Mandibular defect repair by modified platelet-rich plasma combined with nanomaterials

doi:10.3969/j.issn.2095-4344.0918

Abstract

Abstract:

BACKGROUND: With the help of bone tissue engineering, osteogenitor cells from the periosteum taken as “seed cells” are combined with nano-scaffold materials and growth factors to repair bone defects.

OBJECTIVE: To explore the feasibility of reproducing platelet-rich plasma (PRP) using secondary centrifugation method through detecting platelet content, and to compare the osteogenic effects of different materials in different periods in order to explore new ways to repair bone defects with autologous periosteum and autologous active factors.

METHODS: Eighteen New Zealand white rabbits were randomly divided into blank group, pure material group and active material group (n=6 per group). The PRP was prepared 1 day before operation, and the active materials were prepared with nano-hydroxyapatite/collagen/bone morphogenetic proteins (nHAC/BMPs). A rectangular penetrating bone defect animal model was made in the right mandibular body of each New Zealand white rabbit followed by implantation of pure materials, nHAC/BMPs/PRP and nothing in the pure material group, active material group and blank group, respectively. Experimental animals were executed at 4, 8 and 12 weeks after surgery. The mandible specimens were taken and compared among groups through radiography, scanning electron microscopy, and histological observations as well as new bone area calculation in the defect area.

RESULTS AND CONCLUSION: The animal model of penetrating bone defect was successfully constructed and PRP was extracted effectively. The profile and imaging observations of the defect area showed better results in the pure material and active material groups than the blank group at each time. Under the scanning electron microscope, the boundary area of the blank group was mainly surrounded by fibrous tissues; there was a small amount of new bone in the boundary area of the material group; and the fibrous tissue of the active material group was dense and the flaky distribution of new bone was observed. The histological observation showed that the new bone formation in the bone defect area was superior in the material groups than that in the blank group, and there were more new bone and blood vessels in the active material group. Over time, the degraded material was surrounded and replaced by an active bone tissue. The area of new bone at 4 weeks after implantation was ranked as follows: blank group < pure material group < active material group, and there were significant differences between groups. The area of new bone in the blank group was significantly lower than that in the material groups at 8 and 12 weeks after implantation (P < 0.05), while there was no difference between two material groups (P > 0.05). To conclude, the nHAC/BMPs has good biocompatibility and osteoinduction activity in vivo, and it can be used as a scaffold material to guide the growth of regenerated bone tissue to the defect. PRP helps to induce and promote the osteogenesis of active materials and promote bone defect repair.

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

Key words: Platelet-Rich Plasma, Biocompatible Materials, Tissue Engineering

CLC Number:

R318

Xie Li-na, Zhao Bo, Chen Yuan, Jing Xiang-dong. Mandibular defect repair by modified platelet-rich plasma combined with nanomaterials[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(22): 3513-3519.

Figures/Tables 5

2.6 组织学观察造模后4周缺损区成骨情况：空白组缺损区由大量纤维组织、成纤维细胞构成，中央未见成骨；单纯材料组缺损区内由材料、纤维组织及新生骨组织构成，材料之间可见条索状新骨形成；活性材料组缺损区内由材料、纤维组织及新生骨组织完全充填，材料之间有网格状新生骨形成，骨量明显增多。造模后8周空白组缺损边缘可见新骨向中间延伸，单纯材料组缺损区内由材料、纤维组织及新生骨组织填充，材料之间为条索状的新生骨组织，活性材料组缺损区由材料、新生骨和纤维组织填充，材料之间可见片状的新骨形成，分布较广，骨量明显增多；造模后12周空白组缺损中央可见条索状、水滴状的新骨形成，大量纤维组织由脂肪组织替代，单纯材料组缺损区由材料、新生骨组织、纤维组织及少量脂肪组织充填，材料之间为新生骨组织延伸成长条形，骨成熟度增高，活性材料组缺损区由材料、新生骨、纤维及少量脂肪组织填充，大面积片状的新生骨组织，骨组织逐渐成熟，材料进一步降解，残留的材料被活跃生长的骨组织包围并替代，新生骨量增多(见图5)。造模后4周材料内部成骨情况：空白组由大量纤维组织、成纤维细胞构成；单纯材料组材料之间成骨样反应，材料边缘可见新生骨或类骨质包绕材料颗粒，不连续；活性材料组材料颗粒有新生骨形成，骨量明显增多，材料边缘新生骨组织伴新生血管条索状连续生长。造模后8周材料内部成骨情况：空白组缺损中央可见少量散在梭形新骨和新生血管形成；单纯材料组材料之间为片状的新生骨，缺损周边的骨组织伸入材料内与材料内的骨组织连接，材料颗粒少量由骨组织替代；活性材料组材料之间可见片状的新骨形成，分布较广，材料边缘可见连续性新骨形成并伸入到材料内，材料颗粒部分由骨组织完全替代，骨量增多。造模后12周材料内部成骨情况：空白组缺损中央可见条索状新骨伴新生血管形成；单纯材料组材料之间为长条形骨组织，材料颗粒近1/5完全被骨组织替代并连接成片，骨成熟度增高；活性材料组可见大面积片状的新生骨组织，材料降解被活跃生长的骨组织包围并替代，新生骨量明显增多，材料颗粒近1/3被骨组织替代并连接成片，新骨轮廓与原来材料一致(见图6)。"

References

[1] Amir JA, Abbas A, Simin Z, et al. Mandibular rami implant: a new approach in mandibular reconstruction. J Oral Maxillofac Surg.2017; 75(12):2550-2558.

[2] Yang CS, Shen SY, Wu JY, et al. A new modified method for accurate mandibular reconstruction. J Oral Maxillofac Surg. 2018; 11(18): 30-123.

[3] 蔡高锐,刘威,何勇,等.纳米生物材料在骨组织工程中的应用[J].国际骨科学杂志,2017, 38(05):303-306.

[4] 韩倩倩,薛彬,王涵,等.骨组织工程材料的研究进展[J].组织工程与重建外科杂志,2017, 13(06):343-345.

[5] 高伟.同种异体富血小板血浆对兔骨缺损修复作用的实验研究[D]. 河北医科大学. 2017.

[6] Harukazu T, Kazunori Y. 141-Growth factors and other new methods for graft-healing enhancement. Elsevier Inc. 2018; 4(3):111-135.

[7] Magesh DP, Kumaravelu C, Maheshwari GU. Efficacy of PRP in the reconstruction of mandibular segmental defects using iliac bone grafts. J Maxillofac Oral Surg.2013;12 (2):160-167.

[8] Yu T, Pan H, Hu Y, et al. Autologous platelet-rich plasma induces bone formation of tissue-engineered bone with bone marrow mesenchymal stem cells on beta-tricalcium phosphate ceramics. J Orthop Surg Res. 2017; 12(1):178.

[9] 綦惠,靳少锋,陈磊,等.富血小板血浆复合再生支架修复兔骨软骨缺损[J].中国矫形外科杂志,2018, 4(08):740-745.

[10] 陈骏,张庆福,赵云富,等.富血小板血浆在颌面骨修复中的应用研究进展[J].海军医学杂志,2015, 36(1):93-96.

[11] 张喆焱,李晶晶,朱莹,等.富血小板血浆复合羟基磷灰石在即刻种植中骨缺损的应用[J].全科口腔医学电子杂志, 2016, 3(19): 89-90.

[12] 朱韵莹,曾国春,武东辉.种植美学区域的富血小板血浆引导骨再生效果评价[J].当代医学,2017, 23(13): 23-24.

[13] 钱文慧,徐艳,孙颖,等.富血小板血浆修复牙周骨缺损的临床疗效[J].牙体牙髓牙周病学杂志,2014,24(7):415-418.

[14] Dong HL, Keun JR, Jin WK, et al. Bone marrow aspirate concentrate and platelet-rich plasma enhanced bone healing in distraction osteogenesis of the tibia. Clin Orthop Relat Res.2014; 472(12):3789-3797.

[15] Xie LN, P, Wang FZ, Cui F, et al. The effect of platelet-rich plasma with mineralized collagen based scaffold on repair of rabbit mandible defect. J Bioact Compat Polym.2010; 25(6): 603-621.

[16] 张广德,靳霞,李荣亮,等.BMP-9/EPO双基因共转染ADSCs复合nHAC/PLA支架修复兔下颌骨缺损的实验研究[J].中国口腔颌面外科杂志,2017,15(03):202-208.

[17] 王大平,熊建义,朱伟民,等.纳米羟基磷灰石人工骨在骨缺损修复中的临床应用研究[J].中国临床解剖学杂志, 2014, 32(2): 206-209.

[18] 滕宇.亲骨性BMP-2活性多肽及其仿生骨修复材料生物活性的实验研究[M].华中科技大学. 2013.

[19] 张磊.复合BMP-2来源新型短化纳米骨材料在骨修复中的应用硏究[M].山东大学, 2017.

[20] Weimin ZD, Wang JY, Xiong JQ, et al. Study on clinical application of nano-hydroxyapatite bone in bone defect repair. Artif Cells Nanomed Biotechnol. 2015; 43(6):361-365.

[21] Salazar VS, Gamer LW, Rosen V. et al. BMP signalling in skeletal development, disease and repair. Nat Rev Endocrinol. 2016; 12(4): 203-221.

[22] TMcCarrel TM, Mall NA, Lee AS, et al. Considerations for the use of platelet-rich plasma in orthopedics. Sports Med. 2014; 44(8):1025-1036.

[23] 吴珍珍,包崇云,李明政,等.载有人胚胎干细胞的多孔磷酸钙骨水泥与富血小板血浆复合后修复大鼠骨缺损的实验研究[J].中国口腔颌面外科杂志, 2017,15(1):6-10.

[24] 王毅,刘杨,杜军,等.富血小板血浆及富血小板血浆/OAM对种植体周围骨缺损修复的实验研究[J].口腔医学,2017, 37(4): 302-306.

[25] 李思敏,周晋,颜承伟,等.富血小板血浆缓释载体在骨组织工程中的研究进展[J].口腔医学研究, 2015, 31(6):632-634.637.

[26] 付维力,李棋,李箭,等.富血小板血浆在临床骨科中的应用进展[J].中国修复重建外科杂志,2014, 28(10):1311-1316.

[27] Mohammad J, Jayachandran M, Rethi M, et al. Effectiveness of platelet rich plasma and bone graft in the treatment of intrabony defects: a clinico-radiographic study. Open Dent J. 2018;12(3):133-154.

[28] 潘红娟.富血小板血浆制备技术的优化及其组分的检测[D].吉林大学, 2017.

[29] 杨毅,毕鑫,李多玉,等.人工骨材料修复骨缺损:多种复合后的生物学与力学特征[J].中国组织工程研究, 2014,18(16): 2582-2587.

[30] Yohei K, Yoshitomo S, Hirofumi N, et al. Leukocyte concentration and composition in platelet-rich plasma influences the growth factor and protease concentrations. J Orthop Sci, 2016; 21(5): 683-689.

[31] Vishram S, Rashi S, Gaurav S, et al. Platelet rich plasma-A new revolution in medicine. J Anat Soc India, 2017; 66(4): 127-135.