The role of MMPs and TIMPs in regenerative medicine: From pathological ECM remodeling to therapeutic applications
Arya Kazemi, Mobin Fathy, Ali Jahanian, Javad Khanali, Yasamin Ostadi, Amirhesam Babajani, Tahereh Tayebi, Hassan Niknejad
Abstract
Regulation of extracellular matrix (ECM) dynamics is mediated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). While their involvement in many processes is well recognized, their specific impression on regenerative medicine remains an area of active investigation. This review highlighted the impact of MMPs in six fundamental phenomena-tissue remodelling, angiogenesis, cell migration, cell proliferation and growth, immunogenicity, and apoptosis -emphasizing their significance in regenerative medicine. Also, this review offers a novel contribution by evaluating these phenomena across individual organs, an approach that distinguishes it from previous literature which often lacked an organ-specific perspective in the context of regenerative medicine and tissue engineering. In this regard, the role of MMPs has been investigated across various conditions, including neurodegenerative disorders, cardiovascular diseases, cancer, musculoskeletal disorders, liver and lung complications, skin pathologies, and ophthalmologic diseases. This approach gives a more detailed understanding of MMPs behaviour across different biological environments, offering insight into their context-dependent functions. Furthermore, this review discusses current challenges in MMP research, such as the lack of selectivity in available MMP inhibitors, as well as future directions including their potential role in adjuvant therapy and the use of gene editing technologies such as CRISPR and bioengineered delivery systems and nano particles to more precisely modulate local tissue regeneration and improve drug delivery.