国际口腔医学杂志 ›› 2021, Vol. 48 ›› Issue (1): 64-70.doi: 10.7518/gjkq.2021005

• 综述 • 上一篇    下一篇

微环境酸碱度在组织工程骨再生中作用的研究进展

李佩仪,张新春()   

  1. 中山大学附属口腔医院 中山大学光华口腔医学院 广东省口腔医学重点实验室 广州 510055
  • 收稿日期:2020-05-12 修回日期:2020-09-13 出版日期:2021-01-01 发布日期:2021-01-20
  • 通讯作者: 张新春
  • 作者简介:李佩仪,硕士,Email: peiyi6742@163.com
  • 基金资助:
    广东省自然科学基金项目(2019A1515010450);中山大学实验室开放基金项目(201902108)

Research progress on the effects of microenvironment acid-base level in tissue-engineered bone regeneration

Li Peiyi,Zhang Xinchun()   

  1. Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University & Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China
  • Received:2020-05-12 Revised:2020-09-13 Online:2021-01-01 Published:2021-01-20
  • Contact: Xinchun Zhang
  • Supported by:
    The study was supported by Guangdong Basic and Applied Basic Research Foundation(2019A1515010450);the Opening Fund of Laboratory Sun Yat-sen University(201902108)

摘要:

继自体骨移植和异种骨移植后,组织工程骨成为修复颌面骨缺损的新手段。成骨微环境是调动生物材料发挥再生功能的关键,微环境pH通过人工骨表面蛋白吸附、成骨相关细胞迁移、黏附、增殖、分化、骨基质分泌成熟、生物矿化,以及骨缺损区炎症反应、血管重建等修复过程影响组织工程骨再生。利用碱性材料中和缺损区酸性物质,纠正低血流灌注和局部缺氧形成的酸性微环境,创造适合细胞生存和修复的系统网络,可有效提高缺损区骨再生水平,是组织工程学研究的新方向。本文就微环境酸碱度在组织工程骨再生中的作用进行综述,旨在为人工骨材料研发与转化提供参考。

关键词: 骨组织工程, 成骨微环境, 酸碱度, 骨再生

Abstract:

After autogenous and xenogeneic bone transplantation therapy, bone tissue engineering has become a new method to repair maxillofacial bone defects. The osteogenic microenvironment is crucial to mobilising regenerative function of biological materials. The regeneration of tissue-engineered bone is affected by pH microenvironment through various osteogenic processes on the surface of artificial bone, such as protein adsorption, migration, adhesion, proliferation and differentiation of osteogenesis-related cells; secretion, maturation and biomineralisation of bone matrix; inflammatory response and vascular reconstruction of bone defects. Neutralising the acid substance in bone defects with alkaline materials correcting the acid microenvironment caused by hypoperfusion and local hypoxia is a potential method to create a suitable network for cell survival and tissue repair. In this paper, the research progress of microenvironment acid-base level in tissue-engineered bone regeneration is reviewed, providing a reference for the development and transformation of artificial bone materials.

Key words: bone tissue engineering, osteogenic microenvironment, acid-base level, bone regeneration

[1] Yamada M, Egusa H . Current bone substitutes for implant dentistry[J]. J Prosthodont Res, 2018,62(2):152-161.
[2] Patel PP, Buckley C, Taylor BL , et al. Mechanical and biological evaluation of a hydroxyapatite-reinforced scaffold for bone regeneration[J]. J Biomed Mater Res A, 2019,107(4):732-741.
[3] Rai R, Raval R, Khandeparker RV , et al. Tissue engineering: step ahead in maxillofacial reconstruction[J]. J Int Oral Health, 2015,7(9):138-142.
pmid: 26435634
[4] Yang L, Sanderlin E, Justus C , et al. Emerging roles for the pH-sensing G protein-coupled receptors in response to acidotic stress[J]. Cell Heal Cytoskelet, 2015: 99.
[5] Levin LR, Buck J . Physiological roles of acid-base sensors[J]. Annu Rev Physiol, 2015,77:347-362.
pmid: 25340964
[6] Lambert H, Frassetto L, Moore JB , et al. The effect of supplementation with alkaline potassium salts on bone metabolism: a Meta-analysis[J]. Osteoporos Int, 2015,26(4):1311-1318.
[7] Hamm LL, Nakhoul N, Hering-Smith KS . Acidba-se homeostasis[J]. Clin J Am Soc Nephrol, 2015,10(12):2232-2242.
[8] Arnett TR . Acidosis, hypoxia and bone[J]. Arch Biochem Biophys, 2010,503(1):103-109.
doi: 10.1016/j.abb.2010.07.021 pmid: 20655868
[9] Brandao-Burch A, Utting JC, Orriss IR , et al. Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization[J]. Calcif Tissue Int, 2005,77(3):167-174.
[10] Subrahmanyam DK, Vadivelan M, Giridharan S , et al. Wilson,s disease‒a rare cause of renal tubular acidosis with metabolic bone disease[J]. Indian J Nephrol, 2014,24(3):171-174.
[11] Liu W, Wang T, Yang C , et al. Alkaline biodegrada-ble implants for osteoporotic bone defects: importance of microenvironment pH[J]. Osteoporos Int, 2016,27(1):93-104.
[12] Kaunitz JD, Yamaguchi DT . TNAP, TrAP, ecto-purinergic signaling, and bone remodeling[J]. J Cell Biochem, 2008,105(3):655-662.
pmid: 18773425
[13] Monfoulet LE, Becquart P, Marchat D , et al. The pH in the microenvironment of human mesenchymal stem cells is a critical factor for optimal osteogenesis in tissue-engineered constructs[J]. Tissue Eng Part A, 2014,20(13/14):1827-1840.
[14] Hazehara-Kunitomo Y, Hara ES, Ono M , et al. Aci-dic pre-conditioning enhances the stem cell phenotype of human bone marrow stem/progenitor cells[J]. Int J Mol Sci, 2019,20(5):E1097.
[15] Stiers PJ, van Gastel N, Carmeliet G . Targeting the hypoxic response in bone tissue engineering: a ba-lance between supply and consumption to improve bone regeneration[J]. Mol Cell Endocrinol, 2016,432:96-105.
[16] Hao ZC, Song ZH, Huang J , et al. The scaffold microenvironment for stem cell based bone tissue engineering[J]. Biomater Sci, 2017,5(8):1382-1392.
[17] Roach P, Farrar D, Perry CC . Interpretation of protein adsorption: surface-induced conformational chan-ges[J]. J Am Chem Soc, 2005,127(22):8168-8173.
[18] Wu F, Lin DD, Chang JH , et al. Effect of the mate-rials properties of hydroxyapatite nanoparticles on fibronectin deposition and conformation[J]. Cryst Growth Des, 2015,15(5):2452-2460.
[19] Combes C, Rey C . Adsorption of proteins and calcium phosphate materials bioactivity[J]. Biomaterials, 2002,23(13):2817-2823.
doi: 10.1016/s0142-9612(02)00073-x pmid: 12059033
[20] Yadav I, Kumar S, Aswal VK , et al. Structure and interaction in the pH-dependent phase behavior of nanoparticle-protein systems[J]. Langmuir, 2017,33(5):1227-1238.
doi: 10.1021/acs.langmuir.6b04127 pmid: 28079383
[21] Kim J, Somorjai GA . Molecular packing of lysozyme, fibrinogen, and bovine serum albumin on hydrophilic and hydrophobic surfaces studied by infrared-visible sum frequency generation and fluorescence microscopy[J]. J Am Chem Soc, 2003,125(10):3150-3158.
doi: 10.1021/ja028987n pmid: 12617683
[22] Jones KL, Melia CRO . Protein and humic acid adsorption onto hydrophilic membrane surfaces: effects of pH and ionic strength[J]. J Membr Sci, 2000,165(1):31-46.
[23] Kumar S, Aswal VK, Callow P. pH-dependent interaction and resultant structures of silica nanoparticles and lysozyme protein[J]. Langmuir, 2014,30(6):1588-1598.
pmid: 24475981
[24] Raoufi M, Hajipour MJ, Kamali Shahri SM , et al. Probing fibronectin conformation on a protein Corona layer around nanoparticles[J]. Nanoscale, 2018,10(3):1228-1233.
doi: 10.1039/c7nr06970g pmid: 29292453
[25] Aiyelabegan HT, Sadroddiny E . Fundamentals of protein and cell interactions in biomaterials[J]. Bio-med Pharmacother, 2017,88:956-970.
[26] Dolatshahi-Pirouz A, Jensen T, Kraft DC , et al. Fibronectin adsorption, cell adhesion, and proliferation on nanostructured tantalum surfaces[J]. ACS Nano, 2010,4(5):2874-2882.
doi: 10.1021/nn9017872 pmid: 20443575
[27] Khalili AA, Ahmad MR . A review of cell adhesion studies for biomedical and biological applications[J]. Int J Mol Sci, 2015,16(8):18149-18184.
doi: 10.3390/ijms160818149 pmid: 26251901
[28] Ahn H, Kim JM, Lee K , et al. Extracellular acidosis accelerates bone resorption by enhancing osteoclast survival, adhesion, and migration[J]. Biochem Biophys Res Commun, 2012,418(1):144-148.
[29] Li X, Ye JX, Xu MH , et al. Evidence that activation of ASIC1a by acidosis increases osteoclast migration and adhesion by modulating integrin/Pyk2/Src signaling pathway[J]. Osteoporos Int, 2017,28(7):2221-2231.
pmid: 28462470
[30] Webb BA, Chimenti M, Jacobson MP , et al. Dysre-gulated pH: a perfect storm for cancer progression[J]. Nat Rev Cancer, 2011,11(9):671-677.
[31] Paradise RK, Lauffenburger DA, van Vliet KJ. Aci-dic extracellular pH promotes activation of integrin ανβ3[J]. PLoS One, 2011,6(1):e15746.
pmid: 21283814
[32] Kruse CR, Singh M, Targosinski S , et al. The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: in vitro and in vivo study[J]. Wound Repair Regen, 2017,25(2):260-269.
doi: 10.1111/wrr.12526 pmid: 28370923
[33] Galow AM, Rebl A, Koczan D , et al. Increased osteoblast viability at alkaline pH in vitro provides a new perspective on bone regeneration[J]. Biochem Biophys Rep, 2017,10:17-25.
pmid: 28955732
[34] Li JH, Wang GF, Wang DH , et al. Alkali-treated titanium selectively regulating biological behaviors of bacteria, cancer cells and mesenchymal stem cells[J]. J Colloid Interface Sci, 2014,436:160-170.
doi: 10.1016/j.jcis.2014.08.053 pmid: 25268820
[35] Fliefel R, Popov C, Tröltzsch M , et al. Mesenchymal stem cell proliferation and mineralization but not osteogenic differentiation are strongly affected by extracellular pH[J]. J Craniomaxillofac Surg, 2016,44(6):715-724.
doi: 10.1016/j.jcms.2016.03.003 pmid: 27085985
[36] Marie PJ . Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies[J]. Cell Mol Life Sci, 2015,72(7):1347-1361.
[37] Massa A, Perut F, Chano T , et al. The effect of extracellular acidosis on the behaviour of mesenchymal stem cells in vitro[J]. Eur Cell Mater, 2017,33:252-267.
[38] Tao SC, Gao YS, Zhu HY , et al. Decreased extracellular pH inhibits osteogenesis through proton-sensing GPR4-mediated suppression of yes-associated protein[J]. Sci Rep, 2016,6:26835.
pmid: 27256071
[39] Kohn DH, Sarmadi M, Helman JI , et al. Effects of pH on human bone marrow stromal cells in vitro: implications for tissue engineering of bone[J]. J Bio-med Mater Res, 2002,60(2):292-299.
[40] Frick KK, Bushinsky DA . Chronic metabolic acidosis reversibly inhibits extracellular matrix gene expression in mouse osteoblasts[J]. Am J Physiol, 1998,275(5):F840-F847.
doi: 10.1152/ajprenal.1998.275.5.F840 pmid: 9815143
[41] Kato K, Matsushita M . Proton concentrations can be a major contributor to the modification of osteoclast and osteoblast differentiation, working independently of extracellular bicarbonate ions[J]. J Bone Miner Metab, 2014,32(1):17-28.
doi: 10.1007/s00774-013-0462-9
[42] Bushinsky DA . Metabolic alkalosis decreases bone calcium efflux by suppressing osteoclasts and stimulating osteoblasts[J]. Am J Physiol, 1996,271(1 Pt 2):F216-F222.
doi: 10.1152/ajprenal.1996.271.1.F216 pmid: 8760264
[43] Tomura H, Wang JQ, Liu JP , et al. Cyclooxygenase-2 expression and prostaglandin E2 production in response to acidic pH through OGR1 in a human osteoblastic cell line[J]. J Bone Miner Res, 2008,23(7):1129-1139.
doi: 10.1359/jbmr.080236 pmid: 18302504
[44] Okito A, Nakahama KI, Akiyama M , et al. Involvement of the G-protein-coupled receptor 4 in RAN-KL expression by osteoblasts in an acidic environment[J]. Biochem Biophys Res Commun, 2015,458(2):435-440.
[45] Avnet S, Di Pompo G, Lemma S , et al. Cause and effect of microenvironmental acidosis on bone metastases[J]. Cancer Metastasis Rev, 2019,38(1/2):133-147.
[46] Camargo WA, Takemoto S, Hoekstra JW , et al. Effect of surface alkali-based treatment of titanium implants on ability to promote in vitro mineralization and in vivo bone formation[J]. Acta Biomater, 2017,57:511-523.
[47] Adamopoulos IE . Inflammation in bone physiology and pathology[J]. Curr Opin Rheumatol, 2018,30(1):59-64.
[48] Spector JA, Mehrara BJ, Greenwald JA , et al. Osteoblast expression of vascular endothelial growth factor is modulated by the extracellular microenvironment[J]. Am J Physiol Cell Physiol, 2001,280(1):C72-C80.
pmid: 11121378
[49] Zhao FJ, Xie WH, Zhang W , et al. 3D printing nanoscale bioactive glass scaffolds enhance osteoblast migration and extramembranous osteogenesis throu-gh stimulating immunomodulation[J]. Adv Healthc Mater, 2018,7(16):e1800361.
doi: 10.1002/adhm.201800361 pmid: 29952135
[50] Chen Q, Cai J, Li X , et al. Progranulin promotes regeneration of inflammatory periodontal bone defect in rats via anti-inflammation, osteoclastogenic inhibition, and osteogenic promotion[J]. Inflammation, 2019,42(1):221-234.
doi: 10.1007/s10753-018-0886-4 pmid: 30187338
[51] Medzhitov R . Inflammation 2010: new adventures of an old flame[J]. Cell, 2010,140(6):771-776.
doi: 10.1016/j.cell.2010.03.006 pmid: 20303867
[52] Du B, Liu WZ, Deng Y , et al. Angiogenesis and bone regeneration of porous nano-hydroxyapatite/coralline blocks coated with rhVEGF165 in critical-size alveolar bone defects in vivo[J]. Int J Nanome-dicine, 2015,10:2555-2565.
[53] Zhang Y, Huang J, Wang C , et al. Application of HIF-1α by gene therapy enhances angiogenesis and osteogenesis in alveolar bone defect regeneration[J]. J Gene Med, 2016,18(4/5/6):57-64.
doi: 10.1002/jgm.v18.4-6
[54] Shen YH, Liu W, Lin KL , et al. Interfacial pH: a critical factor for osteoporotic bone regeneration[J]. Langmuir, 2011,27(6):2701-2708.
doi: 10.1021/la104876w pmid: 21309596
[55] Liu WL, Wang T, Zhao XL , et al. Akermanite used as an alkaline biodegradable implants for the treatment of osteoporotic bone defect[J]. Bioact Mater, 2016,1(2):151-159.
doi: 10.1016/j.bioactmat.2016.11.004 pmid: 29744404
[56] Li QW, Wang DH, Qiu JJ , et al. Regulating the local pH level of titanium via Mg-Fe layered double hydroxides films for enhanced osteogenesis[J]. Biomater Sci, 2018,6(5):1227-1237.
doi: 10.1039/c8bm00100f pmid: 29589018
[57] Justus CR, Dong LX, Yang LV . Acidic tumor microenvironment and pH-sensing G protein-coupled receptors[J]. Front Physiol, 2013,4:354.
doi: 10.3389/fphys.2013.00354 pmid: 24367336
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