Teratoma development from subcutaneously transplanted embryonic stem cells in prevascularized graft beds

Subcutaneous implantation is favored for its accessibility and safety, making it a valuable site for cell transplantation. However, the relatively poor vascularization of the subcutaneous space hinders the implant's integration with the host tissue and limits the delivery of nutrients and oxygen to the implanted cells. This study tackles this challenge using the subcutaneous prevascularization strategy with a composite scaffold. It is composed of a porous polycaprolactone (PCL) matrix soaked with a methacrylated hyaluronic acid (MeHA) hydrogel. The scaffold shows excellent support for mesenchymal stem cell (MSC) adhesion and survival in vitro. To evaluate its in vivo performance, embryonic stem cells (ESCs) are transplanted into prevascularized graft beds in nude mice. Teratoma formation, a recognized indicator of pluripotency and sustained viability, was observed after ESC transplantation into the prevascularized graft beds, indicating successful engraftment within the engineered PCL/MeHA composite scaffolds. These results demonstrate that PCL/MeHA composite scaffolds, particularly those incorporating lower molecular weight MeHA, can create a vascularized subcutaneous niche that effectively supports the engraftment, survival, and long-term function of cells. This validates their strong potential as a prevascularized platform for enhancing subcutaneous cell transplantation outcomes.