目的: 肌腱粘连和再发断裂是肌腱损伤术后的主要并发症,本文旨在研究出一种能够同时预防肌腱粘连和促进肌腱愈合的生物膜材料,减少肌腱损伤术后的并发症。方法: 本研究制备一种壳聚糖/丝素蛋白(chitosan/silk fibroin,CS/SF)-海藻酸钠(sodium alginate,SA)复合生物膜,该生物膜由壳聚糖/丝素层和海藻酸盐层组装而成。我们检测了该膜的机械性能、亲水性、生物降解性等,并通过体外细胞学实验初步验证了该双层膜的生物学特性。结果: CS/SF膜具有较强的韧性和强度,其中CS/SF 8∶2膜断裂伸长率最大(48.65%),CS/SF 7∶3膜拉伸强度最大(21.19 MPa);CS/SF共混膜的接触角在70o左右,证明其具有较好的亲水性;体外降解实验显示:降解4周后,CS/SF共混膜的残余质量为82%~85%,SA膜的降解残余量为55%,提示该膜能在4周内保持大体的结构完整性。体外细胞学实验显示:腱细胞能在CS/SF膜上快速增殖,提示其对腱细胞增殖有促进作用;成纤维细胞在 SA膜上的增殖较慢,提示其能抑制纤维细胞的生长。结论: 该生物膜具有足够强的机械性能,较好的亲水性,适宜的生物降解性。具有促进肌腱再生和抑制纤维粘连形成的双重功能,在肌腱损伤修复的应用中具有一定的应用前景。
Abstract
Objective Tendon adhesion and rupture are the main complications after tendon injury surgery. This article aims to develop a biofilm material that can simultaneously prevent tendon adhesion and promote tendon healing, reducing the complications after tendon injury surgery. Methods This study prepared a chitosan/silk fibroin (CS/SF)-sodium alginate (SA) composite biofilm, which is composed of a chitosan/silk fibroin layer and an alginate layer. The mechanical properties, hydrophilicity and biodegradability of the membranes were examined in this study, The biological characteristics of the bilayer membrane were tested through in vitro cytology experiments. Results CS/SF membrane has strong toughness and strength, with CS/SF 8: 2 membrane having the highest elongation at break (48.65%) and CS/SF 7: 3 membrane having the highest tensile strength (21.19 MPa); The contact angle of CS/SF blend film is around 70o, indicating its good hydrophilicity; In vitro degradation experiments showed that after 4 weeks of degradation, the residual mass of CS/SF blend membrane was 82% to 85%, and the residual degradation amount of SA membrane was 55%, indicating that the membrane can maintain overall structural integrity within 4 weeks. In vitro cytology experiments showed that tendon cells can rapidly proliferate on the CS/SF membrane, indicating their promoting effect on tendon cell proliferation; The slow proliferation of fibroblasts on the SA membrane suggests their ability to inhibit the growth of fibroblasts. Conclusion The biofilm has strong mechanical properties, good hydrophilicity, and suitable biodegradability. It has dual functions of promoting tendon regeneration and inhibiting fiber adhesion formation, and has certain application prospects in tendon injury repair.
关键词
双层生物膜 /
肌腱粘连 /
肌腱修复
Key words
bilayer biofilm /
tendon adhesion /
tendon repair
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] JIA Q, CHEN D, GUO J, et al.Risk factors associated with tendon adhesions after hand tendon repair[J]. Front Surg, 2023, 10: 1121892.
[2] RETTING AC, LIOTTA FJ, KLOOTWYK TE, et al.Potential risk of rerupture in primary achilles tendon repair in athletes younger than 30 years of age[J]. Am J Sports Med, 2005, 33(1): 119-123.
[3] DY CJ, HERNANDEZ-SORIA A, MA Y, et al.Complications after flexor tendon repair: a systematic review and meta-analysis[J]. J Hand Surg Am, 2012, 37(3): 543-551.
[4] CHEN R, CHEN F, CHEN K, et al.Advances in the application of hydrogel-based scaffolds for tendon repair[J]. Genes Dis, 2023, 11(4): 101019.
[5] ZHANG H, DAI Y, LONG H, et al.Tendon Stem/Progenitor Cell-Laden Nanofiber Hydrogel Enhanced Functional Repair of Patellar Tendon[J]. Tissue Eng Part A, 2023, 29(5-6): 150-160.
[6] PRAKASH S, KALRA P, DHAL A.Flexor tendon repair with amniotic membrane[J]. Int Orthop, 2020, 44(10): 2037-2045.
[7] 吴佩耀. 肌腱修复用各向异性纤维膜材料的制备及其应用基础研究[D]. 昆明: 昆明理工大学, 2024.
[8] ALIMOHAMMADI M, AGJLI Y, FAKHRAEI O, et al.Electrospun Nanofibrous Membranes for Preventing Tendon Adhesion[J]. ACS Biomater Sci Eng, 2020, 6(8): 4356-4376.
[9] GENG Y, XUE H, ZHANG Z, et al.Recent advances in carboxymethyl chitosan-based materials for biomedical applications[J]. Carbohydr Polym, 2023, 305: 120555.
[10] WU H, LIN K, ZHAO C, et al.Silk fibroin scaffolds: A promising candidate for bone regeneration[J]. Front Bioeng Biotechnol, 2022, 10: 1054379.
[11] ZHOU Z, CUI J, WU S, et al.Silk fibroin-based biomaterials for cartilage/osteochondral repair[J]. Theranostics, 2022, 12(11): 5103-5124.
[12] GUAN W, GAO H, SUN S, et al.Multi-scale, multi-level anisotropic silk fibroin/metformin scaffolds for repair of peripheral nerve injury[J]. Int J Biol Macromol, 2023, 246: 125518.
[13] TUWALSKA A, GRABAKA-ZIELINSKA S, SIONKOWSKA A.Chitosan/Silk Fibroin Materials for Biomedical Applications-A Review[J]. Polymers (Basel), 2022, 14(7): 1343.
[14] XING X, HAN Y, CHENG H.Biomedical applications of chitosan/silk fibroin composites: A review[J]. Int J Biol Macromol, 2023, 240: 124407.
[15] NAGAKURA T, HIRATA H, TSUJII M, et al.Effect of viscous injectable pure alginate sol on cultured fibroblasts[J]. Plast Reconstr Surg, 2005, 116(3): 831-838.
[16] NAMABA J, SHIMADA K, SAITO M, et al.Modulation of peritendinous adhesion formation by alginate solution in a rabbit flexor tendon model[J]. J Biomed Mater Res B Appl Biomater, 2007, 80(1): 273-279.
[17] KULIG D, ZIMOCH-KORZYCKA A, JARMOLUK A, et al.Study on Alginate-Chitosan Complex Formed with Different Polymers Ratio[J]. Polymers (Basel), 2016, 8(5): 167.
[18] WANG Y, BELLA E, LEE CS, et al.The synergistic effects of 3-D porous silk fibroin matrix scaffold properties and hydrodynamic environment in cartilage tissue regeneration[J]. Biomaterials, 2010, 31(17): 4672-4681.
[19] RANJAN A, WEBSTER TJ.Increased endothelial cell adhesion and elongation on micron-patterned nano-rough poly (dimethylsiloxane) films[J]. Nanotechnology, 2009, 20(30): 305102.
[20] BAJPAI SK, SHARMA S.Investigation of swelling/degradation behaviour of alginate beads crosslinked with Ca2+ and Ba2+ ions-ScienceDirect[J]. React Funct Polym, 2004, 59(2): 129-140.
[21] LI X, GAO C, RUI CHENTIAN, et al.Fabrication of super hydrophilic surface on FeCrAl-WM with ridged microstructure for Joule-heating catalyst support by UV-laser microprocessing[J]. Journal of manufacturing processes, 2024, 109: 447-459.
[22] ANDARAWIS-PURI, FLATOW EL, SOSLOWSKY LJ.Tendon basic science: Development, repair, regeneration, and healing[J]. J Orthop Res, 2015, 33(6): 780-784.
[23] TSURUMARU N, ARAI M, TERUYA K, et al.Seprafilm as a new antifibrotic agent following trabeculectomy in rabbit eyes[J]. Jpn J Ophthalmol, 2009, 53(2): 164-170.
[24] 陆康. 微结构丝素蛋白薄膜的仿生制备及其在肌腱修复中的应用[D]. 重庆: 中国人民解放军陆军军医大学, 2021.
[25] 赵健平. 三维仿生粘附性纤维支架促进肌腱修复的基础研究[D]. 南宁: 广西医科大学, 2022.
[26] 路明宽, 蔡传栋, 王伟, 等. 防肌腱粘连膜制备材料的研究进展[J]. 上海交通大学学报 (医学版), 2021, 41(4): 550-553.
基金
湖南航天医院院级基金“PLGA-H2O2可控释氧型组织工程材料促进种子细胞存活与成骨分化并用于修复极限股骨缺损的实验研究”(2022yj05)