Ultrasound-triggered biomimetic ultrashort peptide nanofiber hydrogels promote bone regeneration by modulating macrophage and the osteogenic immune microenvironment

Zhang, Fan; Lv, Mingchen; Wang, Siyuan; Li, Mengyao; Wang, Yu; Hu, Congjiao; H, Wei; Wang, Xuekui; Wang, Xiaogang; Liu, Zhiduo; Fan, Zhen; Du, Jianzhong; Sun, Yao

doi:10.1016/j.bioactmat.2023.08.008

Cited by 23 publications

(6 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Depending on the local bone microenvironment, macrophages can be polarized into either classically activated (M1) and alternatively activated (M2) phenotypes [ 27 ]. M1 macrophages can be activated by LPS or pro-inflammatory cytokines, participate in host defense processes, and highly express iNOS and CD86 [ 28 ]. M2 macrophages can be activated by IL-4, play a role in promoting tissue repair and highly express receptor molecules Arg-1 and CD206 [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Macrophage exosomes modified by miR-365-2-5p promoted osteoblast osteogenic differentiation by targeting OLFML1

Hou,

Zhang,

et al. 2024

Regenerative Biomaterials

View full text Add to dashboard Cite

In the bone immune microenvironment, immune cells can regulate osteoblasts through a complex communication network. Macrophages play a central role in mediating immune osteogenesis, exosomes derived from them have osteogenic regulation and can be used as carriers in bone tissue engineering. However, there are problems with exosomal therapy alone, such as poor targeting, and the content of loaded molecules cannot reach the therapeutic concentration. In this study, macrophage-derived exosomes modified with miR-365-2-5p were developed to accelerate bone healing. MC3T3-E1 cells were incubated with the culture supernatants of M0, M1 and M2 macrophages, and it was found that the culture medium of M2 macrophages had the most significant effects in contributing to osteogenesis. High-throughput sequencing identified that miR-365-2-5p was significantly expressed in exosomes derived from M2 macrophages. We incubated MC3T3-E1 with exosomes overexpressing or knocking down miR-365-2-5p to examine the biological function of exosome miR-365-2-5p on MC3T3-E1 differentiation. This findings suggested that miR-365-2-5p secreted by exosomes increased the osteogenesis of MC3T3-E1. Moreover, miR-365-2-5p had a direct influence over osteogenesis for MC3T3-E1. Sequencing analysis combined with dual luciferase detection indicated that miR-365-2-5p binded to the 3'UTR of OLFML1. In summary, exosomes secreted by M2 macrophages targeted OLFML1 through miR-365-2-5p to facilitate osteogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Macrophage exosomes modified by miR-365-2-5p promoted osteoblast osteogenic differentiation by targeting OLFML1

Hou,

Zhang,

et al. 2024

Regenerative Biomaterials

View full text Add to dashboard Cite

show abstract

“…In this process, macrophages’ TCA cycle and glycolysis metabolism are activated, providing the cells with additional energy and metabolic intermediates. Additionally, it is involved in regulating antioxidant stress response and cell death ( Figure 5C ) [ 103 ]. OI-modified DBM scaffolds (OI/CS/DBM scaffolds) regulate inflammation by metabolites, thereby regulating macrophage polarization and improving the inflammatory microenvironment of bone defects [ 104 ].…”

Section: Mitochondrial Targeted Biomaterials For Bone Repairmentioning

confidence: 99%

Research progresses on mitochondrial-targeted biomaterials for bone defect repair

Wang,

Liu,

Zhou

et al. 2024

Regenerative Biomaterials

View full text Add to dashboard Cite

In recent years, the regulation of the cell microenvironment has opened up new avenues for bone defect repair. Researchers have developed novel biomaterials to influence the behavior of osteoblasts and immune cells by regulating the microenvironment, aiming to achieve efficient bone repair. Mitochondria, as crucial organelles involved in energy conversion, biosynthesis, and signal transduction, play a vital role in maintaining bone integrity. Dysfunction of mitochondria can have detrimental effects on the transformation of the immune microenvironment and the differentiation of stem cells, thereby hindering bone tissue regeneration. Consequently, targeted therapy strategies focusing on mitochondria have emerged. This approach offers a wide range of applications and reliable therapeutic effects, thereby providing a new treatment option for complex and refractory bone defect diseases. In recent studies, more biomaterials have been used to restore mitochondrial function and promote positive cell differentiation. The main directions are mitochondrial energy metabolism, mitochondrial biogenesis, and mitochondrial quality control. In this review, we investigated the biomaterials used for mitochondria-targeted treatment of bone defect repair in recent years from the perspective of progress and strategies. We also summarized the micro-molecular mechanisms affected by them. Through discussions on energy metabolism, oxidative stress regulation, and autophagy regulation, we emphasized the opportunities and challenges faced by mitochondria-targeted biomaterials, providing vital clues for developing a new generation of bone repair materials.

show abstract

“…Bone regeneration was induced by the sustained release of SDF-1α in situ, which signals for the homing of host MSCs. Zhang et al, constructed an alginate hydrogel loaded with peptide nanofibers made of two ultrashort peptides for the self-assembly and the stimulation of the M2 phenotype [147]. Following this, the hydrogel was applied to treat bone defects in mice, and upon ultrasound stimulation, the nanofibers were released from the hydrogel.…”

Section: Bioactive Molecules-loaded Hydrogelsmentioning

confidence: 99%

Advanced Hydrogel-Based Strategies for Enhanced Bone and Cartilage Regeneration: A Comprehensive Review

De Leon-Oliva,

Boaru,

Perez-Exposito

et al. 2023

Gels

View full text Add to dashboard Cite

Bone and cartilage tissue play multiple roles in the organism, including kinematic support, protection of organs, and hematopoiesis. Bone and, above all, cartilaginous tissues present an inherently limited capacity for self-regeneration. The increasing prevalence of disorders affecting these crucial tissues, such as bone fractures, bone metastases, osteoporosis, or osteoarthritis, underscores the urgent imperative to investigate therapeutic strategies capable of effectively addressing the challenges associated with their degeneration and damage. In this context, the emerging field of tissue engineering and regenerative medicine (TERM) has made important contributions through the development of advanced hydrogels. These crosslinked three-dimensional networks can retain substantial amounts of water, thus mimicking the natural extracellular matrix (ECM). Hydrogels exhibit exceptional biocompatibility, customizable mechanical properties, and the ability to encapsulate bioactive molecules and cells. In addition, they can be meticulously tailored to the specific needs of each patient, providing a promising alternative to conventional surgical procedures and reducing the risk of subsequent adverse reactions. However, some issues need to be addressed, such as lack of mechanical strength, inconsistent properties, and low-cell viability. This review describes the structure and regeneration of bone and cartilage tissue. Then, we present an overview of hydrogels, including their classification, synthesis, and biomedical applications. Following this, we review the most relevant and recent advanced hydrogels in TERM for bone and cartilage tissue regeneration.

show abstract

Ultrasound-triggered biomimetic ultrashort peptide nanofiber hydrogels promote bone regeneration by modulating macrophage and the osteogenic immune microenvironment

Cited by 23 publications

References 51 publications

Macrophage exosomes modified by miR-365-2-5p promoted osteoblast osteogenic differentiation by targeting OLFML1

Macrophage exosomes modified by miR-365-2-5p promoted osteoblast osteogenic differentiation by targeting OLFML1

Research progresses on mitochondrial-targeted biomaterials for bone defect repair

Advanced Hydrogel-Based Strategies for Enhanced Bone and Cartilage Regeneration: A Comprehensive Review

Contact Info

Product

Resources

About