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(BBSRC DTP CASE) Jellyfish-collagen hydrogels for culture and differentiation of human mesenchymal stem cells and 3D cartilage bioprinting


Project Description

We are looking for an enthusiastic and talented graduate from a relevant biomedical or materials science degree to develop next-generation, sustainable collagen-based scaffolds for stem cell culture, differentiation, and 3D bioprinting, aimed at tissue regeneration applications. Tissues such as cartilage have limited capacity of regeneration due to low cell content and vascularisation. Replacement of the diseased or damaged tissues with laboratory-grown/3D printed substitutes or addition of pluripotent/multipotent cells to promote repair are possible strategies. Collagen-based substrates and scaffolds provide the right environment to support cell proliferation and differentiation, critical to the regeneration process. Often the collagen used in these applications is of mammalian origin (bovine, murine, porcine), with the concomitant risks of zoonotic disease transmission and additional problems derived from heterogeneity, batch-to-batch consistency and cultural and religious issues. In this project we collaborate with Jellagen Marine Technologies (www.jellagen.co.uk), a company that manufactures collagen extracted from a jellyfish that is abundant in the Atlantic. Jellyfish collagen shows similarity to vertebrate fibrillar collagens and represents an attractive alternative substrate for cell culture applications. Jellyfish collagen is free from prions and other disease vectors, is biocompatible, has low immunogenicity profile, shows better batch-to-batch consistency than vertebrate collagen, and is compatible with existing cell culture methodologies.
The aim of the project is to explore newly developed jellyfish collagen hydrogels as substrates for the culture and differentiation of human mesenchymal stem cells (hMSCs). We want to investigate the optimal conditions to induce chondrogenic differentiation of these hMSCs in a 3D jellyfish collagen scaffold and later develop the material as a bioink for 3D bioprinting of cartilage. The ultimate goal is producing engineered cartilage to replace tissue damaged by degenerative conditions such as osteoarthritis or intervertebral disc degeneration.
The project will provide training in biomaterial preparation, modification and characterisation, stem cell culture and differentiation, 3D bioprinting, quantitative PCR, flow cytometry, confocal and fluorescence microscopy, metabolic assays, immunocytochemistry, histology and atomic force microscopy. As part of the CASE agreement with Jellagen the student will spend some research time on the company premises. This will enhance the student understanding of the commercial applications of jellyfish collagen and the landscape of hydrogel commercial uses in tissue regeneration.

http://www.manchester.ac.uk/research/jordi.bella
http://www.manchester.ac.uk/research/s.richardson
http://www.manchester.ac.uk/research/marco.domingos
http://www.jellagen.co.uk

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Hodgkinson T, Stening JZ, White LJ, Shakesheff KM, Hoyland JA, Richardson SM (2019). Microparticles for controlled growth differentiation factor 6 delivery to direct adipose stem cell-based nucleus pulposus regeneration. J Tissue Eng Regen Med (2019), 13: 1406-1417
Raphael B, Khalil T, Workman VL, Smith A, Brown CP, Streuli C, Saiani A, Domingos M (2017). 3D cell bioprinting of self-assembling peptide-based hydrogels. Materials Lett, 190: 103-106
Pugliano M, Vanbellinghen X, Schwinte P, Benkirane-Jessel N, Keller L (2017). Combined jellyfish collagen type II, human stem cells and TGF-β3 as a therapeutic implant for cartilage repair. J Stem Cell Ther, 7: 4
Bella J and Hulmes DJ (2017). Fibrillar collagens. Subcell Biochem, 82: 457-490
Bella J (2016). Collagen structure: new tricks from a very old dog. Biochem J, 473: 1001-1025

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