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Hamilton, Lloyd George (2009) New injectable scaffolds for cell and drug delivery. PhD thesis, University of Nottingham.

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Abstract

An injectable scaffold system for the delivery of cells and growth factors was developed in this project to enhance healing of bone fractures. The project was focused to meet the clinical need for an off-the-shelf synthetic biodegradable bone graft material. The concept required the injection of a paste to fill defects then rapidly solidify to a mechanically supportive macroporous structure. The injectable paste was developed from a two-component biodegradable microparticle scaffold based on poly(lactic-co-glycolic acid) (PLGA) and comprised of a versatile temperature insensitive (type 1) carrier and an adhesive (type 2) component made temperature sensitive with the addition of poly(ethylene glycol) (PEG) as a plasticizer. The plasticized adhesive type 2 component achieved wet compressive strengths up to 18 MPa at 37 °C after 24 hours. The sintering strategy utilised the changes in viscoelastic and mechanical properties that occur in the glass transition region of amorphous polymers. The specific mechanism devised in this thesis exploited the biocompatibility and diffusivity of PEG to increase polymer glass transition temperature in the wet sintering process.

The solidification speed was demonstrated by rheological assessment of storage modulus and wet compressive strengths up to 2 MPa after 15 minutes at 37 °C. Restricting particle size distribution to narrow 100 µm bands controlled porosity between 35-65%. The interconnectivity of the macroporous structures was demonstrated by the invasion of 3T3 cells seeded on the outer surface of the scaffold and evaluated by microcomputed tomography. The innocuous nature of the solidification process was demonstrated by the survival and proliferation of in situ seeded primary human fibroblasts, osteoblasts and murine C2C12 cells. The multifunctional type 1 component acted as a porous spacer, protein delivery vehicle and cell carrier when modified with polyethylenimin. The potential use of the scaffold as a controlled delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2) was demonstrated by the sustained differentiation of murine C2C12 myoblast to osteogenic alkaline phosphatase positive cells over 28 days.

In this thesis a novel sintering mechanism has been developed that facilitates control of pore size and porosity of injectable scaffolds. The benign nature of the process facilitates the potential use of this injectable system as a delivery vehicle for cell and growth factor therapy.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Shakesheff, K.M.
Keywords:	Regenerative medicine, cell delivery, drug delivery, injectable scaffold, BMP-2, bone, osteoblast, PLGA
Subjects:	R Medicine > R Medicine (General) > R855 Medical technology. Biomedical engineering. Electronics
Faculties/Schools:	UK Campuses > Faculty of Science > School of Pharmacy
Item ID:	11017
Depositing User:	EP, Services
Date Deposited:	25 Feb 2010 09:30
Last Modified:	19 Oct 2017 11:33
URI:	https://eprints.nottingham.ac.uk/id/eprint/11017

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