Alendronate-functionalized double network hydrogel scaffolds for effective osteogenesis

Guoke Tang; Liang Zhu; Weiheng Wang; Dongqing Zuo; Changgui Shi; Xiaojie Yu; Rui Chen

doi:10.3389/fchem.2022.977419

Alendronate-functionalized double network hydrogel scaffolds for effective osteogenesis

Front Chem. 2022 Aug 17:10:977419. doi: 10.3389/fchem.2022.977419. eCollection 2022.

Authors

Guoke Tang^{1

2}, Liang Zhu², Weiheng Wang¹, Dongqing Zuo², Changgui Shi¹, Xiaojie Yu³, Rui Chen¹

Affiliations

¹ Department of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, China.
² Department of Orthopedics, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
³ Department of Orthopedics, Hunan Aerospace Hospital, Changsha, Hunan, China.

Abstract

Development of artificial bone substitutes mimicking the extracellular matrix is a promising strategy for bone repair and regeneration. In views of the actual requirement of biomechanics, biodegradability, and bioactivity, herein, a double-network (DN) hydrogel was constructed by interspersing a methacrylated gelatin (GelMA) network into alendronate (ALN)-modified oxidized alginate (OSA) network via Schiff base reaction and photo-crosslinking process to promote in situ bone regeneration. This GelMA@OSA-ALN DN hydrogel possessed favorable network and pores, good biocompatibility, and enhanced biomechanics. Notably, the introduction of Schiff base furnished the ND hydrogel scaffold with pH-responsive biodegradation and sustained ALN drug release delivery, which could provide effective bioactivity, upregulate osteogenesis-related genes, and promote the cell viability, growth, proliferation, and osteogenesis differentiation for bone regeneration. Therefore, we provide a new insight to develop functional DN hydrogel scaffold toward governing the on-demand drug release and achieving the stem cell therapy, which will be developed into the minimally invasive gelling system to prolong local delivery of bisphosphonates for the bone-related diseases.

Keywords: ALN; DN hydrogel; GelMA; OSA; osteogenic differentiation; schiff base.