Revolutionizing bone regeneration: advanced biomaterials for healing compromised bone defects

Abstract

In this review, we explore the application of novel biomaterial-based therapies specifically targeted towards craniofacial bone defects. The repair and regeneration of critical sized bone defects in the craniofacial region requires the use of bioactive materials to stabilize and expedite the healing process. However, the existing clinical approaches face challenges in effectively treating complex craniofacial bone defects, including issues such as oxidative stress, inflammation, and soft tissue loss. Given that a significant portion of individuals affected by traumatic bone defects in the craniofacial area belong to the aging population, there is an urgent need for innovative biomaterials to address the declining rate of new bone formation associated with age-related changes in the skeletal system. This article emphasizes the importance of semiconductor industry-derived materials as a potential solution to combat oxidative stress and address the challenges associated with aging bone. Furthermore, we discuss various material and autologous treatment approaches, as well as in vitro and in vivo models used to investigate new therapeutic strategies in the context of craniofacial bone repair. By focusing on these aspects, we aim to shed light on the potential of advanced biomaterials to overcome the limitations of current treatments and pave the way for more effective and efficient therapeutic interventions for craniofacial bone defects.

Keywords: biomaterials; craniofacial bone defects; engineered biomaterials; oxidative stress; reactive oxygen species; semiconductors.

FIGURE 1

Digital image of a large cranial defect (A) with mesh implant (B).

FIGURE 2

Proposed mechanism of healing CSDs over time: (A) Critical sized defect; (B) Endothelial Cells and Mesenchymal Stem Cells arrive in bone defect; (C) Antioxidant activity (NRF2, SOD1, GPX, CAT); (D) Angiogenic transcription markers expressed (HIF, ANG1, VEGF); (E) Vascular tubule formation; (F) Osteogenic transcription (RUNX2, OSX); (G) Collagen matrix formation; (H) Bone matrix protein synthesis (ALP, COL, OCN); (I) Bone formation; (J) Healed CSDs.

FIGURE 3

MRGPRD (MAS-related GPR family member D), FFAR3 (a G-protein-coupled receptor), GABAaR (gamma-aminobutyric acid type A receptor), GABBR1-2 (gamma-aminobutyric acid type B receptor subunit 1–2), GLRA1-4 (glycine receptor alpha 1–4), and GAD (glutamate decarboxylase) are all involved in the control of muscle tonicity. GABA is a major neurotransmitter that is generated in the central nervous system (CNS) and spinal cord, and its action controls muscle tonicity both centrally and peripherally. BAIBA is a myokine secreted from skeletal muscles that has direct effects on bone/osteocytes in mice. Exercise promotes the secretion of both myokines and osteokines, which can have autocrine and paracrine effects. It is hypothesized that muscle tonicity could potentially influence the release of myokines, which could in turn affect the levels of BAIBA, and vice versa. The receptors for GABA and BAIBA mediate their functions, and certain SNPs may act as modifiers of these effects. Thus, muscle tonicity may represent a novel mechanism for the regulation of myokine release and its effects on bone and muscle.

FIGURE 4

Tissue Engineering in Craniofacial Bone Regeneration. Many strategies have been used to induce bone regeneration in craniofacial defects and have employed various biomaterial formats (e.g., nanoparticles, scaffolds, implants) and/or bioactive factor release (e.g., small molecule, drug) to induce angiogenesis and osteogenesis for bone formation using clinically relevant animal models.

FIGURE 5

(A) Schematic of PECVD process to form SiONx coatings for Ti implants. (B) Surface formation of hydroxyl, phosphate, and carbonate groups that make up bone mineral hydroxyapatite when introduced to in vitro environment.

FIGURE 6

Effect of small molecular delivery of Si⁴⁺ that rescues human endothelial cell angiogenesis when exposed to reactive oxygen species and normal conditions. Primary human endothelial cells showed thick and dense tubules when exposed to 1.0 mM ionic Si (A) vs no Si treatment exhibiting immature tubule formation (B) in 24 h in vitro. HUVECs under ROS conditions (H₂O₂) showed increased angiogenic marker expression vs no Si ion treatments (C) (All experiments were performed with n = 6 per group according to protocols and methods published by Monte et al. (Monte et al., 2018).

FIGURE 7

In Vitro and In Vivo model of NRF2 effect on (A) angiogenesis and (B) osteogenesis in bone regeneration.

FIGURE 8

Micro-CT of compromised wound healing environment shows decreased bone formation in targeted area (A) Quantification of bone volume (B) Bone healing in control vs (C) irradiated animal defect and bone healing.

FIGURE 9

Compromised healing model of bone regeneration. DCE-MRI of compromised wound healing environment shows decreased tissue perfusion in targeted area.