Versatile-in-All-Trades: Multifunctional Boron-Doped Calcium-Deficient Hydroxyapatite Directs Immunomodulation and Regeneration


PAZARÇEVİREN A. E. , Akbaba S., EVİS Z., TEZCANER A.

ACS Biomaterials Science and Engineering, vol.8, no.7, pp.3038-3053, 2022 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 8 Issue: 7
  • Publication Date: 2022
  • Doi Number: 10.1021/acsbiomaterials.2c00242
  • Journal Name: ACS Biomaterials Science and Engineering
  • Journal Indexes: Science Citation Index Expanded, Scopus, BIOSIS, Chemical Abstracts Core, Compendex, EMBASE, MEDLINE
  • Page Numbers: pp.3038-3053
  • Keywords: boron, hydroxyapatite/tricalcium phosphate, immunomodulation, angiogenesis, osteogenesis, PHYSICOCHEMICAL PROPERTIES, DIFFERENTIATION, BIOCOMPATIBILITY, VASCULARIZATION, ANTIBACTERIAL, ANGIOGENESIS, OSTEOGENESIS, MACROPHAGES, MIGRATION, STRONTIUM

Abstract

© 2022 American Chemical Society. All rights reserved.Osseointegration of implants depends on several intertwined factors: osteogenesis, angiogenesis, and immunomodulation. Lately, novel reinforcements allowing faster bonding with osseous tissue have been explored intensively. In this study, we hypothesized the use of boron as a major multifunctional ion to confer versatility to calcium-deficient hydroxyapatite (cHA) synthesized by a wet precipitation/microwave reflux method. By synthesis of boron-doped calcium-deficient hydroxyapatite (BcHA), we expected to obtain an osteoimmunomodulatory and regenerative nanoreinforcement. BcHA was found to possess a pure HA phase, a greater surface area (66.41 m2/g, p = 0.028), and cumulative concentrations of Ca (207.87 ± 6.90 mg/mL, p < 0.001) and B (112.70 ± 11.79 mg/mL, p < 0.001) released in comparison to cHA. Osteogenic potential of BcHA was analyzed using human fetal osteoblasts. BcHA resulted in a drastic increase in the ALP activity (1.11 ± 0.11 mmol/gDNA·min, p < 0.001), biomineralization rate, and osteogenic gene expressions compared to cHA. BcHA angiogenic potential was investigated using human umbilical cord vein endothelial cells. Significantly, the highest VEGF-A release (1111.14 ± 87.82 in 4 h, p = 0.009) and angiogenic gene expressions were obtained for BcHA-treated samples. These samples were also observed to induce a more prominent and highly branched tube network. Finally, inflammatory and inflammasome responses toward BcHA were elucidated using human monocyte-derived macrophages differentiated from THP-1s. BcHA exhibited lower CAS-1 release (50.18 ± 5.52 μg/gDNAμg/gDNA) and higher IL-10 release (126.97 ± 15.05 μg/gDNA) than cHA. In addition, BcHA treatment led to increased expression of regenerative genes such as VEGF-A, RANKL, and BMP-2. In vitro results demonstrated that BcHA has tremendous osteogenic, angiogenic, and immunomodulatory potential to be employed as a "versatile-in-all-trades" modality in various bone tissue engineering applications.