Job Information
- Organisation/Company: Université Sorbonne Paris Nord
- Research Field: Chemistry
- Researcher Profile: Recognised Researcher (R2), Leading Researcher (R4), First Stage Researcher (R1), Established Researcher (R3)
Offer Description
PhD
Myelomeningocele (MMC) is a severe congenital malformation characterized by a spinal opening and exposure of the spinal cord to the intrauterine environment during pregnancy. Its etiology is multifactorial and has been associated with folate metabolism disorders and maternal diabetes. Furthermore, to date, no specific genetic cause has been identified.(1) The incidence of this malformation remains high, at approximately 1 in 2,000 live births worldwide,(2) despite folic acid supplementation as a preventive measure.
The malformation can be surgically closed after birth; however, this does not restore normal function of the affected portion of the spinal cord. Therefore, the development of minimally invasive approaches, which are essential for performing surgery early during pregnancy, could reduce the maternal surgical morbidity associated with the procedure. To address these challenges, we propose to develop a bioactive and biodegradable patch designed to protect the spinal cord from amniotic fluid during pregnancy and to be delivered through a minimally invasive surgical approach (percutaneous access with a 2 mm diameter instrument) at an earlier gestational age.
The BEST team has developed bioactive implants and demonstrated excellent mechanical properties, including shape-memory behavior, as well as good biocompatibility with reduced inflammatory responses. PCL-based bioactive membranes have also demonstrated promising biological responses.(3–11) Building on these previous studies, we propose to develop a biomaterial capable of covering the lesion, promoting the growth of a covering epithelium, and providing a watertight barrier to protect the spinal cord. Such a device could be positioned over the lesion using a minimally invasive approach, thereby reducing maternal and obstetric morbidity. The objective of this PhD project is to develop an implant designed to cover and protect the spinal cord exposed in utero, while promoting the proliferation of a covering epithelium to limit cerebrospinal fluid leakage, thereby reducing the progression of hydrocephalus and providing a watertight protective barrier for the spinal cord.
The first part of this PhD project will focus on the development by electrospinning and characterization of an ideal bioactive membrane, based on the laboratory’s previous work, in order to meet the specifications required for the intended application.(4–5) The second part of the thesis will investigate the biological response in vitro, including cell adhesion and proliferation, using different cell types. In parallel, part of the project will focus on investigating the biodegradation of the implant in amniotic fluid. The final part of the thesis will be dedicated to the development of a biological adhesive, building on the laboratory’s previous work, to secure the implant over the malformation during implantation.
This project is being conducted in collaboration with the maternity unit of Necker Hospital (Prof. Julien Stirnemann, Université de Paris and Institut IMAGINE), a reference center for the prenatal management of congenital malformations, with particular expertise in fetoscopic prenatal surgery. This collaboration will also enable the performance of an in vivo animal study, such as in a sheep model, to assess the performance of the patch in parallel with the in vitro investigations. These results will contribute to the development of a patch capable of covering the defect associated with MMC while meeting the complex specifications required for this clinical application. This research is of major importance for enabling the development of early minimally invasive surgery for MMC, with the aim of reducing maternal morbidity while improving the prognosis associated with this severe congenital malformation.
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- Chouirfa H. et al., ACS Applied Materials & Interfaces, 2018, 10 (2), 1480-1491.
- Chouirfa H. et al., Biointerphases, 2017, 12, 02C418.
- Pereira C. et al., JOM the journal of the Minerals, Metals & Materials Society, 2022, 74, 87-95.
- Lam M. et al., IRBM, 2022, 43(6), 687-693.
- Lam M. et al., Today communications, 2022, 31, 103318.
Laboratory: Laboratoire de Chimie bioorganique, biophysique et biomatériaux pour la santé
Field of research: Biomaterials, polymeres chemistry
Skills : Biomaterials, polymer chemistry, surface and polymer characterization
Knowledge : Biomaterials, biology (in vitro and in vivo tests)
Where to apply
Website: https://rubis.univ-spn.fr/offres/voir/244
Requirements
Specific Requirements
Master 2
Experience in biomaterials chemistry and polymer chemistry; knowledge of biology.
Work Location(s)
- Number of offers available: 1
- Company/Institute: Université Sorbonne Paris Nord
- Country: France
- City: Villetaneuse
- Postal Code: 93430
- Street: 99, avenue Jean-Baptiste Clément
Contact
Website: https://www.univ-spn.fr/
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