Overview of methods for enhancing bone regeneration in distraction osteogenesis: Potential roles of biometals

Abstract

Background Distraction osteogenesis (DO) is a functional tissue engineering approach that applies gradual mechanical traction on the bone tissues after osteotomy to stimulate bone regeneration. However, DO still has disadvantages that limit its clinical use, including long treatment duration Methods Review the current methods of promoting bone formation and consolidation in DO with particular interest on biometal. Results Numerous approaches, including physical therapy, gene therapy, growth factor-based therapy, stem-cell-based therapy, and improved distraction devices, have been explored to reduce the DO treatment duration with some success. Nevertheless, no approach to date is widely accepted in clinical practice due to various reasons, such as high expense, short biologic half-life, and lack of effective delivery methods. Biometals, including calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), manganese (Mn), and cobalt (Co) have attracted attention in bone regeneration attributed to their biodegradability and bioactive components released during in vivo degradation. Conclusion This review summarizes the current therapies accelerating bone formation in DO and the beneficial role of biometals in bone regeneration, particularly focusing on the use of biometal Mg and its alloy in promoting bone formation in DO. Translational potential: The potential clinical applications using Mg-based devices to accelerate DO are promising. Mg stimulates expression of multiple intrinsic biological factors and the development of Mg as an implantable component in DO may be used to argument bone formation and consolidation in DO.

Targeting Endogenous Hydrogen Peroxide at Bone Defects Promotes Bone Repair

“…[ 30,31,53 ] Moreover, Mn 2+ ions, the degradation product of MnO 2 , have been shown to promote osteogenic activity. [ 34 ] In a recent study, the Mn 2+ ions released from Mn‐TCP bioceramics not only promoted the differentiation of osteoblasts, but also inhibited the formation and function of osteoclasts, and ultimately accelerated bone regeneration under osteoporotic conditions in vivo. [ 36 ] Moreover, Mn 2+ ions also play a crucial role in immunomodulation.…”

“…[ 32,33 ] Incorporation of Mn 2+ into bioactive glass has been shown to promote osteogenesis. [ 34 ] Manganese‐doped β‐tricalcium phosphate (Mn‐TCP) has also been reported to facilitate BMSC adhesion. [ 35,36 ] Therefore, the application of MnO 2 in bone defects may function to reduce ROS level, provide oxygen supply, and boost Mn 2+ metabolism to facilitate bone formation.…”

Promoting osteointegration effect of Cu-alloyed titanium in ovariectomized rats

“…Copper (Cu) is a unique metal that is not only a commonly used alloying element in metals but also an essential trace metal element in human body that plays important roles in maintaining human health. It is noteworthy that Cu can regulate the expression of related genes in the process of angiogenesis and bone remodeling [ 18 , 19 ]. Relevant study [ 20 ] showed that, compared with bare Ti6Al4V alloy, a Cu-rich diamond-like (Cu/a-C: H) film coated on Ti6Al4V alloy surface could significantly up-regulate the expressions of vascular endothelial cell growth factor (VEGF), alkaline phosphatase (ALP), osteocalcin (OCN) and other growth factors, which expressively promoted the proliferation of vascular cells and enhanced osteogenic activity in rabbits.…”

Overview of Physical and Pharmacological Therapy in Enhancing Bone Regeneration Formation During Distraction Osteogenesis

“…Further understanding the role of these hormones, thereby facilitates hormone-related bio-therapeutics into the clinical setting. In addition, Mg, Zn, Cu, Mn and Co have been proved to exert favorable effects on bone regeneration ( Li et al, 2021 ). Although the research on biologics is still in its infancy, it can be seen as a promising approach for its good biocompatibility.…”