Development, characterization and encapsulation of drug loaded microgels in bioinks aimed at dentoalveolar bioprinting

Efficient delivery of growth factors and signaling molecules has an important impact on the outcome of tissue engineering strategies. However, maintaining the optimum concentration of such molecules is a challenge due to the short biological half-life on one hand, and the possibility of uncontrolled differentiation, inflammation and carcinogenicity on the other hand. While bioprinting has led to significant hope in regeneration strategies aimed at dentoalveolar region, inherent complexity and heterogeneity of these tissues highlights the demand for controlled delivery of targeted signaling molecules.

While various release systems, have been designed to be incorporated in tissue engineering scaffolds, poly-n-isopropylacrylamide (pNIPAM) based microgels are interesting considering their highly controllable properties and their ability to be incorporated in 3D bioprinting strategies. In this study, pNIPAM-based microgels were developed and characterized using a factorial design of experiments, and were encapsulated in bioinks for bioprinting of dentoalveolar tissues.

For this purpose, methylcellulose was selected as a co-monomer to induce degradability, considering its limited functional groups preventing reactions with the drugs, and novel pNIPAM-methylcellulose microgels have been synthesized through a one-step precipitation polymerization. Genipin, a natural compound known to promote odontoblastic differentiation of dental pulp stem cells, was used as a model drug to be encapsulated in the microgels, and a factorial set of experiments was designed to evaluate the effects of different synthesis parameters on final properties of the microgels.

The microgels were then encapsulated in gelMA for extrusion 3D bioprinting, and the bioprinted constructs were evaluated to analyze the effect of the drug delivery systems incorporated. The results determined optimum conditions for drug loading and sustained release from the microgels, leading to opportunities for addressing biological heterogeneity of dentoalveolar tissues in bioprinting strategies through incorporation of tissue specific factors, further enhancing capability of bioprinting to address complexities of natural tissues.

A presentation by Mehdi Salar Amoli, PhD candidate, Surface and Interface Engineered Materials (SIEM), KU Leuven / OMFS IMPATH Research Group, Faculty of Medicine, Department of Imaging and Pathology, KU Leuven and Oral and Maxillofacial Surgery, University Hospitals Leuven.

About Mehdi Salar Amoli
I am a PhD candidate at Surface and Interface Engineered Materials and OMFS-IMPATH, KU Leuven, supervised by Prof. Veerle Bloemen and Prof. Reinhilde Jacobs. I studied biomaterials and tissue engineering at Amirkabir University of Technology, Iran, working on multiphasic chitosan scaffolds for cartilage regeneration. Further, I obtained my master’s degree at Imperial College London in biomaterials and tissue engineering, and worked under supervision of Prof. Molly Stevens on developing non-viral methods for nucleic acid delivery to the cells. I am currently working on development of bioinks for regeneration of the heterogeneous dentoalveolar tissues through bioprinting cell encapsulated materials.

About KU Leuven, OMFS-IMPATH research group
The OMFS-IMPATH research group relates to the development and validation of surgical tools and image-based solutions to advance in oromaxillofacial surgery, with an ultimate aim to obtain an optimized treatment outcome while minimizing the peri- and postsurgical risks, such as neurovascular trauma.

In order to achieve this, global integration of digital datasets will enable the creation of a virtual replica of the patient. This may allow full simulation of the surgery as well as of its expected outcome. While the latter may help to further modify and finetune the planned surgery, the former integrated virtual data may allow presurgical simulations, development of image-based surgical tools, and navigation.

Mehdi Salar Amoli is speaker at the 2022 edition of the 3D BioPrinting Conference.

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