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.