In the pursuit of dendrimer alternatives, hyperbranched polymers have found increasing interest from academia and industry in a broad range of fields due to their topological and synthetic advantages. Hyperbranched polyglycerol (HPG), as the name implies, is a hyperbranched polymer with about 50–65% dendrimeric structure. Due to its ease in synthesis, globular nature, versatility in terms of functionalization, and superb biocompatibility profiles HPG provides a promising class of materials suitable for numerous applications in nanomedicine and biomedical technologies. The structural features of HPG can be easily tailored by adopting different synthetic methodologies. In this review, we briefly explore the synthesis of HPGs starting from the traditional Lewis acid based approaches to recent advances including the development of high MW HPGs, biodegradable HPGs, co-block HPGs and sustainable or ‘green’ HPG synthesis. The robust history of HPG biocompatibility is extensively reviewed giving examples of both in vitro and in vivo models. In particular, HPG showed very minimal polymer accumulation in vital organs after intravenous injection compared to other polymers widely used for various biomedical applications. HPG is well tolerated in mice and rats, and has been found to be non-immunogenic to date. Due to its demonstrated safety profile and multifunctionality, HPG has been extensively studied for different biomedical applications including as macromolecular therapeutics, multivalent inhibitors/scavengers, in controlled drug delivery systems, in organ preservation, dialysis and cell surface engineering, as imaging agents and theranostics, in the development of anti-fouling surfaces and proteomics reagents. We highlight these applications along with its advantages. Finally, we conclude by providing a future prospective of HPG as one of the promising PEG alternatives with a great potential to enter clinical trials in the near future.

Nanomaterials in the blood must mitigate the immune response to have a prolonged vascular residency in vivo. The composition of the protein corona that forms at the nano-biointerface may be directing this, however, the possible correlation of corona composition with blood residency is currently unknown. Here‚ we report a panel of new soft single molecule polymer nanomaterials (SMPNs) with varying circulation times in mice (t_1/2β ~ 22 to 65 h) and use proteomics to probe protein corona at the nano-biointerface to elucidate the mechanism of blood residency of nanomaterials. The composition of the protein opsonins on SMPNs is qualitatively and quantitatively dynamic with time in circulation. SMPNs that circulate longer are able to clear some of the initial surface-bound common opsonins, including immunoglobulins, complement, and coagulation proteins. This continuous remodelling of protein opsonins may be an important decisive step in directing elimination or residence of soft nanomaterials in vivo.

Antithrombotic surfaces that prevent coagulation activation without interfering with haemostasis are required for blood-contacting devices. Such materials would restrain device-induced thrombogenesis and decrease the need for anticoagulant use, thereby reducing unwanted bleeding. Here, by optimizing the interactions with coagulation factor XII rather than preventing its surface adsorption, we develop a substrate-independent antithrombotic polymeric coating with sheltered positive charges. The antithrombic properties of the coating were demonstrated in vitro with human blood and in vivo using a carotid artery–jugular vein shunt model in rabbits. The coating exhibits a strong interaction with factor XII, but results in a low reciprocal activation of the contact pathway that triggers clot formation. These findings contradict the prevailing strategy of designing antithrombotic materials through protein-repelling surfaces. Overall, the polymeric coating we describe can benefit most blood-contacting devices and is a useful engineering guideline for designing surfaces with improved antithrombotic properties.