Accelerated Bone Regeneration by an Astaxanthin-Modified Antioxidant Aerogel through Relieving Oxidative Stress via the NRF2 Signaling Pathway

Abstract

Bone regeneration of critical-sized bone defects (CSBDs) with biomimetic collagen-based aerogels remains a significant challenge due to the oxidative stress on the microenvironment. The excessive oxidative stress could induce apoptosis and dysfunction of host-derived cells. Astaxanthin (ATX) exhibits excellent antioxidant ability to block free radical chain reactions. In the present study, hybrid antioxidant collagen-derived aerogels (ATX–Col aerogels) were fabricated by a simple one-step method through the covalent cross-linking of Col and ATX. The resulting ATX–Col aerogels show porous and interconnected structures due to freeze-drying strategies. The ATX–Col aerogels exhibited excellent biocompatibility and biosafety. Furthermore, ATX–Col aerogels demonstrated favorable antioxidant capacity by eliminating intracellular ROS by activating the NRF2 signaling pathway. Finally, excellent reparative effects in repairing rat cranial defects were observed in ATX–Col aerogels. Taken together, ATX–Col aerogels can accelerate bone regeneration by relieving oxidative stress via the NRF2 signaling pathway and act as a potential bone graft for CSBD. This study provides a simple method of developing antioxidant aerogels for bone regeneration.

3D Printing of Cobalt‐Incorporated Chloroapatite Bioceramic Composite Scaffolds with Antioxidative Activity for Enhanced Osteochondral Regeneration

“…[29] Therefore, sufficient antioxidant was needed to compete against oxidative damage and protect the growth of new tissues. [30,31] Accordingly, it suggested that Co-ClAP/PLGA scaffolds removed excess ROS in osteochondral defects, maintained a beneficial regeneration microenvironment, regulated the immune microenvironment, thereby promoting the integrated regeneration of articular cartilage and subchondral bone.…”

Bioengineering Composite Aerogel-Based Scaffolds That Influence Porous Microstructure, Mechanical Properties and In Vivo Regeneration for Bone Tissue Application

“…Though bone is a dynamic tissue that is able to continuously remodel, and also to repair itself in case of injury, some traumatic and pathologic lesions are so extensive that they exceed the organism’s regeneration capacity [ 12 , 13 , 14 , 15 , 16 ]. Moreover, with an increasingly aging world population, and increased demand for higher health standards and quality of life, it has become imperative to develop strategies to overcome bone regeneration obstacles [ 12 , 17 , 18 , 19 ].…”

“…Moreover, with an increasingly aging world population, and increased demand for higher health standards and quality of life, it has become imperative to develop strategies to overcome bone regeneration obstacles [ 12 , 17 , 18 , 19 ]. Since there are limitations to the use of autografts and allografts for surgical filling of large bone void defects [ 14 , 15 , 16 , 18 , 19 , 20 ], in recent decades, bone tissue engineering has been developing biomimetic alloplastic graft biomaterials inspired by the above-mentioned macro and microstructure of bone, as well as by its ECM physicochemical features [ 2 , 11 , 13 , 14 , 16 , 21 , 22 ].…”

“…More recently, due to these outstanding characteristics, as well as the possibility of using a variety of raw materials in their composition [ 32 , 36 ], aerogels are also being applied in the biomedical and pharmaceutical fields, namely as scaffolds for tissue regeneration, wound healing dressings, carriers for drug delivery, biosensors for diagnostics [ 29 , 33 , 34 , 36 , 37 ], antimicrobial activity agents and decontaminating compounds [ 34 ]. Accordingly, as observed in Figure 2 b, aerogel-based scaffolds are being developed specifically for bone tissue regeneration, resorting to organic natural (silk fibroin, chitosan, cellulose, starch, alginate) [ 14 , 15 , 17 , 24 , 32 , 38 ] or synthetic polymers (poly(e–caprolactone) (PCL)) [ 17 ] and inorganic compounds (cellulose nanocrystals, β–Tricalcium phosphate, silica, hydroxyapatite) [ 18 , 20 , 36 , 39 ], or a combination of both (composite/hybrid) (e.g., silica–silk fibroin) [ 11 , 30 , 33 ].…”