Hierarchically Assembled Type I Collagen Fibres as Biomimetic Building Blocks of Biomedical Membranes

Abstract

Wet spinning is an established fibre manufacturing route to realise collagen fibres with preserved triple helix architecture and cell acceptability for applications in biomedical membranes. However, resulting fibres still need to be chemically modified post-spinning to ensure material integrity in physiological media, with inherent risks of alteration of fibre morphology and with limited opportunities to induce fibrillogenesis following collagen fixation in the crosslinked state. To overcome this challenge, we hypothesised that a photoactive type I collagen precursor bearing either single or multiple monomers could be employed to accomplish hierarchically assembled fibres with improved processability, macroscopic properties and nanoscale organisation via sequential wet spinning and UV-curing. In-house-extracted type I rat tail collagen functionalised with both 4-vinylbenzyl chloride (4VBC) and methacrylate residues generated a full hydrogel network following solubilisation in a photoactive aqueous solution and UV exposure, whereby ~85 wt.% of material was retained following 75-day hydrolytic incubation. Wide-angle x-ray diffraction confirmed the presence of typical collagen patterns, whilst an averaged compression modulus and swelling ratio of more than 290 kPa and 1500 wt.% was recorded in the UV-cured hydrogel networks. Photoactive type I collagen precursors were subsequently wet spun into fibres, displaying the typical dichroic features of collagen and regular fibre morphology. Varying tensile modulus (E = 5 ± 1 − 11 ± 4 MPa) and swelling ratio (SR = 1880 ± 200 − 3350 ± 500 wt.%) were measured following post-spinning UV curing and equilibration with phosphate‑buffered saline (PBS). Most importantly, 72-h incubation of the wet spun fibres in PBS successfully induced renaturation of collagen-like fibrils, which were fixed following UV-induced network formation. The whole process proved to be well tolerated by cells, as indicated by a spread-like cell morphology following a 48-h culture of L929 mouse fibroblasts on the extracts of UV-cured fibres.

Retracted: A Photoclick Thiol‐Ene Collagen‐Based Hydrogel Platform for Skeletal Muscle Tissue Engineering

“…All samples revealed a J ‐shaped stress–strain curve during compression, reflecting the strain‐hardening behavior of collagen‐based materials. [ 6,28–30 ] At the same time, no mechanical break was observed following hydrogel compression up to 50%, unlike the case of previously reported UV‐cured methacrylated collagen networks. [ 28b,29 ] This observation agrees with the selectivity of the thiol‐ene crosslinking reaction, and the increased homogeneity (and compressibility) of the respective network architecture.…”

“…[ 6,28–30 ] At the same time, no mechanical break was observed following hydrogel compression up to 50%, unlike the case of previously reported UV‐cured methacrylated collagen networks. [ 28b,29 ] This observation agrees with the selectivity of the thiol‐ene crosslinking reaction, and the increased homogeneity (and compressibility) of the respective network architecture. [ 31 ] Given that the compression tests were carried out in the water‐swollen samples, swelling studies were therefore carried out to understand the behavior of this material in a near‐physiologic environment.…”

“…Cells were incubated (37 °C, 5% CO 2 ) in DMEM supplemented with FCS (10%) and penicillin streptomycin (PenStrep, 1%), to reach 50% confluence in a 96-well plate. The dry samples of CollPEG3.5, CollPEG4, and CollPEG4.5 were gamma sterilized (29)(30)(31)(32)(33)(34)(35)(36)(37)(38), and a fraction of these sterilized samples treated in FCS-supplemented DMEM (50 vol%) overnight (samples coded as CollPEG3.5 + FCS, CollPEG4 + FCS, and CollPEG4.5 + FCS).…”

“…Considering the orthogonality of the presented thiol-ene reaction, these results, therefore, suggest that the presence of the PEG crosslinker mediates the diffusion and retention of water in the corresponding covalent networks, yielding higher values of SR compared to the case of PEG-free UV-cured RTC-based hydrogels. [28,29] To elucidate this point, the swelling kinetics of the thiol-ene networks were analyzed. The swelling of hydrogels typically includes i) the diffusion of water molecules, ii) the hydration and relaxation of polymer chains, and iii) the expansion of the polymer network.…”

Membrane and Membrane Bioreactors Applied to Health and Life Sciences

“…A new sequential fabrication route of wet spinning combined with UV curing has been presented by Yin et al [1] for the development of hierarchically organised collagen membranes that are customised to the requirements of healthcare applications, e.g., chronic wounds, tendon rupture, and orthopaedic defects. Despite its inherent bio-functionalities being critical to the clinical outcome, type I collagen is less prone to offer fibre control with respect to synthetic polymers, given its complex hierarchical organisation spanning from the nano-up to the macro-scale.…”