While endovascular interventions can restore perfusion in peripheral arterial disease (PAD), they often induce mechanical injury to the endothelium, resulting in luminal denudation and high rates of restenosis and vessel re-occlusion. In recent years, perivascular stem cell therapies, such as pericyte-based therapies, have shown promising benefits in addressing PAD complications by improving perfusion of the ischemic environment. However, such therapies face significant clinical challenges with low cell retention after transplantation and limited long-term efficacy. Injectable scaffolds can provide a protective environment and a minimally invasive approach for delivering such therapeutic cells to ischaemic tissues.

In this work, I developed a series of injectable scaffolds with shear‑thinning hydrogels formed through electrostatic interactions between negatively charged polysaccharides, such as kappa‑carrageenan (kC) and sacran (Sa), and positively charged proteins, such as gelatin type B (Gb), for targeted cell delivery and arterial endothelial repair. Furthermore, the scaffolds were reinforced with either polycaprolactone (PCL) short nanofibers or silicate nanoclay (NC), which improved the hydrogels’ mechanical properties as measured by rheology. The injection force using clinically relevant needles was less than 100 N, and there was no significant reduction in viability of encapsulated cells after injection, for up to 1 week of culture.

The therapeutic potential of the scaffolds was assessed using umbilical cord pericytes (UCPs) and pericyte-like adipose-derived stem cells (ASCs), pro‑angiogenic and regenerative perivascular cells, in an ex vivo femoral artery injury model under static and dynamic conditions. Perivascular administration of pericyte‑loaded scaffold significantly improved the recovery of endothelial coverage in treated groups compared to untreated injured arteries, corresponding to an 89% restoration index after 1 week of culture. kC- and Sa-based injectable biomaterials combined with pericytes provide a novel and effective therapy for promoting re-endothelialisation in PAD. Additionally, these scaffolding systems can be applied to different fields of tissue engineering and regenerative medicine, such as a sustained-release carrier for growth factors, 3D bioprinting, and in vitro modelling.