Current Modalities for Fracture Healing Enhancement

Chun, You Seung; Lee, Dong Hwan; Won, Tae Gu; Kim, Yuna; Shetty, Asode Ananthram; Kim, Seok Jung

doi:10.1007/s13770-021-00399-0

Cited by 6 publications

(5 citation statements)

References 47 publications

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“…Fracture healing is a complex restorative process, and delayed or non-union of fractures can occur in certain cases [ 32 , 33 ]. Chun et al demonstrated that stem cell therapy can effectively promote fracture healing but could be primarily complicated by a risk of infection [ 34 ]. Among stem cell types, BMSCs exhibit strong osteogenic potential and have been shown to facilitate both osteogenesis and vascular regeneration, ultimately contributing to bone repair [ 33 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Silencing p75NTR regulates osteogenic differentiation and angiogenesis of BMSCs to enhance bone healing in fractured rats

Wu,

Yang,

Wang

2024

J Orthop Surg Res

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Background Fractures heal through a process that involves angiogenesis and osteogenesis but may also lead to non-union or delayed healing. Bone marrow mesenchymal stem cells (BMSCs) have been reported to play a pivotal role in bone formation and vascular regeneration and the p75 neurotrophin receptor (p75NTR) as being an important regulator of osteogenesis. Herein, we aim to determine the potential mediation of BMSCs by p75NTR in bone healing. Methods Rat BMSCs were identified by flow cytometry (FCM) to detect cell cycle and surface markers. Then transfection of si/oe-p75NTR was performed in BMSCs, followed by Alizarin red staining to detect osteogenic differentiation of cells, immunofluorescence double staining was performed to detect the expression of p75NTR and sortilin, co-immunoprecipitation (CO-IP) was conducted to analyze the interaction between p75NTR and sortilin, and EdU staining and cell scratch assay to assess the proliferation and migration of human umbilical vein endothelial cells (HUVECs). The expression of HIF-1α, VEGF, and apoptosis-related proteins were also detected. In addition, a rat fracture healing model was constructed, and BMSCs-si-p75NTR were injected, following which the fracture condition was observed using micro-CT imaging, and the expression of platelet/endothelial cell adhesion molecule-1 (CD31) was assessed. Results The results showed that BMSCs were successfully isolated, p75NTR inhibited apoptosis and the osteogenic differentiation of BMSCs, while si-p75NTR led to a decrease in sortilin expression in BMSCs, increased proliferation and migration in HUVECs, and upregulation of HIF-1α and VEGF expression. In addition, an interaction was observed between p75NTR and sortilin. The knockdown of p75NTR was found to reduce the severity of fracture in rats and increase the expression of CD31 and osteogenesis-related proteins. Conclusion Silencing p75NTR effectively modulates BMSCs to promote osteogenic differentiation and angiogenesis, offering a novel perspective for improving fracture healing.

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Section: Discussionmentioning

confidence: 99%

Silencing p75NTR regulates osteogenic differentiation and angiogenesis of BMSCs to enhance bone healing in fractured rats

Wu,

Yang,

Wang

2024

J Orthop Surg Res

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“…BMSCs have significant potential to differentiate into osteoblasts and, hence, promote fracture healing . Recent studies have shown that BMSCs derived from fracture nonunion patients have low osteogenic marker expression and impaired osteogenic differentiation, which partly accounts for the delayed fracture union. , However, the potential mechanism underlying impaired osteogenesis remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…44 Though FRI is associated with several microorganisms, S. aureus is the most common pathogenic bacterium. 28,58 To evaluate the efficacy of antagomiR-708-5p in fracture nonunion, we established an infected fracture nonunion model by seeding a femur fracture site in mice with S. aureus. In a previous study, our team synthesized a multifunctional HA hydrogel using positively charged QA, which displayed excellent antiinflammatory properties.…”

Section: Discussionmentioning

confidence: 99%

Injectable Bacteria-Sensitive Hydrogel Promotes Repair of Infected Fractures via Sustained Release of miRNA Antagonist

Chen

Zhou

et al. 2022

ACS Appl. Mater. Interfaces

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Fracture nonunion can result in considerable physical harm and limitation of quality of life in patients, exerting an extensive economic burden to the society. Nonunion largely results from unresolved inflammation and impaired osteogenesis. Despite advancements in surgical techniques, the indispensable treatment for nonunion is robust anti-inflammation therapy and the promotion of osteogenic differentiation. Herein, we report that plasma exosomes derived from infected fracture nonunion patients (Non-Exos) delayed fracture repair in mice by inhibiting the osteogenic differentiation of bone marrow stromal cells in vivo and in vitro. Unique molecular identifier microRNA-sequencing (UID miRNA-seq) suggested that micro-RNA-708-5p (miR-708-5p) was overexpressed in Non-Exos. Mechanistically, miR-708-5p targeted structure-specific recognition protein 1, thereby suppressing the Wnt/β-catenin signaling pathway, which, in turn, impaired osteogenic differentiation. AntagomicroRNA-708-5p (antagomiR-708-5p) could partly reverse the above process. A bacteria-sensitive natural polymer hyaluronic-acid-based hydrogel (HA hydrogel) loaded with antagomiR-708-5p exhibited promising effects in an in vivo study through antibacterial and pro-osteogenic differentiation functions in infected fractures. Overall, the effectiveness and reliability of an injectable bacteriasensitive hydrogel with sustained release of agents represent a promising approach for infected fractures.

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“…Bone can be damaged by almost any pathological insult, such as infection, direct trauma, tumours, or long-term stress. Bone tissue can be completely regenerated under normal healing conditions [31]. However, nonunion and delayed union fractures remain challenges in clinical practice.…”

Section: Required Clinical Features Of Nanoscaled Materialsmentioning

confidence: 99%

Tissue-Engineered Nanomaterials Play Diverse Roles in Bone Injury Repair

et al. 2023

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Nanomaterials with bone-mimicking characteristics and easily internalized by the cell could create suitable microenvironments in which to regulate the therapeutic effects of bone regeneration. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone injury repair. First, an overview of the hierarchical architecture from the macroscale to the nanoscale of natural bone is presented, as these bone tissue microstructures and compositions are the basis for constructing bone substitutes. Next, urgent clinical issues associated with bone injury that require resolution and the potential of nanomaterials to overcome them are discussed. Finally, nanomaterials are classified as inorganic or organic based on their chemical properties. Their basic characteristics and the results of related bone engineering studies are described. This review describes theoretical and technical bases for the development of innovative methods for repairing damaged bone and should inspire therapeutic strategies with potential for clinical applications.

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Current Modalities for Fracture Healing Enhancement

Cited by 6 publications

References 47 publications

Silencing p75NTR regulates osteogenic differentiation and angiogenesis of BMSCs to enhance bone healing in fractured rats

Silencing p75NTR regulates osteogenic differentiation and angiogenesis of BMSCs to enhance bone healing in fractured rats

Injectable Bacteria-Sensitive Hydrogel Promotes Repair of Infected Fractures via Sustained Release of miRNA Antagonist

Tissue-Engineered Nanomaterials Play Diverse Roles in Bone Injury Repair

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