Stem cell-mediated bone formation on biomimetic 3-D matrices

Marta Monteiro Silva Carvalho

Key information

Authors:

Marta Monteiro Silva Carvalho (Marta Monteiro Silva Carvalho)

Supervisors:

Deepak Vashishth; Cláudia Alexandra Martins Lobato da Silva (CLÁUDIA ALEXANDRA MARTINS LOBATO DA SILVA- Investigadora)

Published in

12/04/2018

Abstract

Bone tissue engineering aims to generate functional bone tissue, fabricating biocompatible and biodegradable scaffolds, and developing new approaches to enhance the functionality and bioactivity of the scaffolds, such as the use of growth factors, bioactive peptides or extracellular matrix (ECM) components. Numerous pre-clinical trials with different animal models have generated optimistic results, however, the difficulty to translate it into a clinical setting suggests that some limitations and concerns remain and need to be further addressed to design enhanced bone grafts for bone fracture repair treatment. By looking deep into nature, we observe that each tissue has its own ECM, with different composition regarding its specificity. It is known that most of the outstanding properties of the bone are related to its matrix constitution. More specifically bone extracellular matrix is composed by an organic and inorganic part, composed by collagen, non-collagenous proteins and hydroxyapatite. Although in smaller amounts, noncollagenous bone proteins can be found in the bone matrix and they have been reported to play important roles in bone mineralization and cellular activities, in particular osteocalcin (OC) and osteopontin (OPN). We evaluated the role of OC and OPN at the cellular level by investigating osteogenic differentiation of mesenchymal stem/stromal cells (MSC) derived from OC-/- OPN-/- mice. We observed that osteogenic differentiation is impaired and, using spectroscopic analysis, we confirmed that mineralization is delayed and the mineral formed by these cells is not mature enough after 21 days of osteogenic differentiation. Therefore, we concluded that OC and OPN are important regulators of bone mineralization at a cellular level, providing new insights into forming high quality bone, relevant for treatment of fracture healing in older and osteoporotic bone. By understanding the fundamental roles of OC and OPN, we applied the synergistic effect of these proteins and developed biomimetic scaffolds for bone tissue engineering that enhance and accelerate the process of bone repair.