^{Extracellular Matrices for Bone Regeneration: A Literature Review}

Abstract

The gold standard material for bone regeneration is still autologous bone, a mesenchymal tissue that consists mainly of extracellular matrix (ECM) (90% v/v) and little cellular content (10% v/v). However, the fact that decellularized allogenic bone grafts often present a clinical performance comparable to autologous bone grafts demonstrates the crucial role of ECM in bone regeneration. For long, the mechanism by which bone allografts function was not clear, but recent research has unveiled many unique characteristics of ECM that seem to play a key role in tissue regeneration. This is further confirmed by the fact that synthetic biomaterials with composition and properties resembling bone ECM present excellent bone regeneration properties. In this context, ECM molecules such as glycosaminoglycans (GAGs) and self-assembly peptides (SAPs) can improve the performance of bone regeneration biomaterials. Moreover, decellularized ECM derived either from native tissues such as bone, cartilage, skin, and tooth germs or from cells such as osteoblasts, chondrocytes, and stem cells has shown promising results in bone regeneration applications. Understanding the role of ECM in bone regeneration is crucial for the development of the next generation of biomaterials for bone tissue engineering. In this sense, this review addresses the state-of-the-art on this subject matter.

Radix Salviae miltiorrhizae improves bone microstructure and strength through Wnt/β‐catenin and osteoprotegerin/receptor activator for nuclear factor‐κB ligand/cathepsin K signaling in ovariectomized rats

“…Glycosaminoglycans are one kind of extracellular matrix mainly found in cartilage, which bind to hydroxyapatite and contribute to osteoblasts differentiation and mineralization (Mansour, Mezour, Badran, & Tamimi, ) and appear red after staining with Safranin O. As shown in Figure b,c, the thickness of cartilage adjacent to the growth plate was significantly reduced in rat femoral heads of the OVX control group when compared with those in the Sham controls ( p < 0.05), showing that OVX may impede osteoblasts differentiation and bone formation.…”

Feeling Things Out: Bidirectional Signaling of the Cell–ECM Interface, Implications in the Mechanobiology of Cell Spreading, Migration, Proliferation, and Differentiation

“…Tissues under constant mechanical loading (e.g., bone) exhibit exceedingly high elastic moduli ( E ≈ 2.5 GPa) whereas internal organs that undergo extensive deformation (e.g., lung) can have E < 500 Pa. Stiffness, the magnitude of local forces sensed by adherent cells, is largely governed by the protein composition of the ECM with higher concentrations of fibrillar collagens, and in some cases proteoglycans, directly correlating to a stiff (high E ) matrix 8. For instance, proteomic analysis of bone ECM have estimated collagen I constitutes upward of 90% of the organic phase 9. As collagens are synthesized and inserted into the matrix, cells organize collagen fibers in various orientations and crosslinked states.…”

3D Bone Biomimetic Scaffolds for Basic and Translational Studies with Mesenchymal Stem Cells

“…Matrix components are input factors for the cells and affect their morphology, cytoskeletal organization, and integrin expression profile, as extensively investigated [ 38 ]. The aim to produce a physiologically relevant microenvironment for MSCs and, thereby, elicit appropriate responses for specific applications, has fueled the production of an overwhelming variety of scaffolding materials resembling bone ECM in terms of composition and properties, through chemical/physical modification processes [ 7 , 8 , 9 , 39 ]. A common strategy has been to combine synthetic polymers with HA in order to improve their bioactivity.…”

“…Bone ECM itself has been employed after specific manipulations such as decellularization, demineralization, or deproteination [ 39 ]. The resulting modified ECM offered the advantage of displaying, simultaneously, many different chemical and physical instructive signals for the host cells, preserved osteoconductive and osteoinductive properties [ 61 , 62 , 63 ], and showed promising results also for potential exploitation in cartilage regeneration [ 64 , 65 ].…”