Fracture healing research: Recent insights

Steppe, Lena; Megafu, Michael; Tschaffon-Müller, Miriam Eva Angelica; Ignatius, Anita; Haffner‐Luntzer, Melanie

doi:10.1016/j.bonr.2023.101686

Cited by 7 publications

(3 citation statements)

References 148 publications

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“…Bone fracture healing is a highly complex process involving different tissues and cell types [ 7 ]. For successful bone regeneration, the distinct but overlapping healing phases have to be well-organized and regulated [ 32 ]. The data from this study provide a comprehensive, descriptive analysis of the spatio-temporal localization of different immune and bone cell subsets (immune cells: macrophages of different polarization states, CD4+ and CD8+ T cells, B cells; bone cells: osteoblasts and osteoclasts) throughout the healing of a femur fracture with a stable fixation in a mouse osteotomy model [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Complex Spatio-Temporal Interplay of Distinct Immune and Bone Cell Subsets during Bone Fracture Healing

Schlundt,

Saß,

Bucher

et al. 2023

Cells

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Background: The healing of a bone injury is a highly complex process involving a multitude of different tissue and cell types, including immune cells, which play a major role in the initiation and progression of bone regeneration. Methods: We histologically analyzed the spatio-temporal occurrence of cells of the innate immune system (macrophages), the adaptive immune system (B and T lymphocytes), and bone cells (osteoblasts and osteoclasts) in the fracture area of a femoral osteotomy over the healing time. This study was performed in a bone osteotomy gap mouse model. We also investigated two key challenges of successful bone regeneration: hypoxia and revascularization. Results: Macrophages were present in and around the fracture gap throughout the entire healing period. The switch from initially pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype coincided with the revascularization as well as the appearance of osteoblasts in the fracture area. This indicates that M2 macrophages are necessary for the restoration of vessels and that they also play an orchestrating role in osteoblastogenesis during bone healing. The presence of adaptive immune cells throughout the healing process emphasizes their essential role for regenerative processes that exceeds a mere pathogen defense. B and T cells co-localize consistently with bone cells throughout the healing process, consolidating their crucial role in guiding bone formation. These histological data provide, for the first time, comprehensive information about the complex interrelationships of the cellular network during the entire bone healing process in one standardized set up. With this, an overall picture of the spatio-temporal interplay of cellular key players in a bone healing scenario has been created. Conclusions: A spatio-temporal distribution of immune cells, bone cells, and factors driving bone healing at time points that are decisive for this process—especially during the initial steps of inflammation and revascularization, as well as the soft and hard callus phases—has been visualized. The results show that the bone healing cascade does not consist of five distinct, consecutive phases but is a rather complex interrelated and continuous process of events, especially at the onset of healing.

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Section: Discussionmentioning

confidence: 99%

Complex Spatio-Temporal Interplay of Distinct Immune and Bone Cell Subsets during Bone Fracture Healing

Schlundt,

Saß,

Bucher

et al. 2023

Cells

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“…Bone is an organ with the rare ability to regenerate without scar formation, allowing complete restoration of form and function. Despite all the promising new technologies to improve fracture care that have been introduced over the past decades from basic, translational and clinical research, 5%–10% of all fractures still fail to heal successfully or heal with delay ( 1 ). In addition, global population growth and aging have led to a significant 30% increase in the total number of fractures occurring worldwide between 1990 and 2018 ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to the complications associated with reduced bone strength (implant loosening and construct failure), these patients also have reduced biological potential for regeneration, often resulting in delayed fracture healing. As a result, osteoporotic fractures are a major source of suffering for these patients and a dramatic socioeconomic burden for society ( 1 ). Fractures occurring in the working-age population are related to considerable direct expenses and a substantial loss in productivity ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Promoting bone callus formation by taking advantage of the time-dependent fracture gap strain modulation

Wähnert,

Miersbach,

Colcuc

et al. 2024

Front. Surg.

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Delayed union and non-union of fractures continue to be a major problem in trauma and orthopedic surgery. These cases are challenging for the surgeon. In addition, these patients suffer from multiple surgeries, pain and disability. Furthermore, these cases are a major burden on healthcare systems. The scientific community widely agrees that the stability of fixation plays a crucial role in determining the outcome of osteosynthesis. The extent of stabilization affects factors like fracture gap strain and fluid flow, which, in turn, influence the regenerative processes positively or negatively. Nonetheless, a growing body of literature suggests that during the fracture healing process, there exists a critical time frame where intervention can stimulate the bone's return to its original form and function. This article provides a summary of existing evidence in the literature regarding the impact of different levels of fixation stability on the strain experienced by newly forming tissues. We will also discuss the timing and nature of this “window of opportunity” and explore how current knowledge is driving the development of new technologies with design enhancements rooted in mechanobiological principles.

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Hydrogel Microsphere‐Encapsulated Bimetallic Nanozyme for Promoting Diabetic Bone Regeneration via Glucose Consumption and ROS Scavenging

Hui,

Mao,

Rui

et al. 2024

Adv Healthcare Materials

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The healing of bone defects among diabetic patients presents a critical challenge due to the pathological microenvironment, characterized by hyperglycemia, excessive reactive oxygen species (ROS) production, and inflammation. Herein, multifunctional composite microspheres, termed GMAP are developed, using a microfluidic technique by incorporating Au@Pt nanoparticles (NPs) and GelMA hydrogel to modulate the diabetic microenvironment for promoting bone regeneration. The GMAP enables the sustained release of Au@Pt NPs, which function as bimetallic nanozymes with dual enzyme‐like activities involving glucose oxidase and catalase. The synergistic effect allows for efficient glucose consumption and ROS elimination concurrently. Thus, the GMAP effectively protects the proliferation of bone marrow mesenchymal stem cells (BMSCs) under adverse high‐glucose conditions. Furthermore, it also promotes the osteogenic differentiation and paracrine capabilities of BMSCs, and subsequently inhibits inflammation and enhances angiogenesis. In vivo diabetic rats bone defect model, it is demonstrated that GMAP microspheres significantly improve bone regeneration, as verified by micro‐computed tomography and histological examinations. This study provides a novel strategy for bone regeneration by modulating the diabetic microenvironment, presenting a promising approach for addressing the complex challenges associated with bone healing in diabetic patients.

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Fracture healing research: Recent insights

Cited by 7 publications

References 148 publications

Complex Spatio-Temporal Interplay of Distinct Immune and Bone Cell Subsets during Bone Fracture Healing

Complex Spatio-Temporal Interplay of Distinct Immune and Bone Cell Subsets during Bone Fracture Healing

Promoting bone callus formation by taking advantage of the time-dependent fracture gap strain modulation

Hydrogel Microsphere‐Encapsulated Bimetallic Nanozyme for Promoting Diabetic Bone Regeneration via Glucose Consumption and ROS Scavenging

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