Functional Biomaterials for Bone Regeneration: A Lesson in Complex Biology

Abstract

Bone is a hard yet dynamic tissue with remarkable healing capacities. Research to date has greatly advanced the understanding of how bone heals and has led to marked success in the treatment of bone injuries. Nevertheless, the effective treatment of nonunions and large bone defects continues to present a challenge for orthopedic surgeons. Biomaterials provide researchers with a powerful instrument to potentially guide effective bone tissue regeneration in challenging healing environments. However, the most appropriate biomaterial for bone tissue engineering continues to be an area of intense debate. Indeed, the mechanical properties of real bone can be reproduced in vitro but the development of a functional bone substitute goes beyond the sole mechanical properties. The faithful reproduction of bone as a functional organ requires the combination of different cell types and temporal regulation of the molecular signaling involved during the different stages of bone formation and regeneration. This is not at all a trivial task. Herein, critical aspects of bone healing/regeneration including mechanical loading, inflammation, vascularization, and innervation are described. The success and the challenges behind the development of biomaterials, and the technologies used to functionalize them, in order to support the underlying cellular mechanisms are also highlighted.

Stable Reference Genes for qPCR Analysis in BM-MSCs Undergoing Osteogenic Differentiation within 3D Hyaluronan-Based Hydrogels

“…It could be considered that certain limitations are evident in this study, such as the use of only one cell type and the investigation of only one HA-based biomaterial under osteogenic culture conditions. However, given the widespread use of MSCs and HA-based hydrogels in tissue reparative approaches [46,47] and the known inter-individual heterogeneity of MSCs, the robust nature of our findings suggest that the use of the identified reference genes may serve to improve RT-qPCR-based assessments of phenotypic changes in osteogenic cultures. Further studies to determine the most appropriate reference genes for other MSC-relevant differentiation protocols (such as chondrogenesis), and when utilizing other widely used hydrogels (such as fibrin or collagen-and gelatin-based materials), should also be performed as a matter of urgency in an attempt to advance the field of MSC-based musculoskeletal regenerative approaches.…”

Simultaneous incorporation of PTH(1–34) and nano-hydroxyapatite into Chitosan/Alginate Hydrogels for efficient bone regeneration

“…Autogenous transplantation, the gold standard method for bone therapy, is limited for the lack of sources of autografts [ 7 , 8 ], besides it also has a risk of infection, nerve damage and other postoperative complications [ 9 ]. To address these challenges, researchers have focused on the development of novel biomaterials with potential in tissue engineering and regeneration to facilitate bone regeneration [ [10] , [11] , [12] , [13] ]. Among synthetic biomaterials, hydrogels consisting of natural or synthetic polymers that exhibit excellent mechanical properties and biocompatibility are ideal scaffolds to emulate extracellular matrices for cell proliferation and differentiation [ 12 , [14] , [15] , [16] , [17] ], thus leading to broad utilization in bone regeneration.…”

A Novel Approach to Enhance Bone Regeneration by Controlling the Polarity of GaN/AlGaN Heterostructures

“…[ 1,2 ] Biomaterials are considered a powerful tool to potentially guide rapid and effective bone regeneration in challenging healing environments. [ 3 ] A growing number of strategies such as bioactive coating, chemical modification, stiffness regulation, and micropatterning have been developed to improve biomaterials for bone regeneration. [ 4–7 ] However, current biomaterials for bone regeneration are still difficult to translate into clinical applications.…”

“…[ 4–7 ] However, current biomaterials for bone regeneration are still difficult to translate into clinical applications. [ 3 ]…”