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Can Polyurethane Biomaterials Open a New Era in Tissue Engineering?

Can polyurethane biomaterials open a new era in tissue engineering/regenerative medicine?

Tissue engineering/regenerative medicine (TERM) combines three-dimensional matrices, also known as scaffolds, cells and bioactive molecules (e.g. proteins, growth factors) to design functional constructs that have the capability to restore, maintain or improve the functionality of damaged tissues or whole organs.

The proper design of the 3D matrix that provides the structural and mechanical support to the regeneration process is a key aspect to stimulate and guide the formation of a new functional tissue. Hence, the optimal 3D scaffold should finely replicate in vitro the physico-chemical properties of the native tissue, thus inducing construct integration in the host tissue, while providing the proper cues to the cells it interacts with to guide their behaviour, cross-talk and differentiation towards to desired phenotypes.

In order to design scaffolds with the previously described properties, the selection of the raw material and the scaffolding technology is a crucial issue. Both natural and synthetic polymers have been investigated in the literature for scaffold fabrication. The former have been extensively explored for clinical application due to their high biocompatibility and the advantage of inducing a weak inflammatory response. However, they usually need to be cross-linked or blended with synthetic materials to improve their mechanical properties and modulate their degradation kinetics, and they suffer for high composition variability.

Synthetic polymers play a fundamental role in TERM as their properties make it possible to overcome some drawbacks of natural polymers; moreover, they are biocompatible and biodegradable, and show high workability and good mechanical and physical properties that can be foreseen and controlled in a reproducible manner. In this scenario, polyurethane biomaterials could gain increasing interest in the future as their highly documented chemical versatility could be successfully exploited to design polymers with conveniently tuned physico-chemical properties to meet the strict requirements for their application in TERM.

Polyurethanes (IUPAC abbreviation PUR, but commonly abbreviated PU) form a large family of polymeric materials with an enormous diversity of chemical compositions and properties. They have found wide spread application in a number of technological areas and a range of commodity products, such as polymers for clothing, automotive, footwear, furnishings, construction, paints and coatings. The wide range of properties that can be achieved with polyurethane chemistry also attracted the attention of developers of biomedical devices who saw promise in the mechanical flexibility of these materials, combined with their high tear strength. In fact, their segmented block copolymeric character endows them with a wide range of versatility in terms of tailoring their physical properties, blood and tissue compatibility, and more recently their biodegradation character. Initially, polyurethanes have been evaluated for long-term implants, such as cardiac pacemaker and vascular grafts.

However, this kind of application fell under scrutiny with the failure of pacemaker leads and breast implant coatings containing PUs in the 1980s. Knowledge gained throughout the 1990s has not only yielded novel PUs with improved biostability for in vivo long-term applications but has also been translated to form a new class of bioresorbable materials, which backbone contains chemical linkages that are biodegradable in the biological environment. Polyurethanes possess a complex structure that typically comprises three monomers a diisocyanate: a macrodiol and a chain extender. Because of these three degrees of freedom, a virtually infinite number of materials can be synthesized. Biomimetic synthetic PUs can be produced to elicit specific cellular functions and direct tissue formation mediated by biomolecular recognition. This goal can be achieved by both surface and bulk modifications with bioactive molecules that can incur specific interactions with cell receptors.

Over the last few decades, PUs have been extensively investigated in both hard and soft tissue engineering, in the form of injectable hydrogels or implantable devices (prefabricated scaffolds). In hard tissue engineering, PU-based constructs have been designed with the optimal flexibility and load bearing properties for orthopedic applications. In this context, in order to enhance the modest osteoconductivity of PU-based constructs, recent literature has explored the possibility of designing composite biomaterials based on PUs and ceramic particles, thus combining in one device the good mechanical strength of polyurethanes and the osteoconductive potential of ceramics, such as calcium phosphates.

Similarly, in soft tissue engineering, PU-based constructs with proper mechanical and structural properties have found wide application in the repair and regeneration of cardiac tissue, blood vessels, peripheral nerves and skin. Recently, PUs have been made antibacterial by (i) introducing antibacterial moieties along their backbone, (ii) loading PUs with antibacterial agents or (iii) treating construct surface to impart antibacterial potential. PUs are currently under extensive investigation in drug delivery, in the form of injectable hydrogels, including PU-based thermosensitive sol-gel systems, or nano- and micro-particles with improved encapsulation efficiency and prolonged payload release over time.

The high potential of PUs in the biomedical field also lies in their high workability. Workability makes it possible to fabricate PU-based constructs via both conventional (e.g. salt leaching, gas foaming, electrospinning, phase separation) and advanced (e.g. bioprinting, fused deposition modelling, pressure assisted micro-syringe) fabrication technologies. The proper exploitation of PU high versatility could thus lead in the future to the fabrication of the optimal scaffolds for the repair and regeneration of almost all tissues of the human body. Hence, polymers that belong to the wide family of polyurethanes could realistically open the way to a new era in the biomedical field, thanks to the possibility to synthesize ad-hoc designed biomaterials suitable to a variety of fabrication technologies and applications.

 

Monica Boffito is a Research Associate at Politecnico di Torino, Italy and works in the research group headed by Prof. Gianluca Ciardelli.

 

Monica will attend the Global Biomaterials & Tissue Engineering Congress with the presentation ‘Polyurethanes: a promising platform for tissue engineering and regenerative medicine’. To find out more, please see the agenda.

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