Joris van Dongen

309 Adipose ECM hydrogels to release paracrine factors INTRODUCTION Adipose tissue has a beneficial role in wound healing. 1,2 Yet the underlying pathways are not completely understood. This renders adipose tissue a novel, intriguing and exciting territory in science, especially in the field of wound healing. Lipografting is used in reconstructive- and plastic surgery to restore loss of volume after breast surgery or to treat burn wounds and augment wound healing. 3,4 Short term results of lipografting are good, however, on the long-term; graft take survival is variable ranging from 20-90% loss of volume after injection. 1 In this way, the clinical efficacy of lipografting is only temporary. To improve tissue grafting, scientists implemented a technique where they combined adipose tissue-derived stromal cells (ASC) with fat tissue. 5 The adipose tissue comprises parenchyma (adipocytes) and stroma. Stroma comprises vasculature (endothelial and smooth muscle cells as well as pericytes, adipose tissue- derived stromal/stem cells (ASCs) and fibroblasts embedded and held together by the extracellular matrix (ECM). The stroma is also known as the stromal vascular fraction (SVF). In general, most studies focus on ASCs as optimal candidates for repair of tissue damage or to facilitate angiogenesis, for example in orthopaedics and cardiology. 6-9 The secretome of ASCs stimulates angiogenesis which augments local tissue perfusion. This paracrine action of ASCs comprises secretion of pro-regenerative factors such as VEGF, FGF, and HGF. In addition, ASCs contribute to repair via differentiation into parenchymal or stromal cells, such as smooth muscle cells, pericytes, fibroblasts, adipocytes or osteoblasts, depending on the damaged tissue. 8 We have shown that ASC-derived pericytes both promote and stabilize vascularization in vitro and in vivo in a NOTCH2-dependent fashion. 10,11 In these studies we also cultured ASCs in 3D matrices of commercial extracellular matrix i.e. Matrigel®. In the last 5 years, there is a new, promising player arising in this field: the stromal vascular fraction. 12-14 Mechanical isolation of SVF is faster and easier than the isolation and culture of ASCs. 15 SVF is shown to improve wound healing rates faster compared to the injection of ASCs alone because it contains multiple cell types including vasculature, fibroblasts and ECM, which are important in the wound healing process. Moreover, ECM serves as a slow growth factor reservoir to which cells are able to attach to and can be supported by in growth and proliferation. In the past years, ECM has been studied increasingly and different regenerative therapies, with the use of ECM, are developing in various medical fields. 16 ECM