Bone Engineering Scaffolds With Exosomes: A Promising Strategy for Bone Defects Repair

Abstract

The treatment of bone defects is still an intractable clinical problem, despite the fact that numerous treatments are currently available. In recent decades, bone engineering scaffolds have become a promising tool to fill in the defect sites and remedy the deficiencies of bone grafts. By virtue of bone formation, vascular growth, and inflammation modulation, the combination of bone engineering scaffolds with cell-based and cell-free therapy is widely used in bone defect repair. As a key element of cell-free therapy, exosomes with bioactive molecules overcome the deficiencies of cell-based therapy and promote bone tissue regeneration via the potential of osteogenesis, angiogenesis, and inflammation modulation. Hence, this review aimed at overviewing the bone defect microenvironment and healing mechanism, summarizing current advances in bone engineering scaffolds and exosomes in bone defects to probe for future applications.

Engineering exosomes and biomaterial-assisted exosomes as therapeutic carriers for bone regeneration

“…A range of biomaterial scaffolds endows exosomes with desirable pharmaceutical acceptability by extending exosome storage time and altering the release properties, thereby overcoming the drawbacks of natural exosomes. The use of biomaterial-assisted exosomes has proven to be a novel strategy for regenerating bone tissues [ 125 ]. Biomaterials employed for scaffolds can be divided into metal materials, bioactive ceramics, hydrogels and synthetic polymers.…”

Hyaluronic acid-based hydrogels: As an exosome delivery system in bone regeneration

“…Recently, exosomes have been widely used for bone regeneration due to their biocompatibility, biostability and low immunogenicity (Tan et al, 2020;Wang et al, 2020). In the bone defects microenvironment consisting of various cells, such as osteoblasts, osteoclasts, endothelial cells, immune cells, and MSCs, exosomes can participate in the regulation of angiogenesis, osteogenesis and inflammation by being phagocytosed by these target cells and interacting with them (Safari et al, 2021;Zhu et al, 2021;Zhang et al, 2022). For instance, Kang et al (2022) designed an exosome-functionalized cell-free PLGA/Exo-Mg-GA MOF composite scaffold that simultaneously enhances angiogenesis, osteogenesis, and antiinflammatory capacity.…”

“…As is known to us, the lack of a vascular network at the bone defect will prevent the formation of new bone, and adequate blood supply is an important basis for bone generation (Wu et al, 2021;Zhang et al, 2022). Angiogenesis and osteogenesis are closely related, and only by improving both at the same time can the remodeling of new bone be better improved (Behera et al, 2021;Wu et al, 2021).…”

“…It has been demonstrated that once the length of the bone defect exceeds 2 to 2.5 times the diameter of the damaged bone, the self-healing ability of bone tissue alone is not enough (Wiese and Pape, 2010). Hence, some additional clinical treatments are needed to keep the bone defect site stable and create a suitable microenvironment for bone regeneration, thus achieving better bone regeneration and functional reconstruction of the defect site (Elliott et al, 2016;Zhang et al, 2022). Currently, autografts and allografts remain the main methods for repairing bone defects (Dimitriou et al, 2011;Chen and Lv, 2018).…”

“…Recently, exosomes derived from different kinds of cells have shown enormous potential in bone regeneration and repair as a key element of cell-free therapy (Zhai et al, 2020). This cell-free therapy strategy based on exosomes not only avoids the immune risks relevant to cell therapy and improves the low homing efficiency of transplanted cells, but it also can achieve the repair and regeneration of the defective bone tissue by regulating the inflammatory response and promoting angiogenesis and osteogenesis (Eggenhofer et al, 2014;Sun et al, 2022;Zhang et al, 2022). And since exosomes do not have the ability to selfreplicate, the risk of iatrogenic tumor formation is also greatly reduced (Sun et al, 2022).…”