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.

项目概要（摘要） 开放性脊柱裂或脊髓脊膜膨出 (MMC) 是一种破坏性的神经先天性缺陷，其特征是 胚胎期脑脊液中脊柱神经管闭合的原发性衰竭。 发育中的胎儿中 MMC 引起的（脑脊液）泄漏可能会导致一系列异常，包括 后脑疝和脑干异常也可能导致脊髓暴露于羊水中。 造成脊髓孔以下身体部位部分或完全瘫痪的重大风险。 最近的随机试验表明，开腹胎儿手术可有效减少产后神经系统疾病 发病率，表现为产后脑积水的发生率和严重程度降低以及对药物的需求减少 然而，由于开腹胎儿手术已被发现与出生后脑室-腹膜分流有关。 母婴发病的可能性增加，创新的微创胎儿镜技术进行修复 尽管如此，MMC 因其侵入性较小而受到越来越多的关注，因为它可以通过小规模部署补丁。 用于覆盖缺陷的套管针端口和展开的补片可能非常麻烦，因此无法控制 此外，惰性补片需要进行产后去除手术，从而延长手术时间。 较高的手术费用和对婴儿和父母的心理创伤对某些人来说是长期有效的。 用于阻挡缺陷的网状贴片也存在很大的争议，需要一种“智能”贴片。 是自膨胀的，不可渗透以阻止脑脊液泄漏，并且可生物降解以适应以下方案 最近，我们尝试开发一种用于胎儿镜手术的“智能贴片”，以促进伤口愈合。 通过混合两种聚合物，有望同时解决所有障碍。 已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片 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、细胞附着亲和力和生物降解性是当前的目标。 该项目的目的是评估新设计的补丁的功能如何有助于保护受影响的人 我们使用绵羊 MMC 模型来缓解与 MMC 缺陷相关的并发症。 开发完成后，我们希望进一步评估新的 PLA/PCL 贴剂在以下方面的功效：(1) 减少 MMC 上胎儿镜覆盖的手术时间，(2) 提供足够的屏障来阻止 CSF 泄漏并保护 暴露脊髓以减轻损伤，这将有助于保留甚至改善受影响的运动功能 功能，以及（3）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 如果成功，我们设计的新补丁将有助于推进胎儿镜检查方法成为最可靠的方法。 MMC 缺陷的产前管理程序这将大大改善结果。 胎儿镜下 MMC 修复，促进 MMC 手术治疗范式的转变。

项目成果

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

在体外模拟胎儿环境中人羊水对聚（L-乳酸）和聚（ε-己内酯）贴片的生物降解。

• 发表时间: 2022-03-10
• 影响因子: 4.6
• 作者: Tatu, Rigwed R;Oria, Marc;Rao, Marepalli B;Peiro, Jose L;Lin, Chia
• 通讯作者: Lin, Chia

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

脊柱裂修复的硬脑膜替代品：过去、现在和未来。

• 发表时间: 2022-05
• 作者: Miyabe, Marcos M;Murphy, Kendall P;Oria, Marc;Duru, Soner;Lin, Chia;Peiro, Jose L
• 通讯作者: Peiro, Jose L

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

视黄酸诱导的脊柱裂大鼠模型中神经祖细胞过早分化为星形胶质细胞。

• 发表时间: 2022
• 作者: Oria, Marc;Pathak, Bedika;Li, Zhen;Bakri, Kenan;Gouwens, Kara;Varela, Maria Florencia;Lampe, Kristin;Murphy, Kendall P;Lin, Chia;Peiro, Jose L
• 通讯作者: Peiro, Jose L

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。

• 发表时间: 2024-03-03
• 作者: Guan, Tianyuan;Tatu, Rigwed;Wima, Koffi;Oria, Marc;Peiro, Jose L;Lin, Chia;Rao, Marepalli B
• 通讯作者: Rao, Marepalli B