As a non-antibody scaffold, monobodies based on the fibronectin type III (FN3) domain overcome antibody size and complexity while maintaining analogous binding loops. However, antibodies and their derivatives remain the gold standard for the design of new therapeutics. In response, clinical-stage therapeutic proteins based on the FN3 domain are beginning to use native fibronectin function as a point of differentiation. The small and simple structure of monomeric monobodies confers increased tissue distribution and reduced half-life, whilst the absence of disulphide bonds improves stability in cytosolic environments. Where multi-specificity is challenging with an antibody format that is prone to mis-pairing between chains, multiple FN3 domains in the fibronectin assembly already interact with a large number of molecules. As such, multiple monobodies engineered for interaction with therapeutic targets are being combined in a similar beads-on-a-string assembly which improves both efficacy and pharmacokinetics. Furthermore, full length fibronectin is able to fold into multiple conformations as part of its natural function and a greater understanding of how mechanical forces allow for the transition between states will lead to advanced applications that truly differentiate the FN3 domain as a therapeutic scaffold.

No abstract

Compression therapy is the current evidence-based approach to manage venous leg ulcers (VLU); however, adherence is a major barrier to successful treatment. Combination approaches may relieve the burden of treatment by shortening the time to ulcer healing. This scoping review conducted by Australian researchers aimed to establish the evidence of effectiveness of various adjuvant methods on wound healing and recurrence. Randomized Controlled Trials (RCTs), and Systematic Reviews (SR) and Meta-Analyses (MA) on VLU management approaches published from January 2015 to December 2018 were included in this review. The articles included in the scoping review were grouped according to the management approaches, including (1) pharmaceutical interventions, (2) surgical interventions, (3) topical agents, (4) the use of devices, and (5) other, such as physiotherapy and psychological interventions. Results of this scoping review indicate that there is a limited high-quality evidence of effectiveness in most adjuvant therapies on wound healing and recurrence. Given the lowquality evidence observed in this scoping review for adjuvant treatments, the implication for practice is that current management guidelines be followed. Further rigorous studies have the potential to produce better quality evidence. Quality of evidence can be improved by ensuring large sample sizes of a single etiology wounds, standardizing reporting outcomes, and maintaining detailed and evidence-based protocols in physiological or psychological interventions.