This work was published in the journal Biomaterials, in the framework of Marta Evangelista’s PhD works. My other colleagues at INEB involved in this work are Mário Barbosa and Cristina Barrias, and it was carried out in collaboration with Professor David J. Mooney‘s Group, from Harvard University (USA).
Evangelista MB, Hsiong S, Fernandes R, Sampaio P, Kong HJ, Barrias CC, Salema R, Barbosa MA, Mooney DJ, Granja PL. Upregulation of bone cell differentiation through immobilization within a synthetic extracellular matrix. Biomaterials 2007;28:3644-55.
There is a need for new therapeutic strategies to treat bone defects caused by trauma, disease or tissue loss. Injectable systems for cell transplantation have the advantage of allowing the use of minimally invasive surgical procedures, and thus for less discomfort to patients.
In the present study, it is hypothesized that Arg-Gly-Asp (RGD)-coupled in a binary (low and high molecular weight) injectable alginate composition is able to influence bone cell differentiation in a three-dimensional (3D) structure. Viability, metabolic activity, cytoskeleton organization, ultrastructure and differentiation (alkaline phosphatase (ALP), von Kossa, alizarin red stainings and osteocalcin quantification) of immobilized cells were assessed.
Cells within RGD-modified alginate microspheres were able to establish more interactions with the synthetic extracellular matrix as visualized by confocal laser scanning microscope and transmission electron microscopy imaging, and presented a much higher level of differentiation (more intense ALP and mineralization stainings and higher levels of osteocalcin secretion) when compared to cells immobilized within unmodified alginate microspheres. These findings demonstrate that peptides covalently coupled to alginate were efficient in influencing cell behavior within this 3D system, and may provide adequate preparation of osteoblasts for cell transplantation.