Photo-crosslinked adhesive hydrogel loaded with extracellular vesicles promoting hemostasis and liver regeneration

Abstract

Hepatectomy is an effective surgical method for the treatment of liver diseases, but intraoperative bleeding and postoperative liver function recovery are still key issues. This study aims to develop a composite hydrogel dressing with excellent hemostatic properties, biocompatibility, and ability to promote liver cell regeneration. The modified gelatin matrix (GelMA, 10%) was mixed with equal volumes of sodium alginate-dopamine (Alg-DA) at concentrations of 0.5%, 1%, and 2%. Then a cross-linking agent (0.1%) was added to prepare different composite hydrogels under UV light, named GelMA/Alg-DA-0.5, GelMA/Alg-DA-1 and GelMA/Alg-DA-2, respectively. All the prepared hydrogel has a porous structure with a porosity greater than 65%, and could be stabilized in a gel state after being cross-linked by ultraviolet light. Physicochemical characterization showed that the elastic modulus, water absorption, adhesion, and compressibility of the composite hydrogels were improved with increasing Alg-DA content. Furthermore, the prepared hydrogel exhibits in vitro degradability, excellent biocompatibility, and good hemostatic function. Among all tested groups, the group of GelMA/Alg-DA-1 hydrogel performed the best. To further enhance its application potential in the field of liver regeneration, adipose-derived mesenchymal stem cell exosomes (AD-MSC-Exo) were loaded into GelMA/Alg-DA-1 hydrogel. Under the same conditions, GelMA/Alg-DA-1/Exo promoted cell proliferation and migration more effectively than hydrogels without extracellular vesicles. In conclusion, the prepared GelMA/Alg-DA-1 composite hydrogel loaded with AD-MSC-Exo has great application potential in liver wound hemostasis and liver regeneration.

Methacrylated Gelatin as a Scaffold for Mechanically Isolated Stromal Vascular Fraction for Cutaneous Wound Repair

“…Moreover, we are confident that the swelling, biodegradability, and hemolysis characteristics are in line with the ones measured and described by Xia et al The authors demonstrated a hemolysis rate of less than 5%, which indicates good blood compatibility. GelMA alone showed a swelling rate of around 18% and a remaining mass of roughly 4.5% over the course of 21 days [ 40 ]. However, combining GelMA with alginate did result in a significantly more stable construct with a remaining mass of circa 20%.…”

Hydrogels as carriers deliver stem cells/exosomes for liver injury

“…In addition, bleeding time (all data were shown as mean ± standard deviation, n = 4) was greater than 200 s in the control group, whereas in the hydrogel group it was less than 100 s. Also, no significant post-operative adhesions were seen in the experimental group compared to the control group. Wu et al 112 developed a composite hydrogel encapsulating MSCs-exos, which in addition to having good biocompatibility and hemostatic properties, encouraged hepatocyte proliferation by releasing exosomes. Thus, injectable hydrogels serve as potential new modalities for liver regeneration after hepatectomy.…”

“…132 Furthermore, GelMA is an extracellular matrix (ECM)-like hydrogel material due to the incorporation of the arginine–glycine–aspartate (RGD) sequence and matrix metalloproteinase (MMP) motifs, which stimulates cell adhesion and proliferation. 133 Xia et al 112 designed a photo-crosslinked hydrogel loaded with exosomes composed of GelMA, dopamine-modified alginate (Alg-DA), and exos (GelMA/Alg-DA/Exo). The hydrogel was applied after hepatectomy and demonstrated good adhesion and biocompatibility, and effective haemostasis while also promoting hepatocyte regeneration.…”

Biomaterial‐Facilitated Local Delivery of Stem Cell‐Derived Small Extracellular Vesicles: Perspectives in Surgical Therapy

“…developed a photo‐crosslinked adhesive HG containing GelMA and sodium alginate‐dopamine for regional delivery of adipose MSC‐derived sEVs. [ 156 ] The sEV‐embedding composite HG increased blood coagulation indices and improved the cell proliferation and migration of LO2 hepatocytes, thereby simultaneously promoting liver wound hemostasis and liver regeneration.…”