Preprint / Version 1

Metal Organic Framework-Incorporated Three-Dimensional (3D) Bio-Printable Hydrogels to Facilitate Bone Repair: Preparation and In Vitro Bioactivity Analysis

Authors

  • Cho-E Choi Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada
  • Aishik Chakraborty Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada
  • Hailey Adzija Department of Chemistry, The University of Western Ontario, London, ON N6A 5B9, Canada
  • Yasmeen Shamiya Department of Chemistry, The University of Western Ontario, London, ON N6A 5B9, Canada
  • Khaled Hijazi Collaborative Specialization in Musculoskeletal Health Research and Bone and Joint Institute, The University of Western Ontario, London, ON N6A 5B9, Canada
  • Ali Coyle School of Biomedical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada
  • Amin Rizkalla Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada
  • David Holdsworth Department of Medical Biophysics, The University of Western Ontario, London, ON N6A 5B9, Canada
  • Arghya Paul Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada

Keywords:

nanocomposite hydrogels, bone repair, regenerative medicine, 3D printing, stem cells

Abstract

Hydrogels are three-dimensional (3D) water-swellable polymeric matrices that are used extensively in tissue engineering and drug delivery. Hydrogels can be conformed into any desirable shape using 3D bio-printing, making them suitable for personalized treatment. Among the different 3D bio-printing techniques, digital light processing (DLP)-based printing offers the advantage of quickly fabricating high resolution structures, reducing the chances of cell damage during the printing process. Here, we have used DLP to 3D bio-print biocompatible gelatin methacrylate (GelMA) scaffolds intended for bone repair. GelMA is biocompatible, biodegradable, has integrin binding motifs that promote cell adhesion, and can be crosslinked easily to form hydrogels. However, GelMA on its own is incapable of promoting bone repair and must be supplemented with pharmaceutical molecules or growth factors, which can be toxic or expensive. To overcome this limitation, we introduced zinc-based metal-organic framework (MOF) nanoparticles into GelMA that can promote osteogenic differentiation, providing safer and more affordable alternatives to traditional methods. Incorporation of this nanoparticle into GelMA hydrogel has demonstrated significant improvement across multiple aspects, including bio-printability, and favorable mechanical properties (showing a significant increase in the compressive modulus from 52.14 ± 19.42 kPa to 128.13 ± 19.46 kPa with the addition of ZIF-8 nanoparticles). The designed nanocomposite hydrogels can also sustain drug (vancomycin) release (maximum 87.52 ± 1.6% cumulative amount) and exhibit a remarkable ability to differentiate human adipose-derived mesenchymal stem cells toward the osteogenic lineage. Furthermore, the formulated MOF-integrated nanocomposite hydrogel offers the unique capability to coat metallic implants intended for bone healing. Overall, the remarkable printability and coating ability displayed by the nanocomposite hydrogel presents itself as a promising candidate for drug delivery, cell delivery and bone tissue engineering applications. Keywords: nanocomposite hydrogels, bone repair, regenerative medicine, 3D printing, stem cells

Author Biographies

Aishik Chakraborty, Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada

Collaborative Specialization in Musculoskeletal Health Research and Bone and Joint Institute, The University of Western Ontario, London, ON N6A 5B9, Canada

Khaled Hijazi, Collaborative Specialization in Musculoskeletal Health Research and Bone and Joint Institute, The University of Western Ontario, London, ON N6A 5B9, Canada

School of Biomedical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada

Amin Rizkalla, Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada

Dentistry, The University of Western Ontario, London, ON N5A 5B9, Canada

Arghya Paul, Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada

School of Biomedical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada

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