A Novel Smart Patch for the Fetoscopic Procedure to Repair Spina Bifida

一种用于胎儿镜手术修复脊柱裂的新型智能贴片

• 批准号: 10597659
• 负责人: Chia-Ying James Lin
• 金额: $ 30.63万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10597659
• 关键词: Action Potentials; Address; Adverse effects; Affect; Affinity; Amniotic Fluid; Animals; Astrocytes; Attention; Biodegradation; Biological Process; Biomedical Engineering; Body part; Brain Stem; Cannulas; Caring; Cell Differentiation process; Cerebellum; Cerebrospinal Fluid; Characteristics; Chitosan; Clinical; Clinical Research; Congenital Abnormality; Data; Defect; Development; Devices; Dorsal; Effectiveness; Enzymes; Equation; Excision; Exposure to; Failure; Fetal Development; Fetus; Fibroblasts; Film; Glass; Goals; Human; Hydrocephalus; Implant; Incidence; Infant; Intervention; Investigation; Limb structure; Long-Term Survivors; Magnetic Resonance Imaging; Mechanics; Meningomyelocele; Modeling; Monitor; Morbidity - disease rate; Motor; Motor Evoked Potentials; Muscle; Natural regeneration; Nerve; Nervous System Trauma; Neural Tube Closure; Neural tube; Neurologic; Neurons; Neuroprotective Agents; Newborn Infant; Open Spina Bifida; Operative Surgical Procedures; Orphan; Paralysed; Parents; Patch Tests; Pathology; Peritoneal; Physiological; Polyesters; Polylysine; Polymers; Procedures; Process; Reflex action; Research Project Grants; Risk; Rolipram; Scheme; Secure; Severities; Shapes; Sheep; Site; Spinal; Spinal Cord; Spinal Dysraphism; System; Techniques; Temperature; Testing; Time; Tissues; Tonsil; Transition Temperature; Translations; Trocars; Ventricular; Vertebral column; Walking; Water; biomaterial compatibility; caprolactone; cost; design; efficacy evaluation; fetal; fetus surgery; hindbrain; improved; improved outcome; innovation; malformation; matrigel; minimally invasive; nerve stem cell; neural; novel; postnatal; prenatal; preservation; psychological trauma; randomized trial; randomized, clinical trials; repaired; scaffold; seal; sheep model; spinal cord repair; tissue repair; wound closure; wound healing

Project Summary (Abstract) Open spina bifida or myelomeningocele (MMC) is a devastating neurologic congenital defect characterized by primary failure of neural tube closure of the spinal column during the embryologic period. Cerebrospinal fluid (CSF) leak caused by MMC in the developing fetus can result in a constellation of anomalies that include hindbrain herniation and brain-stem abnormalities. The exposure of extruded spinal cord to amniotic fluid also poses a significant risk for inducing partial or complete paralysis of the body parts beneath the spinal aperture. A recent randomized trial demonstrated that open fetal surgery is effective in reducing the postnatal neurologic morbidity, as evidenced by decreased incidence and severity of postnatal hydrocephalus and reduced need for postnatal ventricular-peritoneal shunting. However, as open fetal surgery has been noticed to be associated with increased potential for maternal-fetal morbidities, innovative minimally invasive fetoscopic techniques to repair MMC are receiving growing attentions for their less invasiveness. Nonetheless, deploying patches through small trocar ports and unfolding patches for defect coverage can be extremely cumbersome and thus uncontrollably prolongs the surgical duration. Moreover, inert patches necessitate postnatal removal surgeries, which lead to higher surgical costs and psychological trauma to the infant and parents. The long-term effectiveness for some mesh-like patches to barrier the defect is also debating. There is an enormous need to obtain a “smart” patch that is self-expanding, impermeable to cease the CSF leaking and biodegradable to accommodate the scheme of wound healing. Recently we have attempted to develop such a “smart patch” for the fetoscopic procedure to repair MMC that hopefully addresses all the hurdles aforementioned concurrently. By blending two polymers that have been utilized in fabricating biodegradable spinal implants, we developed a new patch made with poly(ε-caprolactone) (PCL) and poly(L-lactide) that possesses desired characteristics of shape retention, water-tightness, biocompatibility, affinity for cellular attachment, and biodegradation. The goal of the current project is to assess how the features of the newly designed patch can contribute to the protection of affected spinal cord that in turn alleviates complications associated with MMC defect. Using a sheep MMC model we have developed, we would like to further assess the efficacies of the new PLA/PCL patch in: (1) reducing the procedure time of fetoscopic coverage on MMC, (2) providing adequate barrier to stop CSF leak and protect the exposed spinal cord to mitigate the damage, which will help preserve and even improve the affected motor function, and (3) guiding and enhancing wound closure of MMC without tethering the spinal cord as our defined aims. If successful, our designed new patch will help advance fetoscopic approaches to become the most reliant procedure for the prenatal management of the MMC defect. This will greatly improve the outcome of the fetoscopic MMC repair, and facilitate the paradigm shifting for the surgical care of MMC.

项目摘要（摘要） 开放性脊柱裂或脊髓脊膜膨出（MMC）是一种毁灭性的神经先天性缺陷，其特征在于： 在胚胎时期脊柱神经管闭合的原发性失败。脑脊液 (CSF)MMC在发育中的胎儿中引起的泄漏可能导致一系列异常，包括 后脑脑疝和脑干异常将挤压的脊髓暴露于羊水中也 引起脊柱孔下的身体部分的部分或完全麻痹的显著风险。一 最近的随机试验表明，开放式胎儿手术可有效减少出生后神经功能障碍， 发病率，表现为出生后脑积水的发生率和严重程度降低， 出生后脑室-腹腔分流术。然而，由于开放式胎儿手术已被注意到与 增加母胎发病率的可能性，创新的微创胎儿镜技术， MMC因其侵袭性小而受到越来越多的关注。尽管如此，通过小型 用于缺损覆盖的套管针端口和展开的补片可能非常麻烦 延长手术时间。此外，惰性贴片需要产后移除手术，这导致 手术费用较高，对婴儿和父母造成心理创伤。对某些人来说， 网状补片来阻挡缺陷也在争论中。人们迫切需要获得一种“智能”贴片， 是自膨胀的，不可渗透的，以停止CSF泄漏和可生物降解的，以适应方案， 伤口愈合最近，我们试图开发一种用于胎儿镜检查的“智能贴片”， 修复MMC，希望同时解决上述所有障碍。通过混合两种聚合物， 已被用于制造可生物降解的脊柱植入物，我们开发了一种新的补丁， 聚（ε-己内酯）（PCL）和聚（L-丙交酯）具有所需的形状保持特性， 水密性、生物相容性、对细胞附着的亲和性和生物降解性。当前的目标 项目是评估新设计的补丁的功能如何有助于保护受影响的 脊髓，这反过来又加剧了与MMC缺陷相关的并发症。使用绵羊MMC模型，我们有 开发，我们想进一步评估新的PLA/PCL补片的功效：（1）减少 MMC上胎儿镜覆盖的手术时间，（2）提供足够的屏障以阻止CSF泄漏并保护 暴露脊髓以减轻损伤，这将有助于保护甚至改善受影响的运动 引导和增强MMC的伤口闭合，而不像我们定义的那样束缚脊髓 目标。如果成功，我们设计的新补丁将有助于推进胎儿镜方法，成为最可靠的 MMC缺陷的产前管理程序。这将极大地改善 胎儿镜下MMC修复，并促进MMC手术治疗的范式转变。

项目成果

Dural substitutes for spina bifida repair: past, present, and future.

• DOI: 10.1007/s00381-022-05486-8
• 发表时间: 2022-05
• 期刊: Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery

Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model.

• DOI: 10.3389/fnmol.2022.888351
• 发表时间: 2022
• 期刊: FRONTIERS IN MOLECULAR NEUROSCIENCE
• 影响因子: 4.8
• 作者: Oria, Marc;Pathak, Bedika;Li, Zhen;Bakri, Kenan;Gouwens, Kara;Varela, Maria Florencia;Lampe, Kristin;Murphy, Kendall P.;Lin, Chia-Ying;Peiro, Jose L.
• 通讯作者: Peiro, Jose L.

Biodegradation of poly(L-lactic acid) and poly(ε-caprolactone) patches by human amniotic fluid in an in-vitro simulated fetal environment.

• DOI: 10.1038/s41598-022-07681-8
• 发表时间: 2022-03-10
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Tatu RR;Oria M;Rao MB;Peiro JL;Lin CY
• 通讯作者: Lin CY

Profile of a Multivariate Observation under Destructive Sampling-A Monte Carlo Approach to a Case of Spina Bifida.

破坏性采样下的多变量观察概况 - 脊柱裂病例的蒙特卡罗方法。

• DOI: 10.3390/bioengineering11030249
• 发表时间: 2024
• 期刊: Bioengineering (Basel, Switzerland)
• 作者: Guan,Tianyuan;Tatu,Rigwed;Wima,Koffi;Oria,Marc;Peiro,JoseL;Lin,Chia-Ying;Rao,MarepalliB
• 通讯作者: Rao,MarepalliB