Fracture healing: from molecular and cellular mechanisms to therapeutic strategies
Abstract
Fracture healing is a highly orchestrated regenerative process that depends on precise temporal and spatial coordination of immune, vascular, neural, and skeletal signaling programs. Disruption of these interconnected pathways, whether due to local injury factors, systemic disease, aging, or metabolic dysregulation, can impair repair and result in delayed union or nonunion. Understanding the molecular mechanisms that integrate inflammation resolution, progenitor cell fate decisions, neurovascular coupling, and endochondral bone formation is therefore essential for improving clinical outcomes. Recent advances show that fracture repair is governed by dynamic signaling networks linking immune cells, mesenchymal progenitors, endothelial and neural components, and the extracellular matrix. Key pathways regulating cytokine signaling, angiogenesis, mechanotransduction, hypoxia sensing, and osteochondral differentiation have emerged as critical determinants of healing efficiency and quality. These insights have reshaped therapeutic strategies, enabling the development of targeted interventions, including growth factor and anabolic therapies, immunomodulatory agents, cell- and gene-based approaches, extracellular vesicles, and biomaterial-assisted delivery systems. In this review, we synthesize current mechanistic understanding of both physiological and impaired fracture healing, with an emphasis on intercellular signaling and pathway-level regulation. We critically evaluate emerging…
Read the paper
Related studies
- Effectiveness of Bisphosphonates and Denosumab on Risk of Vertebral Fractures in Prostate Cancer Patients Under Androgen Deprivation Therapies: A Real-World Prospective Study
- Osteoporosis-related fractures after spinal cord injury: a retrospective study from Brazil
- Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men
- Lack of Association between Vitamin D Insufficiency and Cardiovascular or Fracture Risk: A UK Biobank Study
- Muscle strength and body composition are clinical indicators of osteoporosis
- Incidence of bone protection and associated fragility injuries in patients with proximal femur fractures
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.