Ultrasound-controlled release of growth factors from lyophilized platelet-loaded thermoresponsive hydrogel

Abstract

Platelet-rich plasma (PRP) and hyaluronic acid (HA) injection is commonly used for the treatment of osteoarthritis. However, the immediate bolus release of growth factors from PRP and inability of HA to stay in situ limit their beneficial therapeutic effects. An injectable, biocompatible, and thermoresponsive hydrogel (mPEG-PLGA-BOX block copolymer) is applicable for a long-term ultrasound-triggered lyophilized platelet (LP) release. In this study, an US-controlled release thermoresponsive hydrogel system loaded with LPs was evaluated for its long-term pharmacokinetics in a dry culture chamber at 37 °C. At 0.5 wt% constituent ratio of the LP-loaded hydrogels (0.2 ± 0.6 mV positively charged, which would be suitable for the treatments of negatively charged cartilages), the release amount of growth factors (PDGF-B and TGFβ-1) from the hydrogel could be increased to ∼300-folds in the presence of US (1 MHz, 0.4 W/cm2, 5% duty cycle, 5 min) compared to the amount in the absence of US during the 2 weeks of evaluation period. In comparison to 0.5 wt% of the LP-loaded HA (−2.4 ± 1.1 mV negatively charged), which had only a 5-day release ability, the US-controlled release thermoresponsive hydrogel system may be a more suitable platform for diseases that needed long-term treatments.