Abstract

Engineering biomaterials that mimic the extracellular matrix (ECM) of bone is of significant importance since most of the outstanding properties of the bone are due to matrix constitution. Bone ECM is composed of a mineral part comprising hydroxyapatite and of an organic part of primarily collagen with the rest consisting on non-collagenous proteins. Collagen has already been described as critical for bone tissue regeneration; however, little is known about the potential effect of non-collagenous proteins on osteogenic differentiation, even though these proteins were identified some decades ago. Aiming to engineer new bone tissue, peptide-incorporated biomimetic materials have been developed, presenting improved biomaterial performance. These promising results led to ongoing research focused on incorporating non-collagenous proteins from bone matrix to enhance the properties of the scaffolds namely in what concerns cell migration, proliferation, and differentiation, with the ultimate goal of designing novel strategies that mimic the native bone ECM for bone tissue engineering applications. Overall, this review will provide an overview of the several non-collagenous proteins present in bone ECM, their functionality and their recent applications in the bone tissue (including dental) engineering field.

Highlights

  • New promising solutions for bone tissue engineering have been developed over the last years following the dramatic increase of the number of bone-related medical conditions that require clinical interventions

  • This review aims to present a summary of the different non-collagenous proteins found in bone extracellular matrix (ECM) and their important functions in context of bone tissue engineering applications, on their role in cell adhesion, proliferation, osteogenic differentiation, and angiogenic capacity

  • Alsanea and colleagues demonstrated that dental pulp stem cells incorporated within a collagen scaffold in the presence of dentin matrix protein 1 (DMP-1) can differentiate into odontoblast-like cells, secreting a highly vascularized collagenous matrix [196]

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Summary

Introduction

New promising solutions for bone tissue engineering have been developed over the last years following the dramatic increase of the number of bone-related medical conditions that require clinical interventions. CGRP might play a crucial role in promoting osteoblast proliferation and differentiation by bonding with functional receptors and transporters on the osteogenic cells and by stimulating growth factors production, such as BMP-2 [14]. The field has shifted towards investigating the interaction between extracellular matrix (ECM) proteins and cell membrane receptors [5] This approach avoids the use of growth factors and better mimics the bone ECM, reducing the side effects and increasing the efficiency of bone healing process. This review aims to present a summary of the different non-collagenous proteins found in bone ECM and their important functions in context of bone tissue engineering applications, on their role in cell adhesion, proliferation, osteogenic differentiation, and angiogenic capacity

Bone Extracellular Matrix
Exploiting Non-Collagenous Proteins in Bone Tissue Engineering Applications
Proteoglycans
Glycoproteins
Alkaline Phosphatase
Osteonectin
Tetranectin
RGD-Containing Glycoproteins
Gla-Containing Proteins
Osteocalcin
Matrix Gla Protein
Serum Proteins
Synergistic Biomimetic Strategies
Native ECM as a Biomaterial Source
Findings
Concluding Remarks and Future Perspective
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