Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

Abstract

The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects. The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site. However, the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of pro-osteogenic factors. In this study, a polylactic acid (PLLA)/hyaluronic acid (HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique. The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers (PLLA/HA@Irisin) achieved its sustained release. In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was improved by PLLA/HA@Irisin, as evidenced by a significant increase in alkaline phosphatase (ALP) activity and matrix mineralization. Mechanistically, PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway. To assess the therapeutic effectiveness, PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats. The results at four and eight weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation, as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels. The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum, showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.

Electrospun radially oriented berberine-PHBV nanofiber dressing patches for accelerating diabetic wound healing

“…In other words, electrospun nanofibers are highly biomimetic materials, which have been broadly demonstrated to provide an appropriate environment to improve the migration, proliferation, adhesion and even differentiation, as well as the secretion and remodeling of extracellular matrix (ECM) of skin-associated cells [ 14 , 15 ]. In the last two decades, the initially single-fluid blending electrospinning process [ 16 , 17 ] has moved forward to the coaxial [ 18 , 19 ], side-by-side [ 20 ], tri-axial [ 21 , 22 ], tri-fluid side-by-side [ 23 ] and their combinations [ 24 , 25 ], as well as needless and surface-free electrospinning [ 26 ]. All these progresses have been inevitably based on the innovations of electrospinning spinneret [ 27 , 28 ].…”