Grant: Discovery Horizons

The peripheral nervous system has the unique capacity to regenerate axons upon lesion. However, functional recovery after a peripheral nerve injury is challenging for growing axons across large gaps. Biomaterials are used as tools in regenerative medicine to support axon outgrowth and offer enhanced conditions for nerve regeneration. However, biomaterial efficiency greatly depends on their ability to interact with cells and support their survival and proliferation. We developed a novel biomaterial featuring interconnected microchannels analogous to the extracellular matrix. Our goal is to assess and fine-tune the potential of this biomaterial to enhance human stem cell engraftment and differentiation, following these three specific aims: Aim 1. We will determine the optimal composition and surface adhesion parameters of our scaffold for stem cell engraftment and survival. We will assess whether covalently linked adhesion peptides can significantly influence stem cell engraftment. Advancing biomaterial composition and surface requires elaborate know-how in material sciences and engineering, especially in the field of biomaterials. Aim 2. We will investigate how this biomaterial influences stem cell proliferation and differentiation. Using an engineered pluripotent stem cell model, we will establish by transcriptomics the molecular impact of our biomaterial on stem cell differentiation. Determining the molecular underpinnings of stem cell engraftment in the biomaterial requires knowledge and expertise in stem cell biology and computational biology. Aim 3. We will assess the regenerative potential of the biomaterial in vivo. We will implant the scaffold into a mouse sciatic nerve section and determine whether it provides a suitable topography for in vivo neurite outgrowth, and has an impact on the walking patterns. Reconstructive surgery with the biomaterial necessitates skills in neurosurgery while nerve recovery evaluation asks for expertise in kinematics. The combination of three technologies i.e., engineered biomaterial, open-loop perfusion bioreactor, and stem cells, is an unconventional, yet highly innovative strategy. It represents an ingenious approach that goes beyond current research paradigms. By combining our interdisciplinary expertise, this project will generate important advances for productive clinical translation in the realm of personalized regenerative medicine.