Oscillating Fluid Flow Activated Osteocyte Lysate‐Based Hydrogel for Regulating Osteoblast/Osteoclast Homeostasis to Enhance Bone Repair

Abstract

As major regulators on bone formation/resorption in response to mechanical stimuli, osteocytes have shown great promise for restoring bone injury. However, due to the unmanageable and unabiding cell functions in unloading or diseased environments, the efficacy of osteogenic induction by osteocytes has been enormously limited. Herein, a facile method of oscillating fluid flow (OFF) loading for cell culture is reported, which enables osteocytes to initiate only osteogenesis and not the osteolysis process. After OFF loading, multiple and sufficient soluble mediators are produced in osteocytes, and the collected osteocyte lysates invariably induce robust osteoblastic differentiation and proliferation while restraining osteoclast generation and activity under unloading or pathological conditions. Mechanistic studies confirm that elevated glycolysis and activation of the ERK1/2 and Wnt/𝜷-catenin pathways are the major contributors to the initiation of osteoinduction functions induced by osteocytes. Moreover, an osteocyte lysate-based hydrogel is designed to establish a stockpile of "active osteocytes" to sustainably deliver bioactive proteins, resulting in accelerated healing through regulation of endogenous osteoblast/osteoclast homeostasis.

Osteocyte Mechanotransduction in Orthodontic Tooth Movement

“…This fluid flow leads to a strain-driven interstitial fluid movement through the canaliculi and along the osteocyte processes, which is sensed and transduced by the osteocytes [ 51 ]. This interstitial fluid flow stimulates signaling molecule production by osteocytes that stimulate osteoclastic bone resorption, or osteoblastic bone formation [ 14 , 52 ]. Mechanotransduction then comprises the translation of canalicular flow by osteocytes into cell signals that recruit osteoclasts and osteoblasts [ 44 •, 45 ].…”

Recent advances in primary cilia in bone metabolism

“…As well as Liu ( 25 ) also reported that the primary cilia of osteoblasts in rats exposed to microgravity rapidly became shorter or even disappeared, and this phenomenon was accompanied by a significant reduction in osteogenic differentiation and mineralization of osteoblasts. In addition, it has been shown that cellular function can barely be maintained under conditions without mechanical loading and the effect of inducing osteoblasts to become bone cells is greatly limited ( 34 ), whereas primary cilia, as an important part of mechanotransduction, are involved in mechanosensing and signaling that regulates the behavior of mesenchymal bone progenitors, osteoblasts and osteoclasts ( 35 ).…”