Bisphosphonate-functionalized poly(amido amine) crosslinked 2-hydrox-yethyl methacrylate hydrogel as tissue engineering scaffold


Guven M. N., Balaban B., Demirci G., Acar H. Y., Okay O., AVCI SEMİZ D.

EUROPEAN POLYMER JOURNAL, vol.159, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 159
  • Publication Date: 2021
  • Doi Number: 10.1016/j.eurpolymj.2021.110732
  • Journal Name: EUROPEAN POLYMER JOURNAL
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, Aerospace Database, Chemical Abstracts Core, Communication Abstracts, INSPEC, Metadex, Civil Engineering Abstracts
  • Keywords: Hydrogels, Bisphosphonates, Poly(amido amine)s, Biomineralization, Crosslinker, STEM-CELL DIFFERENTIATION, HYALURONIC-ACID HYDROGEL, IN-VITRO, BONE, MINERALIZATION, HYDROXYAPATITE, POLYMERS, BIOMINERALIZATION, CALCIFICATION, DEGRADATION
  • Istanbul Technical University Affiliated: Yes

Abstract

The first water soluble, bisphosphonate (BP, not bisphosphonic acid)-functionalized poly(amido amine) macromer (PAA-BP) is synthesized and used as a crosslinker for synthesis of a biodegradable and biocompatible hydrogel for tissue engineering scaffolds. The synthesis of PAA-BP is performed in three steps, the first two giving the control macromers (PAA-NHBoc and PAA-NH2): i) Michael addition reaction of N,N'-methylene bisacrylamide and N-Boc-1,6-hexanediamine (acrylamide/amine ratios of 1.2), ii) deprotection of Boc-protected amine groups, iii) Michael addition reaction of the amine groups with tetraethyl vinylidene bisphosphonate. The degree of BP substitution is 50% and molecular weight of the PAA-BP macromer is found to be 4800 g/mol. These macromers are incorporated into hydrogels by copolymerization with 2-hydroxyethyl methacrylate and the influence of bisphosphonate functionality on hydrogel properties; degradation, swelling, mechanical and mineralization, is investigated. The mineralization abilities, hence the mechanical properties of the hydrogels are strongly influenced by the BP functionality; PAA-BP forming strong (E = 83 +/- 1 kPa) hydrogel-apatite composites, PAA-NH2 also working to a lesser degree (E = 54 +/- 3 kPa). Cytocompatibility of the hydrogels is observed on Saos-2 human osteosarcoma, U-2 OS human bone osteosarcoma epithelial, C2C12 mouse myoblast muscle and NIH mouse embryonic fibroblast 3T3 cells. PAA-BP crosslinked hydrogels facilitate adhesion of C2C12 cells after mineralization. In summary, BP-functionalized hydrogel may have a potential impact on bone tissue engineering.