A tough act to follow: collagen hydrogel modifications to improve mechanical and growth factor loading capabilities

[EN] Collagen hydrogels are among the most well-studied platforms for drug delivery and in situ tissue engineering, thanks to their low cost, low immunogenicity, versatility, biocompatibility, and similarity to the natural extracellular matrix (ECM). Despite collagen being largely responsible for the tensile properties of native connective tissues, collagen hydrogels have relatively low mechanical properties in the absence of covalent cross-linking. This is particularly problematic when attempting to regenerate stiffer and stronger native tissues such as bone. Furthermore, in contrast to hydrogels based on ECM proteins such as fibronectin, collagen hydrogels do not have any growth factor (GF)-specific binding sites and often cannot sequester physiological (small) amounts of the protein. GF binding and in situ presentation are properties that can aid significantly in the tissue regeneration process by dictating cell fate without causing adverse effects such as malignant tumorigenic tissue growth. To alleviate these issues, researchers have developed several strategies to increase the mechanical properties of collagen hydrogels using physical or chemical modifications. This can expand the applicability of collagen hydrogels to tissues subject to a continuous load. GF delivery has also been explored, mathematically and experimentally, through the development of direct loading, chemical cross-linking, electrostatic interaction, and other carrier systems. This comprehensive article explores the ways in which these parameters, mechanical properties and GF delivery, have been optimized in collagen hydrogel systems and examines their in vitro or in vivo biological effect. This article can, therefore, be a useful tool to streamline future studies in the field, by pointing researchers into the appropriate direction according to their collagen hydrogel design requirements.This work was supported by Medical Research Scotland, EPSRC (through a programme grant EP/P001114/1) and a programme of research funded by the Sir Bobby Charlton Foundation. M.S.S. acknowledges support from a grant from the UK Regenerative Medicine Platform 'Acellular/Smart Materials - 3D Architecture' (MR/R015651/1). The graphical abstract was created using BioRender.com.Sarrigiannidis, S.; Rey, JM.; Dobre, O..; González-García, C.; Dalby, M.; Salmerón Sánchez, M. (2021). A tough act to follow: collagen hydrogel modifications to improve mechanical and growth factor loading capabilities. Materials Today Bio. 10(1):1-22. https://doi.org/10.1016/j.mtbio.2021.10009812210

Chiral Tartaric Acid Improves Fracture Toughness of Bioactive Brushite-Collagen Bone Cements

Brushite cements are promising bone regeneration materials with limited biological and mechanical properties. Here, we engineer a mechanically improved brushite-collagen type I cement with enhanced biological properties by use of chiral chemistry; d- A nd l-tartaric acid were used to limit crystal growth and increase the mechanical properties of brushite-collagen cements. The impact of the chiral molecules on the cements was examined with Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). A 3-point bend test was utilized to study the fracture toughness, and cell attachment and morphology studies were carried out to demonstrate biocompatibility. XRD and SEM analyses showed that l-, but not d-tartaric acid, significantly restrained brushite crystal growth by binding to the {010} plane of the mineral and increased brushite crystal packing and the collagen interaction area. l-Tartaric acid significantly improved fracture toughness compared to traditional brushite by 30%. Collagen significantly enhanced cell morphology and focal adhesion expression on l-tartaric acid-treated brushite cements.Scopu