Neutrophils in Biomaterial-Guided Tissue Regeneration: Matrix Reprogramming for Angiogenesis

Abstract

Biomaterial-guided in situ tissue regeneration uses biomaterials to stimulate and guide the body's endogenous, regenerative processes to drive functional tissue repair and regeneration. To be successful, cell migration into the biomaterials is essential, which requires angiogenesis to maintain cell viability. Neutrophils, the first cells responding to an implanted biomaterial, are now known to play an integral part in angiogenesis in multiple tissues and exhibit considerable potential for driving angiogenesis in the context of tissue regeneration. In terms of biomaterial-guided in situ tissue regeneration, harnessing the proangiogenic potential of the neutrophil through its robust secretion of matrix metalloproteinase 9 (MMP-9) may provide a mechanism to improve biomaterial performance by initiating matrix reprogramming. This review will discuss neutrophils as matrix reprogrammers and what is currently known about their ability to create a microenvironment that is more conducive for angiogenesis and tissue regeneration through the secretion of MMP-9. It will first review a set of ground-breaking studies in tumor biology and then present an overview of what is currently known about neutrophils and MMP-9 in biomaterial vascularization. Finally, it will conclude with potential strategies and considerations to engage neutrophils in biomaterial-guided angiogenesis and in situ tissue regeneration.

BRCA1-Associated Protein Is a Potential Prognostic Biomarker and Is Correlated With Immune Infiltration in Liver Hepatocellular Carcinoma: A Pan-Cancer Analysis

“…Neutrophils are early infiltrating inflammatory cells, which play a key role in initiating and expanding inflammatory response. Matrix metalloproteinase (MMP) secreted by neutrophils can reshape extracellular matrix, reduce the cell interaction, and enable tumor cells to escape immune surveillance and promote distant metastasis ( Fetz et al, 2020 ; Liu and Liu, 2020 ). These all indicate that tumor-infiltrating immune cells play an important role in tumor progression.…”

In Vivo Modulation of Angiogenesis and Immune Response on a Collagen Matrix via Extracorporeal Shockwaves

“…In this context, neutrophils were found to play an important role, especially by providing MMP-9 to the sites of vessel formation [ 49 ]. This effect seems to be relevant in tumor angiogenesis [ 50 , 51 ] as well as in cases of tissue transplantation [ 49 ], and biomaterial tissue integration [ 52 ]. MMP-9 is stored by neutrophils in secretory granules and released upon a corresponding stimulus as pro-MMP-9.…”

“…One mechanism of action that is proposed for the proangiogenic effects of MMP-9 is the degradation of the extracellular matrix by the protein that facilitates tissue remodeling and thereby also activates bound factors such as VEGF [ 49 ]. Neutrophils are considered to be matrix programmers which play an important role in any kind of tissue regeneration [ 52 ]. All the more interesting is that we observed that ESWT could be able to elevate the expression of the main neutrophil marker MMP-9.…”

Skin wound healing assisted by angiogenic targeted tissue engineering: A comprehensive review of bioengineered approaches

“…Meanwhile, there are some studies indicated the significant role of the immune system and inflammatory cells in the process of tissue angiogenesis. Neutrophils, as the first cells responding to the implanted biomaterial, and macrophages are now found to play an integral role in angiogenesis in multiple tissues and exhibit considerable potential for angiogenic‐based tissue regeneration 60‐62 . In terms of biomaterial‐guided in‐situ tissue regeneration, application of the pro‐angiogenic potential of the neutrophils with biomaterial carrier/scaffold due to their robust secretion of matrix metalloproteinase‐9 (MMP‐9) can improve biomaterial performance by initiating matrix reprogramming.…”

“…In fact, such an angiogenic effect is a mutual regulated event occurred between neutrophils and biomaterial. Thus, in‐situ tissue angiogenesis as a novel and attractive approach can be provided through the design of immunomodulatory biomaterials which harness the pro‐angiogenic potential of neutrophils to drive matrix reprogramming 61,63 …”