Albumin-based hydrogels are increasingly attractive in tissue engineering because they provide a xeno-free, biocompatible and potentially patient-specific platform for tissue engineering and drug delivery. The majority of research on albumin hydrogels has focused on bovine serum albumin (BSA), leaving human serum albumin (HSA) comparatively understudied. Different gelation methods are usually employed for HSA and BSA, and variations in the amino acid sequences of HSA and BSA exist; these account for differences in the hydrogel properties. Heat-induced gelation of aqueous HSA is the easiest method of synthesizing HSA hydrogels however hydrogel opacity and poor cell attachment limit their usefulness in downstream applications. Here, a solution to this problem is presented. Stable and translucent HSA hydrogels were created by controlled thermal gelation and the addition of sodium chloride. the resulting bio-inert hydrogel was then subjected to air plasma treatment which functionalised its surface, enabling the attachment of basement membrane matrix (Geltrex). In vitro survival and proliferation studies of foetal human osteoblasts subsequently demonstrated good biocompatibility of functionalised albumin hydrogels compared to untreated samples. Thus, air plasma treatment enables functionalisation of inert heat-derived HSA hydrogels with extracellular matrix proteins and these may be used as a xeno-free platform for biomedical research or cell therapy. Albumin is an abundant non-glycosylated, 66.4 kDa protein in human serum that has a physiological half-life of approximately 19 days. It is synthesized predominantly by hepatocytes and poorly excreted through the renal glomerulus 1. Being poorly metabolised and weakly immunogenic, it is stable in vivo. Albumin is also versatile, acting as a weak pH buffer, and as a stabiliser to important proteins, hormones, metal ions, nanoparticles and drugs, making it an attractive biomaterial. These desirable attributes have led to extensive research into albumin as a protein conjugate for drug delivery and pharmacotherapy 1-3. However, the use of albumin-based hydrogels in biomedical research is comparatively under-studied 4. Recently, we demonstrated that human serum albumin (HSA) embedded in a fibrin hydrogel significantly promoted osteoblast differentiation and vascular self-organisation of human endothelial cells 5. However, high cell numbers (10 6 cells/ml or greater) degrade these fibrin-based hydrogels within 8-10 days making it unsuitable for studying long term bone development and implantation into animal models. Furthermore, it was anticipated that the implantation of fibrin-based scaffolds into bone would accelerate its degradation in vivo because of the presence of serum fibrinolytics and movement of bone during locomotion. Therefore, albumin-based hydrogels were explored as an alternative material for scaffolds. Heat-derived bovine serum albumin (BSA) hydrogels (20% w/v) exhibit high Young's modulus (~ 55 kPa) and longer degradation periods (~ 4 to 8 weeks) in vitro and...