Methacrylation increase growth and differentiation of primary human osteoblasts for gelatin hydrogels
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ORIGINAL ARTICLE
Methacrylation increase growth and differentiation of primary human osteoblasts for gelatin hydrogels Mousumi Sukul 1 & Giuseppe Cama 2,3 & Peter Dubruel 2 & Janne Elin Reseland 1 & Håvard J. Haugen 1 Received: 22 January 2020 / Accepted: 15 April 2020 # The Author(s) 2020
Abstract The role of gelatin methacrylate hydrogels with varying degrees of methacrylation (69% and 84%) was accessed with FTIR, NMR, microCT, and subsequent exposure to human osteoblasts. The cells responded positively to the degree of methacrylation and showed attachment, growth, and proliferated on both hydrogels. The cell reacted differently to the degree of methacrylation with higher proliferation on higher substitution; however, cell differentiation behavior was improved for less substitution. The secretion of late osteogenic markers (osteoprotegerin (OPG), osteopontin (OPN), and osteocalcin (OCN)) and angiogenic factor vascular endothelial growth factor (VEGF) was increased for gelatin methacrylate hydrogels with 69% degree of methacrylation and thus would be the better candidate for future bone regenerative applications amongst the three tested hydrogels.
1 Introduction Hydrogels, a specific class of hydrated polymers, are potential candidates for bone augmentation. Hydrogels can mimic the extracellular matrix of bone and integrate well with surrounding tissue, allowing a stabilized anchorage with host bone [1, 2]. They are degradable by endogenous enzymes or hydrolysis, which renders them the advantage of avoiding the complicacy of surgical removal of the implant and subsequent inflammation [3, 4]. In the water-rich environment, hydrogels form a fibrous network, presenting the ability to entrap bioactive molecules and control the release as required to promote the healing process [5–7]. Flexible polymer chains of hydrogels enable them to be easily tailored to obtain required forms and shapes for implantation. Concentration of polymers, crosslinkers, and degree of crosslinking allows for the
* Håvard J. Haugen [email protected] 1
Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Blindern, P.O. Box 1109, 0317 Oslo, Norway
2
Polymer Chemistry & Biomaterials Group (PBM), Centre of Macromolecular Chemistry, Department of Organic and Macromolecular Chemistry, Ghent University, S4-Bis Krijgslaan 281, 9000 Ghent, Belgium
3
CAM Bioceramics B.V., Zernikedreef 6, 2333 CL Leiden, The Netherlands
control over the physical properties of hydrogels such as pore size, porosity, rigidity, and degradation [8, 9]. Gelatin is a natural hydrophilic polymer well known for its use in different areas of tissue engineering including skin, neuron, cartilage, and bone [10–13]. Rising interesting in gelatin-based biomaterials is because of the fact that they are biocompatible, non-antigenic, and biodegradable [14, 15]. Due to the presence of a large number of functional groups in the side chains, gelatin readily binds to chemical crosslinkers [16, 17]. Bulcke et al. developed a methacrylic anhydride cro
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