with PCL scaffolds, a small amount of bone was formed irregularly and the cavity de⁃ fect was slightly reduced, leaving most of the defect area unrepaired; PCL ⁃ Mg group: skull bone defect implanted with PCL⁃Mg scaffolds, new bone grew along⁃ side the scaffolds 4 weeks after surgery and continued to grow 8 weeks after sur⁃ gery, forming a thicker layer of new bone at the bone defect area. PCL: polycapro⁃ lactone. Scale bar=2 mm
Figure 2 Micro⁃CT reconstructed images of SD rats with skull defects after 4 and 8 weeks of scaffolds implantation surgery 2 SD 4 8 micro⁃CT
图 大鼠颅骨缺损行支架植入术后 周及 周骨缺损区 三维重建图像
和（1 743.55 ± 11.21）mg/cm3 PCL
，对照组与 组比较
BV/TV、BMD的差异无统计学意义（P＞0.05），PCL⁃Mg
BV/TV：4
组与对照组差异具有统计学意义（ 周：
0.001 ，8 0.001 ；BMD ：4 = 0.016
P ＜ 周：P ＜ 周：P ，
8 周：P＜0.001）。 ，PCL⁃Mg BV、
此外 组大鼠新生
BS、BS/TV、Tb.Th、Tb.N 4 8
在 周和 周均显著高于其
Tb.Sp
余两组，而 显著降低。
H&E 染色、Glodner VG
通过 染色和 染色从组织层面上观察颅骨缺损修复水平，组织形态学染
micro⁃CT 4）。对照组
色结果与 有相似的趋势（图仅有薄层纤维结缔组织覆盖于骨缺损部位，骨缺
损几乎无愈合；PCL
组沿着支架表面形成少量未矿化的骨组织，留有大量未充填的间隙，同时骨缺损
区域表面形成了较厚的纤维组织；PCL⁃Mg
组在支架处形成较厚的矿化新骨，在支架相互连接的孔隙中充满了骨胶原纤维组织，表现出增强的骨再生行为。
大鼠主要组织器官（心、肝、脾、肺和肾）H&E 5
染色切片如图 所示，各组大鼠的主要组织器官未见明显差异，无明显炎症或异常破坏。
BV: bone volume; BV/TV: bone volume/total volume; BS: bone surface; BS/TV: bone surface/total volume; Tb. Th: trabecular thickness; Tb. Sp: trabec ⁃ ular separation; Tb. N: trabecular number; BMD: bone mineral density. Control group: untreated bone defect; PCL group: skull bone defect implanted with PCL scaffolds; PCL⁃Mg group: skull bone defect implanted with PCL⁃Mg scaffolds. PCL: polycaprolactone. ns: P＞0.05，*: P＜0.05, **:
P＜
0.01, ***: P＜0.001
Figure 3 Quantitative analysis of the new bone in bone defect areas of SD rats after 4 and 8 weeks of scaffolds implantation surgery 3 SD 4 8
图 大鼠颅骨缺损行支架植入术后 周及 周后骨缺损区新生骨定量分析
3 讨 论骨组织工程支架虽然已经从传统细胞种子支架发展到无细胞支架，但这也对其生物活性提出了更高的要求，以募集、诱导和活化内源性细胞解
决骨缺损修复的挑战［18⁃19］，目前已经开发了许多生
BTE
支架［20⁃22］，包括天然或合成聚合物材料来制备物（例如胶原蛋白、纤维蛋白、透明质酸、壳聚糖或
聚乳酸、PCL、聚乳酸⁃羟基乙酸共聚物等）、生物金
H&E, Goldner and VG staining results at 8 weeks after operation displayed the skull defect repair effect at the organizational level (scale bar=500 μm and 50 μm). The control group only had a thin layer of fibrous tissue covering the bone defect area with almost no bone tissue healing. The PCL group formed a small amount of unmineralized bone tissue alongside the scaffolds and thick fibrous tissue formed on the surface of the bone defect area, leaving a large number of unfilled gaps. The PCL⁃Mg group formed thicker mineralized new bone and the in⁃ terconnected pores of the scaffold were filled with bone and collagen fiber tissue, exhibiting enhanced bone regeneration behavior. Control group: untreated bone defect; PCL group: skull bone defect implanted with PCL scaffolds; PCL⁃Mg group: skull bone defect implanted with PCL⁃Mg scaffolds. PCL: polycaprolactone
Figure 4 Histological staining images of SD rats with skull defects after 8 weeks of scaffolds implantation surgery
4 SD 8
图 大鼠颅骨缺损行支架植入术后 周骨缺损区组织学染色结果
H & E staining of major organs, including heart, liver, spleen, lung, and kidney, from different groups of rats at 8 weeks are used to assess the biosafety of the scaffolds. As is illustrated in the H & E staining images, there was no obvious influence on the major organs of each group of SD rats, indicating good biosafety of both PCL and PCL⁃Mg scaffolds (scale bar=100 μm). Control group: untreated bone defect; PCL group: skull bone defect implanted with PCL scaffolds; PCL⁃Mg group: skull bone defect implanted with PCL⁃Mg scaffolds. PCL: polycaprolactone Figure 5 H&E staining images of major organ sections (heart, liver, spleen, lung, and kidney) of SD rats with skull defects after 8 weeks of scaffolds implantation surgery
5 SD 8 H&E图 大鼠颅骨缺损行支架植入术后 周主要脏器切片（心、肝、脾、肺和肾）的 染色结果
属（例如钽、钛、铁、镁等）、生物陶瓷（例如羟基磷灰石，磷酸钙、生物活性玻璃等）及生物复合材料
/ （如金属涂覆磷酸钙，羟基磷灰石 壳聚糖凝胶
PCL Mg等）。而关于 基支架与可生物降解金属 结
合的报道较少。研究表明，Mg
在降解的过程中，释
Mg2 增强了降钙素基因相关肽（calcitonin gene放的 +
related peptide，CGRP）的合成及其在骨膜感觉神经末梢的释放，CGRP可以提高骨膜干细胞（periosteum derived stem cells，PDSCs）的成骨分化能力，是骨缺Mg2
损愈合过程中 +促进骨再生的主要机制［ 23 ⁃ 25］。
Mg Mg而与其他含 化合物或镁合金相比，纯 微粒
的降解速度更快，可以高效提供镁离子［26］。本研
PCL⁃Mg支架孔径约为（480 ± 25）μm，孔隙率究中
66%，有研究提出孔径200～600 μm
约为 是确保细胞生长、营养扩散、维持成骨和成血管潜在空间的
最佳孔径［14, 27］，本研究设计的多孔结构为可以满足细胞迁移和营养交换，并提供必要的机械支撑。
Mg
此外，适当的金属 掺入增加了粗糙度，改善了其润湿性，其亲水性的增加有利于植入支架上的
细胞黏附、增殖和分化［28］。压缩强度的提高表明
Mg
适当的 掺入有助于机械性能的增强，这可能与
颗粒分散或键能增加有关［29⁃30］，但其具体机制仍然未知。另外，通过与静电纺丝和盐浸等方法制备
Mg支架相比，3D PCL⁃Mg
的含 打印制备的 支架在相同孔隙率的条件下具有更高的压缩模量［31 ⁃ 34］。
PCL在本实验中，应用于大鼠颅骨缺损修复的 支
3 wt% Mg，micro⁃CT
架含 数据结合组织学切片结果
Mg
证实了 在骨缺损愈合中的促进作用，相较于
PCL
支架，其获得了更多的骨体积以及更优的骨小
4～8梁结构，并观察到从术后 周缺损区域内的持
PCL⁃Mg
续成骨，表明 组在早期和晚期均能促进骨
H&E形成。此外，本实验通过大鼠主要脏器 切片评估支架材料的长期安全性，支架材料及其缓慢
Mg2+
释放的 离子不会造成任何实质性损伤。
3D Mg综上，本研究通过 打印制备了 掺杂的
PCL基支架。PCL⁃Mg
支架具有良好的生物相容性
3D和增强的成骨活性，这为 打印骨组织工程支架材料应用于颌面部骨缺损修复提供了一定依据。
Li XY performed the experiments and wrote【Author contributions】
the article. Li Q, Dai Z, Ding M performed the experiments and revised the article. Dong H, Dong QS, Bai J, Mou YB revised the article. All au⁃ thors read and approved the final manuscript as submitted.参考文献
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