Enhanced Neovascularization Using Injectable and rhVEGF‐Releasing Cryogel Microparticles

Abstract

Cryogels are gel networks or scaffolds with a large porous structure; they can be tailored for injectability and for possessing a shape‐memory ability. Herein, a growth factor‐releasing cryogel microparticle (CMP) system is fabricated, and the therapeutic efficacy of recombinant human vascular endothelial growth factor (rhVEGF)‐loaded CMP (V‐CMP) for neovascularization is investigated. To prepare the cryogels, both methacrylated chitosan (Chi‐MA) and methacrylated chondroitin sulfate (CS‐MA) are used, and crosslinking using a radical crosslinking reaction is established. The physical, mechanical, and biological properties of the cryogels are analyzed by varying the amount of CS‐MA used. The cryogels are then pulverized, and microsized CMPs are fabricated. CMPs dispersed in saline demonstrate a shear‐thinning property, and can thus be extruded through a 23G needle. Additionally, V‐CMP exhibit a sustained release profile of rhVEGF and enhance the in vitro proliferation of endothelial cells. Finally, neovascularization and effective tissue necrosis prevention are observed when V‐CMPs are injected into a hindlimb ischemia mouse model. Thus, the injectable V‐CMP system developed herein demonstrates a high potential utility in various tissue regeneration applications based on cell or growth factor delivery.

Cryogels: Advancing Biomaterials for Transformative Biomedical Applications

“…An injectable cryogel microparticle (CMP) system has been studied for growth factor delivery in tissue regeneration applications [ 46 ]. The system utilizes methacrylated chitosan and chondroitin sulfate crosslinked through a radical crosslinking reaction to create a growth factor-releasing CMP.…”

“…Cryogels have emerged as highly versatile and promising biomaterials with numerous applications in various biomedical fields. Extensive research has been conducted to explore the potential of cryogels composed of different materials, such as alginate, chitosan, silk fibroin, gelatin, agarose, and cellulose derivatives, for tissue engineering, controlled drug delivery, regenerative medicine, and other therapeutic strategies [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ].…”

“…pH-sensitive chitosan-based cryogels offer a promising approach for controlled and targeted drug delivery [ 45 ]. Injectable cryogel microparticles enable sustained release of growth factors for tissue regeneration [ 46 ]. Chitosan-based polyelectrolyte complex (PEC) cryogels and aerogels show sustainable release and thermal stability for effective drug delivery [ 47 , 48 ].…”