Shape memory bone screws loading L-arginine and Ca²⁺ propagate mechanical stimulation, energize bone cells and augment bone regeneration

Abstract

Metallic bone screws are clinically used to fix the fractured bone fragments in bone defect treatment; yet they present compromised therapeutic efficacy due to poor osseointegration and tissue support. Here, we develop a novel thermoresponsive shape memory (SMP) bone screw with osteogenesis-angiogenesis coupling for enhanced bone regeneration. The SMP bone screws are prepared by die casting of shape memory polyurethane/hydroxyapatite (PU/HA) composite, coated with L-arginine (Arg) and calcium ions (Ca2+). The SMP bone screw could shrink and be easily reshaped at room temperature (25°C) and then rapidly recover to its original state (37°C), granting it robust internal fixation capacity (2-fold increase in pull-out force) and beneficial compressive force to nearby tissues. Additionally, the long-term release of L-arginine and calcium ions synergistically activate the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathway of native cells. Synergized with its shape memory function, the SMP bone screw activated calcium signaling pathway under the stimulation of mechanical stress, promote the activation of various osteogenic pathways (e.g. PI3K-Akt signaling pathway), and upregulate the NO-cGMP pathway by regulating the influx of calcium ions and arginine to synchronously coordinate osteogenesis and angiogenesis to accelerate bone repair. We envision that our slot-in, snap-back and homeothermal shape memory bone screw, with its easily reshaped and fast stress release properties and osteogenesis-angiogenesis coupling efficacy, can shed new light on the development of clinical bone screws.