Engineering microparticles based on solidified stem cell secretome with an augmented pro-angiogenic factor portfolio for therapeutic angiogenesis

• DOI: 10.1016/j.bioactmat.2022.03.015
• Publication Date: 2022-04-02T04:32:54Z
• Authors: Thomas Später; Marisa Assunção; Kwok Keung Lit; Guidong Gong; Xiaoling Wang; Yi-Yun Chen; Ying Rao; Yucong Li; Chi Him Kendrick Yiu; Matthias W. Laschke; Michael D. Menger; Dan Wang; Rocky S. Tuan; Kay-Hooi Khoo; Michael Raghunath; Junling Guo; Anna Blocki
• Keywords: Therapeutic angiogenesis; Decellularization; Biomaterial

Tissue (re)vascularization strategies face various challenges, as therapeutic cells do not survive long enough in situ, while the administration of pro-angiogenic factors is hampered by fast clearance and insufficient ability to emulate complex spatiotemporal signaling. Here, we propose address these limitations engineering a functional biomaterial capable capturing concentrating activities mesenchymal stem (MSCs). In particular, dextran sulfate, high molecular weight sulfated glucose polymer, supplemented MSC cultures, interacts with MSC-derived extracellular matrix (ECM) components facilitates their co-assembly accumulation pericellular space. Upon decellularization, resulting sulfate-ECM hybrid material can be processed into MIcroparticles SOlidified Secretome (MIPSOS). The insoluble format MIPSOS protects protein from degradation, facilitating sustained release. Proteomic analysis demonstrates that are highly enriched factors, an enhanced bioactivity when compared naïve ECM (cECM). Consequently, intravital microscopy full-thickness skin wounds treated accelerated revascularization healing, far superior potential cECM. Hence, microparticle-based solidified cell secretome provides promising platform major current angiogenesis approaches.