Open Positions

PhD POSITION:
Engineered highly vascularized niches: bringing new blood to regenerative therapies

Despite substantial progress, the generation of tissues and organs of sufficient size and complexity for clinical application in humans remains a major challenge[2], [3]. The rapid and scalable establishment of a functional vascular network within the engineered construct has emerged as one of the most critical bottlenecks. Such a network is essential for delivering oxygen and nutrients
throughout the tissue and ensuring the efficient removal of metabolic waste. Without adequate vascularization, engineered tissues inevitably suffer from hypoxia, cell death, tissue necrosis, and ultimately graft failure. This limitation is not only a major roadblock to tissue engineering but alsoa critical challenge for numerous cell-based therapies, in which an appropriate microenvironment and timely vascularization are essential to support cell survival, function, and biointegration.

To address this challenge, two principal strategies have emerged: (i) in vitro pre-vascularizationthrough the incorporation of exogenous endothelial cells that form functional vascular networks and anastomose with the host vasculature upon implantation, and (ii) in vivo vascularization through the spontaneous ingrowth of host-derived blood vessels upon implantation. Although the latter approach offers significant advantages in terms of simplicity or clinical translation its application remains limited by the slow and poorly controlled kinetics of host-driven vascularization[3]. Hence, the development of novel technologies for engineering artificial tissues and enhancing the efficacy of cell therapies represents the next major challenge in bioengineered regenerative therapies.

The bioengineering team of the Laboratory of Regenerative Hematopoiesis has successfully established several biomaterial-assisted extramedullary bone marrow niche models to study hematopoiesis[4], [5]. Leveraging this expertise, we recently developed a unique approach that combines a biomaterial scaffold for de novo volume creation with pre-conditioned stromal cells to trigger a rapid and robust host-derived pro-angiogenic response. Within 3 weeks, the engineered niche develops a functional vascular network exceeding 250 vessels/mm², providing efficient nutrient and oxygen delivery throughout the construct (see whole-mount confocal image above).

Once vascularized, these niches can enhance the engraftment, survival, and functionality of transplanted therapeutic cells. Using our patented delivery method, these therapeutic cells can be administered directly into the pre-vascularized niche through a minimally invasive procedure.This feature is particularly attractive for endocrine (i.e. diabetes) and extramedullary hematopoietic
tissue engineering applications, where bioactive molecules or blood components must be released directly into the circulation. Alternatively, these highly vascularized niches can serve as a vascular template for the generation of larger and more complex engineered tissues and organs. Overall, by overcoming one of the major barriers in tissue engineering, this technology has the potential to accelerate the clinical translation of regenerative therapies and organ replacement strategies.

We are seeking funding for this position through the very competitive University of Lausanne Faculty of Biology and Medicine PhD 2027 fellowship program. Other grant applications are ongoing for funding decisions in 2027, and open positions will be posted in our lab website. Self-funded individuals or UNIL PhD fellowship candidates interested in this project should send their CV, motivation letter and references to both Dr. Bonini (fabien.bonini@unil.ch) and Prof. Naveiras (join.naveiras-group@unil.ch) with the subject title “Candidature Engineered highly vascularized niches”.

We seek a highly motivated PhD candidate with a strong background in biology and a particular interest in stem cell biology, regenerative medicine, and translational research. The candidate should be eager to work in an interdisciplinary environment spanning biology, chemistry, and bioengineering, and motivated to develop expertise in these areas during the project. Experience
with mammalian cell culture, 3D culture systems, vascular biology, organoids, or animal experimentation is highly encouraged but not required. The PhD project will offer extensive training in advanced cell culture models, bioengineering approaches, biomaterials, flow cytometry, data analysis, and other complementary techniques relevant to tissue regeneration and cell therapy within a highly translational lab environment.

[1] B. J. Haas and J. L. Whited, ‘Advances in Decoding Axolotl Limb Regeneration’, Trends in Genetics, vol. 33, no. 8, pp. 553–565, Aug. 2017, doi:10.1016/j.tig.2017.05.006.
[2] N. Lv et al., ‘Research progress of vascularization strategies of tissue-engineered bone’, Front. Bioeng. Biotechnol., vol. 11, p. 1291969, Jan. 2024, doi:10.3389/fbioe.2023.1291969.
[3] E. A. Margolis, N. E. Friend, M. W. Rolle, E. Alsberg, and A. J. Putnam, ‘Manufacturing the multiscale vascular hierarchy: progress toward solving the grand challenge of tissue engineering’, Trends in Biotechnology, vol. 41, no. 11, pp. 1400–1416, Nov. 2023, doi: 10.1016/j.tibtech.2023.04.003.
[4] D. N. Tavakol et al., ‘Injectable, scalable 3D tissue-engineered model of marrow hematopoiesis’, Biomaterials, vol. 232, p. 119665, Feb. 2020, doi:10.1016/j.biomaterials.2019.119665.
[5] F. Schyrr et al., ‘Inducible CXCL12/CXCR4–dependent extramedullary hematopoietic niches in the adrenal gland’, Blood, vol. 144, no. 9, pp. 964–976, Aug. 2024, doi: 10.1182/blood.2023020875.

MASTER’S THESIS POSITION:
Separation of primary cell adipocytes by Deterministic Lateral Displacement