One-step Preparation of an Injectable Hydrogel Scaffold System Capable of Sequential Dual-growth Factor Release to Maximize Bone Regeneration.

Numerous growth factors are involved in the natural bone healing process, which is precisely controlled in a time and concentration-dependent manner. Mimicking the secretion pattern of growth factors could be an effective means to maximize the bone regeneration effect. However, achieving the sequential delivery of various growth factors without the use of multiple materials or complex scaffold designs is challenging. Herein, an injectable poly(organophosphazene) hydrogel scaffold (IPS) encapsulating BMP-2 and TGFβ-1 (IPS_BT) was studied to mimic the sequential secretion of growth factors involved in natural bone healing. We designed the IPS_BT system to release TGFβ-1 slowly while retaining BMP-2 for a longer period of time. When IPS_BT was injected in vivo, the hydrogel was replaced by bone tissue. In addition, angiogenic (CD31 and αSMA) and stemness (Nanog and SOX2) markers were highly upregulated in the early stages of bone regeneration. The IPS system developed in this study has promising applications in tissue engineering because (1) various amounts of the growth factors could be loaded in one step, (2) the release pattern of each growth factor could be controlled via differences in their molecular interactions, and (3) the injected IPS could be degraded and replaced with regenerated bone tissue. This article is protected by copyright. All rights reserved.