A porous and elastic biomaterial for transplantations

Applied to the reconstruction of an artificial bone marrow niche, this approach allowed the group to highlight signs of ectopic hematopoietic differentiation in the absence of any associated ossification, a world first.

The field of regenerative medicine has offered many new perspectives in therapeutic tissue repair by replacing a defective group of cells or even whole organs in cases of serious injury or incurable illnesses. However, the transition from in vitro to in vivo is often a critical and precarious step in the success of bioengineered transplants. Ideally, this transition should be as non-invasive as possible, both for the cells and the patient, ensuring cell survival and integration of the implantation via rapid graft vascularization.

In order to meet these conditions, the collaborative teams of Olaia Naveiras (EPFL) and Thomas Braschler (UNIGE) have developed a biomaterial made from cellulose which is perfectly biocompatible and biodegradable, close to a targeted clinical formulation developed by Volumina-Medical SA. The surface of these macroporous microcarriers allows, after modification by bioactive molecules (like collagen), cell adhesion and large-scale 3D culture. In this study, the researchers were able to co-culture both stromal and hematopoietic stem and progenitor cells. In this model of bone marrow in vitro, they were able to demonstrate that in the absence of exogenous cytokines, stromal cells were able to support hematopoietic progenitor cells for up to 12 days.

After this phase of in vitro culture, the seeded biomaterial was concentrated in the form of a

“paste” and injected subcutaneously in vivo. This step was made possible by a compaction system using capillary action to drain any residual culture medium in a controlled manner without disrupting the cell viability within the co-cultured microcarriers. Once dehydrated, the living biomaterial can be transferred to a syringe by a plug-and-play needle attachment. This allows for a minimally invasive injection into the target tissue, and after implantation, was able to show a remarkable maintenance of high cell viability post-injection.

In the case of the reconstitution of a hematopoietic niche, after 12 weeks in the subcutaneous tissue of immunocompromised mice, the group demonstrated histological indices of extramedullary hematopoietic differentiation without associated ossification, as well as highly thorough vascularization of the graft. This success demonstrates an optimal structure for the survival of transplanted cells and the persistence of a reconstituted niche in vivo beyond the act of transplantation.

As the methodology is simple, inexpensive, and scalable, this system hints at a novel non-invasive transplantation technique of living materials capable of scaling towards a large number of cells. This economical approach allowed, among other things, these researchers to model an extramedullary bone marrow to allow the study of stroma-hematopoietic cell interactions. Besides potential use in regenerative medicine, this method could be applied for future studies of personalized models of human hematological pathologies.