The osteogenic microenvironment (OME) significantly influences bone repair; however, reproducing its dynamic activation and repair processes remains challenging. In this study, we designed injectable porous microspheres modified with composite peptides to investigate cascade alterations in OME and their underlying mechanisms. Poly l -lactic acid microfluidic microspheres underwent surface modifications through alkaline hydrolysis treatment, involving heterogeneous grafting of bovine serum albumin nanoparticles with stem cell-homing peptides (BNP@SKP) and BMP-2 mimicking peptides (P24), respectively. These modifications well-organized the actions of initial release and subsequent in situ grafting of peptides. Cellular experiments demonstrated varied degrees of chemotactic recruitment and osteogenic differentiation in mesenchymal stem cells. Further biological analysis revealed that BNP@SKP targeted the Ras/Erk axis and upregulated matrix metalloproteinase (MMP)2 and MMP9 expression, thereby enhancing initial chemotaxis and recruitment. In vivo studies validated the establishment of a dynamically regulated OME centered on the microspheres, resulting in increased stem cell recruitment, sequential activation of the differentiation microenvironment, and facilitation of in situ osteogenesis without ectopic ossification. In conclusion, this study successfully fabricated composite peptide-modified microspheres and systematically explored the mechanisms of bone formation through sequential activation of OME via heterogeneous grafting of signaling molecules. This provides theoretical evidence for biomaterials based on microenvironment regulation.
Complications of diabetes are the main cause of death and disability in diabetic patients. Cardiovascular diseases, especially diabetic cardiomyopathy, are one of the major complications and causes of death in type 2 diabetes. Peptide drugs have a better effect on improving cellular
oxidative damage, reducing tissue inflammation and inhibiting intracellular calcium overload. The application of nanotechnology to the preparation of peptide drugs and myocardial injury can effectively improve myocardial stun, arrhythmia and myocardial systolic dysfunction in patients with
type 2 diabetes. The use of nanotechnology to develop more stable Glucagon-like peptide 1 analogues or sustained-release preparations, improve patient compliance and improve the efficacy of diabetes, is of great significance for the prevention and treatment of diabetic cardiomyopathy. Therefore,
this study used nanotechnology to prepare PLGA-GLP-1 nanoparticles using polyglycolic acid glycolic acid as a drug carrier, which achieved long-acting drug and its morphology by transmission electron microscopy. At the same time, this study explored the anti-cardiomyocyte injury and anti-myocardial
damage of PLGA-GLP-1 nanocomposite peptide and its molecular mechanism by using animal models and cell models. Experimental studies have shown that PLGA-GLP-1 nanocomposite peptide has a protective effect on myocardial injury in diabetic rats. Its mechanism is related to the PLGA-GLP-1 nanocomposite
peptide enhancing the body’s antioxidant capacity, anti-cardiomyocyte apoptosis, and promoting mitochondrial DNA repair in cardiomyocytes.
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