摘要
背景
前磨牙拔除后的上颌尖牙内收是正畸治疗中耗时较长的阶段。多种辅助方法,包括血小板浓缩物、骨皮质切开术和 piezocision(压电骨皮质切开术),已被提出用于加速牙齿移动;然而,其相对有效性和安全性仍不明确。
目的
评价血小板浓缩物、骨皮质切开术和 piezocision 作为前磨牙拔除后上颌尖牙内收辅助手段的有效性和安全性。
方法
检索 PubMed/MEDLINE、Scopus 和 Cochrane CENTRAL,检索时间从建库至 2026 年 4 月 30 日。纳入比较富血小板血浆、可注射富血小板纤维蛋白、富白细胞和血小板纤维蛋白、骨皮质切开术或 piezocision 与常规上颌尖牙内收的随机对照试验。研究筛选、数据提取和使用 RoB 2 进行的偏倚风险评估均由研究者独立完成。研究结果采用叙述性综合。
结果
共纳入 25 项随机研究。骨皮质切开术和 piezocision 通常在术后早期增加尖牙内收量,但在若干试验中该效应随时间推移而减弱。血小板浓缩物的研究结果不一致,从无显著效应到小幅或暂时性移动增加不等。这些干预措施缩短尖牙内收总持续时间的证据有限。各组间的支抗丧失和牙周结局总体相似,而关于倾斜、牙根吸收、疼痛和不良反应的研究结果则存在差异。4 项研究偏倚风险低,21 项研究存在一些担忧。
结论
骨皮质切开术和 piezocision 可能提高上颌尖牙早期内收速率,而血小板浓缩物的效应则较不一致。当前证据尚不能确定其能可靠缩短总内收持续时间,也不支持对各干预措施进行明确排序。仍需设计更规范的随机试验。
系统评价注册
注册号 CRD420261287411。
关键词:加速正畸、尖牙内收、骨皮质切开术、piezocision、富血小板纤维蛋白、富血小板血浆
引言
正畸治疗的持续时间受多种因素影响,包括错𬌗畸形的严重程度、所采用的治疗力学机制、对正畸力的生物学反应以及患者的依从性。治疗时间延长与不良反应风险增加相关,包括菌斑堆积、白垩色斑块、牙周状况恶化以及根尖外吸收(1)。因此,旨在缩短治疗时间同时保持有效支抗控制、牙周健康和精确牙齿移动的策略具有相当大的临床意义。在此背景下,加速正畸技术已成为一种在不影响治疗效果的前提下提高治疗效率的有前景的方法。
前磨牙拔除后行上颌尖牙内收是正畸治疗中矫正牙列拥挤和双颌前突的常规组成部分。然而,尖牙内收通常需要数月才能完成,因为牙齿移动必须跨越拔牙间隙,并受到牙周膜重塑和牙槽骨改建等生物学过程的限制。为克服这些限制并缩短总体治疗时间,已开发出多种加速正畸方法。这些策略旨在增强牙齿移动背后的生物学反应,包括手术干预、物理刺激技术、药物制剂和局部给药的生物介质(2)。这些方法在潜在生物学机制、临床适用性以及加速正畸牙齿移动的疗效方面各不相同。
骨皮质切开术和 piezocision 是研究最广泛的加速正畸牙齿移动的手术方法之一。骨皮质切开术涉及在翻瓣后制造可控的皮质骨损伤,而 piezocision 则利用微创、不翻瓣的皮质切开。这两种技术被认为通过触发区域加速现象(RAP)来增强牙齿移动,RAP 是一种局部生物学反应,其特征是手术损伤后骨改建和骨转换的短暂增加,最初由 Frost 描述(3)。这种增强的改建活动伴随骨密度暂时降低,有利于牙齿在正畸力作用下更快速地移动。随后,piezocision 作为传统骨皮质切开术的微创替代方法被引入,旨在实现相当的生物学效应,同时尽量减少手术创伤、患者不适和术后并发症(4)。
随机试验报告了关于骨皮质切开术和 piezocision 对上颌尖牙内收效果的不一致结果。虽然多项研究显示术后早期牙齿移动增强,但其他研究报告与常规内收方法相比,加速效果甚微或无显著差异(5–8)。此外,加速效应的持续时间及其对尖牙内收总持续时间的影响仍不明确。
生物学辅助手段如富血小板血浆(PRP)和可注射富血小板纤维蛋白(i-PRF)已被局部应用于增强上颌尖牙内收(9–12)。同样,富白细胞-血小板纤维蛋白(L-PRF)也已在其置入前磨牙拔牙窝后进行了研究(13)。然而,由于制备方案、给药方案、应用频率、正畸力学机制、随访时间以及用于评估治疗结果的方法存在相当大的差异,这些研究之间进行有意义的比较具有挑战性。
既往综述已评估了尖牙内收过程中的骨皮质切开术和压电骨皮质切开术,但证据受限于样本量小和手术方案异质性(14)。血小板浓缩物通常与手术加速技术分开评估,且尽管操作程序存在重要差异,不同制备物常被归为一组。因此,这些干预措施的比较有效性仍不清楚。尖牙内收的初始加速是否能随时间维持、是否缩短总体内收持续时间,或是否影响支抗、牙根吸收、牙周健康、疼痛或其他不良结局,也尚不确定。
本系统综述旨在评估研究血小板浓缩物、骨皮质切开术和压电骨皮质切开术作为前磨牙拔除后上颌尖牙内收辅助干预措施的随机对照试验。将其有效性与传统正畸内收在尖牙内收速率和总体内收持续时间方面进行比较。还评估了次要结局,包括支抗丧失、牙根吸收、牙周健康、疼痛和其他报告的不良反应。
方法
本系统综述旨在评估血小板浓缩物、骨皮质切开术和压电骨皮质切开术在加速前磨牙拔除后上颌尖牙内收中的有效性。本综述按照系统综述和荟萃分析优先报告条目2020指南(15)进行计划和报告。
在研究选择和数据提取完成之前制定了方案,并提交至国际系统综述前瞻性注册库。已发布的Prospero记录注册号为CRD420261287411。
综述问题按照PICOS格式构建:
人群(P):使用固定正畸矫治器在前磨牙拔除后接受上颌尖牙内收的青少年和成人。
干预(I):血小板浓缩物,包括富血小板血浆、可注射富血小板纤维蛋白和富白细胞-血小板纤维蛋白;骨皮质切开术辅助正畸;或压电骨皮质切开术辅助正畸。
对照(C):无生物学或手术加速程序的传统上颌尖牙内收。
结局(O)
主要结局:上颌尖牙内收速率和尖牙内收总持续时间。
次要结局:支抗丧失、尖牙倾斜和旋转、牙根吸收、牙周参数、疼痛、肿胀、不适、患者报告结局以及干预相关不良反应。
研究设计(S):随机对照试验(RCT)(平行或口内分半设计)。
文献检索
在PubMed/MEDLINE、Scopus和Cochrane对照试验中心注册库(CENTRAL)中进行了全面的电子文献检索。这些数据库的选择基于机构图书馆的可获得性及其与生物医学、牙科和对照试验文献的相关性。检索于2026年5月5日至5月8日之间进行。本综述考虑了截至2026年4月30日发表的文献。检索策略结合了受控词汇术语(适用时使用MeSH术语)和与正畸尖牙内收及加速正畸干预相关的自由文本关键词。检索词包括以下组合:“canine retraction”、“maxillary canine movement”、“orthodontic tooth movement”、“accelerated orthodontics”、“platelet-rich plasma” OR “PRP”、“platelet-rich fibrin” OR “PRF”、“injectable platelet-rich fibrin” OR “i-PRF”、“leukocyte platelet-rich fibrin” OR “L-PRF”、“corticotomy”、“corticotomy-assisted orthodontics”、“piezocision”和“randomized controlled trial”。(表1)。
Table 1. Search strategy and search terms used.
| Database | Search query | Results |
|---|---|---|
| PubMed | ((canine retraction OR maxillary canine retraction OR orthodontic space closure) AND (platelet-rich plasma OR platelet-rich fibrin OR injectable platelet-rich fibrin OR leukocyte platelet-rich fibrin OR corticotomy OR piezocision) AND (randomised OR randomized OR clinical trial)) | 291 |
| Scopus | TITLE-ABS-KEY((“canine retraction” OR “orthodontic space closure” OR “maxillary canine”) AND (“platelet-rich plasma” OR “platelet-rich fibrin” OR “injectable platelet-rich fibrin” OR “leukocyte platelet-rich fibrin” OR corticotomy OR piezocision) AND (randomised OR randomized OR “clinical trial”)) | 447 |
| Cochrane | ((canine retraction OR orthodontic space closure) AND (platelet-rich plasma OR platelet-rich fibrin OR injectable platelet-rich fibrin OR L-PRF OR corticotomy OR piezocision)) | 279 |
| Total | Records identified across all searched databases before deduplication | 1,017 |
根据情况使用了布尔运算符(AND、OR)和数据库特定筛选器。检索策略根据各数据库的索引系统和检索要求进行了调整。此外,对所有纳入研究和相关综述文章的参考文献列表进行了人工筛选,以识别电子检索过程中可能遗漏的潜在合格研究。
研究选择的纳入和排除标准
纳入标准:
涉及青少年或成人接受固定正畸矫治器前磨牙拔除后上颌尖牙内收的随机对照试验(平行或分口设计)。
评估PRP、i-PRF、L-PRF、骨皮质切开术或压电骨皮质切开术与常规尖牙内收相比较的研究。
报告与尖牙内收速率、量或持续时间相关结局且数据可提取的研究。
以英文发表的全文文章。
排除标准:
评估其他正畸移动或加速技术但无单独尖牙内收数据的研究。
使用隐形矫治器、可摘矫治器、正颌手术、牵张成骨或牙槽牵张的研究。
患有颅面畸形、活动性牙周病、全身性疾病或使用影响骨代谢药物的参与者。
缺乏常规对照组、相关结局数据或随机设计的研究。
使用准随机或其他可预测分配方法(如奇偶患者编号)的研究。
病例报告、综述、会议摘要、动物/实验室研究以及非英文或非全文出版物。
研究选择
由两名评价者(A.K.V和A.S)根据预定义的合格标准独立筛选标题和摘要。随后由同一批评价者独立评估潜在合格研究的全文。任一阶段的意见分歧均通过讨论解决,必要时咨询其他评价者(A.M和M.S.R)。
数据提取
收集并制表以下信息:
作者和年份
国家
研究设计
随机化/分配方法
样本量
参与者年龄
错𬌗畸形/拔牙模式
牙弓/牙齿移动
干预类别
对照
随访
报告的结局
由两名独立评价者使用标准化Microsoft Excel表格提取数据。提取的信息包括研究特征、随机化和分配程序、参与者人口学特征、错𬌗畸形和拔牙模式、牙弓/牙齿移动、干预类别、对照、随访和报告的结局。各纳入研究的详细特征见表2。差异通过讨论解决,必要时咨询第三和第四评价者(A.M.和M.S.R.)。S.K.交叉核对提取的数据。纳入研究中未发现重复或重叠的发表文献。
Table 2. Study characteristics of included studies.
| Study | Country | Study design/randomization | Sample | Intervention | Comparator | Follow-up | Main outcome |
|---|---|---|---|---|---|---|---|
| Alfailany et al. ( 7 ) | Syria | Parallel RCT; computer-generated sequence; opaque envelopes | n = 51 | Corticotomy | Conventional control | To completion | Canine retraction |
| Eid and El-Kalza ( 27 ) | Egypt | RCT with split-mouth component; computer-generated allocation | n = 30 | Piezocision | Contralateral control | 12 weeks | Canine retraction |
| Abbas et al. ( 5 ) | Egypt | Split-mouth RCT; coin toss | n = 20 | Corticotomy; piezocision | Contralateral control | 3 months | Canine retraction |
| Raj et al. ( 28 ) | India | Split-mouth RCT; computer-generated allocation | n = 20 | Piezocision | Contralateral control | 90 days | Canine retraction |
| Yıldırım et al. ( 29 ) | Turkey | Split-mouth RCT; computer-generated sequence; sealed envelopes | n = 15 | Piezocision | Contralateral control | 28 days | Canine retraction |
| Fernandes et al. ( 8 ) | Brazil | Randomized trial with split-mouth comparisons; software-generated allocation | n = 47 | Corticotomy; piezocision | Contralateral control | 24 weeks | Canine retraction |
| Moradinejad et al. ( 30 ) | Iran | Split-mouth RCT; restricted randomization; coin toss for side | n = 32 | Piezocision | Contralateral control | 9 weeks | Canine retraction; anchorage loss |
| Al-A’athal et al. ( 31 ) | Jordan | Split-mouth RCT; permuted blocks; opaque envelopes | n = 23 | Piezocision | Contralateral control | 12 weeks | Canine retraction; anchorage loss |
| Syal et al. ( 32 ) | India | Prospective randomized split-mouth study; exact side sequence not reported | n = 12 | Piezocision | Contralateral control | 3 months | Canine retraction |
| Angel et al. ( 10 ) | India | Split-mouth RCT; computer-generated sequence; opaque envelopes | n = 10 | PRP | Contralateral control | 60 days | Canine retraction |
| El Timamy et al. ( 9 ) | Egypt | Split-mouth RCT; computer-generated sequence; opaque envelopes | n = 15 | PRP | Contralateral placebo control | 4 months | Canine retraction |
| Raza et al. ( 22 ) | India | Split-mouth RCT; computer-generated sequence; opaque envelopes | n = 10 | Corticotomy | Contralateral control | To completion | Canine retraction; duration |
| Gupta et al. ( 18 ) | India | Split-mouth RCT; block randomization; opaque envelopes | n = 35 | L-PRF | Contralateral control | 4 months/to completion | Canine movement; duration |
| Alfawal et al. ( 6 ) | Syria | RCT with split-mouth control; computer-generated sequence; opaque envelopes | n = 34 | Piezocision | Contralateral control | 4 months | Canine retraction; duration |
| Aboul-Ela et al. ( 23 ) | Egypt | Split-mouth randomized study; coin toss | n = 13 | Corticotomy | Contralateral control | 4 months | Canine retraction |
| Zeitounlouian et al. ( 12 ) | Syria | Split-mouth RCT; computer-generated side allocation | n = 21 | i-PRF | Contralateral control | 5 months | Canine retraction |
| Arora et al. ( 19 ) | India | Split-mouth randomized study; opaque-envelope side allocation | n = 14 | PRP | Contralateral control | 4 months | Canine retraction |
| Krishna et al. ( 13 ) | India | Split-mouth RCT; computer-generated side allocation | n = 16 analyzed | L-PRF | Contralateral control | 8 weeks | Canine retraction |
| Jahanbakhshi et al. ( 24 ) | Iran | Split-mouth randomized trial; sequence method not reported | n = 15 | Corticotomy | Contralateral control | ≈4 months | Canine retraction |
| Al-Naoum et al. ( 25 ) | Syria | Split-mouth RCT; sealed-envelope side allocation | n = 30 | Corticotomy | Contralateral control | 12 weeks | Canine retraction |
| Naji et al. ( 11 ) | Syria | Parallel RCT with split-mouth control; sealed-envelope allocation | n = 40 | PRP; i-PRF | Contralateral placebo control | 12 weeks | Canine retraction |
| Sharma et al. ( 26 ) | India | Split-mouth RCT; randomization stated; sequence method not reported | n = 14 analyzed | Corticotomy | Contralateral control | To completion | Canine retraction; anchorage |
| Gupta et al. ( 20 ) | India | Split-mouth RCT; drawing lots | n = 16 | L-PRF | Contralateral control | 5 months | Canine retraction |
| Pradhan et al. ( 33 ) | India | Prospective split-mouth randomized study; independent side allocation | n = 15 | Piezocision | Contralateral control | To completion | Retraction duration; root resorption |
| El Gazzar et al. ( 21 ) | Egypt | Split-mouth RCT; drawing lots | n = 20 reported | PRP | Contralateral control | 4 months | Canine retraction |
曾考虑在各干预组内及在可比随访时间点进行定量合成。然而,干预方案、正畸力学机制、结局评估和随访方面的差异限制了可比性,且以分口试验为主的研究未能一致提供配对方差数据。因此,对研究结果进行了叙述性综合。
偏倚风险评估
偏倚风险由两名评价者(A.K.V)和(A.S)使用修订版Cochrane随机试验偏倚风险工具(RoB 2)(16, 17)独立评估,分歧通过讨论或咨询第三和第四名评价者(A.M.和M.S.R.)解决。N.P.S.对偏倚风险评估进行了交叉核对。评估重点关注干预分配对上前牙犬齿远移的影响,并评价了五个领域:随机化过程产生的偏倚、偏离预期干预、结局数据缺失、结局测量以及报告结果的选择。每个领域被评为低偏倚风险、存在一些担忧或高偏倚风险,并根据RoB 2算法确定总体判断。对于分口试验,评估还考虑了侧别分配的随机化和隐藏、结局评估的盲法、配对观察的完整性以及配对设计统计分析的适当性(图1)。
[图:纳入研究的偏倚风险交通灯图(RoB 2)。]

采用GRADE方法评估主要结局和关键次要结局的证据确定性。(表3)从偏倚风险、不一致性、间接性、不精确性和发表偏倚方面对证据进行评价,确定性分级为高、中、低或极低。由于未进行荟萃分析,关于不一致性和不精确性的判断基于研究结果的方向和一致性、样本量以及所报告估计值的精确度。
Table 3. Primary numerical outcomes of the included studies.
| Study | Intervention | Follow-up | Key numerical result (intervention vs. control) | Total retraction duration | Main finding |
|---|---|---|---|---|---|
| Alfailany et al. ( 7 ) | Corticotomy | To completion | M1: 2.79 ± 0.39 vs. 1.12 ± 0.16 mm | NR | Greater movement during the first 2 months |
| Eid and El-Kalza ( 27 ) | Piezocision | 12 weeks | Single: 4.49 ± 0.34 vs. 2.77 ± 0.29 mm; multiple: 4.68 ± 0.27 vs. 2.79 ± 0.29 mm | NR | Both protocols increased retraction |
| Abbas et al. ( 5 ) | Corticotomy; piezocision | 3 months | T6: corticotomy 1.22 ± 0.08 vs. 0.58 ± 0.04 mm; piezocision 0.99 ± 0.10 vs. 0.60 ± 0.04 mm | NR | Both increased movement; corticotomy generally greater |
| Raj et al. ( 28 ) | Piezocision | 90 days | 4.25 ± 0.60 vs. 2.88 ± 0.40 mm at 90 days | NR | Greater movement at all assessed intervals |
| Yıldırım et al. ( 29 ) | Piezocision | 28 days | 1.27 ± 0.36 vs. 0.70 ± 0.25 mm at 28 days | NR | Greater early distalization |
| Fernandes et al. ( 8 ) | Corticotomy; piezocision | 24 weeks | Corticotomy: 3.83 ± 1.00 vs. 3.97 ± 1.41 mm; piezocision: 2.93 ± 1.11 vs. 4.05 ± 0.96 mm | NR | No corticotomy benefit; piezocision lower than control |
| Moradinejad et al. ( 30 ) | Piezocision | 9 weeks | 3.56 ± 0.05 vs. 2.42 ± 0.06 mm at 9 weeks | NR | Greater movement; effect decreased over time |
| Al-A’athal et al. ( 31 ) | Piezocision | 12 weeks | Average facial height: 1.48 ± 0.74 vs. 1.88 ± 0.83 mm; high facial height: 1.40 ± 0.85 vs. 1.76 ± 0.62 mm | NR | No significant acceleratory effect |
| Syal et al. ( 32 ) | Piezocision | 3 months | 3.97 ± 1.54 vs. 1.78 ± 0.42 mm | NR | Greater retraction with piezocision |
| Angel et al. ( 10 ) | PRP | 60 days | 3.19 ± 0.27 vs. 2.30 ± 0.20 mm | NR | Greater movement over 2 months |
| El Timamy et al. ( 9 ) | PRP | 4 months | Total: 4.57 ± 1.32 vs. 4.53 ± 1.12 mm | NR | Early benefit only; total movement similar |
| Raza et al. ( 22 ) | Corticotomy | To completion | M1: 1.36 ± 0.33 vs. 0.81 ± 0.06 mm | 5.7 vs. 7.1 months | Faster early movement and shorter retraction duration |
| Gupta et al. ( 18 ) | L-PRF | 4 months/to completion | Cusp movement: 3.53 ± 0.23 vs. 2.71 ± 0.22 mm | 6.01 ± 0.53 vs. 6.77 ± 0.49 months | Greater cusp movement; greater tipping also observed |
| Alfawal et al. ( 6 ) | Piezocision | 4 months | M1: 1.65 ± 0.40 vs. 0.83 ± 0.18 mm | ≈1.17-month reduction reported | Early acceleration with diminishing effect |
| Aboul-Ela et al. ( 23 ) | Corticotomy | 4 months | M1: 1.89 vs. 0.75 mm/month | NR | Marked early acceleration; little difference by month 4 |
| Zeitounlouian et al. ( 12 ) | i-PRF | 5 months | Total: 3.90 ± 1.36 vs. 3.94 ± 1.12 mm | NR | No sustained overall benefit |
| Arora et al. ( 19 ) | PRP | 4 months | M1: 1.355 ± 0.699 vs. 1.265 ± 0.698 mm | NR | No significant difference at any interval |
| Krishna et al. ( 13 ) | L-PRF | 8 weeks | 2.29 ± 0.19 vs. 2.01 ± 0.30 mm | NR | Small but significant increase in movement |
| Jahanbakhshi et al. ( 24 ) | Corticotomy | ≈4 months | Overall: 1.8 ± 0.17 vs. 1.1 mm/month | NR | Greater retraction velocity, largest early |
| Al-Naoum et al. ( 25 ) | Corticotomy | 12 weeks | Week 1: 0.739 ± 0.365 vs. 0.201 ± 0.149 mm/week | NR | Greater velocity throughout follow-up |
| Naji et al. ( 11 ) | PRP; i-PRF | 12 weeks | PRP 21 d: 1.95 ± 1.47 vs. 1.15 ± 1.04 mm; i-PRF total: 4.60 ± 2.26 vs. 4.88 ± 2.16 mm | NR | PRP benefit limited to first 21 days; no i-PRF benefit |
| Sharma et al. ( 26 ) | Corticotomy | To completion | T1: 1.276 ± 0.390 vs. 0.818 ± 0.181 mm | NR | Greater movement only during the first two intervals |
| Gupta et al. ( 20 ) | L-PRF | 5 months | Total: 6.407 ± 0.336 vs. 5.546 ± 0.663 mm | NR | Greater total movement, mainly in first 2 months |
| Pradhan et al. ( 33 ) | Piezocision | To completion | Monthly movement not reported | 4.66 ± 0.52 vs. 5.72 ± 0.65 months | Shorter canine distalization duration |
| El Gazzar et al. ( 21 ) | PRP | 4 months | Total: 4.331 ± 0.163 vs. 4.274 ± 0.139 mm | NR | Statistically significant but small total difference |
结果
通过数据库检索共识别1,017条记录。去除336条重复记录后,筛选681条记录,最终检索42篇报告。3篇报告无法获取,对39篇全文文章进行合格性评估。排除14项研究后,25项随机对照试验纳入定性综合(图2)。纳入研究发表于2011年至2026年,主要采用裂口设计,研究双侧前磨牙拔除后的上颌尖牙回缩。评估的干预措施包括血小板浓缩物(9项研究)、骨皮质切开术(8项研究)和piezocision(10项研究),一些多臂试验贡献于一个以上类别(5–13,18–33)。样本量范围为10至51名参与者,干预方案、正畸力学、支抗方法、随访期和结局评估技术存在相当大的差异。
[图:PRISMA 2020流程图:1,017条记录;去除336条重复记录;筛选681条;评估39篇全文;排除14篇;25项随机对照试验]

关于犬齿回缩,血小板浓缩物显示出不一的结果。PRP在一些研究中显示加速移动,但在其他研究中未显示显著或持续的获益(9–11, 19, 21)。各单项研究报告的数值主要结局总结于表4。同样,i-PRF未显示一致的持续加速效应,一项研究报告在单一随访间隔期间有显著差异,另一项研究未发现显著的总体获益(11, 12)。L-PRF通常增强早期犬齿回缩,尽管效应往往温和且随时间减弱(13, 18, 20)。在大多数研究中,骨皮质切开术与术后早期犬齿回缩增加相关(5, 7, 22–26),尽管效应趋于随时间减弱,且一项研究发现与传统回缩相比无显著优势(8)。一项研究报告骨皮质切开术后犬齿回缩总持续时间缩短(22)。同样,在大多数试验中,压电骨皮质切开术在最初数周或数月内加速犬齿回缩(5, 6, 27–30, 32, 33),但获益通常随时间减弱。两项研究报告无显著加速效应(8, 31),且重复压电骨皮质切开术与单次手术相比未提供额外获益(27)。跨各类别,在回缩早期阶段观察到加速,而关于犬齿回缩总持续时间缩短的证据有限。各单项研究报告的数值主要结局总结于表4。
Table 4. Certainty of evidence for the main outcomes using the GRADE approach.
| Outcome/intervention | Summary of findings | Main reasons for downgrading | Certainty |
|---|---|---|---|
| Canine retraction rate/amount—PRP | Variable early effect; benefit was absent or not sustained in some studies | Risk of bias, inconsistency, imprecision | Very low |
| Canine retraction rate/amount—i-PRF | No consistent sustained increase in retraction | Risk of bias, imprecision | Low |
| Canine retraction rate/amount—L-PRF | Generally greater early movement | Risk of bias, imprecision | Low |
| Canine retraction rate/amount—corticotomy | Generally greater early movement; effect decreased with time | Risk of bias, imprecision | Low |
| Canine retraction rate/amount—piezocision | Greater early movement in most studies, with some null findings | Risk of bias, imprecision | Low |
| Total canine retraction duration | Evidence was limited; some studies reported shorter duration with L-PRF, corticotomy, or piezocision | Risk of bias, sparse data, imprecision | Low to very low |
| Anchorage loss | No consistent difference between intervention and control groups | Risk of bias, imprecision | Low to very low |
| Root resorption | Findings were limited and not fully consistent across interventions | Risk of bias, inconsistency, imprecision | Low to very low |
| Pain/adverse effects | Effects were mainly transient; adverse-event reporting was limited | Risk of bias, imprecision, limited reporting | Low to very low |
次要结局显示干预组与对照组之间在支抗丧失方面无一致差异,尽管一些研究报告干预侧犬齿倾斜更大(18, 27)。关于牙根吸收的研究结果相互矛盾,一些骨皮质切开术研究报告吸收减少,而一项压电骨皮质切开术研究发现吸收增加(5, 22, 27);其他几项研究报告无显著差异(20, 26, 28, 33)。牙周参数在组间通常相当。术后疼痛和不适常在手术后或注射后最初几天内报告,但随时间消退。除一例报告压电骨皮质切开术后骨隔离(8)外,不良事件有限。偏倚风险评估显示,四项研究的总体偏倚风险低,21项研究引起一些担忧。主要结局的证据确定性范围从低至极低。确定性主要受偏倚风险担忧、样本量小、某些结局结果不一致以及次要结局报告有限所限制。GRADE评估总结于表3。
讨论
本系统评价评估了25项关于上颌犬齿回缩期间血小板浓缩物、骨皮质切开术和压电骨皮质切开术的随机研究。大多数干预措施在早期观察期产生犬齿回缩的一定增加。效应通常在最初数周或数月内最大,此后趋于减弱。然而,加速的幅度和持续时间在各研究间存在差异,且更高的每月移动速率并未一致转化为犬齿回缩总持续时间的缩短。
血小板浓缩物的研究结果不一。几项PRP研究报告在早期随访期内犬齿回缩更大(9–11, 21)。相比之下,Arora等发现与传统回缩无显著差异(19)。El Timamy等报告早期移动增加,但四个月后PRP侧与对照侧的总移动相似(9)。i-PRF试验未证明一致的持续加速效应。Zeitounlouian等仅在某一月度间隔内发现显著差异,而五个月后两侧总移动几乎相同(12)。Naji等未发现显著加速效应(11)。
在纳入的三项试验中,L-PRF均产生了更大的移动,尽管效应的大小和持续时间有所不同(13, 18, 20)。Krishna等报告八周内额外移动0.28 mm(13)。Gupta等发现差异集中在最初两个月内(20)。较晚的Gupta试验报告四个月内尖牙牙尖移动更大,但伴随更大的倾斜(18)。因此,更大的牙冠移动可能并不代表整体牙齿移动的等量增加。
血小板浓缩物方案的差异可能部分解释了研究间的差异。PRP和i-PRF注射于尖牙邻近组织,而L-PRF置于拔牙窝内。制备方法、离心方案、激活方式、剂量、应用部位和给药频率也有所不同。因此,这些制剂不应被视为单一统一的干预措施。制备和应用方案的这种变异性可能影响了生物学反应,并导致了各研究报告的不一致结果。血小板浓缩物方案的标准化将提高未来研究的可比性。
大多数骨皮质切开术研究报告术后早期尖牙回缩更快(5, 7, 22–26)。Aboul-Ela等发现最初两个月差异最大,第三和第四个月差异较小(23)。Sharma等同样报告仅在前两个3周间隔内出现显著加速(26)。Alfailany等观察到最初两个月移动更大,但该效应在后期阶段或回缩完成时未能维持(7)。然而,Fernandes等发现骨皮质切开术后累积尖牙回缩无显著增加(8)。
仅有有限数量的骨皮质切开术研究报告了尖牙回缩的总持续时间。Raza等发现骨皮质切开侧完成回缩需要5.7个月,对照侧需要7.1个月(22)。其他试验主要报告固定间隔内的移动。因此,其研究结果显示了早期移动速率的增加,但并未证实整个回缩阶段被一致缩短。
大多数 piezocision 研究也报告早期观察期内移动更大(5, 6, 27–30, 32, 33)。Alfawal等发现最初两个月效应最大,并报告回缩持续时间缩短约1.17个月(6)。Pradhan等也报告 piezocision 侧持续时间更短(33)。Eid和El-Kalza发现单次和重复 piezocision 均增加移动,但重复应用未提供显著的额外获益(27)。
并非所有研究都支持 piezocision。Al-A’athal等在两个面高度组中均未发现显著增加(31)。Fernandes等报告 piezocision 侧累积尖牙回缩低于对照侧(8)。皮质切口的数量、深度和位置、施力时机、支抗和结局测量的差异可能导致了研究结果的变异性。手术技术的差异也可能影响区域加速现象,使得研究间的直接比较变得困难。
多项研究评估了支抗丧失,但干预组与对照组之间未发现一致差异(5–8, 11, 12, 20, 23, 26, 30, 31)。尖牙倾斜和旋转未一致减少。Eid和El-Kalza报告 piezocision 后倾斜更大(27),而Gupta等发现L-PRF放置后牙尖移动更大并伴随更大倾斜(18)。这些发现表明牙冠移动的加速不一定改善牙齿移动的质量。
关于牙根吸收的研究结果也不一致。Abbas等和Raza等报告骨皮质切开侧吸收较少(5, 22)。Eid和El-Kalza发现 piezocision 后吸收评分更高(27)。其他研究报告干预组与对照组之间无显著差异(20, 26, 28, 33)。影像学方法和随访时间各不相同,限制了研究间的比较。
干预侧与对照侧的牙周结局总体相似。大多数试验未报告探诊深度、附着水平、牙龈退缩或菌斑相关指数方面具有临床重要性的差异(5, 23, 26, 28)。随访时间相对较短,未评估长期牙周效应。
疼痛和不适主要局限于干预后最初几天。骨皮质切开术与短暂的术后疼痛、肿胀或不适相关(22, 25, 26)。Piezocision 通常与较低的并发症发生率相关,尽管Fernandes等报告了一例骨死骨形成(8)。PRP注射在一些研究中引起短期疼痛,但未与严重并发症相关(9, 10, 21)。L-PRF放置后未报告重大不良事件(13, 18)。
在解读这些研究结果时,应考虑总体偏倚风险。四项研究被判定为低偏倚风险,其余21项研究存在一些担忧。最常见的担忧包括分配不明确、试验方案未注册或回顾性注册、盲法报告不完整以及分析不确定性。三项裂口设计研究使用独立样本检验进行干预-对照比较(20, 32, 33),而一项研究报告了不一致的统计方法(24)。由于无法根据报告数据重新进行配对分析,这些发现被谨慎解读。证据确定性普遍为低至极低,表明对观察效应的大小和一致性信心有限。
大多数研究样本量较小。尽管裂口设计减少了受试者间的变异性,但需要适当的配对分析(16)。此外,许多研究使用单一牙齿标志点测量牙冠移动。当移动更多通过倾斜而非整体远移发生时,这可能高估加速效应。
本综述的主要优势在于仅纳入评估同一临床治疗阶段的随机研究。血小板浓缩物、骨皮质切开术和压电骨切开术被一并考虑,移动速率与持续时间、支抗丧失、牙根吸收、牙周结局、疼痛和不良反应一同评估。
现有证据表明,骨皮质切开术和压电骨切开术可在术后早期增加上颌尖牙内收。血小板浓缩物也可能产生早期增加,但其效果一致性较差。三种方法在所有研究中均未显示出一致的获益,证据不支持对干预措施进行可靠的排序。
本综述的发现应在纳入研究的特征范围内解读。大多数试验纳入接受双侧上颌第一前磨牙拔除的健康青少年或年轻成人,并采用裂口设计。因此,结果最适用于具有相似临床特征的患者,而对其在其他患者群体和治疗方案中的普适性仍不确定。
局限性
由于干预方案、正畸力学机制、随访间隔和结局评估方法存在临床和方法学异质性,加之以裂口设计为主的试验中配对方差数据报告不一致,未进行Meta分析。这也限制了研究间的直接比较。大多数试验样本量较小,许多研究存在偏倚风险担忧。尖牙内收持续时间的报告频率低于固定间隔内的移动量,使得难以确定早期加速是否导致总治疗时间的有意义缩短。施力方式、支抗系统和尖牙内收评估方法的差异进一步限制了研究间的直接比较。随访期通常较短,限制了对治疗稳定性、牙周健康和牙根吸收等长期结局的评估。由于纳入单个干预-结局比较的研究少于10项,无法正式评估发表偏倚。小型单中心试验占主导也意味着不能排除小样本研究效应。在解读本综述的发现时应考虑这些局限性。
临床意义与未来展望
对于临床实践,骨皮质切开术和压电骨切开术可能加速上颌尖牙内收的初始阶段。然而,其获益似乎在术后早期最为显著,当前证据未能确定尖牙内收完整持续时间的持续缩短。相比之下,PRP、i-PRF和L-PRF等血小板浓缩物的有效性不一致,目前不能推荐作为可靠的独立加速方法。总体而言,干预组与对照组之间在牙周健康或支抗丧失方面未报告一致差异,尽管这些结局在各研究中未得到统一评估。
未来的随机对照试验应采用标准化的血小板制备方案、手术技术、正畸方案和结局评估方法,以提高研究间的可比性。需要足够效力的多中心试验并延长随访,以确定早期加速是否能在不损害牙周健康、牙根吸收或长期稳定性的情况下有意义地缩短尖牙内收持续时间。未来研究还应评估患者报告结局、成本效益以及可能影响治疗反应的患者特异性因素,以支持更可预测和个体化的正畸治疗。
结论
骨皮质切开术和压电骨切开术可能在内收早期增加上颌尖牙内收,而血小板浓缩物的效果一致性较差。这些干预措施缩短尖牙内收完整持续时间的证据仍然有限。由于方案、结局测量和偏倚风险的差异,无法确定各技术之间的明确优越性。
资助声明
作者声明本研究及/或其发表未获得财务支持。
脚注
[内容请查看原文]
数据可用性声明
本研究中呈现的原创性贡献已包含在文章/补充材料中,如需进一步咨询,请联系通讯作者。
作者贡献
AK:调查研究、撰写——原始草稿、撰写——审阅与编辑。AS:调查研究、撰写——原始草稿、撰写——审阅与编辑。AK和AS对本工作贡献均等,共同享有第一作者身份。AM:概念构思、资源提供、撰写——审阅与编辑。MSR:监督指导、撰写——审阅与编辑。SK:验证、撰写——审阅与编辑。NPS:验证、撰写——审阅与编辑。
利益冲突
作者声明本研究的开展不存在任何可能被解释为潜在利益冲突的商业或财务关系。
生成式人工智能声明
作者声明在本文稿的创作过程中使用了生成式人工智能。生成式人工智能工具仅用于在文稿准备期间改善语法、拼写、标点及语言表达的清晰度。人工智能未参与科学内容、数据分析、结果解释或结论的形成。所有内容均由作者审阅、核实并批准,作者对最终文稿承担全部责任。
本文中图表旁提供的任何替代文本(alt text)均由Frontiers在人工智能支持下生成,并已尽合理努力确保其准确性,包括在可能情况下由作者进行审阅。如您发现任何问题,请联系我们。
出版商注
本文中表达的所有主张仅代表作者本人观点,不一定代表其所属机构、出版商、编辑及审稿人的观点。本文中可能评估的任何产品或其制造商可能提出的任何主张,均不受出版商保证或认可。
参考文献
[内容请查看原文]
关联数据
数据可用性声明
本研究中呈现的原创性贡献已包含在文章/补充材料中,如需进一步咨询,请联系通讯作者。
查看英文原文▾
Abstract
Background
Maxillary canine retraction following premolar extraction is a time-consuming phase of orthodontic treatment. Various adjunctive methods, including platelet concentrates, corticotomy, and piezocision, have been proposed to accelerate tooth movement; however, their relative effectiveness and safety remain unclear.
Objective
To evaluate the effectiveness and safety of platelet concentrates, corticotomy, and piezocision as adjuncts to maxillary canine retraction after premolar extraction.
Methods
PubMed/MEDLINE, Scopus, and Cochrane CENTRAL were searched from inception to April 30, 2026. Randomized controlled trials comparing platelet-rich plasma, injectable platelet-rich fibrin, leukocyte and platelet-rich fibrin, corticotomy, or piezocision with conventional maxillary canine retraction were included. Study selection, data extraction, and risk-of-bias assessment using RoB 2 were performed independently. Findings were synthesized narratively.
Results
Twenty-five randomized studies were included. Corticotomy and piezocision generally increased canine retraction during the early postoperative period, although the effect decreased over time in several trials. Platelet concentrates produced inconsistent findings, ranging from no significant effect to small or temporary increases in movement. Evidence that these interventions shortened the complete duration of canine retraction was limited. Anchorage loss and periodontal outcomes were generally similar between groups, while findings for tipping, root resorption, pain, and adverse effects varied. Four studies had a low risk of bias, 21 raised some concerns.
Conclusion
Corticotomy and piezocision may increase rate of early maxillary canine retraction, while the effects of platelet concentrates are less consistent. Current evidence does not establish a reliable reduction in total retraction duration or support a clear ranking of the interventions. Better standardized randomized trials are required.
Systematic Review Registration
identifier CRD420261287411.
Keywords: accelerated orthodontics, canine retraction, corticotomy, piezocision, platelet-rich fibrin, platelet-rich plasma
Introduction
The duration of orthodontic treatment is influenced by several factors, including the severity of the malocclusion, the treatment mechanics employed, the biological response to orthodontic forces, and patient compliance. Prolonged treatment duration has been associated with an increased risk of adverse effects, including plaque accumulation, white spot lesions, periodontal deterioration, and external apical root resorption (1). Therefore, strategies aimed at reducing treatment time while maintaining effective anchorage control, periodontal health, and precise tooth movement are of considerable clinical interest. In this context, accelerated orthodontic techniques have emerged as a promising approach to enhance treatment efficiency without compromising treatment outcomes.
Premolar extraction followed by maxillary canine retraction is a routine component of orthodontic treatment for the correction of dental crowding and bimaxillary proclination. However, canine retraction often requires several months to complete, as tooth movement must occur across the extraction space and is limited by the biologic processes of periodontal ligament remodeling and alveolar bone turnover. To overcome these limitations and reduce overall treatment duration, various accelerated orthodontic approaches have been developed. These strategies aim to enhance the biological response underlying tooth movement and include surgical interventions, physical stimulation techniques, pharmacological agents, and locally administered biological mediators (2). These approaches differ in their underlying biological mechanisms, clinical applicability, and efficacy in enhancing the rate of orthodontic tooth movement.
Corticotomy and piezocision are among the most extensively investigated surgical approaches for accelerating orthodontic tooth movement. Corticotomy involves the creation of controlled cortical bone injuries, typically following flap elevation, whereas piezocision utilizes minimally invasive, flapless cortical incisions. Both techniques are believed to enhance tooth movement by triggering the Regional Acceleratory Phenomenon (RAP), a localized biological response characterized by a transient increase in bone remodeling and turnover following surgical injury, as originally described by Frost (3). This heightened remodeling activity, accompanied by a temporary reduction in bone density, facilitates more rapid tooth movement under orthodontic forces. Piezocision was subsequently introduced as a less invasive alternative to conventional corticotomy, aiming to achieve comparable biological effects while minimizing surgical trauma, patient discomfort, and postoperative morbidity (4).
Randomized trials have reported inconsistent findings regarding the effect of corticotomy and piezocision on maxillary canine retraction. While several studies have demonstrated enhanced tooth movement during the early postoperative phase, others have reported minimal or no significant acceleration compared with conventional retraction methods (5–8). Furthermore, the longevity of the acceleratory effect and its impact on the overall duration of canine retraction remain unclear.
Biological adjuncts such as platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) have been locally applied to enhance maxillary canine retraction (9–12). Similarly, leukocyte- and platelet-rich fibrin (L-PRF) has been investigated following its placement within premolar extraction sockets (13). However, meaningful comparisons among these studies are challenging because of considerable variations in preparation protocols, dosage regimens, application frequency, orthodontic mechanics, follow-up duration, and methods used to assess treatment outcomes.
Previous reviews have assessed corticotomy and piezocision during canine retraction, but the evidence is limited by small sample sizes and heterogeneity in surgical protocols (14). Platelet concentrates have generally been evaluated separately from surgical acceleration techniques, and different preparations have often been grouped despite important procedural differences. As a result, the comparative effectiveness of these interventions remains unclear. It is also uncertain whether the initial acceleration of canine retraction is sustained over time, reduces overall retraction duration, or affects anchorage, root resorption, periodontal health, pain, or other adverse outcomes.
The present systematic review aimed to evaluate randomized controlled trials investigating platelet concentrates, corticotomy, and piezocision as adjunctive interventions for maxillary canine retraction following premolar extraction. Their effectiveness was compared with conventional orthodontic retraction with respect to the rate of canine retraction and overall retraction duration. Secondary outcomes, including anchorage loss, root resorption, periodontal health, pain, and other reported adverse effects, were also assessed.
Methodology
The present systematic review was conducted to evaluate the effectiveness of platelet concentrates, corticotomy, and piezocision in accelerating maxillary canine retraction following premolar extraction. The review was planned and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines (15).
A protocol was prepared before completion of study selection and data extraction and was submitted to the International Prospective Register of Systematic Reviews. The registration number for the published Prospero record is CRD420261287411.
The review question was structured according to the PICOS format:
Population (P): Adolescents and adults undergoing maxillary canine retraction after premolar extraction using fixed orthodontic appliances.
Intervention (I): Platelet concentrates, including platelet-rich plasma, injectable platelet-rich fibrin, and leukocyte and platelet-rich fibrin; corticotomy-assisted orthodontics; or piezocision-assisted orthodontics.
Comparator (C): Conventional maxillary canine retraction without a biological or surgical acceleration procedure.
Outcomes (O)
Primary Outcomes: Rate of maxillary canine retraction and total duration of canine retraction.
Secondary Outcomes: Anchorage loss, canine tipping and rotation, root resorption, periodontal parameters, pain, swelling, discomfort, patient-reported outcomes, and intervention-related adverse effects.
Study design (S): Randomized controlled trials (RCTs) (parallel or split mouth).
Literature search
A comprehensive electronic literature search was conducted in PubMed/MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL). These databases were selected based on availability through the institutional library and their relevance to biomedical, dental, and controlled-trial literature. Searches were conducted between May 5 and May 8, 2026. The review considered literature published up to April 30, 2026. The search strategy combined controlled vocabulary terms (MeSH terms where applicable) and free-text keywords related to orthodontic canine retraction and accelerated orthodontic interventions. Search terms included combinations of: “canine retraction”, “maxillary canine movement”, “orthodontic tooth movement”, “accelerated orthodontics”, “platelet-rich plasma” OR “PRP”, “platelet-rich fibrin” OR “PRF”, “injectable platelet-rich fibrin” OR “i-PRF”, “leukocyte platelet-rich fibrin” OR “L-PRF”, “corticotomy”, “corticotomy-assisted orthodontics”, “piezocision”, and “randomized controlled trial”. (Table 1).
Table 1. Search strategy and search terms used.
| Database | Search query | Results |
|---|---|---|
| PubMed | ((canine retraction OR maxillary canine retraction OR orthodontic space closure) AND (platelet-rich plasma OR platelet-rich fibrin OR injectable platelet-rich fibrin OR leukocyte platelet-rich fibrin OR corticotomy OR piezocision) AND (randomised OR randomized OR clinical trial)) | 291 |
| Scopus | TITLE-ABS-KEY((“canine retraction” OR “orthodontic space closure” OR “maxillary canine”) AND (“platelet-rich plasma” OR “platelet-rich fibrin” OR “injectable platelet-rich fibrin” OR “leukocyte platelet-rich fibrin” OR corticotomy OR piezocision) AND (randomised OR randomized OR “clinical trial”)) | 447 |
| Cochrane | ((canine retraction OR orthodontic space closure) AND (platelet-rich plasma OR platelet-rich fibrin OR injectable platelet-rich fibrin OR L-PRF OR corticotomy OR piezocision)) | 279 |
| Total | Records identified across all searched databases before deduplication | 1,017 |
Boolean operators (AND, OR) and database-specific filters were applied as appropriate. The search strategy was adapted for each database according to its indexing system and search requirements. Additionally, the reference lists of all included studies and relevant review articles were manually screened to identify potentially eligible studies that may have been missed during the electronic search.
Inclusion and exclusion criteria for study selection
Inclusion Criteria:
Randomized controlled trials (parallel or split-mouth) involving adolescents or adults undergoing maxillary canine retraction after premolar extraction with fixed orthodontic appliances.
Studies evaluating PRP, i-PRF, L-PRF, corticotomy, or piezocision compared with conventional canine retraction.
Studies reporting outcomes related to the rate, amount, or duration of canine retraction with extractable data.
Full-text articles published in English.
Exclusion Criteria:
Studies evaluating other orthodontic movements or acceleration techniques without separate canine retraction data.
Studies using clear aligners, removable appliances, orthognathic surgery, distraction osteogenesis, or alveolar distraction.
Participants with craniofacial anomalies, active periodontal disease, systemic conditions, or medications affecting bone metabolism.
Studies lacking a conventional control group, relevant outcome data, or a randomized design.
Studies using quasi-randomized or otherwise predictable allocation methods, such as odd/even patient numbering.
Case reports, reviews, conference abstracts, animal/laboratory studies, and non-English or non-full-text publications.
Study selection
Titles and abstracts were screened independently by two reviewers (A.K.V and A.S) against the predefined eligibility criteria. Full texts of potentially eligible studies were then assessed independently by the same reviewers. Disagreements at either stage were resolved through discussion and, when required, consultation with additional reviewers (A.M and M.S.R).
Data extraction
The following information was collected and tabulated:
Author and year
Country
Study design
Randomization/allocation method
Sample size
Participants age
Malocclusion/extraction pattern
Arch/tooth movement
Intervention category
Comparator
Follow up
Outcomes reported
Data were extracted using a standardized Microsoft Excel sheet by two independent reviewers. Extracted information included study characteristics, randomization and allocation procedures, participant demographics, malocclusion and extraction patterns, arch/tooth movement, intervention category, comparators, follow-up, and outcomes reported. The detailed characteristics of each of the included studies are explained in Table 2. Discrepancies were resolved through discussion and, when necessary, consultation with third and fourth reviewers (A.M. and M.S.R.). S.K. Cross-checked the extracted data. No duplicate or overlapping publications were identified among the included studies.
Table 2. Study characteristics of included studies.
| Study | Country | Study design/randomization | Sample | Intervention | Comparator | Follow-up | Main outcome |
|---|---|---|---|---|---|---|---|
| Alfailany et al. ( 7 ) | Syria | Parallel RCT; computer-generated sequence; opaque envelopes | n = 51 | Corticotomy | Conventional control | To completion | Canine retraction |
| Eid and El-Kalza ( 27 ) | Egypt | RCT with split-mouth component; computer-generated allocation | n = 30 | Piezocision | Contralateral control | 12 weeks | Canine retraction |
| Abbas et al. ( 5 ) | Egypt | Split-mouth RCT; coin toss | n = 20 | Corticotomy; piezocision | Contralateral control | 3 months | Canine retraction |
| Raj et al. ( 28 ) | India | Split-mouth RCT; computer-generated allocation | n = 20 | Piezocision | Contralateral control | 90 days | Canine retraction |
| Yıldırım et al. ( 29 ) | Turkey | Split-mouth RCT; computer-generated sequence; sealed envelopes | n = 15 | Piezocision | Contralateral control | 28 days | Canine retraction |
| Fernandes et al. ( 8 ) | Brazil | Randomized trial with split-mouth comparisons; software-generated allocation | n = 47 | Corticotomy; piezocision | Contralateral control | 24 weeks | Canine retraction |
| Moradinejad et al. ( 30 ) | Iran | Split-mouth RCT; restricted randomization; coin toss for side | n = 32 | Piezocision | Contralateral control | 9 weeks | Canine retraction; anchorage loss |
| Al-A’athal et al. ( 31 ) | Jordan | Split-mouth RCT; permuted blocks; opaque envelopes | n = 23 | Piezocision | Contralateral control | 12 weeks | Canine retraction; anchorage loss |
| Syal et al. ( 32 ) | India | Prospective randomized split-mouth study; exact side sequence not reported | n = 12 | Piezocision | Contralateral control | 3 months | Canine retraction |
| Angel et al. ( 10 ) | India | Split-mouth RCT; computer-generated sequence; opaque envelopes | n = 10 | PRP | Contralateral control | 60 days | Canine retraction |
| El Timamy et al. ( 9 ) | Egypt | Split-mouth RCT; computer-generated sequence; opaque envelopes | n = 15 | PRP | Contralateral placebo control | 4 months | Canine retraction |
| Raza et al. ( 22 ) | India | Split-mouth RCT; computer-generated sequence; opaque envelopes | n = 10 | Corticotomy | Contralateral control | To completion | Canine retraction; duration |
| Gupta et al. ( 18 ) | India | Split-mouth RCT; block randomization; opaque envelopes | n = 35 | L-PRF | Contralateral control | 4 months/to completion | Canine movement; duration |
| Alfawal et al. ( 6 ) | Syria | RCT with split-mouth control; computer-generated sequence; opaque envelopes | n = 34 | Piezocision | Contralateral control | 4 months | Canine retraction; duration |
| Aboul-Ela et al. ( 23 ) | Egypt | Split-mouth randomized study; coin toss | n = 13 | Corticotomy | Contralateral control | 4 months | Canine retraction |
| Zeitounlouian et al. ( 12 ) | Syria | Split-mouth RCT; computer-generated side allocation | n = 21 | i-PRF | Contralateral control | 5 months | Canine retraction |
| Arora et al. ( 19 ) | India | Split-mouth randomized study; opaque-envelope side allocation | n = 14 | PRP | Contralateral control | 4 months | Canine retraction |
| Krishna et al. ( 13 ) | India | Split-mouth RCT; computer-generated side allocation | n = 16 analyzed | L-PRF | Contralateral control | 8 weeks | Canine retraction |
| Jahanbakhshi et al. ( 24 ) | Iran | Split-mouth randomized trial; sequence method not reported | n = 15 | Corticotomy | Contralateral control | ≈4 months | Canine retraction |
| Al-Naoum et al. ( 25 ) | Syria | Split-mouth RCT; sealed-envelope side allocation | n = 30 | Corticotomy | Contralateral control | 12 weeks | Canine retraction |
| Naji et al. ( 11 ) | Syria | Parallel RCT with split-mouth control; sealed-envelope allocation | n = 40 | PRP; i-PRF | Contralateral placebo control | 12 weeks | Canine retraction |
| Sharma et al. ( 26 ) | India | Split-mouth RCT; randomization stated; sequence method not reported | n = 14 analyzed | Corticotomy | Contralateral control | To completion | Canine retraction; anchorage |
| Gupta et al. ( 20 ) | India | Split-mouth RCT; drawing lots | n = 16 | L-PRF | Contralateral control | 5 months | Canine retraction |
| Pradhan et al. ( 33 ) | India | Prospective split-mouth randomized study; independent side allocation | n = 15 | Piezocision | Contralateral control | To completion | Retraction duration; root resorption |
| El Gazzar et al. ( 21 ) | Egypt | Split-mouth RCT; drawing lots | n = 20 reported | PRP | Contralateral control | 4 months | Canine retraction |
Quantitative synthesis was considered within individual intervention groups and at comparable follow-up points. However, differences in intervention protocols, orthodontic mechanics, outcome assessment, and follow-up limited comparability, and paired variance data were not consistently available from the predominantly split-mouth trials. Therefore, the findings were synthesized narratively.
Risk of bias assessment
Risk of bias was assessed independently by two reviewers (A.K.V) and (A.S) using the revised Cochrane Risk of Bias tool for randomized trials (RoB 2) (16, 17), with disagreements resolved through discussion or consultation with third and fourth reviewers (A.M. and M.S.R.). N.P.S. Cross-checked the risk of bias assessment. The assessment focused on the effect of assignment to the intervention on maxillary canine retraction and evaluated five domains: bias arising from the randomization process, deviations from intended interventions, missing outcome data, outcome measurement, and selection of the reported result. Each domain was rated as low risk of bias, some concerns, or high risk of bias, and an overall judgment was determined according to the RoB 2 algorithm. For split-mouth trials, assessments additionally considered randomization and concealment of side allocation, blinding of outcome assessment, completeness of paired observations, and the appropriateness of statistical analyses for the paired design (Figure 1).
[图:Risk of bias traffic light plot for included studies (RoB 2).]

The certainty of evidence for the primary and key secondary outcomes was assessed using the GRADE approach (16). (Table 3) Evidence was evaluated for risk of bias, inconsistency, indirectness, imprecision, and publication bias, and certainty was rated as high, moderate, low, or very low. As meta-analysis was not performed, judgments regarding inconsistency and imprecision were based on the direction and consistency of findings, sample sizes, and precision of the reported estimates.
Table 3. Primary numerical outcomes of the included studies.
| Study | Intervention | Follow-up | Key numerical result (intervention vs. control) | Total retraction duration | Main finding |
|---|---|---|---|---|---|
| Alfailany et al. ( 7 ) | Corticotomy | To completion | M1: 2.79 ± 0.39 vs. 1.12 ± 0.16 mm | NR | Greater movement during the first 2 months |
| Eid and El-Kalza ( 27 ) | Piezocision | 12 weeks | Single: 4.49 ± 0.34 vs. 2.77 ± 0.29 mm; multiple: 4.68 ± 0.27 vs. 2.79 ± 0.29 mm | NR | Both protocols increased retraction |
| Abbas et al. ( 5 ) | Corticotomy; piezocision | 3 months | T6: corticotomy 1.22 ± 0.08 vs. 0.58 ± 0.04 mm; piezocision 0.99 ± 0.10 vs. 0.60 ± 0.04 mm | NR | Both increased movement; corticotomy generally greater |
| Raj et al. ( 28 ) | Piezocision | 90 days | 4.25 ± 0.60 vs. 2.88 ± 0.40 mm at 90 days | NR | Greater movement at all assessed intervals |
| Yıldırım et al. ( 29 ) | Piezocision | 28 days | 1.27 ± 0.36 vs. 0.70 ± 0.25 mm at 28 days | NR | Greater early distalization |
| Fernandes et al. ( 8 ) | Corticotomy; piezocision | 24 weeks | Corticotomy: 3.83 ± 1.00 vs. 3.97 ± 1.41 mm; piezocision: 2.93 ± 1.11 vs. 4.05 ± 0.96 mm | NR | No corticotomy benefit; piezocision lower than control |
| Moradinejad et al. ( 30 ) | Piezocision | 9 weeks | 3.56 ± 0.05 vs. 2.42 ± 0.06 mm at 9 weeks | NR | Greater movement; effect decreased over time |
| Al-A’athal et al. ( 31 ) | Piezocision | 12 weeks | Average facial height: 1.48 ± 0.74 vs. 1.88 ± 0.83 mm; high facial height: 1.40 ± 0.85 vs. 1.76 ± 0.62 mm | NR | No significant acceleratory effect |
| Syal et al. ( 32 ) | Piezocision | 3 months | 3.97 ± 1.54 vs. 1.78 ± 0.42 mm | NR | Greater retraction with piezocision |
| Angel et al. ( 10 ) | PRP | 60 days | 3.19 ± 0.27 vs. 2.30 ± 0.20 mm | NR | Greater movement over 2 months |
| El Timamy et al. ( 9 ) | PRP | 4 months | Total: 4.57 ± 1.32 vs. 4.53 ± 1.12 mm | NR | Early benefit only; total movement similar |
| Raza et al. ( 22 ) | Corticotomy | To completion | M1: 1.36 ± 0.33 vs. 0.81 ± 0.06 mm | 5.7 vs. 7.1 months | Faster early movement and shorter retraction duration |
| Gupta et al. ( 18 ) | L-PRF | 4 months/to completion | Cusp movement: 3.53 ± 0.23 vs. 2.71 ± 0.22 mm | 6.01 ± 0.53 vs. 6.77 ± 0.49 months | Greater cusp movement; greater tipping also observed |
| Alfawal et al. ( 6 ) | Piezocision | 4 months | M1: 1.65 ± 0.40 vs. 0.83 ± 0.18 mm | ≈1.17-month reduction reported | Early acceleration with diminishing effect |
| Aboul-Ela et al. ( 23 ) | Corticotomy | 4 months | M1: 1.89 vs. 0.75 mm/month | NR | Marked early acceleration; little difference by month 4 |
| Zeitounlouian et al. ( 12 ) | i-PRF | 5 months | Total: 3.90 ± 1.36 vs. 3.94 ± 1.12 mm | NR | No sustained overall benefit |
| Arora et al. ( 19 ) | PRP | 4 months | M1: 1.355 ± 0.699 vs. 1.265 ± 0.698 mm | NR | No significant difference at any interval |
| Krishna et al. ( 13 ) | L-PRF | 8 weeks | 2.29 ± 0.19 vs. 2.01 ± 0.30 mm | NR | Small but significant increase in movement |
| Jahanbakhshi et al. ( 24 ) | Corticotomy | ≈4 months | Overall: 1.8 ± 0.17 vs. 1.1 mm/month | NR | Greater retraction velocity, largest early |
| Al-Naoum et al. ( 25 ) | Corticotomy | 12 weeks | Week 1: 0.739 ± 0.365 vs. 0.201 ± 0.149 mm/week | NR | Greater velocity throughout follow-up |
| Naji et al. ( 11 ) | PRP; i-PRF | 12 weeks | PRP 21 d: 1.95 ± 1.47 vs. 1.15 ± 1.04 mm; i-PRF total: 4.60 ± 2.26 vs. 4.88 ± 2.16 mm | NR | PRP benefit limited to first 21 days; no i-PRF benefit |
| Sharma et al. ( 26 ) | Corticotomy | To completion | T1: 1.276 ± 0.390 vs. 0.818 ± 0.181 mm | NR | Greater movement only during the first two intervals |
| Gupta et al. ( 20 ) | L-PRF | 5 months | Total: 6.407 ± 0.336 vs. 5.546 ± 0.663 mm | NR | Greater total movement, mainly in first 2 months |
| Pradhan et al. ( 33 ) | Piezocision | To completion | Monthly movement not reported | 4.66 ± 0.52 vs. 5.72 ± 0.65 months | Shorter canine distalization duration |
| El Gazzar et al. ( 21 ) | PRP | 4 months | Total: 4.331 ± 0.163 vs. 4.274 ± 0.139 mm | NR | Statistically significant but small total difference |
Results
A total of 1,017 records were identified through database searches. After the removal of 336 duplicates, 681 records were screened, resulting in 42 reports sought for retrieval. Three reports could not be obtained, and 39 full-text articles were assessed for eligibility. Following exclusion of 14 studies, 25 randomized controlled trials were included in the qualitative synthesis (Figure 2). The included studies, published between 2011 and 2026, predominantly used a split-mouth design and investigated maxillary canine retraction following bilateral premolar extraction. Interventions evaluated included platelet concentrates (9 studies), corticotomy (8 studies), and piezocision (10 studies), with some multi-arm trials contributing to more than one category (5–13, 18–33). Sample sizes ranged from 10 to 51 participants, with considerable variation in intervention protocols, orthodontic mechanics, anchorage methods, follow-up periods, and outcome assessment techniques.
[图:PRISMA 2020 flow diagram: 1,017 records; 336 duplicates removed; 681 screened; 39 full texts assessed; 14 excluded; 25 R]

Regarding canine retraction, platelet concentrates demonstrated variable results. PRP showed accelerated movement in some studies but no significant or sustained benefit in others (9–11, 19, 21). The numerical primary outcomes reported by individual studies are summarized in Table 4. Similarly, i-PRF did not show a consistent sustained acceleratory effect, with one study reporting a significant difference during a single follow-up interval and another finding no significant overall benefit (11, 12). L-PRF generally enhanced early canine retraction, although the effect was often modest and diminished over time (13, 18, 20). Corticotomy was associated with increased canine retraction during the early postoperative period in most studies (5, 7, 22–26), although the effect tended to decrease with time, and one study found no significant advantage over conventional retraction (8). One study reported a reduction in overall canine retraction duration following corticotomy (22). Likewise, piezocision accelerated canine retraction during the initial weeks or months in most trials (5, 6, 27–30, 32, 33), but the benefit generally lessened over time. Two studies reported no significant acceleratory effect (8, 31), and repeated piezocision did not provide additional benefit compared with a single procedure (27). Across the categories, acceleration was observed during the early stages of retraction, whereas there was limited evidence for a reduction in the total duration of canine retraction. The primary numerical outcomes reported by the individual studies are summarized in Table 4.
Table 4. Certainty of evidence for the main outcomes using the GRADE approach.
| Outcome/intervention | Summary of findings | Main reasons for downgrading | Certainty |
|---|---|---|---|
| Canine retraction rate/amount—PRP | Variable early effect; benefit was absent or not sustained in some studies | Risk of bias, inconsistency, imprecision | Very low |
| Canine retraction rate/amount—i-PRF | No consistent sustained increase in retraction | Risk of bias, imprecision | Low |
| Canine retraction rate/amount—L-PRF | Generally greater early movement | Risk of bias, imprecision | Low |
| Canine retraction rate/amount—corticotomy | Generally greater early movement; effect decreased with time | Risk of bias, imprecision | Low |
| Canine retraction rate/amount—piezocision | Greater early movement in most studies, with some null findings | Risk of bias, imprecision | Low |
| Total canine retraction duration | Evidence was limited; some studies reported shorter duration with L-PRF, corticotomy, or piezocision | Risk of bias, sparse data, imprecision | Low to very low |
| Anchorage loss | No consistent difference between intervention and control groups | Risk of bias, imprecision | Low to very low |
| Root resorption | Findings were limited and not fully consistent across interventions | Risk of bias, inconsistency, imprecision | Low to very low |
| Pain/adverse effects | Effects were mainly transient; adverse-event reporting was limited | Risk of bias, imprecision, limited reporting | Low to very low |
Secondary outcomes showed no consistent differences in anchorage loss between intervention and control groups, although some studies reported greater canine tipping on the intervention side (18, 27). Findings on root resorption were conflicting, with some corticotomy studies reporting reduced resorption, while one piezocision study found increased resorption (5, 22, 27); several others reported no significant differences (20, 26, 28, 33). Periodontal parameters were generally comparable between groups. Postoperative pain and discomfort were commonly reported during the first few days after surgery or injection but subsided with time. Apart from one reported case of bone sequestration following piezocision (8), adverse events were limited. Risk of bias assessment revealed that four studies had a low overall risk of bias and 21 raised some concerns. The certainty of evidence ranged from low to very low across the main outcomes. Certainty was limited primarily by risk-of-bias concerns, small sample sizes, inconsistent findings for some outcomes, and limited reporting of secondary outcomes. The GRADE assessment is summarized in Table 3.
Discussion
This systematic review evaluated 25 randomized studies on platelet concentrates, corticotomy, and piezocision during maxillary canine retraction. Most interventions produced some increase in canine retraction during the early observation period. The effect was usually greatest during the first few weeks or months and tended to decrease thereafter. However, the magnitude and duration of acceleration varied across studies, and a greater monthly rate of movement did not consistently translate into a shorter total duration of canine retraction.
The findings for platelet concentrates were variable. Several PRP studies reported greater canine retraction during the early follow up period (9–11, 21). In contrast, Arora et al. found no significant difference from conventional retraction (19). El Timamy et al. reported an early increase in movement, but total movement after four months was similar between the PRP and control sides (9). The i-PRF trials did not demonstrate a consistent sustained acceleratory effect. Zeitounlouian et al. found a significant difference during only one monthly interval, while total movement after five months was almost identical between sides (12). Naji et al. did not find a significant acceleratory effect (11).
L-PRF produced greater movement in all three included trials, although the size and duration of the effect differed (13, 18, 20). Krishna et al. reported an additional 0.28 mm of movement over eight weeks (13). Gupta et al. found that the difference was concentrated within the first two months (20). The later Gupta trial reported greater canine cusp movement over four months, but this was accompanied by greater tipping (18). Greater crown movement may therefore not represent an equivalent increase in bodily tooth movement.
Variation in platelet concentrate protocols may partly account for the differences between studies. PRP and i-PRF were injected into the tissues adjacent to the canine, whereas L-PRF was placed within the extraction socket. Preparation methods, centrifugation protocols, activation, dosage, application site, and frequency of administration also differed. These preparations should therefore not be considered as a single uniform intervention. Such variability in preparation and application protocols may have influenced the biological response and contributed to the inconsistent findings reported across studies. Standardization of platelet concentrate protocols would improve comparability in future research.
Most corticotomy studies reported faster canine retraction during the early postoperative period (5, 7, 22–26). Aboul-Ela et al. found the greatest difference during the first two months, with a smaller difference during the third and fourth months (23). Sharma et al. similarly reported significant acceleration during the first two 3-week intervals only (26). Alfailany et al. observed greater movement during the first two months, but the effect was not maintained during the later stages or at completion of retraction (7). Fernandes et al., however, found no significant increase in cumulative canine retraction after corticotomy (8).
Only a limited number of corticotomy studies reported the total duration of canine retraction. Raza et al. found that completion required 5.7 months on the corticotomy side and 7.1 months on the control side (22). Other trials mainly reported movement over fixed intervals. Their findings therefore show an increase in the early rate of movement but do not establish that the full retraction phase was consistently shortened.
Most piezocision studies also reported greater movement during the early observation period (5, 6, 27–30, 32, 33). Alfawal et al. found the largest effect during the first two months and reported a reduction of approximately 1.17 months in retraction duration (6). Pradhan et al. also reported a shorter duration on the piezocision side (33). Eid and El-Kalza found that both single and repeated piezocision increased movement, but repeated application did not provide a significant additional benefit (27).
Not all studies favoured piezocision. Al-A’athal et al. found no significant increase in either facial height group (31). Fernandes et al. reported lower cumulative canine retraction on the piezocision side than on the control side (8). Differences in the number, depth, and position of cortical incisions, timing of force application, anchorage, and outcome measurement may have contributed to the variation in findings. Variation in surgical technique is also likely to influence the regional acceleratory phenomenon, making direct comparison between studies difficult.
Anchorage loss was assessed in several studies, but no consistent difference was found between intervention and control groups (5–8, 11, 12, 20, 23, 26, 30, 31). Canine tipping and rotation were not consistently reduced. Eid and El-Kalza reported greater tipping after piezocision (27), while Gupta et al. found greater cusp movement together with greater tipping after L-PRF placement (18). These findings indicate that acceleration of crown movement does not necessarily improve the quality of tooth movement.
The findings for root resorption were also mixed. Abbas et al. and Raza et al. reported less resorption on corticotomy sides (5, 22). Eid and El-Kalza found higher resorption scores after piezocision (27). Other studies reported no significant difference between intervention and control groups (20, 26, 28, 33). The imaging methods and follow-up periods varied, which limited comparison between studies.
Periodontal outcomes were generally similar between intervention and control sides. Most trials did not report clinically important differences in probing depth, attachment level, gingival recession, or plaque-related indices (5, 23, 26, 28). The follow-up periods were relatively short, and long-term periodontal effects were not assessed.
Pain and discomfort were mainly confined to the first few days after intervention. Corticotomy was associated with transient postoperative pain, swelling, or discomfort (22, 25, 26). Piezocision was generally associated with less morbidity, although Fernandes et al. reported one case of bone sequestration (8). PRP injections caused short-term pain in some studies but were not associated with serious complications (9, 10, 21). No major adverse effects were reported after L-PRF placement (13, 18).
The overall risk of bias should be considered when interpreting these findings. Four studies were judged to have a low risk of bias, while the remaining 21 raised some concerns. The most frequent concerns were unclear allocation, absence or retrospective registration of a trial protocol, incomplete reporting of blinding, and uncertainty regarding analyses. Three split-mouth studies used independent-samples tests for intervention–control comparisons (20, 32, 33), while one study reported inconsistent statistical methods (24). These findings were interpreted cautiously, as paired re-analysis was not possible from the reported data. The certainty of evidence was generally low to very low, indicating limited confidence in the magnitude and consistency of the observed effects.
Most studies had small sample sizes. Although split-mouth designs reduce variability between participants, they require appropriate paired analysis (16). In addition, many studies measured crown movement using a single dental landmark. This may overestimate acceleration when greater movement occurs through tipping rather than bodily distalization.
The main strength of this review was its restriction to randomized studies evaluating the same clinical phase of treatment. Platelet concentrates, corticotomy, and piezocision were considered together, and movement rate was assessed alongside duration, anchorage loss, root resorption, periodontal outcomes, pain, and adverse effects.
The available evidence suggests that corticotomy and piezocision can increase maxillary canine retraction during the early postoperative period. Platelet concentrates may also produce an early increase, but their effects were less consistent. None of the three approaches showed a uniform benefit across all studies, and the evidence does not support a reliable ranking of the interventions.
The findings of this review should be interpreted within the characteristics of the included studies. Most trials enrolled healthy adolescents or young adults undergoing bilateral maxillary first premolar extraction and used split-mouth designs. Therefore, the results are most applicable to patients with similar clinical characteristics, while their generalizability to other patient groups and treatment protocols remains uncertain.
Limitations
Meta-analysis was not performed because of clinical and methodological heterogeneity across intervention protocols, orthodontic mechanics, follow-up intervals, and outcome assessment methods, together with inconsistent reporting of paired variance data in the predominantly split-mouth trials. This also limited direct comparison between studies. Most trials included small sample sizes, and many raised concerns regarding risk of bias. The duration for canine retraction was reported less frequently than movement over fixed intervals, making it difficult to determine whether early acceleration resulted in a meaningful reduction in overall treatment time. Differences in force application, anchorage systems, and methods used to assess canine retraction further limited direct comparison across studies. Follow-up periods were generally short, limiting assessment of long-term outcomes such as treatment stability, periodontal health, and root resorption. Publication bias could not be formally assessed because fewer than 10 studies contributed to individual intervention–outcome comparisons. The predominance of small, single-center trials also means that small-study effects cannot be excluded. These limitations should be considered when interpreting the findings of this review.
Clinical implications & future scope
For clinical practice, corticotomy and piezocision may accelerate the initial phase of maxillary canine retraction. However, their benefits appear greatest during the early postoperative period, and current evidence does not establish a consistent reduction in the complete duration of canine retraction. In contrast, platelet concentrates such as PRP, i-PRF, and L-PRF have shown inconsistent effectiveness and cannot currently be recommended as reliable standalone acceleration methods. Overall, no consistent differences in periodontal health or anchorage loss were reported between intervention and control groups, although these outcomes were not uniformly assessed across studies.
Future randomized controlled trials should adopt standardized platelet preparation protocols, surgical techniques, orthodontic protocols, and outcome assessment methods to improve comparability between studies. Adequately powered multicenter trials with longer follow-up are needed to determine whether early acceleration results in meaningful reductions in canine retraction duration without compromising periodontal health, root resorption, or long-term stability. Future studies should also evaluate patient-reported outcomes, cost-effectiveness, and patient-specific factors that may influence treatment response to support more predictable and individualized orthodontic care.
Conclusion
Corticotomy and piezocision may increase maxillary canine retraction during the early stages of retraction, whereas the effects of platelet concentrates are less consistent. Evidence that these interventions shorten the complete duration of canine retraction remains limited. No clear superiority among the techniques could be established because of variation in protocols, outcome measurement, and risk of bias.
Funding Statement
The author(s) declared that financial support was not received for this work and/or its publication.
Footnotes
[内容请查看原文]
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
Author contributions
AK: Investigation, Writing – original draft, Writing – review & editing. AS: Investigation, Writing – original draft, Writing – review & editing. AK and AS contributed equally to this work and share first authorship. AM: Conceptualization, Resources, Writing – review & editing. MSR: Supervision, Writing – review & editing. SK: Validation, Writing – review & editing. NPS: Validation, Writing – review & editing.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that generative AI was used in the creation of this manuscript. Generative AI tools were used solely to improve grammar, spelling, punctuation, and language clarity during manuscript preparation. The AI did not contribute to the scientific content, data analysis, interpretation of results, or conclusions. All content was reviewed, verified, and approved by the authors, who take full responsibility for the final manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
[内容请查看原文]
Associated Data
Data Availability Statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
兽研