VEGF‐delivering PEG hydrogels promote vascularization in the porcine subcutaneous space

Abstract

For cell therapies, the subcutaneous space is an attractive transplant site due to its large surface area and accessibility for implantation, monitoring, biopsy, and retrieval. However, its poor vascularization has catalyzed research to induce blood vessel formation within the site to enhance cell revascularization and survival. Most studies focus on the subcutaneous space of rodents, which does not recapitulate important anatomical features and vascularization responses of humans. Herein, we evaluate biomaterial‐driven vascularization in the porcine subcutaneous space. Additionally, we report the first use of cost‐effective fluorescent microspheres to quantify perfusion in the porcine subcutaneous space. We investigate the vascularization‐inducing efficacy of vascular endothelial growth factor (VEGF)‐delivering synthetic hydrogels based on 4‐arm poly(ethylene) glycol macromers with terminal maleimides (PEG‐4MAL). We compare three groups: a non‐degradable hydrogel with a VEGF‐releasing PEG‐4MAL gel coating (Core+VEGF gel); an uncoated, non‐degradable hydrogel (Core‐only); and naïve tissue. After 2 weeks, Core+VEGF gel has significantly higher tissue perfusion, blood vessel area, blood vessel density, and number of vessels compared to both Core‐only and naïve tissue. Furthermore, healthy vital signs during surgery and post‐procedure metrics demonstrate the safety of hydrogel delivery. We demonstrate that VEGF‐delivering synthetic hydrogels induce robust vascularization and perfusion in the porcine subcutaneous space.

Antioxidative, Anti-Inflammatory, Antibacterial, Photo-Cross-Linkable Hydrogel of Gallic Acid–Chitosan Methacrylate: Synthesis, In Vitro, and In Vivo Assessments

“…The depth of cell infiltration into the hydrogel was determined using ImageJ from Masson Trichrome images ( n = 3). As for the measurement of fibrous capsule thickness, 10 serial measurements at the same interval were made using ImageJ across the whole view of the Masson Trichrome image ( n = 3) . The paraffin-embedded slides were dewaxed, dehydrated by gradient ethanol, antigenically repaired, immersed in 0.3% H 2 O 2 , and blocked by 3% bovine albumin serum.…”

“…As for the measurement of fibrous capsule thickness, 10 serial measurements at the same interval were made using ImageJ across the whole view of the Masson Trichrome image (n = 3). 29 The paraffin-embedded slides were dewaxed, dehydrated by gradient ethanol, antigenically repaired, immersed in 0.3% H 2 O 2 , and blocked by 3% bovine albumin serum. Rabbit anti-CD163 (1:500, Servicebio) and anti-CD11b (1:500, Servicebio) primary antibodies were incubated at 4 °C overnight to identify M1 and M2 macrophages, respectively.…”

3D bioprinted mesenchymal stem cell laden scaffold enhances subcutaneous vascularization for delivery of cell therapy

“…To this end, several strategies are explored to enhance vascularization in the subcutaneous microenvironment (Pepper et al 2015 ). Among these, local supply of pro-angiogenic factors like vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) can effectively stimulate the formation of new blood vessels (Quizon et al 2024 ; Xu et al 2018 ). Similarly, platelet rich plasma (PRP) hydrogels are shown to improve vascularization in various preclinical models (Paez-Mayorga et al 2020a ).…”