In vivo biosafety and histocompatibility of absorbable poly-D,L-lactic acid screws implanted with ultrasound-assisted technology

doi:10.3969/j.issn.2095-4344.2324

Abstract

Abstract:

BACKGROUND: According to the characteristics of low glass transition temperature of poly-D,L-lactic acid, we developed a new ultrasonic welding device to treat limb fractures with restorable poly-D,L-lactic acid screws. But whether the physical properties of poly-D,L-lactic acid changed by ultrasound has impact on material safety is unknown. In addition, under high intensity ultrasound action, the effects of absorbable screws on tissues around the absorbable screws remain unclear.

OBJECTIVE: To evaluate the biosafety and histocompatibility of ultrasound-assisted absorbable poly-D,L-lactic acid screws in rats.

METHODS: Twenty-four adult SD rat models of 1.6 mm-sized bone defects were made in the anterior side of the right tibial shaft, and then randomly divided into two groups. Absorbable poly-D,L-lactic acid screws were implanted in the experimental group and nothing was implanted in the control group. At postoperative 1, 3, 7 and 14 days and 2, 4, 6, and 8 weeks, routine blood tests, blood biochemical and serum inflammatory indicators were detected. At postoperative 2 weeks and 1, 3 and 6 months, gross observation, X-ray imaging, and histological observation of the bone defects were performed. This study was approved by the Animal Ethics Committee, West China Hospital of Sichuan University, China.

RESULTS AND CONCLUSION: (1) In both experimental and control groups, after surgery, wounds healed well without signs of infection and rejection, and there were no abnormal fluctuations in routine blood tests, biochemical and inflammatory indicators. (2) Gross observation revealed that by 1 month after surgery, absorbable poly-D,L-lactic acid screws began to degrade with a small amount of cartilage callus crawling towards the center; by 6 months after surgery, there were a large amount of new bone around the screws, and no abnormal reactive hyperplasia was observed in the surrounding tissues. (3) X-ray showed that the bone defect area in the experimental group was gradually reduced, and by 6 months after surgery, there were a large amount of new bone, and no abnormal reaction of the surrounding bone matrix was observed. (4) Histological observation revealed that at 2 weeks after surgery, the interface between the screws and the bone was clear, adjacent bone trabeculae did not grow in the screws, and fibrous tissue proliferated and covered the surface of the materials. The screws gradually degraded, new bone tissue gradually increased and matured. (5) These results suggest that ultrasound-assisted absorbable poly-D,L-lactic acid screws exhibit good biosafety and histocompatibility and can degrade gradually in vivo.

Key words: ultrasound-assisted, ultrasound-bonding, absorbable material, absorbable screws, poly-D,L-lactic acid, bone defect model, biosafety, histocompatibility

CLC Number:

Lei Senlin, Liu Hongyuan, Yang Hongsheng, Xiong Yan, Duan Hong. In vivo biosafety and histocompatibility of absorbable poly-D,L-lactic acid screws implanted with ultrasound-assisted technology[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(34): 5454-5460.

Figures/Tables 7

References

[1] PISTNER H, GUTWALD R, ORDUNG R, et al. Poly(L-lactide): a long-term degradation study in vivo. I.Biological results. Biomaterials.1993;14(9):671-677.

[2] ITO H, MATSUNO T, MINAMI A. Fixation with poly-L-lactide screws in hip osteotomies. Clin Orthop Relat Res. 2006;(444): 169-175.

[3] SUURONEN R, POHJONEN T, HIETANEN J, et al. A 5-year in vitro and in vivo study of the biodegradation of polylactide plates.J Oral Maxillofac Surg.1998;56(5):604-615.

[4] PILONE A, DE MAIO N, PRESS K, et al. Ring-opening homo and copolymerization of lactides and-caprolactone by salalen aluminum complexes.Dalton Trans.2015;44(5):2157-2165.

[5] 王勇平,刘小荣,蒋垚.可吸收材料在骨折内固定中的临床应用[J].中国组织工程研究,2013,17(4):712-719.

[6] TANG J, HU JF, GUO WC, et al. Research and application of absorbable screw in orthopedics: a clinical review comparing PDLLA screw with metal screw in patients with simple medial malleolus fracture.Chin J Traumatol.2013;16(1):27-30.

[7] PERREN SM. Evolution of the internal fixation of long bone fractures.J Bone Joint Surg Br.2002;84(8):1093-1110.

[8] 刘桂桢.外消旋聚乳酸/多壁碳纳米管复合材料的制备及表征[D].湘潭:湘潭大学,2011.

[9] 刘亚慧,林书玉,郭树琴,等.高强度聚焦超声的原理和应用[J].现代生物医学进展,2008,8(7):1344-1345,1352.

[10] ROCCHIO TM. Resorbable Polymer Pin Inserted with Ultrasound Activated BoneWelding Technique Compared with a Screw for Osteotomy Fixation in the Reverse L Bunion Correction.Clin Podiatr Med Surg.2018;35(4):373-385.

[11] RHA EY, PAIK H, BYEON J. Bioabsorbable plates and screws fixation in mandible fractures: clinical retrospective research during a 10-year period.Ann Plast Surg.2015;74(4):432-436.

[12] REN J, ZHAO P, REN T, et al. Poly (D, L-lactide)/ nano-hydroxyapatite composite scaffolds for bone tissue engineering and biocompatibility evaluation.J Mater Sci Mater Med.2008;19(3):1075-1082.

[13] SINIKUMPU J, SERLO W. Biodegradable poly-L-lactide-co- glycolide copolymer pin fixation of a traumatic patellar osteochondral fragment in an 11-year-old child: A novel surgical approach. Exp Ther Med.2017;13(1):242-246.

[14] TAN JS, FOO AT, CHEW WC, et al. Articularly placed interfragmentary screw fixation of difficult condylar fractures of the hand.J Hand Surg.2011;36(4):604-609.

[15] LINTZ F, PUJOL N, PANDEIRADA C, et al. Hybrid fixation: evaluation of a novel technique in adult osteochondritis dissecans of the knee.Knee Surg Sports Traumatol Arthrosc. 2011;19(4):568-571.

[16] 赵学寨,李海军,孟彩云,等.可吸收螺钉与金属螺钉内固定修复踝关节骨折:生物相容性及踝关节功能比较[J].中国组织工程研究, 2016,20(31):4687-4692.

[17] BIAN D, ZHOU W, DENG J, et al. Development of magnesium-based biodegradable metals with dietary trace element germanium as orthopaedic implant applications.Acta Biomater.2017;64:421-436.

[18] 魏世成,郑谦,赵宗林.超高分子量聚D,L乳酸小夹板螺钉的组织反应与降解动物实验研究[J].华西口腔医学杂志,1999,17(1): 66-68.

[19] CAMATHIAS C, GÖGÜS U, HIRSCHMANN MT, et al.Implant failure after biodegradable screw fixation in osteochondritis dissecans of the knee in skeletally immature patients. Arthroscopy. 2014;31(3):410-415.

[20] AN J, JIA P, ZHANG Y, et al. Use of biodegradable plates and screws in the treatment of pediatric facial bone fractures. Egypt J Oral Maxillofac Surg.2016;7(3):86-93.

[21] MATSUSUE T, HANAFUSA S, YAMAMURA T, et al. Tissue reaction of bioabsorbable ultra high strength poly (L-Lactide) rod.A long-term study in rabbits.Clin Orthop Relat Res.1995; 317:246-253.

[22] HOOGENBOOM M, EIKELENBOOM D, DEN BROK MH, et al. Mechanical High-Intensity Focused Ultrasound Destruction of Soft Tissue: Working Mechanisms and Physiologic Effects. Ultrasound Med Biol.2015;41(6):1500-1517.

[23] RICHLAND BK, ELLSTROM C, AHMAD A, et al. Resorbable Plates Prevent Regression in Pediatric Mandibular Distraction Osteogenesis.Ann Plast Surg.2017;78:S204-S207.

[24] MCLEOD NMH, GIJN DV. Use of ultrasound-activated resorbable sheets and pins in the management of fractures of the condylar neck of the mandible: a case series.Br J Oral Maxillofac Surg.2018;56(3):182-185.

[25] ABDELGALIL K, LOUKOTA R. Fixation of comminuted diacapitular fractures of the mandibular condyle with ultrasound-activated resorbable screws.Br J Oral Maxillofac Surg.2008;46(6):482-484.

[26] LEE J H, PARK JH. The Clinical Usefulness of Ultrasound-Aided Fixation Using an Absorbable Plate System in Patients with Zygomatico-Maxillary Fracture.Arch Plast Surg. 2013;40(4):330-334.

[27] 陈犹白,张海钟.超声辅助内固定术治疗面中部骨折的疗效分析[J].中华医学杂志,2013,93(18):1418-1421.

[28] NEUMANN H, BREER S, REIMERS N, et al. Osteosynthesis- screw augmentation by ultrasound-activated biopolyme-an ovine in vivo study assessing biocompatibility and bone-to-implant contact. J Orthop Surg Res. 2015;10(1): 18-24.

[29] SCHNEIDER M, SEINIGE C, PILLING E, et al. Ultrasound-aided resorbable osteosynthesis of fractures of the mandibular condylar base: an experimental study in sheep.Br J Oral Maxillofac Surg.2012;50(6):528-532.

[30] MAI R, LAUER G, PILLING E, et al. Bone welding-A histological evaluation in the jaw.Ann Anat.2007;189(4): 350-355.

[31] LANGHOFF JD, KUEMMERLE JM, MAYER J, et al. An Ultrasound Assisted Anchoring Technique (BoneWelding® Technology) for Fixation of Implants to Bone-A Histological Pilot Study in Sheep. Open Orthop J.2009;3(1):40-47.

[32] PILLING E, MAI R, THEISSIG F, et al. An experimental in vivo analysis of the resorption to ultrasound activated pins (Sonic weld) and standard biodegradable screws (ResorbX) in sheep. Br J Oral Maxillofac Surg.2007;45(6):447-450.

[33] ARNOLDI J, HENRY P, PROCTER P, et al. In Vivo Tissue Response to Ultrasound Assisted Application of Biodegradable Pins into Cortical and Cancellous Bone Structures: A Histological and Densitometric Analysis in Rabbits. J Biomater Sci Polym Ed.2012;23(5):663-676.

[34] DAVIDSON SR, JAMES DF. Drilling in Bone: Modeling Heat Generation and Temperature Distribution.J Biomech Eng. 2003;125(3):305-314.

[35] 陈蕾,戴红莲,闵玉华.聚乳酸及其复合材料的研究进展[J].生物骨科材料与临床研究,2005,8(2):45-48.

[36] CARVALHO AC, QUEIROZ TP, OKAMOTO R, et al. Evaluation of bone heating, immediate bone cell viability, and wear of high-resistance drills after the creation of implant osteotomies in rabbit tibias.Int J Oral Maxillofac Implants. 2011;26(6):1193-1201.

[37] MEAD RN, RYU J, LIU S, et al. Supraphysiologic temperature enhances cytotoxic effects of bupivacaine on bovine articular chondrocytes in an in vitro study.Arthroscopy. 2012;28(3): 397-404.

[38] NEUMANN H, SCHULZ AP, BREER S, et al. Refixation of Osteochondral Fractures by an Ultrasound-Activated Pin System–An Ovine In Vivo Examination Using CT and Scanning Electron Microscope.Open Orthop J. 2015;9(1): 7-14.

[39] 贺争鸣,邢瑞昌,方喜业,等.论实验动物福利､动物实验与动物实验替代方法[J].实验动物科学,2005,22(1):61-64.

[40] 孙立魁,辛仁东,谢克勤.浅谈医疗器械安全性评价的动物试验替代趋势[J].中国医疗器械信息,2010,16(8):53-54.