Degradable materials for 3D tissue engineering scaffolds

Lead Research Organisation: University of Warwick
Department Name: Chemistry

Abstract

The development of bioengineered implants in which the implant is derived from the patient's own tissues and is tailored to the patients needs, represents an exciting direction for regenerative medicine. To achieve this, a vital step is the development of polymeric 3D scaffolds for tissue engineering that can ultimately degrade to leave only the bioengineered implant. Microsystems technology, specifically microstereolithography (MSL), has advanced to enable a very high level of control over the building of 3D objects. Many of the limited range of monomer resins currently available for application with MSL technologies are founded around acrylate-based technologies thus resulting in highly crosslinked acrylate-based materials that result cannot be degraded under physiological conditions. The realisation of a fully bioresorbable material would eliminate the retention of a non-natural element to the implant that can lead to rejection from the body or increased pain/irritation for the patient. The application of microstereolithography techniques with suitable monomer resins would enable the realisation of biocompatible, biodegradable, patient-tailored tissue engineering scaffolds that can act as a bioengineered living implant derived from the patient's own cells, designed to perfectly fit the area required, capable of self-maintenance thus closely resembling the natural part. This approach could potentially transform the treatment of many tissue replacement therapies, especially with respect to degenerative disorders such as back disc or bone degeneration associated with ageing. This proposal is focused on examining the synthesis of ketene acetal-based monomer resins that can be applied in photo-cured microstereolithographic resins to access polyester and poly(ortho ester) materials with huge potential application in tissue engineering and regenerative medicine.

Planned Impact

This project aims to develop a new class of degradable biomaterial with defined 3-dimensional structure using 3D rapid manufacture techniques (specifically microstereolithography). It is envisaged that the application of commercially attainable MSL systems for rapid prototyping of these new materials will ultimately enable patient specific bioengineered implants to be realized in a cost-effective and efficient manner. In the long term, control over the properties of the materials will enable them to be applied in a range of areas such as ligament/tendon replacement and intervertebral back-disc regeneration, addressing degenerative disorders associated with an ageing population and developing patient specific treatments. The derivation of the implant from the patients own cells will greatly reduce the probability of rejection, design to fit the size requirement of the patient will result in reduced irritation and degradability will result in the ability to synthesize a fully living implant. The scope of this grant application is to develop the fundamental materials technology. Nonetheless, the new materials developed herein will enable precise design of many degradable structures with controllable features that for example can be applied as degradable sutures thus enhancing the short term impact of this study.

Publications

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Description This project aimed to develop a new class of degradable biomaterial with defined 3-dimensional structure using 3D rapid manufacture techniques (specifically microstereolithography, MSL). This technique enables the layer-by-layer manufacture of 3D objects and can translate an infinite range of shapes. Ultimately, this work is focused on delivering materials that are suitable for use in bioengineered implants, whereby the implant is wholly constituted from the patient's own tissues. In order to achieve this custom design shapes will be produced based on magnetic resonance imaging (MRI) or computerised tomography (CT) scans with the implant being manufactured as required and seeded with the patient's own cells and implanted. Degradation of the biomaterial scaffold in combination with cell proliferation will result in a 'natural', fully living replacement implant that will have a high probability of acceptance, be a precise fit for the patient thus reducing irritation and will be capable of self maintenance. Development of suitable materials would enable the application of this technology in a range of clinical areas such as ligament/tendon replacement and intervertebral back-disc or bone regeneration, addressing degenerative disorders associated with an ageing population in a patient-specific manner.

A vital step in the development of this potentially transformative regenerative medicine is the development of fully degradable, biocompatible polymeric 3D scaffolds, requiring a step-change in approach on the boundaries of chemistry and mechanical engineering. This proposal has delivered materials that can be applied in 3D microstereolithography that can support cell growth and fully degrade to non-toxic by-products using poly(carbonate)s that can be crosslinked to form the appropriate structures using radical 'thiol-ene' chemistry. Furthermore, we have demonstrated the ability to use this versatile chemistry to influence the growth of human mesenchymal stem cells on different surfaces has been investigated. The highly versatile nature of these materials and the application of commercially attainable MSL systems for rapid prototyping will ultimately enable the realisation of this technology in a cost-effective and efficient manner that will further it's potential for application in the clinic as well as in many other potential applications.
Exploitation Route Through this work, we have found a way to create controllable polymer scaffolds that could be used to create advanced materials to influence cell behaviour and create a new type of patient specific tissue engineering scaffold. There is a lot of work still to do in order to translate these materials but this is underway in my lab following from this grant
Sectors Healthcare

 
Description We have built upon the work undertaken in this grant to design new materials for 3DP that are attracting significant commercial interest and will form the basis of a spin out company later this year.
First Year Of Impact 2017
Sector Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description BBSRC Grouped
Amount £332,942 (GBP)
Funding ID BB/I002286/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2011 
End 09/2014