胺解改性聚L-谷氨酸苄酯引导骨再生膜的制备

doi:10.7503/cjcu20180354

摘要/Abstract

摘要：

以聚L-谷氨酸苄酯(PBLG)为原料, 通过溶剂浇铸与粒子沥滤法分别构建PBLG单层致密和PBLG单层多孔膜, 利用乙醇胺对薄膜表面改性, 构筑双层引导骨再生膜. 研究了不同胺解改性时间对PBLG-s-PHEG双层膜亲水性和力学性能的影响, 结果表明, 随着PBLG分子量的增大, 薄膜的力学性能增强而降解速率减缓. 延长胺解改性时间可提高薄膜亲水性和体内外降解速率. 细胞实验结果表明, 双层薄膜的致密结构能够有效阻隔成纤维细胞的侵入, 多孔结构能够支持细胞贴壁黏附和铺展. 体外生物活性评价结果表明, 表面改性的PBLG基材料可用于体内骨缺损修复. 本文所构建的双层引导骨再生膜在体外具有良好的力学性能和降解性能, 与组织具有一定的贴合性, 同时可有效阻碍成纤维细胞侵入, 具有潜在应用价值.

关键词: 聚L-谷氨酸苄酯, 乙醇胺解, 引导骨再生膜

Abstract:

Guided bone regeneration film plays an important role in bone defect reconstruction. In this paper, poly(γ-benzyl-L-glutamate)(PBLG) was used as raw materials to construct dense films and porous films by solvent casting and particle leaching. And the bilayers guided bone regeneration membrane was constructed by ethanolamine amine membrane modification on the surface. The effect of different modification time on the hydrophilicity and mechanical properties of the films was investigated. The results show that with the increase of the molecular weight of PBLG, the mechanical strength of the film increases and the degradation rate is getting slower. Prolonging the time of amine modification can improve the hydrophilicity of the film and the degradation rate both in vivo and in vitro. Through cell experiments, it was found that the dense layer could effectively block the invasion of fibroblasts, and the porous layer can support adherence and spread of cells. Surface-modified PBLG-based materials were demonstrated to be useful for repair of bone defects in vivo by in vitro bioactivity evaluation. The guided bone regeneration membrane constructed has good mechanical properties, degradation performance, and a certain degree of fit with the tissue. And it could effectively inhibit the infiltration of fibroblasts. The membrane has potential application value.

Key words: Poly(γ-benzyl-L-glutamate)(PBLG);, Ethanolamine ammonolysis, Guided bone regeneration

中图分类号:

O631

TrendMD:

陆嘉玮, 张坤玺, 虞玺, 颜世峰, 尹静波. 胺解改性聚L-谷氨酸苄酯引导骨再生膜的制备. 高等学校化学学报, 2019, 40(3): 601.

LU Jiawei,ZHANG Kunxi,YU Xi,YAN Shifeng,YIN Jingbo. Preparation of Amine-modified Poly(γ-benzyl-L-glutamate) Guided Bone Regeneration Film^†. Chem. J. Chinese Universities, 2019, 40(3): 601.

图/表 16

Scheme 1 Fabrication of amine-modified PBLG guided bone regeneration filmAfter cell seeding, the barrier function and biocompatibility of the membranes were evaluated.

Scheme 2 Schematic diagram of barrier function characterization of membrane(A) PBLG-s-PHEG bilayer films; (B) PBLG-s-PHEG-SPM.

Table 1 Molecular weight and distribution of PBLG with different molar ratio of monomer(A) and initiator(I)

Entry	n(A)/n(I)	M_w	M_η	Polydispersity
1	50	11×10⁴	8×10⁴	2.449
2	100	25×10⁴	18×10⁴	1.742

Fig.1 1H NMR(A) and FTIR(B) spectra of PBLG(a) and PBLG-s-PHEG(b)

Fig.2 SEM images of the sarface(A1, B1) and cross-section(A2, B2) of PBLG-s-PHEG-SDM(A1, A2) and PBLG-s-PHEG-SPM(B1, B2)

Fig.3 SEM image of cross-section of PBLG-s-PHEG(A) and thickness(B) of PBLG-s-PHEG-SDM(a),PBLG-s-PAEG-SPM(b) and PBLG-s-PHEG(c)

Fig.4 Mechanical strength of PBLG-s-PHEG membranes with different Mη of PBLG and different reaction time(A) Tensile strength; (B) suture retention strength. Mη of PBLG: (C) 8×104; (D) 18×104.

Fig.5 Variation of the contact angle of the PBLG membranes with different Mη and reacton timeMη of PBLG: (A) 8×104; (B) 18×104.

Fig.6 Images of the model of bone defect and adhesion of bilayer membranes after surface hydroxyl modification(A1) Model of bone defect; (A2) PBLG bilayer membranes; (A3) PBLG-s-PHEG membranes.

Fig.7 In vitro degradation of PBLG bilayer membrances(a) and PBLG-s-PHEG membranes(b) with different reacting time and Mn of PBLG in PBS solutionMn of PBLG: (A) 8×104; (B) 18×104.

Fig.8 SEM images of PBLG-s-PHEG membranes in vitro degradation with PBLG-s-PHEG-SDM membrane(A1—A3) and PBLG-s-PHEG-SPM membrane(B1—B3) at 7 d(A1, B1), 84 d(A2, B2) and 126 d(A3, B3)

Fig.9 In vivo degradation of the PBLG-s-PHEG membranes with 7 d(A1—A3), 84 d(B1—B3) and 126 d(C1—C3)(A1—C1) Cross appearance images; (A2—C2) SEM images; (A3—C3) H&E images.

Fig.10 Degradation of mass change of the PBLG-s-PHEG member with Mη of PBLG of 8×104 and reaction time of 12 h in vivo

Fig.11 Images of L929 fibroblasts proliferate on guided bone regeneration membrane(A) L929 fibroblasts proliferate on the dense structure of the PBLG-s-PHEG bilayers film; (B) L929 fibroblasts proliferate on the porous structure of the PBLG-s-PHEG bilayer membranes; (C) L929 fibroblasts proliferate on PBLG-s-PHEG-SPM.

Fig.12 SEM images of the growth of HA on the surface of PBLG-s-PHEG bilayer membranes in SBF solutionTime/d: (A) 0; (B) 3; (C) 7; (D) 14.

Fig.13 Thermogravimetric curve of amine-modified PBLG bilayer membranes in SBF solution with different time

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