The potential therapeutic role of extracellular vesicles in critical-size bone defects: Spring of cell-free regenerative medicine is coming

Abstract

In recent years, the incidence of critical-size bone defects has significantly increased. Critical-size bone defects seriously affect patients’ motor functions and quality of life and increase the need for additional clinical treatments. Bone tissue engineering (BTE) has made great progress in repairing critical-size bone defects. As one of the main components of bone tissue engineering, stem cell-based therapy is considered a potential effective strategy to regenerate bone tissues. However, there are some disadvantages including phenotypic changes, immune rejection, potential tumorigenicity, low homing efficiency and cell survival rate that restrict its wider clinical applications. Evidence has shown that the positive biological effects of stem cells on tissue repair are largely mediated through paracrine action by nanostructured extracellular vesicles (EVs), which may overcome the limitations of traditional stem cell-based treatments. In addition to stem cell-derived extracellular vesicles, the potential therapeutic roles of nonstem cell-derived extracellular vesicles in critical-size bone defect repair have also attracted attention from scholars in recent years. Currently, the development of extracellular vesicles-mediated cell-free regenerative medicine is still in the preliminary stage, and the specific mechanisms remain elusive. Herein, the authors first review the research progress and possible mechanisms of extracellular vesicles combined with bone tissue engineering scaffolds to promote bone regeneration via bioactive molecules. Engineering modified extracellular vesicles is an emerging component of bone tissue engineering and its main progression and clinical applications will be discussed. Finally, future perspectives and challenges of developing extracellular vesicle-based regenerative medicine will be given. This review may provide a theoretical basis for the future development of extracellular vesicle-based biomedicine and provide clinical references for promoting the repair of critical-size bone defects.

Bioprinting of gelatin-based materials for orthopedic application

“…However, in case of a significant fracture defect, the defect site will not heal without the help of implants or surgical intervention. Significant bone fracture defects, also called critical-sized bone defects, are often 1–2 cm in size or bigger or when the bone circumference loss is >50% owing to disease, high-energy trauma, or accident ( Nauth et al, 2018 ; Liu F. et al, 2023 ; Han et al, 2023 ; Su et al, 2023 ; Xia et al, 2023 ). These deformities are challenging to treat since surgical procedures only stabilize the bone fracture.…”

Bone Regeneration Using Mesenchymal Stromal Cells and Biocompatible Scaffolds: A Concise Review of the Current Clinical Trials

“…Several biomaterials have been used in combination with MSCs aiming to promote their adhesion, proliferation, and osteoblastic differentiation, as well as production of the collagen matrix that subsequently undergoes mineralization [11]. Moreover, biomaterials must be resorbable and allow the ingrowth of newly formed blood vessels from the neighboring tissues [12]. The majority of scaffolds investigated for bone regeneration applications are natural polymers (e.g., chitosan, fibrin, hyaluronic acid, and collagen) or synthetic polymers (e.g., polylactic acid, polycaprolactone); bioactive ceramics such as coralline, hydroxyapatite, tricalcium phosphate, sulphate, bioactive glass, and calcium silicate; and hybrid combinations of two or more materials with different properties in the form of copolymers, polymer-polymer blends, or polymer-ceramic composites [13].…”

Long Non-coding RNA-H19 Regulates Osteogenic Differentiation via microRNA-140-5p/Wnt1 Signaling in Bone Marrow Mesenchymal Stem Cells

“…As bone tissue engineering technology has advanced, the use of tissue engineering to construct tissue engineering bone has become one of the most promising methods of bone repair over the past few years [1,2] . Currently, Mesenchymal Stem Cells (MSCs) are used as seed cells for bone tissue engineering.…”