Dual Effect of Curcumin/BMP-2 Loaded in HA/PLL Hydrogels on Osteogenesis In Vitro and In Vivo

Abstract

In the present study, we evaluated the potential of poly-l-lysine/hyaluronic acid (HA/PLL) hydrogels containing curcumin (CUR) and bone morphogenetic protein-2 (BMP-2) as bone tissue regeneration scaffolds. Hydrogels HP-1˜2 were formed by amide bonds via the condensation reactions between 0.02 μmol HA and 0.06–0.12 μmol poly-l-lysine · hydrobromide (PLL · HBr). Physical, chemical, and thermal analyses revealed that the amount of PLL · HBr significantly influenced hydrogel properties. Based on an In Vitro MG-63 cell proliferation test, HP-1˜2 were cytocompatible, and all hydrogels containing different amounts of CUR and BMP-2, except for HA0.02/PLL0.06/CUR20/BMP-2100 (HPCB-4), resulted in cell proliferation above 80%. An In Vitro release test showed that CUR and BMP-2 were consistently released from HA0.02/PLL0.06/CUR15 (HPC), HA0.02/PLL0.06/BMP-2100 (HPB), HA0.02/PLL0.06/CUR15/BMP-210 , 50 , or 100 (HPCB-1˜3), and HA0.02/PLL0.06/CUR10 or 20/BMP-2100 (HPCB-4˜5) for 7 and 28 days, respectively. In Vitro ALP activity and calcium deposition and In Vivo micro-computed tomography (micro-CT) tests demonstrated the potential application of HPCB-3 as bone tissue regeneration scaffolds, suggesting that bone tissue regeneration can be optimized by controlling the amounts of CUR and BMP-2.

Natural and Synthetic Polymers for Bone Scaffolds Optimization

“…Human osteosarcoma derived cells exhibited good viability, proliferation, ALP activity and calcium deposition. In comparison with other polymers, the high bone formation induced by low burst followed by sustained release, guaranteed good results in in vivo tests, too [105,106]. In another study, the hyaluronic acid has been combined with chondroitin 6 sulphate and dermatan sulphate.…”

IL‑17F promotes osteoblastic osteogenesis via the MAPK/ERK1/2 signaling pathway

“…BMP-2 is one the most widely studied BMPs with the most potent bone inductive activity and has been reported to induce osteogenic differentiation in vitro ( 39 , 40 ) and bone formation in vivo ( 41 ). The BMP-2 signaling pathway is a vital positive modulator of bone homeostasis ( 42 , 43 ). BMP-2 binding to its receptors regulates target genes, such as Runx2 and Osterix ( 44 ).…”

Traditional Chinese Medicine Compound-Loaded Materials in Bone Regeneration

“…However, the bioavailability of curcumin is limited due to low aqueous solubility, extremely rapid systemic elimination, and inadequate tissue absorption and degradation (Anand et al, 2007). The high concentration of curcumin caused by inappropriate release behavior is not conducive to cell adhesion and proliferation (Scharstuhl et al, 2009;Jain et al, 2016;Kim et al, 2017). Therefore, the bioavailability and sustained-release kinetics of curcumin have been improved through biomaterial-based administration methods used for the inhibition of osteoclasts and osteosarcoma (Dhule et al, 2012;Heo et al, 2014;Chen X. et al, 2015;Kheiri Manjili et al, 2017;Verma et al, 2019) (Figure 2).…”

“…A study demonstrated that various amounts of curcumin/ BMP-2-loaded poly-L-lysine/hyaluronic acid hydrogels resulted in increased MG-63 cell proliferation after 3 days of culture, and by controlling the amounts of curcumin and BMP-2, the hydrogels showed better osteogenesis with higher in vitro ALP activity and calcium deposition and better in vivo new bone regeneration, as shown by micro-CT analyses. Notably, the incorporation of greater than 15 μM curcumin had negative effects on the proliferation of human osteosarcoma MG-63 cells (Kim et al, 2017). Successful treatment of osteosarcoma requires postsurgical bone defect repair as well as the complete eradication of bone tumor cells in the surrounding tissues (Ma et al, 2018).…”