Construction and performance of a dexamethasone/polycaprolactone collagen scaffold

doi:10.3969/j.issn.2095-4344.2016.03.018

Abstract

Abstract:

BACKGROUND: Tissue engineering scaffold materials have been widely used in all kinds of tissue and nerve repair, but there are many limitations and the effect is not good.
OBJECTIVE: To construct a kind of tissue engineering scaffold material for the regeneration and repair of spinal cord injury.
METHODS: The dexamethasonemicrospheres were prepared by emulsification-solvent evaporation. The comprehensive scores of encapsulation efficiency, drug-loading rate and yield were taken as the indexes. The effect of dosage of dexamethasone and polylactic acid-glycolic acid copolymer and mass fraction of polyvinyl alcohol on formulation process of dexamethasone sustained-release microsphere was inspected by orthogonal experiment. The characterization of microspheres was observed by scanning electron microscope. The nanofiber scaffold of compound dexamethasone microspheres was prepared by taking collagen protein and polycaprolactone as raw materials using electrospinning technology. The mouse bone marrow mesenchymal stem cells were co-cultured with the scaffold for 3 days. Cell morphology was observed by scanning electron microscope. Composite material was implanted into the defect of spinal cord in rats.
RESULTS AND CONCLUSION: The optimal preparation process of dexamethasone sustained-release microspheres: dosage of dexamethasone was 10 mg, dosage of poly lactic acid-glycolic acid copolymer was 80%, mass fraction of polyvinyl alcohol was 0.5%. Appearance of dexamethasone microspheres was smooth, with a round surface. The encapsulation efficiency, drug-loading rate and yield of microspheres were (2.26±0.03)%, (83.62±0.21)% and (90.87±2.45)% respectively. The growth of mouse bone marrow mesenchymal stem cells was good on the surface of compound dexamethasone microspheres. There was no immunological reaction between the implant material and host, and the material was degraded gradually with time. These results demonstrate that the compound dexamethasone microsphere scaffold has good biocompatibility, which is a favorable kind of biological scaffold material.

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

Wang Wei, Qi She-ning, Zhao Hong-bin, Li Zhen-jun, Li Gen, Zhang Xiao-min, Song Xue-wen . Construction and performance of a dexamethasone/polycaprolactone collagen scaffold[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(3): 402-407.

Figures/Tables 7

References

[1] Tabesh H, Amoabediny G, Nik NS, et al. The role of biodegradable engineered scaffolds seeded with Schwann cells for spinal cord regeneration. Neurochem Int. 2009; 54(2):73-83.

[2] 王涛丽,顾兵,李华南,等.急性脊髓损伤后的炎症反应及其抗炎治疗[J].中国药理学通报,2015,(4):452-457.

[3] 冯云枝,凌天牖,吴汉江,等.地塞米松对成纤维细胞增殖及表达细胞间粘附分子-1的影响[J].中国免疫学杂志,2002,18(6): 423-425.

[4] 许剑荣,郑学毅,唐绍生,等.地塞米松对瘢痕疙瘩成纤维细胞基质金属蛋白酶1调控的研究[J].皮肤性病诊疗学杂志,2008,15(6): 310-313.

[5] Jain S, Datta M. Oral extended release of dexamethasone: Montmorillonite–PLGA nanocomposites as a delivery vehicle. Appl Clay Sci. 2015;104:182-188.

[6] Donzelli E, Salvadè A, Mimo P, et al. Mesenchymal stem cells cultured on a collagen scaffold: In vitro osteogenic differentiation. Arch Oral Biol. 200;52(1):64-73.

[7] Shen YH, Shoichet MS, Radisic M. Vascular endothelial growth factor immobilized in collagen scaffold promotes penetration and proliferation of endothelial cells.Acta Biomater. 2008;4(3):477-489.

[8] Zhong S, Teo WE, Zhu X, et al. An aligned nanofibrous collagen scaffold by electrospinning and its effects on in vitro fibroblast culture. J Biomed Mater Res A. 2006;79(3): 456-463.

[9] Bosnakovski D, Mizuno M, Kim G, et al. Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: influence of collagen type II extracellular matrix on MSC chondrogenesis. Biotechnol Bioeng. 2006;93(6):1152-1163.

[10] Rhee SH, Choi JY, Kim HM. Preparation of a bioactive and degradable poly(epsilon -caprolactone)/silica hybrid through a sol-gel method.Biomaterials. 2002;23(24):4915-4921.

[11] 孙彬.新型静电纺丝技术制备功能微纳米纤维及其应用[D].青岛:青岛大学,2014.

[12] 郭廓.真空冷冻干燥技术在生物制药方面的应用[J].生物技术世界,2015,(3):58-60.

[13] 黄小舟,成晓岚,罗宇燕,等.初乳搅拌速率对复乳法制备载蛋白微球性质的影响[J].中山大学学报:自然科学版,2015,3(3): 119-124.

[14] 赵莉,何晨光,高永娟,等.PLGA的不同组成对支架材料性能的影响研究[J].中国生物工程杂志,2008,28(5):22-28.

[15] Wang J, Wang J, Lu P, et al. Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis. Biomaterials. 2015;62:76-87.

[16] Altinova H, Möllers S, Führmann T, et al. Functional improvement following implantation of a microstructured, type-I collagen scaffold into experimental injuries of the adult rat spinal cord. Brain Res. 2014;1585:37-50.

[17] Pawar K, Cummings BJ, Thomas A, et al. Biomaterial bridges enable regeneration and re-entry of corticospinal tract axons into the caudal spinal cord after SCI: Association with recovery of forelimb function. Biomaterials. 2015;65:1-12.

[18] Madigan NN, McMahon S, O'Brien T, et al. Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds. Respir Physiol Neurobiol. 2009;169(2):183-199.

[19] Shi Q, Gao W, Han X, et al. Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in a rat hemisected spinal cord injury model. Sci China Life Sci. 2014;57(2):232-240.

[20] Ghasemi-Mobarakeh L, Prabhakaran MP, Morshed M, et al. Electrospun poly(epsilon-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering. Biomaterials. 2008; 29(34):4532-4539.

[21] Yang F, Murugan R, Wang S, et al. Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials. 2005; 26(15): 2603-2610.

[22] Kabu S, Gao Y, Kwon BK, et al. Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.J Control Release. 2015;219:141-154.

[23] Popat KC, Leoni L, Grimes CA, et al. Influence of engineered titania nanotubular surfaces on bone cells. Biomaterials. 2007; 28(21):3188-3197.

[24] Brammer KS, Choi C, Frandsen CJ, et al. Comparative cell behavior on carbon-coated TiO2 nanotube surfaces for osteoblasts vs. osteo-progenitor cells. Acta Biomater. 2011; 7(6):2697-2703.

[25] Brammer KS, Oh S, Cobb CJ, et al. Improved bone-forming functionality on diameter-controlled TiO(2) nanotube surface. Acta Biomater. 2009;5(8):3215-3223.

[26] Das K, Bose S, Bandyopadhyay A. TiO2 nanotubes on Ti: Influence of nanoscale morphology on bone cell-materials interaction. J Biomed Mater Res A. 2009;90(1):225-237.

[27] Miyauchi T, Yamada M, Yamamoto A, et al. The enhanced characteristics of osteoblast adhesion to photofunctionalized nanoscale TiO2 layers on biomaterials surfaces. Biomaterials. 2010;31(14):3827-3839.

[28] Isa ZM, Schneider GB, Zaharias R, et al. Effects of fluoride-modified titanium surfaces on osteoblast proliferation and gene expression. Int J Oral Maxillofac Implants. 2006; 21(2):203-211.

[29] Brammer KS, Choi C, Frandsen CJ, et al. Hydrophobic nanopillars initiate mesenchymal stem cell aggregation and osteo-differentiation. Acta Biomater. 2011;7(2):683-690.

[30] Yu WQ, Jiang XQ, Zhang FQ, et al. The effect of anatase TiO2 nanotube layers on MC3T3-E1 preosteoblast adhesion, proliferation, and differentiation. J Biomed Mater Res A. 2010; 94(4):1012-1022.

[31] Kommireddy DS, Sriram SM, Lvov YM, et al. Stem cell attachment to layer-by-layer assembled TiO₂ nanoparticle thin films. Biomaterials. 2006;27(24):4296-4303.