Spatiotemporal controlled delivery of insulin via supramolecular albumin stearate nanoparticles as a growth factor-mimetic system for soft tissue regeneration

Biomimetic growth factor substitutes (BGFSs) can be designed to reproduce selected properties of growth-factor such as; presentation during tissue regeneration and controlled local availability. In this study, nanoparticles are designed in such a way that, the nanoparticle does gradient temporal delivery for chemotaxis followed by residual insulin in the nanoparticles for spatial presentation leading to a regenerative nanoparticle of insulin as a growth factor substitute. FTIR and NMR analyses supported the association of stearate with albumin. The optimized nanoparticles had an average diameter of 210 nm by DLS and a zeta potential of -35.6 mV. SEM and HRTEM analyses showed nanoscale and submicroscopic structures with elongated and higher-order morphologies, wherein insulin loading is associated with changes in particle organization. The BGFS showed sustained insulin release for up to 240 hours, with approximately 40% of the insulin released during this period, while the remaining insulin was retained within the matrix. The nanoparticles showed low hemolysis (<5%), high cellular viability (74-94%), and physical stability under refrigerated conditions. In a full-thickness wound model in rats, the formulation is associated with improved wound healing response from histology, including collagen deposition and neovascularization, without detectable hypoglycemia. Overall, the insulin-albumin stearate system shows potential as a controlled-release nanomedicine for soft-tissue regeneration and accelerated wound healing.