Research activities

• Wet-spinning of collagen-derived polypeptides with varied molecular weight

The formation of naturally-derived materials with wet stable fibrous architectures is paramount in order to mimic the features of tissues at the molecular and microscopic scale. Here, we investigated the formation of wet-spun fibres based on collagen-derived polypeptides with comparable chemical composition and varied molecular weight. Gelatin (G) and hydrolysed fish collagen (HFC) were selected as widely-available linear amino-acidic chains of high and low molecular weight, respectively, and functionalised in the wet-spun fibre state in order to preserve the material geometry in physiological conditions. Wet-spun fibre diameter and morphology were dramatically affected depending on the polypeptide molecular weight, wet-spinning solvent and coagulating medium, resulting in either bulky or porous internal geometry.

Both gelatin and HFC solutions were coagulated in specific non-solvents via a syringe pump. Resulting fibres were crosslinked with NHS-activated 1,3-phenylenediacetic acid, showing preserved hydrated morphology. These wet-stable fibres could be used as building block for the design of biomimetic fabric.

• Multi-scale characterisation of highly swollen collagen hydrogels

Around 200,000 patients in the UK have a chronic wound that needs constant care, resulting in a £3 billion annual cost to the NHS. Especially in moist wound healing, the ideal wound dressing material should absorb large amounts of wound exudate whilst remaining mechanically competent in situ. Despite their large hydration, however, current wound dressings still leave much to be desired in terms of mechanical properties in physiological conditions. To address this challenge, a multi-scale approach was pursued for the synthetic design of collagen hydrogels with tunable mechanical properties (from nano- up to the macro-scale), uniquely high swelling ratios and retained (> 70 %) triple-helical features.

Hydrogels were accomplished with three photo-active collagen precursors. Elastic moduli were systematically adjusted in the range of 1-400 kPa via tuning the crosslinker stiffness and secondary interactions, whilst a remarkably high water uptake (up to 2000 wt.-%) was obtained.

• Functionalised chitosan hydrogels with varied drug-loading capability

Advanced bioactive systems are highly desirable for next generation therapeutics. To reach this goal, defined macroscopic properties and spatio-temporal sequestration of extracellular biomacromolecules are crucial. Here, bespoke chitosan hydrogels were accomplished with varied crosslinkers in order to promote systematic electrostatic complexation with model drugs. Resulting networks showed tuneable drug-loading behaviour depending on the electrostatic character of incorporated crosslinkers. In light of this behavior, these hydrogels could be applied as drug reservoirs for e.g. the fabrication of tissue models.

Incubation in varied drug solutions enabled tunable loading of chitosan hydrogels depending on the network architecture at the molecular scale. Drug loading profiles were quantified by measuring the decrease in maximal absorbance during the incubation time.

• Photo-active collagen platform for mechanically competent hydrogels

Collagen is the most abundant structural building block of connective tissues and has been widely applied in healthcare. However, collagen exhibits high swelling but poor elasticity in physiological conditions, resulting in challenging material customisation. Here, covalent functionalisation of type I collagen resulted in photo-active systems with controlled triple helix architecture and tunable degree of functionalisation. Resulting hydrogels were mechanically stable in water, whereby compressive modulus was affected by the network architecture at the molecular scale. Such systems have widespread potential in e.g. chronic wound care solutions and regenerative medicine.

• Triple-helical collagen hydrogels via covalent aromatic functionalisation

Simultaneous control of protein conformation, material properties and biofunctionality is highly challenging in collagen materials. Here, type I collagen was reacted with 1,3-Phenylenediacetic acid (Ph), aiming at reliable biomacromolecular hydrogels. Remarkably, tuneable swellability, degradability, and thermo-mechanical properties were observed, while the triple helix collagen architecture was successfully retained.

Covalent functionalisation of type I collagen with 1,3‑Phenylenediacetic acid (Ph) directly leads to triple-helical hydrogels with controlled degree of crosslinking (C), swelling ratio (SR) and denaturation temperature (T_d), in contrast to state-of-the-art carbodiimide crosslinked collagen.

• Degradation behavior of polyester urethane networks

The biodegradability of polymeric implants is of paramount importance to ensure clinical biomaterial applicability. The hydrolytic degradation of amorphous star-shaped copolyester urethane networks was studied by looking at the change of physical, thermal, and mechanical properties. The star-shaped network architecture was crucial to secure a controlled change of mechanical properties (e.g. Young's modulus) ensuing from a multi-step degradation mechanism.

Molecular changes of polyester urethane network during hydrolytic degradation. A-B) Uptake of water (blue spots) leads to first bond cleavages resulting in dangling chains (C) and entanglements (D). Further bond cleavages yield mass loss (E) and network disintegration (F).

• Design of entropy-elastic gelatin-based hydrogels

Biodegradable, biocompatible, and mechanically-competent biomaterials are highly demanded in regenerative medicine. Gelatin is an interesting biopolymer backbone, since it is non-immunogenic and degradable. However, gelatin suffers from limited material properties. Crosslinking of randomly-coiled chains successfully enabled the suppression of gelatin chain helicity and the development of tuneable entropy-elastic hydrogels.

Tunable entropy-elastic networks were successfully obtained by crosslinking gelatin coiled chains with hexamethylene diisocyanate (HDI) or lysine ethyl ester diisocyanate (LDI) in aqueous system.

• Gelatin-based scaffolds via an integrated foaming-crosslinking process

Biopolymer scaffolds are promising biomaterials for tissue regeneration since they can mimic the extracellular matrix of tissue. However, stabilisation of the porous architecture is challenging. An integrated foaming-crosslinking process was developed to accomplish the formation of gelatin-based scaffolds. A gelatin solution was foamed in the presence of a surfactant and the resulting foam was fixed by chemical crosslinking with a diisocyanate.

Formation of gelatin-based scaffolds by an integrated foaming-crosslinking process. Resulting scaffolds can be casted in different forms and show a highly porous architecture.

• Quantification of the biomaterial immune response in vitro

Lipopolysaccharide endotoxins (LPS) can dramatically impair the clinical biomaterial applicability, since they can induce strong immune responses in vivo. The potential LPS contamination in gelatin scaffolds was quantified by indirectly analysing the TNF-a release of whole blood following incubation in vitro. By using medical-grade gelatin, low-endotoxin scaffolds were successfully synthesised in clean room, ensuring scaffold applicability in vivo.

LPS biomaterial contamination and consequent immune response activation in vivo. LPS are heat-stable and can survive after material sterilisation, inducing macrophage activation and immune responses.