Adipose tissue-derived extracellular matrix hydrogels as a release platform for therapeutic factors
Joris A. van Dongen, B.Sc1,2, Vasilena Getova, B.Sc1, Linda A. Brouwer, BAS1, Gabriel Liguori, MD1, Prashant Sharma, PhD3, Hieronymus P. Stevens, MD, PhD4, Berend van der Lei, MD, PhD2,5, Martin C. Harmsen, PhD1,*
1University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, Groningen, the Netherlands, 2University of Groningen, University Medical Center Groningen, Department of Plastic Surgery, Groningen, the Netherlands, 3University of Groningen, University Medical Center Groningen, Department of Biomedical Engineering, Groningen, the Netherlands, 4Bergman Clinics, location Den Haag, Den Haag, the Netherlands, 5Bergman Clinics, locations Heerenveen, Zwolle and Groningen, the Netherlands.
Prof. dr. Martin C. Harmsen, PhD
Department of Pathology and Medical Biology
University of Groningen
University Medical Center Groningen
9713 GZ Groningen
Introduction: Autologous fat grafting has become an established clinical intervention to promote tissue repair and regeneration. Besides the usual suspects i.e. adipose tissue-derived stromal cells (ASC) that supposedly participate in this regeneration, the role of the non-cellular extracellular matrix (ECM) is largely neglected. The extracellular matrix comprises the base of tissue architecture but the ECM also dictates fate and function of adhered cells, and retains a host of soluble factors that are beneficial in regenerative therapy. In this study, we investigated in vitro the uptake and release of ASC released factors by adipose tissue-derived extracellular matrix (ECM) hydrogels. We envisage that ASC released-factor-loaded ECM hydrogels are a novel therapeutic modality for wound healing.
Material & methods: Lipoaspirates were obtained from donors (n=5) and processed by the use of the fractionation of adipose tissue (FAT) procedure and subsequent decellularization. Finely powdered acellular ECM was evaluated for cell remainders by histological staining and DNA content measurement. Acellular ECM was digested with pepsin and hydrogels were formed at 37 °C. The hydrogels were loaded with ASC-released factors for 24h. Uptake and release of ASC-released factors by the ECM-derived hydrogels were measured with a Luminex immune multiplex assay. The influence of released factors by the ECM hydrogels was assessed with a fibroblast proliferation and migration assay as well as an endothelial angiogenesis assay.
Results: Acellular ECM contained no detectable cell remainders and negligible DNA contents after decellularization. ECM derived hydrogels released several ASC-released factors concurrently. These factors were released in a sustained mode for at least 96h. Functionally, these released factors stimulated fibroblast proliferation and migration as well as angiogenesis.
Conclusion: Adipose tissue-derived extracellular matrix derived hydrogels incubated with released factors by ASC are a promising new therapeutic modality to promote several important wound healing related processes such as fibroblast proliferation and migration as well as angiogenesis. Factors released by ASC are released from hydrogels in a controlled way and thus the clinical effects of the hydrogel can be sustained over time.
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