Bisphosphonate-Conjugated Photo-Crosslinking Polyanionic Hyaluronic Acid Microbeads for Controlled BMP2 Delivery and Enhanced Bone Formation Efficacy

Abstract

In this study, we designed bisphosphonate-conjugated polyanionic hyaluronic acid (HA) microbeads (MBs) for the controlled delivery of bone morphogenetic protein 2 (BMP2). MBs were prepared via the photo-crosslinking of bisphosphonate (alendronate)-conjugated methacrylated HA (Alen-MHA). The polyanionic Alen-MHA MBs actively absorbed cationic BMP2 up to 91.0% of the loading efficacy and displayed a sustained release of BMP2 for 10 days. BMP2/Alen-MHA MBs induced osteogenicrelated genes in cellular experiments and showed the highly increased bone formation efficacy in thigh muscle injection and rat spinal fusion animal models. Thus, BMP2/Alen-MHA MBs provide a promising opportunity to improve the delivery efficiency of BMP2.

The hyaluronic acid gel promotes the formation of osteoblasts mineralized nodules and fracture callus by regulating the expression of Runx2 and osteocalcin

“…Fractures are usually divided into two types: closed and open (19). A closed fracture is a fracture of the bone but not of the skin; In open fractures, the skin is penetrated, leaving the bone exposed (20). Fracture healing is usually divided into three stages: the inflammatory stage, the repair and can mimic the function of extracellular matrix (27,28).…”

Current Understanding of the Applications of Photocrosslinked Hydrogels in Biomedical Engineering

“…Jenjob et al prepared microspheres by photocrosslinking bisphosphonates (alendronate) with methyl methacrylate-modified hyaluronic acid. The adsorption efficiency of the microspheres for cationic bone morphogenetic protein 2 (BMP2) reached 91.0% [50]. Chitosan is formed by removing some acetyl groups from the natural polysaccharide chitin.…”

Biomaterials and Extracellular Vesicle Delivery: Current Status, Applications and Challenges

“…Additionally, anti-oxidants [ 115 ], flavonols [ 116 ], anti-photoaging agents [ 117 ], and peptides [ 118 ] have been delivered using HA. Furthermore, HA has been used to deliver cells (including cell secretome) [ 119 , 120 ], genetic material [ 112 ], growth factors [ 102 , 121 ], and hormones [ 122 ].…”