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期刊：ACS Appl Mater Interfaces

主題：可降解生物材料周邊微環(huán)境pH空間分布及其對破骨細(xì)胞活性的調(diào)節(jié)作用

標(biāo)題：Spatial Distribution of Biomaterial Microenvironment pH and Its Modulatory Effect on Osteoclasts at Early Stage of Bone Defect Regeneration

影響因子：8.097

監(jiān)測指標(biāo)：H+流速

檢測部位：生物材料玻璃材料

H+流速流實(shí)驗(yàn)處理方法：

不同配比的玻璃材料

H+流速流實(shí)驗(yàn)測試液成份：
模擬體液

作者：中科院深圳*技術(shù)研究院潘浩波、劉文龍

文獻(xiàn)簡介

2019年2月，中科院深圳*技術(shù)研究院潘浩波研究員團(tuán)隊(duì)發(fā)表了題為 “Spatial Distribution of Biomaterial Microenvironment pH and Its Modulatory Effect on Osteoclasts at the Early Stage of Bone Defect Regeneration” 的文章，通過關(guān)聯(lián)可降解生物材料周邊微環(huán)境H+離子分布和破骨細(xì)胞活性，旨在描繪 “材料-機(jī)體” 交互作用之 “微環(huán)境” 分布范圍。相關(guān)成果發(fā)表于ACS Applied Materials and Interfaces。
近年來，由人工組織與機(jī)體微環(huán)境交互作用而引起的材料學(xué)及生物學(xué)效應(yīng)受到越來越多的關(guān)注。團(tuán)隊(duì)早期研究發(fā)現(xiàn)pH值在調(diào)控骨修復(fù)過程中破骨與成骨間平衡具有重要作用，并采用微電極技術(shù)初步探明存在微堿性范圍內(nèi)的某一pH 閾值，使得成骨細(xì)胞、破骨細(xì)胞及骨髓基質(zhì)干細(xì)胞在閾值兩側(cè)的活性產(chǎn)生明顯變化（即“開/關(guān)”效應(yīng)）（Liu WL et al., Osteoporosis International, 2016; Shen YH et al., Journal of Materials Chemistry, 2012; Shen YH et al., Langmuir, 2011）。進(jìn)而，本研究采用非損傷微測技術(shù)，考察了系列可降解材料近表面（50-3000μm）氫離子流速及空間分布的梯度效應(yīng)。相對于表面pH微電極，NMT系統(tǒng)在檢測信號(hào)種類，空間和時(shí)間的可控性等方面展現(xiàn)出了獨(dú)到的優(yōu)勢。

結(jié)果證明，破骨細(xì)胞在微堿性環(huán)境中（pH>7.8）的分化及侵蝕骨板能力基本喪失；基于此，團(tuán)隊(duì)制備了系列堿性可降解硅硼酸鹽玻璃，并使用NMT系統(tǒng)描繪出與破骨細(xì)胞產(chǎn)生“開/關(guān)”效應(yīng)相對應(yīng)的材料表面微環(huán)境的影響范圍（400 ± 50 μm）。為研究“材料-骨組織”早期的相互作用，團(tuán)隊(duì)使用建立的小鼠骨缺損動(dòng)物模型（Liu WL et al., Tissue Engineering Part C: Methods, 2016），證明了材料周邊堿性微環(huán)境能促進(jìn)骨質(zhì)疏松骨缺損的快速再生。本研究進(jìn)而表明，對微環(huán)境離子濃度的調(diào)控將為未來新材料的設(shè)計(jì)提供指導(dǎo)意義。

英文摘要

It is generally accepted that biodegradable materials greatly influence the nearby microenvironment where cells reside; however, the range of interfacial properties has seldom been discussed due to technical bottlenecks.

This study aims to depict biomaterial microenvironment boundaries by correlating interfacial H+ distribution with surrounding cell behaviors. Using a disuse-related osteoporotic mouse model, we confirmed that the abnormal activated osteoclasts could be suppressed under relatively alkaline conditions. The differentiation and apatite-resorption capability of osteoclasts were “switched off” when cultured in titrated material extracts with pH values higher than 7.8.

To generate a localized alkaline microenvironment, a series of borosilicates were fabricated and their interfacial H+ distributions were monitored spatiotemporally by employing noninvasive microtest technology. By correlating interfacial H+ distribution with osteoclast “switch on/off” behavior, the microenvironment boundary of the tested material was found to be 400 ± 50 μm, which is broader than the generally accepted value, 300 μm.

Furthermore, osteoporotic mice implanted with materials with higher interfacial pH values and boarder effective ranges had lower osteoclast activities and a thicker new bone.

To conclude, effective proton microenvironment boundaries of degradable biomaterials were depicted and a weak alkaline microenvironment was shown to promote regeneration of osteoporotic bones possibly by suppressing abnormal activated osteoclasts.

中文摘要（谷歌機(jī)翻）

人們普遍認(rèn)為，可生物降解的材料會(huì)極大地影響細(xì)胞所在的附近微環(huán)境。然而，由于技術(shù)瓶頸，很少討論界面性質(zhì)的范圍。

這項(xiàng)研究旨在通過將界面H+分布與周圍細(xì)胞行為相關(guān)聯(lián)來描繪生物材料微環(huán)境的邊界。使用與廢品相關(guān)的骨質(zhì)疏松小鼠模型，我們確認(rèn)了在相對堿性條件下可以抑制異?；罨钠乒羌?xì)胞。當(dāng)在pH值高于7.8的滴定材料提取物中培養(yǎng)時(shí)，破骨細(xì)胞的分化和磷灰石吸收能力被“關(guān)閉”。

為了產(chǎn)生局部的堿性微環(huán)境，制造了一系列的硼硅酸鹽，并采用無創(chuàng)微測試技術(shù)對它們的界面H+分布進(jìn)行了時(shí)空監(jiān)測。通過將界面H+分布與破骨細(xì)胞的“開/關(guān)”行為相關(guān)聯(lián)，發(fā)現(xiàn)被測材料的微環(huán)境邊界為400±50μm，比*的值300μm寬。

此外，植入具有較高界面pH值和邊界有效范圍的材料的骨質(zhì)疏松小鼠的破骨細(xì)胞活性較低，新骨較厚。

總而言之，描繪了可降解生物材料的有效質(zhì)子微環(huán)境邊界，并顯示了弱堿性微環(huán)境可能通過抑制異?；罨钠乒羌?xì)胞來促進(jìn)骨質(zhì)疏松骨骼的再生。