Engineered cell-free scaffold with two-stage delivery of miRNA-26a for bone repair

Abstract

The treatment of non-unions and bone defects is a major challenge. In these situations, autologous bone is the preferred treatment but has several serious limitations. Treatment alternatives including the use of calcium-based scaffolds alone or associated with either growth factors or stem cells have therefore been developed, or are under development, to overcome these shortcomings. Each of these are, however, associated with their own drawbacks, such as the lack of sustained/controlled delivery system for growth factors and poor cell survival and engraftment for stem cells. MicroRNAs (miRNAs), a class of small noncoding RNAs fine-tune the expression of as much as 30% of all mammalian protein-encoding genes. For instance, miRNA26a is able to promote the repair of critical-size calvarial bone defects. Yet, the clinical application of these fascinating molecules has been hampered by a lack of appropriate delivery systems. In an elegant report entitled cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects, Zhang et al. 2016, developped a non-viral vector with high affinity to miR-26a that ensured its efficient delivery in bone defects. Engineered scaffolds were able to induce the regeneration of calvarial bone defects in healthy and osteoporotic mice. Taken together, these data pave the way for the development of advanced bone substitutes that at least will match, and preferably supersede, the clinical efficiency of autologous bone grafts. However, the transfer from the bench to the bedside of such scaffolds requires further investigations including (I) a better understanding of the underlying biological mechanisms involved in bone formation via miRNA26a; (II) evidences of polymer scaffold biocompatibility upon its complete degradation; and (III) demonstration of the engineered scaffold functionality in defects of clinically relevant volume.

Therapeutic application of adipose-derived stromal vascular fraction in diabetic foot

“…Meanwhile, pericytes not only promote the appearance of endothelial progenitor cells but also maintain vascular integrity to form a vascular network [ 63 ]. Studies have shown that ASCs could also participate in the formation of new micro-vessel together with endothelial cells to form a stable vascular network system [ 64 ]. Animal experiments have demonstrated that transplanted ASCs could differentiate into endothelial cells, significantly improving blood flow and capillary density in diabetic and non-diabetic animal models of lower limb ischemia [ 65 ].…”

miRNA-26a-5p Accelerates Healing via Downregulation of PTEN in Fracture Patients with Traumatic Brain Injury

“…These miRNAs regulate target mRNA expression, and stimulating of miRNAs using agomiRNAs can thus modulate mRNA expression 42 . Previous research has largely explored the role of biotic factors in bone remodeling, with few studies exploring the association between TBI-related miRNAs and bone healing 30, 31, 32, 33, 43, 44. Therefore, this study identified miRNA-26a-5p in osteoblasts as a key activator of bone formation in the context of TBI.…”

Lentivirus‑mediated microRNA‑26a overexpression in bone mesenchymal stem cells facilitates bone regeneration in bone defects of calvaria in mice

“…The results of in vitro and in vivo experiments in one study have demonstrated that transfection of miR-26a significantly accelerated the osteogenic differentiation of adipose-derived stem cells in vitro and enhanced new bone formation following miR-26a transfection in vivo ( 32 ). Furthermore, the repair response to critical calvarial bone defects was demonstrated to be strengthened through positive modulation of miR-26a in angiogenic-osteogenic coupling ( 33 ). The underlying mechanism by which miR-26a positively mediates angiogenic-osteogenic coupling may be due to the fact that its high expression in newly formed bones increases vascular endothelial growth factor (VEGF) secretion.…”