Composite clinoptilolite/PCL-PEG-PCL scaffolds for bone regeneration: In vitro and in vivo evaluation

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Pazarçeviren A. E., Dikmen T., Altunbas K., Yaprakci V., Erdemli O., Keskin D., ...More

JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, vol.14, pp.3-15, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 14
  • Publication Date: 2020
  • Doi Number: 10.1002/term.2938
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, BIOSIS, EMBASE, INSPEC, MEDLINE
  • Page Numbers: pp.3-15
  • Keywords: bone union, clinoptilolite, cortex development, PCL-PEG-PCL, zeolite, press-fit scaffold, OSTEOGENIC DIFFERENTIATION, NANOCLAYS, COPOLYMER, MEMBRANES, RELEASE, MATRIX
  • Middle East Technical University Affiliated: Yes


In this study, clinoptilolite (CLN) was employed as a reinforcement in a polymer-based composite scaffold in bone tissue engineering and evaluated in vivo for the first time. Highly porous, mechanically stable, and osteogenic CLN/PCL-PEG-PCL (CLN/PCEC) scaffolds were fabricated with modified particulate leaching/compression molding technique with varying CLN contents. We hypothesized that CLN reinforcement in a composite scaffold will improve bone regeneration and promote repair. Therefore, the scaffolds were analyzed for compressive strength, biodegradation, biocompatibility, and induction of osteogenic differentiation in vitro. CLN inclusion in PC-10 (10% w/w) and PC-20 (20% w/w) scaffolds revealed 54.7% and 53.4% porosity, higher dry (0.62 and 0.76 MPa), and wet (0.37 and 0.45 MPa) compressive strength, greater cellular adhesion, alkaline phosphatase activity (2.20 and 2.82 mg/g(DNA)/min), and intracellular calcium concentration (122.44 and 243.24 g Ca/mg(DNA)). The scaffolds were evaluated in a unicortical bone defect at anterior aspect of proximal tibia of adult rabbits 4 and 8 weeks postimplantation. Similar to in vitro results, CLN-containing scaffolds led to efficient regeneration of bone in a dose-dependent manner. PC-20 demonstrated highest quality of bone union, cortex development, and bone-scaffold interaction at the defect site. Therefore, higher CLN content in PC-20 permitted robust remodeling whereas pure PCEC (PC-0) scaffolds displayed fibrous tissue formation. Consequently, CLN was proven to be a potent reinforcement in terms of promoting mechanical, physical, and biological properties of polymer-based scaffolds in a more economical, easy-to-handle, and reproducible approach.