Controlled Delivery of Epigallocatechin Gallate, Gingerol, Curcumin and Vitamin D3 from Calcium Phosphate Matrix for Bone Tissue Engineering

Yongdeok  Jo

doi:10.7273/000006383

This study aims to understand the potential effects of epigallocatechin gallate (EGCG), ginger extract, curcumin, and vitamin D3 release from calcium phosphate-based matrices on in vitro and in vivo biological properties for bone tissue engineering applications. For critical-sized bone defects caused by trauma or the removal of a tumor, a localized drug delivery system with calcium phosphates (CaPs) is suggested because of its osteoconductivity and osteointegration ability. The three-dimensional printed (3DP) tricalcium phosphate (TCP) is designed for customized implants in low load-bearing sites, while plasma-sprayed hydroxyapatite (HA) coated Ti6Al4V (Ti64) is designed for load-bearing implant applications. These implant systems incorporate natural medicinal compounds and magnesium oxide (MgO) dopant to improve their biological and mechanical properties. EGCG-loaded 3DP TCP scaffolds significantly improve in vitro osteogenesis, anti-osteoclastogenesis, chemoprevention, and vasculogenesis. EGCG increases runt-related transcription factor 2 (RUNX2) and bone gamma-carboxyglutamic acid-containing protein (BGLAP) gene expressions over 16 days, leading to osteoblast differentiation. However, it downregulates the receptor activator of nuclear factor-κB ligand (RANKL), suggesting that RANKL-induced osteoclast differentiation is suppressed. Curcumin is incorporated with CaP matrices to enhance osteogenesis in critical-sized rabbit distal femur model defects. Curcumin functionalized implants also have osteogenesis, anti-cancer and anti-microbial properties in vitro. The biological properties of curcumin further improve when it is incorporated with vitamin D3. The dual drug delivery system shows synergistic bone regeneration in an in vivo rat distal femur critical-sized defect model. Vitamin D3 shows in vitro osteogenesis by upregulating genes related to osteoblastogenesis while downregulating RANKL. When vitamin D3 is incorporated with MgO-doped TCP scaffolds, the functionalized TCP scaffolds improve in vitro osteoblast proliferation by 1.4-fold, compared to the control at day 11. However, the release of vitamin D3 from MgO-doped TCP scaffolds reduces osteoclast viability by 1.9-fold on day 21. Vitamin D3-loaded MgO-doped scaffolds also enhance new bone formation and angiogenic potential in the in vivo rat model. In the presence of ginger extract, the 3DP TCP scaffolds also enhance in vitro human fetal osteoblast cell viability by 1.3-fold on day 11. The ginger extract release inhibits in vitro osteoclast differentiation by reducing RANKL expression. Based on our results, natural medicinal compounds' laden-calcium phosphate-based substrates can promote bone healing while promoting anti-cancer and infection control properties, making it one of the potential candidates for functionalized implants.

Controlled Delivery of Epigallocatechin Gallate, Gingerol, Curcumin and Vitamin D3 from Calcium Phosphate Matrix for Bone Tissue Engineering

Files and links (1)

Abstract

Metrics

Details