H2020Индивидуална стипендия2021–2023

ProRegScaffold · Highly Biomimetic Proregenerative Scaffold for Personalized Nerve Repair

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период
2021-08-01 → 2023-07-31
Финансиране от ЕС
191 852 €
Участници
1
Схема
MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Изработват се персонализирани изкуствени структури чрез 3D принтиране и замразяване, които имитират сложната архитектура на периферните нерви. Те помагат за насочване на растежа на нервните клетки и ускоряване на възстановяването чрез контролирано освобождаване на калциеви йони.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Highly Biomimetic Proregenerative Scaffold for Personalized Nerve Repair

Peripheral nerve injuries, which are common and can cause debilitating sensory sensing and motor dysfunction, pose challenges for tissue engineering and regenerative medicine as neural functions depend on their complex 3D structures and anisotropic mechanical properties. Peripheral nerve tissues include complicated nerve fibers with intricate microscale topography and highly hierarchical geometric structures ranging from micrometer to centimeter levels. Artificial scaffolds are promising alternatives to current gold-standard autograft methodologies without availability limitations and donor site morbidity. A desirable characteristic of these artificial scaffolds is the ability to allow the ingress of cells and control their subsequent differentiation and proliferation within the scaffolds. However, the current engineering technologies are limited in creating hierarchically ordered structures ranging from centimeter to micrometer spatial resolution. Additionally, increased extracellular calcium ion (Ca2+) levels can increase mitochondrial motility, which is necessary for the regulation of Wallerian degeneration and thus accelerate nerve repair. Ca2+ has been implicated as a key messenger in the guidance of developing axons. The concentration of extracellular Ca2+ can mediate the axonal growth cone and its turning behavior. A local, controlled accumulation of released Ca2+ has been shown beneficial for long-term peripheral nerve regeneration. The incorporation of ice-templating and 3D printing technology was implemented to fabricate personalized scaffolds for nerve repair, which can effectively guide the extension of neurites at the single-cell level. The channel sizes of the scaffolds could be easily tuned via annealing in the presence of removable molecules, which addresses the demands for anisotropic scaffolds with precisely tunable porosity. Compared with reported scaffolds and methods, the scaffolds fabricated during this project show high spatial resolution and designed geometry that mimic the complex constructures of native nerve tissues. Furthermore, I developed a NIR-responsive drug loading system based on gelatin/polypyrrole (GB@PPy) nanoparticles for controllable Ca2+ release. Under NIR irradiation, integrated GB@PPy was able to efficiently release Ca2+ to accelerate the growth of neurons.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

According to Allied Market Research, the market for nerve repair and regeneration is expected to reach €11 billion by 2023, with an annual increase of 13%. Autograft, the gold standard, only achieves a success rate of about 45%, despite intrinsic drawbacks including availability and comorbidities. Neural scaffolds offer the bright prospect of nerve injury treatment by guiding axon sprouting and creating a permissive microenvironment. However, current products including NeuraGen® and Neuromaix® failed to find their way towards widespread clinical practice due to their dimensional instability and the mismatch of regenerated axons, as well as showing no effect on the intrinsic regenerative capability of neurons. To address the current technological gap, this project aims to develop a proregenerative scaffold (ProRegScaffold) that completely mimic the microenvironment of host tissues to guide axonal growth, promote regeneration and stimulate integration into the existing healthy tissue. The ProRegScaffold comprises of chitosan/collagen microchannels resembling the geometries of native nervous network, which will be tailored by precisely controlling the growth of ice crystals within digitally predefined moulds. This is an automated method amenable to low-cost and large-scale production. Near infrared light responsive lipid nanoparticles will be introduced and filled with growth factors to activate the intrinsic regenerative capability of neurons. Moreover, I will complement the finite-element method (FEM) with machine learning algorithms to accelerate the design phase, analyze structural mechanics and provide proper parameters of scaffolds allowing faster axon regrowth. This project represents cutting-edge research to screen structure-activity relationships for effective nerve repair, allowing the establishment of a practical personalized neural scaffold.

Оригинален текст от CORDIS (на английски).

Участници

  • KAROLINSKA INSTITUTET · STOCKHOLMКоординаторШвеция

Връзки

Данни: CORDIS, © Европейски съюз