Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
基本信息
- 批准号:10642519
- 负责人:
- 金额:$ 32.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:3-Dimensional5 year oldAffectAgeAge MonthsAlveolarAnatomyAnimal ExperimentsAnimal ModelAnimalsBasic ScienceBirthBone TransplantationBone structureCanis familiarisCellsCicatrixCleft LipCleft lip with or without cleft palateClinicalComplicationCongenital AbnormalityDataData AnalysesDefectDevelopmentDisadvantagedExcisionFetal DeathFoundationsFutureGrowthGrowth and Development functionHumanHypertrophic CicatrixImmunosuppressionImpairmentIncidenceIndividualLeftLip structureMaxillaMeasurementMeasuresMethodsModelingMonkeysMusNatural regenerationOperative Surgical ProceduresOralOrthodonticOutcomeOutcome AssessmentPatientsPatternPerformancePharmacologyPhysiologyPostoperative PeriodProceduresProteinsPubertyPublicationsPublishingQuality of lifeRattusRodentSeveritiesSkeletonSpeechSprague-Dawley RatsStandardizationSurgeonSurgical ModelsSurgical suturesTechnical ExpertiseTechniquesTissue EngineeringTissuesVariantabortionalveolar bonealveolar cleftbone masscleft lip and palateclinically relevantcraniofacialcraniofacial developmentcraniofacial structurecraniofacial tissuefetalfibromodulinimprovedin uteromalformationmechanical loadmodel developmentnoveloperationorthognathicpalate repairpreventregenerative approachrepairedside effectskeletal maturationsocialsoft tissuetreatment strategytwo-dimensionalwound
项目摘要
PROJECT SUMMARY/ABSTRACT
Cleft lip and palate (CLP) is the second most common congenital malformation, affecting one in every 600
births worldwide. Due to the significant lack of local tissue, extensive scarring is a common complication after
early repair of the cleft lip that vitally impacts patients' maxilla growth and development, while an urgent need
exists for seeking effective craniofacial tissue regenerative approaches in early CLP revision. Unfortunately, the
disadvantages of the currently available animal models hurdle them from properly mimicking human CLP
development, particularly the CLP revision outcome assessment. For instance, in utero congenitally induced
models require immense technical expertise and relate to multiple fetal malformations, increased intrauterine
fetal death and abortions, and large variation of the cleft severity. Meanwhile, only dogs and monkeys were used
as surgical-induced models representing the CLP conditions in young patients. Not only being expensive, but
these models are hardly used for cell-based regenerative approaches since immunosuppression has to be
applied to permit heterogeneous cell usage, which may lead to an intricate argument in data interpretation.
Moreover, no published surgical small animal models are accompanied by defect development before puberty,
and thus the impact of early cleft lip repair on craniofacial growth and development has not been fully elucidated.
To conquer these questions, in the current R03 proposal, we intend to establish a novel CLP model in young
rodents to 1) mimic the craniofacial growth deformation observed in CLP patients, 2) evaluate the impacts of
scarring from cleft lip repair on craniofacial growth and development, and 3) set up an easy and standardized
approach to creating consistent defect size among animals, which will be beneficial for further exploring
regenerative strategies in CLP management. Among the commonly used small experimental animals, rats are
extremely useful for conducting basic research involving the skeleton based on the bone mass and structure
measurements, and thus represent reliable and affordable alternatives to large animals. Notably, the craniofacial
growth pattern of rats has been deeply documented and correlated to that of humans, making rats more
advantageous for representing human CLP development than other small animals. Therefore, in AIM 1, unilateral
cleft lip with or without a critical-sized alveolar defect will be generated surgically in rats at the age representing
0.5-year-old human, while the influence of the cleft on their craniofacial growth will be tracked through the period
representing the entire human puberty; and in Aim 2, early cleft lip repair will be applied in CLP rats one week
after the creation of the defects to assess the influence of early cleft lip revision on craniofacial development.
Overall, this study aims to set up the foundation for exploring and unbiasedly evaluating the outcomes of new
regenerative strategies for CLP treatment. If successful, it will pave the path to improve the life quality of patients,
especially growing ones, who suffer from scarring-induced side effects.
项目概要/摘要
唇腭裂 (CLP) 是第二常见的先天性畸形,每 600 人中就有一人患有唇腭裂
全世界的出生率。由于局部组织严重缺乏,广泛的疤痕是术后常见的并发症。
唇裂的早期修复对患者上颌骨的生长和发育至关重要,同时迫切需要
存在的目的是在早期 CLP 修正中寻求有效的颅面组织再生方法。不幸的是,
目前可用的动物模型的缺点阻碍了它们正确模仿人类 CLP
发展,特别是 CLP 修订结果评估。例如,在子宫内先天性诱发
模型需要大量的技术专业知识,并且与多种胎儿畸形、宫内胎儿增加有关
胎儿死亡和流产,以及唇裂严重程度的巨大差异。与此同时,只使用狗和猴子
作为代表年轻患者 CLP 状况的手术诱导模型。不仅价格昂贵,而且
这些模型很难用于基于细胞的再生方法,因为免疫抑制必须
应用于允许异构单元使用,这可能会导致数据解释中的复杂争论。
此外,没有已发表的外科小动物模型在青春期前伴有缺陷发展,
因此早期唇裂修复对颅面生长发育的影响尚未完全阐明。
为了解决这些问题,在当前的 R03 提案中,我们打算在年轻人中建立一种新颖的 CLP 模型
啮齿类动物 1) 模仿 CLP 患者中观察到的颅面生长变形,2) 评估
唇裂修复疤痕对颅面生长和发育的影响,3)建立一个简单且标准化的方法
在动物之间创建一致的缺陷大小的方法,这将有利于进一步探索
CLP 管理中的再生策略。常用的小型实验动物中,有大鼠
对于基于骨量和结构进行涉及骨骼的基础研究非常有用
测量,因此代表了大型动物的可靠且负担得起的替代品。值得注意的是,颅面部
老鼠的生长模式已被深入记录并与人类的生长模式相关,使得老鼠更容易
比其他小动物更有利于代表人类 CLP 发育。因此,在AIM 1中,单方面
具有或不具有临界尺寸的牙槽缺损的唇裂将在代表年龄的大鼠中通过手术产生
0.5岁人类,期间将追踪裂隙对其颅面生长的影响
代表了整个人类的青春期;在目标2中,对CLP大鼠进行一周早期唇裂修复术
创建缺陷后评估早期唇裂修复对颅面发育的影响。
总体而言,本研究旨在为探索和公正评估新方法的结果奠定基础
CLP 治疗的再生策略。如果成功,将为改善患者的生活质量铺平道路,
尤其是正在成长的孩子,他们会遭受疤痕引起的副作用。
项目成果
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