Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis

• DOI: 10.1016/j.mtbio.2023.100813
• Publication Date: 2023-09-28T01:33:10Z
• Authors: Zhaowei Yin; Chaoren Qin; Shaowei Pan; Chen Shi; Guanfu Wu; Yan Feng; Jing Zhang; Ziyi Yu; Bin Liang; Jianchao Gui
• Keywords: Hydrogel; Medicine (General); R5-920; QH301-705.5; Full Length Article; Osteoarthritis; Microfluidics; Mesenchymal stem cells; MicroRNA; Biology (General); Exosomes

Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) (ScASCs). However, it remains unclear which type Exos offers superior therapeutic benefit OA. This study first compared differences between from IPFP (ExosIPFP) and ScAT (ExosScAT) treatment. Results suggested ExosIPFP significantly inhibit degradation cartilage extracellular matrix (ECM) ExosScAT, following this, microRNA (miRNA) expression two types using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen over-expressed ExosScAT (ExosScAT−99b−3p), both vivo vitro experiments demonstrated its efficacy inhibiting ADAMTS4, promoting repair ECM Finally, microfluidic technology performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) encapsulating (HMPs@exos), injectability, sustained release long-term effect on validated. In summary, these results suggest regulates targeting upregulation would enable them exhibit comparable or even effectiveness treatment, making promising approach Considering abundant resources limited availability IPFP, harvested through liposuction could genetically engineered yield Furthermore, encapsulation HMPs provides an injectable local drug system, potentially enhance hold as future strategies.