Preparing the Bone Tissue Regeneration Ground by Exosomes: From Diagnosis to Therapy

Abstract

Bone tissue engineering employs acellular scaffolds or scaffolds, along with cells and growth factors, to provide the mechanical support needed, as well as serve as a delivery vehicle for bioactive molecules to the injury sites. As tissue engineering continues to evolve, it has integrated two emerging fields: stem cells and nanotechnology. A paracrine factor that is found to be responsible for the major regenerative effect in stem cell transplantation is an extracellular vesicle called an ‘exosome’. Recent advances in nanotechnology have allowed the ‘exosome’ to be distinguished from other extracellular vesicles and be polymerized into a well-defined concept. Scientists are now investigating exosome uses in clinical applications. For bone-related diseases, exosomes are being explored as biomarkers for different bone pathologies. They are also being explored as a therapeutic agent where progenitor cell-derived exosomes are used to regenerate damaged bone tissue. In addition, exosomes are being tested as immune modulators for bone tissue inflammation, and finally as a delivery vehicle for therapeutic agents. This review discusses recently published literature on the clinical utilization of exosomes in bone-related applications and the correlated advantages. A particular focus will be placed on the potential utilization of regenerative cell-derived exosomes as a natural biomaterial for tissue regeneration.

Bioactive Scaffolds Integrated with Liposomal or Extracellular Vesicles for Bone Regeneration

“…EVs by themselves or as engineered carriers for the delivery of payloads are an active area of research in the field of bone regenerative medicine [10][11][12]. Compared with liposomes, EVs offer more excellent biocompatibility, efficient cellular internalization, and specific tissue targeting capability [14,15].…”

“…Numerous studies have focused on revealing the functional role of exosomes on bone regeneration both in their naïve and engineered form [10][11][12]. In Section 3.1, we summarize the current understanding of osteoinductive potentials of exosomes isolated from different parental cell sources.…”

“…Herein, we review recent approaches for developing successful bioactive molecule delivery systems in local bone regenerative therapy, particularly through employing liposomal vesicles or extracellular vesicles as drug delivery systems (DDS). In recent years, liposomes or extracellular vesicles have been integrated into various BTE scaffolds via different strategies, in which bound vesicles aimed to exert controlled and sustained release of bioactive cargo accelerating bone regeneration at the local defect site [9][10][11][12]. Liposomes, nanovesicles composed of lipid bilayer(s), have been utilized as versatile DDS since their first discovery in the 1960s, largely because they are biocompatible and capable of incorporating both hydrophilic and hydrophobic molecules [13].…”

Exosomes Engineering and Their Roles as Therapy Delivery Tools, Therapeutic Targets, and Biomarkers

“…It has been shown that various complications can occur in traditional tissue engineering, and the efficiency of regeneration itself can be relatively low. Therefore, due to their good characteristics, minimal side effects, and potentially good efficacy, exosomes have also begun to be used in this field [152][153][154].…”

Exosomes Enhance Adhesion and Osteogenic Differentiation of Initial Bone Marrow Stem Cells on Titanium Surfaces

“…Exosomes are certainly nanoscale intercellular messengers secreted by cells to deliver biological signals. Thus, the "if and how" they regulate the behavior of BMSCs on titanium (Ti) or other materials have become interesting and intriguing (Al-Sowayan et al, 2020). Furthermore, considering the outstanding properties of exosomes (natural origin, cargo representing a rich source of factors, and low immunogenicity), there may be a novel strategy to promote the activity of BMSCs in the process of osseointegration by introducing exosomes.…”