Soft tissue recovery and regrowth largely depend on the formation of new blood vessels to deliver oxygen and nutrients. However, this process, known as vascularization, can be slow, affecting recovery and regrowth after severe injuries or illnesses like cancer. Clinicians typically use bulk hydrogel scaffolds — crosslinked polymer networks — to aid blood vessel formation during reconstructive surgery, but these scaffolds have limitations. They can cause delays leading to complications like seroma (fluid buildup post-surgery), infection, and reconstructive failure. To speed up the formation and patterning of new blood vessels, researchers have combined a novel biomaterial with a microsurgical approach used in reconstructive surgery, allowing for improved soft tissue recovery.

The research team at Penn State (University Park, PA, USA) showed that their technique could accelerate the formation of guided networks of blood vessels through a proof-of-concept seven-day experiment. The researchers had previously engineered granular hydrogel scaffolds (GHS), which are unique biomaterials made from packed gel particles or microgels. Unlike bulk hydrogels, which are commonly used in surgery as a base for revascularization of tissues, GHS enables the blood vessels to regrow in a set pattern. This is in contrast to bulk hydrogels, where the blood vessels adopt a random appearance as they regrow in bulk hydrogels. According to the researchers, their approach could enable tissue repair and regeneration across the body.

Their surgical method employs micropuncture, a technique involving the perforation of an existing blood vessel with a fine needle. This assists cells in rapidly migrating to the surrounding tissue, promoting angiogenic outgrowth – the extension of new blood vessels from existing ones. Micropuncture also minimizes the risks of blood clotting and significant hemorrhaging, common in conventional vascular surgery. After creating the micropuncture, GHS is applied to the wound area, providing a scaffold for blood vessel formation. The distinct void architecture of GHS provides the parameters required to guide the blood vessels as they grow. The effectiveness of the GHS/microsurgery technique was tested on the hind limbs of rats and revealed the formation of blood vessels around the GHS within seven days, without any adverse effects. Additionally, by using GHS of different microgel sizes, researchers could control the distances between capillaries in the resulting vascular pattern.

“Our approach may open opportunities to redefine the tissue vascularization landscape, with widespread applicability in many parts of the human body and for various diseases, including cardiovascular-related ones,” said corresponding author Amir Sheikhi. “We strongly believe that this novel platform of GHS and microsurgery for reconstructive surgery and regenerative medicine will help patients grow new blood vessels rapidly.” 

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