Bioaugmented osteosynthesis: precise monitoring and intervention of the bone healing microenvironment

Fracture healing is a complex physiological process involving osteoblasts, osteoclasts and other cells and molecules. Typical fracture healing can be divided into four stages: inflammatory response, soft callus formation, hard callus formation, and bone remodeling. Osteoclasts play a leading role in hard callus formation and bone remodeling. Alendronate can inhibit osteoclast activity and bone loss in patients with osteoporosis, but it may also inhibit fracture healing. Therefore, whether alendronate can be used after osteoporotic fracture is controversial. In recent years, it has been found that alendronate can not affect the fracture healing, but also reduce the risk of secondary fracture and improve the prognosis of patients. In this article, the mechanism of alendronate and its effect on osteoporotic fracture healing by systemic and local use are reviewed, which can provide a reference for clinical selection of therapeutic drugs. Key words: Osteoporotic fractures; Fracture healing; Alendronate

IntroductionDelayed union and nonunion development remain a major clinical problematic complication during fracture healing, with partially unclear pathophysiology. Incidences range from 5 to 40% in high-risk patients, such as patients with periosteal damage. The periosteum is essential in adequate fracture healing, especially during soft callus formation. In this study, we hypothesize that inducing periosteal damage in a murine bone healing model will result in a novel delayed union model.Materials and methodsA mid-shaft femoral non-critically sized osteotomy was created in skeletally mature C57BL/6 mice and stabilized with a bridging plate. In half of the mice, a thin band of periosteum adjacent to the osteotomy was cauterized. Over 42 days of healing, radiographic, biomechanical, micro-computed tomography and histological analysis was performed to assess the degree of fracture healing.ResultsAnalysis showed complete secondary fracture healing in the control group without periosteal injury. Whereas the periosteal injury group demonstrated less than half as much maximum callus volume (p < 0.05) and bridging, recovery of stiffness and temporal expression of callus growth and remodelling was delayed by 7–15 days.ConclusionThis paper introduces a novel mouse model of delayed union without a critically sized defect and with standardized biomechanical conditions, which enables further investigation into the molecular biological, biomechanical, and biochemical processes involved in (delayed) fracture healing and nonunion development. This model provides a continuum between normal fracture healing and the development of nonunions.

Porous Network Concrete: a bio-inspired building component to make concrete structures self-healing

Effects of low-dose, intermittent treatment with recombinant human parathyroid hormone (1–34) on chondrogenesis in a model of experimental fracture healing

Bone fracture healing is a complex physiological process commonly described by a four-phase model consisting of an inflammatory phase, two repair phases with soft callus formation followed by hard callus formation, and a remodeling phase, or more recently by an anabolic/catabolic model. Data from humans and animal models have demonstrated crucial environmental conditions for optimal fracture healing, including the mechanical environment, blood supply and availability of mesenchymal stem cells. Fracture healing spans multiple length and time scales, making it difficult to know precisely which factors and/or phases to manipulate in order to obtain optimal fracture-repair outcomes. Deformations resulting from physiological loading or fracture fixation at the organ scale are sensed at the cellular scale by cells inside the fracture callus. These deformations together with autocrine and paracrine signals determine cellular differentiation, proliferation and migration. The local repair activities lead to new bone formation and stabilization of the fracture. Although experimental data are available at different spatial and temporal scales, it is not clear how these data can be linked to provide a holistic view of fracture healing. Mathematical modeling is a powerful tool to quantify conceptual models and to establish the missing links between experimental data obtained at different scales. The objective of this review is to introduce mathematical modeling to readers who are not familiar with this methodology and to demonstrate that once validated, such models can be used for hypothesis testing and to assist in clinical treatment as will be shown for the example of atrophic nonunions.

Highlights: Sodium diclofenac is one of NSAID a common treatment to relieve pain associated with bone fractures. Sodium diclofenac with a some dose of body weight could decrease the callus quality on fracture healing. Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac sodium, are standard treatments to relieve pain associated with bone fractures. The bone healing process consists of four stages: inflammation, soft callus formation, complex callus formation, and bone remodeling. Previous studies mentioned that intake of NSAIDs (sodium diclofenac) could inhibit the bone healing process. This study examined the effect of diclofenac sodium intake on callus formation in fracture healing. In this study, thirty-six rats (Rattus Norvegicus) with fractures were used and divided into two groups, namely 18 rats for the control and 18 rats for the treatment group. In the treatment group, each rat was given 1.8 mg sodium diclofenac/150 grams of body weight per day. In the control group, each rat was given CMC-Na 0.5% with equal volume as diclofenac sodium in the treatment group. After 28 days, all the rats were stunned until dead, and the diameter and strength of their calluses were measured. In the treatment group with diclofenac sodium1.8 mg/ 150 grams BW/ 28 days after the tibia bone callus was pressed using the Shimadzu tool, the lowest callus strength was found to be 56.500 N, and the highest callus strength was 59.000 N. The lowest callus diameter in the treatment group was 4 mm, the highest was 5 mm. In the control group, the lowest callus strength was 76 N, and the highest callus strength was 77 N. The lowest callus diameter in the control group was 6 mm, and the highest was 8 mm. The strongest callus in the treatment group was found in the sixth observation, with a value of 59 N and a diameter of 4 mm. In the control group, the highest callus strength was 77 N, with a diameter of 7-8 mm. These measurements were found on the 5th, 7th, 8th, 9th, 16th, and 17th observations. Diclofenac sodium with a dose of 1.8 mg/150 grams of body weight could decrease the callus quality parameters, such as callus strength and diameter on fracture healing.

Impaired soft and hard callus formation during fracture healing in diet-induced obese mice as revealed by 3D contrast-enhanced computed tomography imaging.

Low intensity pulsed ultrasound for fracture healing: A review of the clinical evidence and the associated biological mechanism of action

Thrombospondin-2 spatiotemporal expression in skeletal fractures.

Bone fracture healing is a complex process with distinct phases: the inflammatory phase, the soft and hard callus formation, and the remodeling phase. In older individuals, bone healing can be delayed or disturbed, leading to non-union fractures at worst. The initial healing phases require communication between immune cells and osteoprogenitor cells. However, senescence in these cell types impedes fracture healing by unknown mechanisms. In this issue of the JCI, Saul et al. showed that two distinct senescent p21-expressing cell populations, an osteochondroprogenitor cell and a neutrophil subpopulation, intrinsically impair fracture healing in mice irrespective of age. Genetic ablation of p21-positive cells accelerated fracture healing, while removal of a different senescent cell population, p16-positive cells, made no difference. Conceptually, this view of senescence in fracture healing with a spotlight on osteoimmune cross-talk provides a promising rationale for therapies to boost bone repair at all ages.

A method for repositioning a mandibular fracture with delayed union and/or nonunion

Fracture healing is a complex event that involves the coordination of different processes: initial inflammatory response, soft and hard callus formation, initial bony union and bone remodeling. This well-orchestrated series of biological events follows a specific temporal and spatial sequence that can be affected by biological factors, such as age and bone quality. There is some evidence that increased age is a considerable factor in the inhibition of fracture repair in human subjects. During aging there is an accumulation of damage that depends on the activation of inflammation processes and on changes in the circulating levels of inflammatory cytokines. In addition to the physiological slow down in the repair process, other conditions such as multiple comorbidities leading to polymedication are a frequent occurrence in elderly patients and can have an influence on this process. A further factor that affects bone metabolism is nutrition: bone quality, fragility fractures risk and fracture healing process are all influenced by the nutritional status. This review provides a summary of the immunological aspects of physiological fracture healing and of those nutritional factors which might play an important role in this process.

Bones comprise a significant percentage of human weight and have important physiologic and structural roles. Bone remodeling occurs when healthy bone is renewed to maintain bone strength and maintain calcium and phosphate homeostasis. It proceeds through four phases: (1) cell activation, (2) resorption, (3) reversal, and (4) bone formation. Bone healing, on the other hand, involves rebuilding bone following a fracture. There are two main types of bone healing, primary and secondary. Inflammation plays an integral role in both bone remodeling and healing. Therefore, a tightly regulated inflammatory response helps achieve these two processes, and levels of inflammation can have detrimental effects on bone healing. Other factors that significantly affect bone healing are inadequate blood supply, biomechanical instability, immunosuppression, and smoking. By understanding the different mechanisms of bone healing and the factors that affect them, we may have a better understanding of the underlying principles of bony fixation and thereby improve patient care.

Bone regeneration is a physiological bone formation process involved in routine fracture healing and continuous remodeling throughout adult life. The study's main objective is to determine the role of orthopedic medicines in bone regeneration and healing process. This retrospective study was conducted in a public hospital in Karachi, Pakistan, from February 2023 to June 2023. The study aimed to collect data from 120 bone fracture patients and evaluate the progression of bone healing to identify critical determinants of successful regeneration. Clinical assessments, radiological imaging, and histopathological analyses were conducted to achieve the study's objectives. The study collected data from 120 patients, with a mean age of 45.21±12.3 years. Of these, 70 were male and 50 were female. Upper extremities accounted for 40% of fractures, lower extremities 30%, and axial skeleton 30%. Simple fractures accounted for 50% of cases, while comminuted fractures represented 30% and open fractures 20%. There was a strong positive correlation between fracture severity and the time required for radiographic union, with a correlation coefficient (r) of 0.65 (p &lt; 0.001). Additionally, biomarkers of bone turnover exhibited a moderate positive correlation with radiological healing, with a correlation coefficient (r) of 0.45 (p = 0.003). The study concludes that orthopedic interventions have a high success rate in achieving satisfactory outcomes, with the majority of patients experiencing successful bone healing and restoration of function.

Bone remodeling during fracture repair: The cellular picture