Pullulan microcarriers for bone tissue regeneration

https://doi.org/10.1016/j.msec.2016.03.002Get rights and content

Highlights

  • Porous PULL microspheres were prepared as cell carrier for the first time.

  • Mineralization on the microspheres improved their mechanical properties.

  • Mineralization and SF coating enhanced cell proliferation on PULL microspheres.

Abstract

Microcarrier systems offer a convenient way to repair bone defects as injectable cell carriers that can be applied with small incisions owing to their small size and spherical shape. In this study, pullulan (PULL) microspheres were fabricated and characterized as cell carriers for bone tissue engineering applications. PULL was cross-linked by trisodium trimetaphosphate (STMP) to enhance the stability of the microspheres. Improved cytocompatibility was achieved by silk fibroin (SF) coating and biomimetic mineralization on the surface by incubating in simulated body fluid (SBF). X-ray diffraction (XRD), scanning electron microscopy (SEM) and fluorescent microscopy analysis confirmed biomimetic mineralization and SF coating on microspheres. The degradation analysis revealed that PULL microspheres had a slow degradation rate with 8% degradation in two weeks period indicating that the microspheres would support the formation of new bone tissue. Furthermore, the mechanical tests showed that the microspheres had a high mechanical stability that was significantly enhanced with the biomimetic mineralization. In vitro cell culture studies with SaOs-2 cells showed that cell viability was higher on SF and SBF coated microspheres on 7th day compared to PULL ones under dynamic conditions. Alkaline phosphatase activity was higher for SF coated microspheres in comparison to uncoated microspheres when dynamic culture condition was applied. The results suggest that both organic and inorganic surface modifications can be applied on PULL microspheres to prepare a biocompatible microcarrier system with suitable properties for bone tissue engineering.

Keywords

Pullulan
Bone tissue engineering
Microspheres
Biomimetic mineralization
SF coating

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M.Sc. Hazal Aydogdu is a Research Assistant and Doctorate student of Biomedical Engineering Department at Middle East Technical University. She received her Bachelor's degree in Biology Department and Master's Degree in Biomedical Engineering Department from Middle East Technical University. Her current research interests include the polymeric biomaterials for bone tissue engineering, biomimetic mineralization of materials for biomedical applications.

Dr. Dilek Keskin is currently employed as a full time faculty in Department of Engineering Sciences, METU and also as a member of administrative board of Center of Excellence in Biomaterials and Tissue Engineering, Turkey. She has published 26 papers and 5 book chapters in international journals and books. Her PhD and MSc studies were on controlled drug delivery systems. Her current research interests include polymeric micro and nano drug delivery systems, liposomal systems for targeted drug delivery, biomaterials for skin, bone and cartilage tissue engineering, in vitro and in vivo disease models and regenerative approaches related to them.

Dr. E.T. Baran is currently employed as a Post Doctorate researcher at METU Center of Excellence in Biomaterials and Tissue Engineering, Turkey. He has published 24 papers in international peer reviewed journals, 6 book chapters and has international 1 international patent. His previous studies focused on the application of hydroxyalkonate biopolymers in drug delivery and the use of biological origin polymers for tissue engineering applications. His current research interests include polymer processing, micro-fabrication techniques, synthesis of self-assembly biopolymers, surface modification of biomaterials for cell guidance and using microfabrication techniques for encapsulation of cells and drugs.

Dr. Ayşen Tezcaner is a full faculty member of Department of Engineering Sciences, METU. She is also affiliated in Department of Biotechnology and Department of Biomedical Engineering. She is a member of administrative board of Center of Excellence in Biomaterials and Tissue Engineering of METU. She has published 33 papers in international peer reviewed journals, 5 book chapters. Her current research interests are microcarrier systems and porous three dimensional scaffolds for engineering cartilage, bone and adipose tissue, polymeric nano/μ drug delivery systems.

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