RESUMEN
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a family of chronic disorders along the gastrointestinal tract. Because of its idiopathic nature, IBD does not have a fundamental cure; current available therapies for IBD are limited to prolonged doses of immunomodulatory agents. While these treatments may reduce inflammation, limited therapeutic efficacy, inconsistency across patients, and adverse side effects from aggressive medications remain as major drawbacks. Recently, excessive production and accumulation of neutrophil extracellular traps (NETs) also known as NETosis have been identified to exacerbate inflammatory responses and induce further tissue damage in IBD. Such discovery invited many researchers to investigate NETs as a potential therapeutic target. DNase-I is a natural agent that can effectively destroy NETs and, therefore, potentially reduce NETs-induced inflammations even without the use of aggressive drugs. However, low stability and rapid clearance of DNase-I remain as major limitations for further therapeutic applications. In this research, polymeric nanozymes were fabricated to increase the delivery and therapeutic efficacy of DNase-I. DNase-I was immobilized on the surface of polymeric nanoparticles to maintain its enzymatic properties while extending its activity in the colon. Delivery of DNase-I using this platform allowed enhanced stability and prolonged activity of DNase-I with minimal toxicity. When administered to animal models of IBD, DNase-I nanozymes successfully alleviated various pathophysiological symptoms of IBD. More importantly, DNase-I nanozyme administration successfully attenuated neutrophil infiltration and NETosis in the colon compared to free DNase-I or mesalamine.
RESUMEN
The capability to restore the structure and function of tissues damaged by fatal diseases and trauma is essential for living organisms. Various tissue engineering approaches have been applied in lesions to enhance tissue regeneration after injuries and diseases in living organisms. However, unforeseen immune reactions by the treatments interfere with successful healing and reduce the therapeutic efficacy of the strategies. The immune system is known to play essential roles in the regulation of the microenvironment and recruitment of cells that directly or indirectly participate in tissue remodeling in defects. Accordingly, regenerative immune engineering has emerged as a novel approach toward efficiently inducing regeneration using engineering techniques that modulate the immune system. It is aimed at providing a favorable immune microenvironment based on the controlled balance between pro-inflammation and anti-inflammation. In this review, we introduce recent developments in immune engineering therapeutics based on various cell types and biomaterials. These developments could potentially overcome the therapeutic limitations of tissue remodeling.