可注射nHA/PU复合多孔骨修复支架制备及表征

doi:10.16085/j.issn.1000-6613.2021-0045

摘要/Abstract

摘要：

兼具良好孔隙率和原位任意塑形固化的可注射复合多孔骨修复材料在临床不规则骨缺损的治疗方面显示出巨大的优势。本研究通过优化双组分设计，以水为发泡剂制备可注射纳米羟基磷灰石/聚氨酯（nHA/PU）复合多孔支架。利用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、力学测试及Gillmore针测试等手段对制备的支架进行结构形貌、化学组成、力学性能和固化时间表征。结果表明，本研究制备的可注射nHA/PU复合多孔支架孔隙率高、孔隙贯通性好，孔径分布在100~700μm，适宜细胞和组织向孔内生长；添加20% nHA显著提高了PU支架的力学强度，但降低了支架的孔隙率；可注射支架在8h固化，适宜临床操作。本研究制备的可注射nHA/PU复合多孔支架在不规则骨缺损修复领域具有较大的应用潜力。

关键词: 纳米羟基磷灰石, 聚氨酯, 可注射, 孔隙率, 骨修复

Abstract:

Bone defect repair still represents a challenging issue in clinic. Injectable composite materials for bone repair with good porosity and in situ solidification of arbitrary shape have shown great advantages in the treatment of clinical irregular bone defects. In this study, injectable porous nano hydroxyapatite/polyurethane (nHA/PU) composite scaffolds were fabricated with two-component design and using water as foaming agent. Furthermore, the morphology, chemical composition, internal structure, mechanical properties and curing time of the fabricated scaffold were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), X ray diffraction (XRD), mechanical testing and Gilmore needle testing. The results showed that the injectable nHA/PU composite porous scaffolds were successfully prepared. The scaffolds had high porosity and good pore connectivity. The pore size distribution was 100—700μm, which was suitable for the growth of cells and tissues into the pores. The addition of 20% nHA significantly improved the mechanical strength of the PU porous scaffolds but reduced the porosity of the scaffolds. The injectable scaffolds solidified in 8h, which was suitable for clinical operation. The injectable nHA/PU composite porous scaffold prepared in this study has great potential in the field of irregular bone defect repair.

Key words: nano-hydroxyapatite, polyurethane, injectable, porosity, bone repair

中图分类号:

TB33

李根, 李吉东. 可注射nHA/PU复合多孔骨修复支架制备及表征[J]. 化工进展, 2021, 40(12): 6800-6806.

LI Gen, LI Jidong. Preparation and characterization of injectable nHA/PU composite porous scaffolds for bone repair[J]. Chemical Industry and Engineering Progress, 2021, 40(12): 6800-6806.

图/表 10

表1 可注射PU复合多孔支架的编号及成分

样品编号	组分A	组分B
PU-1	A1	B1
PU-2	A2	B2
PU-3	A2	B1
PU-4	A1	B2

图1 不同A、B组分混合制备的可注射PU复合多孔支架的SEM照片和孔径分布

图2 可注射PU的终凝时间

图3 不同nHA比例制备的可注射PU复合多孔支架的SEM照片和孔径分布

表2 不同nHA比例的PU复合支架的孔隙率和力学性能

样品编号	孔隙率/%	抗压强度/kPa
PU0	75.5±1.7	187±12
PU10	59.8±2.5	332±28
PU20	57.8±2.9	725±31

图4 不同nHA比例PU的初凝时间和终凝时间

*P＜0.05；**P<0.01；***P<0.001

图5 nHA和PU复合支架的XRD图

图6 不同nHA比例的Pre-PU和PU复合支架的红外光谱图

图7 不同nHA含量PU复合支架的TG曲线

表3 PU多孔复合支架的热分析结果

样品编号	初始分解温度/℃	残余质量/%
PU0	287.7	0.15
PU10	291.9	9.8
PU20	292.6	19.8

参考文献 25

1	REICHERT J C, SAIFZADEH S, WULLSCHLEGER M E, et al. The challenge of establishing preclinical models for segmental bone defect research[J]. Biomaterials, 2009, 30(12): 2149-2163.
2	LI J J, ROOHANI-ESFAHANI S I, DUNSTAN C R, et al. Efficacy of novel synthetic bone substitutes in the reconstruction of large segmental bone defects in sheep tibiae[J]. Biomedical Materials, 2016, 11(1): 015016.
3	LI J J, DUNSTAN C R, ENTEZARI A, et al. A novel bone substitute with high bioactivity, strength, and porosity for repairing large and load-bearing bone defects[J]. Advanced Healthcare Materials, 2019, 8(8): e1801298.
4	鹿鸣, 张雪松, 常丽, 等. 可塑型生物活性骨修复材料的制备及性能表征[J]. 中国组织工程研究, 2015, 19(21): 3323-3328.
	LU Ming, ZHANG Xuesong, CHANG Li, et al. Preparation, performance and characterization of bioactive bone materials with plasticity[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(21): 3323-3328.
5	ALARÇIN E, LEE T Y, KARUTHEDOM S, et al. Injectable shear-thinning hydrogels for delivering osteogenic and angiogenic cells and growth factors[J]. Biomaterials Science, 2018, 6(6): 1604-1615.
6	衡立松, 张军, 朱养均, 等. 可注射式磷酸钙骨水泥在肱骨近端骨折中应用观察[J]. 陕西医学杂志, 2016, 45(7): 832-833.
	HENG Lisong, ZHANG Jun, ZHU Yangjun, et al. Application of injectable calcium phosphate cement in proximal humerus fractures[J]. Shaanxi Medical Journal, 2016, 45(7): 832-833.
7	OEZEL L, BÜREN C, SCHOLZ A O, et al. Effect of antibiotic infused calcium sulfate/hydroxyapatite (CAS/HA) insets on implant-associated osteitis in a femur fracture model in mice[J]. PLoS One, 2019, 14(3): e0213590.
8	KHURANA K, GUILLEM-MARTI J, SOLDERA F, et al. Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent[J]. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2020, 108(3): 760-770.
9	SUN W J, ZHOU Y N, ZHANG X R, et al. Injectable nano-structured silicon-containing hydroxyapatite microspheres with enhanced osteogenic differentiation and angiogenic factor expression[J]. Ceramics International, 2018, 44(16): 20457-20464.
10	JAHAN K, MEKHAIL M, TABRIZIAN M. One-step fabrication of apatite-chitosan scaffold as a potential injectable construct for bone tissue engineering[J]. Carbohydrate Polymers, 2019, 203: 60-70.
11	KAWASHITA M, KAWAMURA K, LI Z. PMMA-based bone cements containing magnetite particles for the hyperthermia of cancer[J]. Acta Biomaterialia, 2010, 6(8): 3187-3192.
12	GUELCHER S A. Biodegradable polyurethanes: synthesis and applications in regenerative medicine[J]. Tissue Engineering Part B: Reviews, 2008, 14(1): 3-17.
13	MCBANE J E, SHARIFPOOR S, CAI K H, et al. Biodegradation and in vivo biocompatibility of a degradable, polar/hydrophobic/ionic polyurethane for tissue engineering applications[J]. Biomaterials, 2011, 32(26): 6034-6044.
14	FARRAR D F. Bone adhesives for trauma surgery: a review of challenges and developments[J]. International Journal of Adhesion and Adhesives, 2012, 33: 89-97.
15	MOLINO G, PALMIERI M C, MONTALBANO G, et al. Biomimetic and mesoporous nano-hydroxyapatite for bone tissue application: a short review[J]. Biomedical Materials, 2020, 15(2): 022001.
16	SUN B, ZUO Y, LI J D, et al. High conversion self-curing sealer based on a novel injectable polyurethane system for root canal filling[J]. Materials Science and Engineering C, 2013, 33(6): 3138-3145.
17	YANG W, BOTH S K, ZUO Y, et al. Biological evaluation of porous aliphatic polyurethane/hydroxyapatite composite scaffolds for bone tissue engineering[J]. Journal of Biomedical Materials Research Part A, 2015, 103(7): 2251-2259.
18	CHENG H T, LEE Y S, LIU H C, et al. The effect of component addition order on the properties of epoxy resin/polyurethane resin interpenetrating polymer network structure[J]. Journal of Applied Polymer Science, 2021, 138(7): 49833.
19	LI L M, ZUO Y, ZOU Q, et al. Hierarchical structure and mechanical improvement of an n-HA/GCO–PU composite scaffold for bone regeneration[J]. ACS Applied Materials & Interfaces, 2015, 7(40): 22618-22629.
20	李根, 李炯炯, 李丽梅, 等. 原位自发泡制备磷酸钙/聚氨酯复合骨修复支架[J]. 无机材料学报, 2016, 31(7): 719-725.
	LI Gen, LI Jiongjiong, LI Limei, et al. Preparation of calcium phosphate/polyurethane composite porous scaffolds for bone repair by in situ self-foaming method[J]. Journal of Inorganic Materials, 2016, 31(7): 719-725.
21	WOODARD J R, HILLDORE A J, LAN S K, et al. The mechanical properties and osteoconductivity of hydroxyapatite bone scaffolds with multi-scale porosity[J]. Biomaterials, 2007, 28(1): 45-54.
22	CHEN F P, SONG Z Y, LIU C S. Fast setting and anti-washout injectable calcium-magnesium phosphate cement for minimally invasive treatment of bone defects[J]. Journal of Materials Chemistry B, 2015, 3(47): 9173-9181.
23	HULBERT S F, YOUNG F A, MATHEWS R S, et al. Potential of ceramic materials as permanently implantable skeletal prostheses[J]. Journal of Biomedical Materials Research, 1970, 4(3): 433-456.
24	ZARGHAMI DEHAGHANI M, KAFFASHI B, HAPONIUK J T, et al. Shape memory thin films of polyurethane: does graphene content affect the recovery behavior of Polyurethane nanocomposites?[J]. Polymer Composites, 2020, 41(8): 3376-3388.
25	MOTHÉ C G, DE ARAÚJO C R. Properties of polyurethane elastomers and composites by thermal analysis[J]. Thermochimica Acta, 2000, 357/358: 321-325.

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