Natural Polymers and Osteogenic Cells for Bone Tissue Regeneration
Authors:   , Cao Wei 
Published: March 2023

Bone defects caused by systemic or local factors cannot heal spontaneously. The repair of critical-sized bone defects in clinical practice remains challenging due to limited clinically available bone-defect filling material. To stimulate bone regeneration and resolve this clinical challenge, bone tissue engineering approaches have been developed during the past decades.
Osteocytes have multiple functions in bone tissue. They can sense fluid shear stress as a result of mechanical loading, translating the mechanical stress into the production of biochemical signaling molecules. These effective biomolecules further regulate bone resorption and bone formation. Thus, it may well be that osteocytes not only regulate bone turnover but are also able to enhance osteogenesis of stem cells, suggesting a novel yet unrecognized role of osteocytes in governing bone tissue regeneration. In Chapter 2, we reviewed osteocyte functions in bone, as well as the interaction of osteocytes with other bone cells, and their role in bone remodeling. We hypothesize that osteocytes may have a pivotal role in bone regeneration as well, and thus that bone regeneration may be enhanced effectively and rapidly by optimal usage and stimulation of osteocytes.
Currently available synthetic bone grafts are biocompatible and osteoconductive, but the majority of these biomaterials lack osteoinductivity. Biomaterials coated with various growth factors, proteins, and/or drugs promote the expansion and osteogenic differentiation of precursor cells. However, these growth factors or drugs might cause local and systemic adverse effects that hinder the clinical application for bone regeneration. Therefore, the search for safe and effective biomaterials to promote bone regeneration is still ongoing. In Chapter 3, we concluded that our results indicate a possible role of k-carrageenan in pre-osteoblast adhesion, spreading, migration, metabolic activity, proliferation, and osteogenic differentiation. This study fully explored the influence of k-carrageenan on cell function from different aspects that are needed for bone regeneration. The current results suggest that k-carrageenan might be a promising factor to functionalize bone graft and for enhanced osseointegration of implants.
The search for cost-effective bioactive agents that can be incorporated in biomimetic calcium phosphate coating on an implant surface to improve implant osseointegration is still ongoing. k-Carrageenan could be a potent factor to improve implant osteoinductivity and osseointegration when incorporated in a calcium phosphate coating on titanium implants. In Chapter 4, we successfully incorporated k-carrageenan in an octa-calcium phosphate (OCP) coating on a titanium surface using a biomimetic co-precipitation technique. We found that k-carrageenan in the OCP coating increased pre-osteoblast spreading, proliferation, and metabolic activity, as well as alkaline phosphatase (ALP) activity, matrix mineralization, and osteogenic gene expression suggesting that k-carrageenan-functionalized OCP coating might improve osseointegration of titanium dental or orthopedic implants.
Confined cell-cell and/or cell-scaffold interactions in three-dimensional (3D)-printed scaffolds containing β-tricalcium phosphate (TCP) limit bone regeneration and large bone defect repair. Stem cell culture systems have attracted considerable attention as a way to better mimic the complex interactions between individual cells and scaffolds that occur in vivo. Spheroids might be a promising strategy to improve cell-cell and/or cell-scaffold interactions to achieve ideal bone regeneration. In Chapter 5, we successfully developed self-assembled stem cells from human exfoliated deciduous teeth (SHEDs) µ-spheroids that enhanced the osteogenic potential of 3D-printed hydroxypropyl methylcellulose/polyethylenimine/β-TCP composite scaffolds in vitro and in vivo, suggesting that SHEDs µ-spheroids may be promising in bone tissue engineering for bone regeneration.
Collectively, natural polymers and osteogenic cells do affect bone tissue regeneration. Bone regeneration modulated by osteocytes, k-carrageenan, and SHEDs µ-spheroids is promising in bone tissue engineering. Investigation of these processes provides further opportunities to learn and elucidate the mechanisms involved, leading to the development of new strategies for bone regeneration.