Viable osteoblastic potential of cortical reamings from intramedullary nailing

Journal of Orthopaedic Research, 2005

We hypothesise that following a bone fracture there is systemic recruitment of bone forming cells to a fracture site. A rabbit ulnar osteotomy model was adapted to trace the movement of osteogenic cells. Bone marrow mesenchymal stem cells from 41 NZW rabbits were isolated, culture-expanded and fluorescently labelled. The labelled cells were either re-implanted into the fracture gap (Group A); into a vein (Group B); or into a remote tibial bone marrow cavity 48 h after the osteotomy (Group C) or 4 weeks before the osteotomy was established (Group D), and a control group (Group E) had no labelled cells given. To quantify passive leakage of cells to an injury site, inert beads were also co-delivered in Group B. Samples of the fracture callus tissue and various organs were harvested at discrete sacrifice time-points to trace and quantify the labelled cells. At 3 weeks following osteotomy, the number of labelled cells identified in the callus of Group C, was significantly greater than following IV delivery, Group B, and there was no difference in the number of labelled cells in the callus tissues, between Groups C and A, indicating the labelled bone marrow cells were capable of migrating to the fracture sites from the remote bone marrow cavity. Significantly fewer inert beads than labelled cells were identified in Group B callus, suggesting some of the bone-forming cells were actively recruited and selectively chosen to the fracture site, rather than passively leaked into the circulation and to bone injury site. This investigation supports the hypothesis that some osteoblasts involved in fracture healing were systemically mobilised and recruited to the fracture from remote bone marrow sites.

Acta Orthopaedica Scandinavica, 1970

Introduction.. . Literature Review Blood supply of the diaphyseal bone on nailing. Periosteal bone reaction after nailing. Reaming of the medullary cavity. . Fracture stability on nailing.. .. . Fracture stability and healing pattern. Nailing and reaming in relation to fat embolism Material and Methods. Premises. Material. Methods. Operative procedure. Recording methods .

Journal of Orthopaedic Research, 2010

Substance P (SP) has been shown in vitro to stimulate both formation and resorption of bone. This seemingly contradictory observation could be explained by in vivo variations in skeletal loading and rate of bone turnover, features which may be explored during different phases of fracture healing. In 50 SD rats, the right tibia was fractured and fixed with an intramedullary pin in straight alignment and in anterior angulation resulting in a convex and concave side under different load. Fracture repair was assessed by radiography, histology, and semi-quantitative immunohistochemistry of SP nerve fiber occurrence at days 7, 21, 35, 56, and 84 post-fracture. During regeneration, days 7-35, abundant SP-nerve ingrowth was observed in the fracture callus reaching a side-symmetrical peak at day 21 in straight fractures. In angulated fractures, the SP peak was also observed at day 21 on the concave loaded side, but not until day 35 on the convex unloaded side. Each SP-peak coincided with cortical bridging. During remodeling, days 35-84, a side-symmetrical disappearance of SP-positive fibers was seen in straight fractures. The same pattern was seen on the concave loaded side of angulated fractures. However, on the convex unloaded side, where resorption now took place, SP-fibers remained until the end of the experiment. Our study suggests that neuronal SP during bone regeneration has a stimulatory role on bone formation, while during remodeling increased SP fiber density in unloaded areas may be related to bone resorption.

2021

Fracture healing is the most common regeneration form in clinical practice. Bone as a tissue has the unique ability to heal itself without forming a scar. After the fracture, a chain of healing reactions is activated, both at the cellular and tissue level, that lead to full bridging of the gap between the two bony ends of the fracture. There are many immune cells that take part in this healing process and they play a significant role. There are three sequential phases to the process of fracture healing that remain independent. It has been revealed that the immune cells take part not only in the inflammation phase but also in the repair phase, where some of these cells act as intermediates to the transformation of soft callus to hard callus. In conclusion, immune cells serve as initial responders at the site of injury, restore vasculature, and initiate cascades of signals to recruit cells to carry out the repair processes. Thus the immune system can be considered a promising therapeu...

EFORT Open Reviews

The ability to enhance fracture healing is paramount in modern orthopaedic trauma, particularly in the management of challenging cases including peri-prosthetic fractures, non-union and acute bone loss. Materials utilised in enhancing fracture healing should ideally be osteogenic, osteoinductive, osteoconductive, and facilitate vascular in-growth. Autologous bone graft remains the gold standard, providing all of these qualities. Limitations to this technique include low graft volume and donor site morbidity, with alternative techniques including the use of allograft or xenograft. Artificial scaffolds can provide an osteoconductive construct, however fail to provide an osteoinductive stimulus, and frequently have poor mechanical properties. Recombinant bone morphogenetic proteins can provide an osteoinductive stimulus; however, their licencing is limited and larger studies are required to clarify their role. For recalcitricant non-unions or high-risk cases, the use of composite graft...

The Journal of Bone & Joint Surgery, 2006

Background: Heterotopic bone formation has been observed in patients with traumatic brain injury; however, an association between such an injury and enhanced fracture-healing remains unclear. To test the hypothesis that traumatic brain injury causes a systemic response that enhances fracture-healing, we established a reproducible model of traumatic brain injury in association with a standard closed fracture and measured the osteogenic response with an in vitro cell assay and assessed bone-healing with biomechanical testing. Methods: A standard closed femoral fracture was produced in forty-three Sprague-Dawley rats. Twenty-three of the rats were subjected to additional closed head trauma that produced diffuse axonal injury similar to that observed in patients with a traumatic brain injury. Twenty-one days after the procedure, all animals were killed and fracture-healing was assessed by measuring callus size and by mechanical testing. Sera from the animals were used in subsequent in vitro experiments to measure mitogenic effects on established cell lines of committed osteoblasts, fibroblasts, and mesenchymal stem cells. Results: Biomechanical assessment demonstrated that the brain-injury group had increased stiffness (p = 0.02) compared with the fracture-only group. There was no significant difference in torsional strength between the two groups. Cell culture studies showed a significant increase in the proliferative response of mesenchymal stem cells after exposure to sera from the brain-injury group compared with the response after exposure to sera from the fractureonly group (p = 0.0002). This effect was not observed in fibroblasts or committed osteoblasts. Conclusions: These results support data from previous studies that have suggested an increased osteogenic potential and an enhancement of fracture-healing secondary to traumatic brain injury. Our results further suggest that the mechanism for this enhancement is related to the presence of factors in the serum that have a mitogenic effect on undifferentiated mesenchymal stem cells. Clinical Relevance: Fracture-healing may be enhanced by an associated traumatic brain injury. Further understanding of this systemic response could lead to important insights about systemic therapeutic strategies for the enhancement of skeletal repair.

Journal of Orthopaedic Science, 2001

Calcified Tissue International, 2010

Fracture healing is a complex process that involves several cell types; as a previous report suggested an increase in osteoblast (OB) precursors in peripheral blood during this process, this paper examines the role of circulating bone cell precursors in this process in the light of a prior suggestion that OB precursors are increased. Nine healthy men less than 60 years old with traumatic fractures were enrolled. The parameters circulating OB precursors (osteocalcin?/alkaline phosphatase?/CD15cells) and osteoclast precursors (CD14?/CD11b?/vitronectin receptor ? cells) were measured by flow cytometry; bone formation markers and TGFb1, by ELISA; and PTH, by RIA in serum on arrival at the emergency department (baseline) and 15 days after fracture. Bone cell precursors behaved differently during healing. TGFb1 was inversely correlated with OB number, but increased their degree of maturation at baseline. Bone formation markers and TGFb1 were increased after fracture, whereas PTH was decreased. The TGFb1 increase was directly correlated with age, whereas age was not correlated with the precursors. In conclusion, we confirm the role of TGFb1 in fracture healing; and its possible role in the control of pre-OB homeostasis. There was no variation in circulating precursor cells during healing, though the increase in TGFb1 may suggest increased pre-OB maturation and homing to the injured site.

Seminars in Cell & Developmental Biology, 2008

Fracture healing is a complex event that involves the coordination of a variety of different processes. Repair is typically characterized by four overlapping stages: the initial inflammatory response, soft callus formation, hard callus formation, initial bony union and bone remodeling. However, repair can also be seen to represent a juxtaposition of two distinct forces: anabolism or tissue formation, and catabolism or remodeling. These anabolic/catabolic concepts are useful for understanding bone repair without giving the false impression of temporally distinct stages that operate independently. They are also relevant when considering intervention.

Acta Orthopaedica, 1985

In an attempt to determine the effects of peripheral nerve lesions on fracture healing, radiographic, histomorphometric and chemical methods were used to evaluate callus formation in tibial fractures of rats with sciatic denervation. Fracture union by bridging external callus was more rapid in denervated limbs than in controls. By contrast, external calluses of denervated fractures were smaller and less dense and contained less collagenous matrix (hydroxyproline) and minerals (calcium, phosphorus) than controls. The RNNDNA ratio decreased more rapidly in denervated calluses than in controls. Mineralization of collagenous matrix (estimated from the calciudhydroxyproline ratio) was not affected by denervation.

Journal of Orthopaedic Trauma, 2019

Ongoing studies investigating fracture healing have uncovered and allowed investigators to gain a better understanding of where the variety of cells, which participate in this process, originate, and how they communicate as well as how they can be enhanced to successfully heal a fracture when the process has slowed or failed completely. This brief review will highlight some of the recent findings regarding the role the immune system in fracture healing and how these cells communicate with each other during the healing process. In addition, two 2 methods that have recently been shown to be promising techniques in supporting fracture when it stalls or reversing the process, when the fracture has failed to heal, will also be described.

BMC biotechnology, 2016

The human body has an extensive capacity to regenerate bone tissue after trauma. However large defects such as long bone fractures of the lower limbs cannot be restored without intervention and often lead to nonunion. Therefore, the aim of the present study was to assess the pool and biological functions of human mesenchymal stromal cells (hMSCs) isolated from different bone marrow locations of the lower limbs and to identify novel strategies to prime the cells prior to their use in bone fracture healing. Following, bone marrow from the ilium, proximal femur, distal femur and proximal tibia was aspirated and the hMSCs isolated. Bone marrow type, volume, number of mononuclear cells/hMSCs and their self-renewal, multilineage potential, extracellular matrix (ECM) production and surface marker profiling were analyzed. Additionally, the cells were primed to accelerate bone fracture healing either by using acoustic stimulation or varying the initial hMSCs isolation conditions. We found th...

Biomaterials, 2001

Fracture healing could be stimulated with osteoinductive bone morphogenetic proteins (bmp's), such as osteogenic protein-1 (OP-1), but little is known about its e!ectiveness in stimulation of fracture healing. In this study, biomechanical and histological aspects of fracture healing after an injection of OP-1 in the fracture gap were investigated. In 40 goats, a closed fracture was created in the left tibia. The fractures were stabilized with an external "xator and the animals were assigned to four di!erent groups: no injection, injection of 1 mg OP-1, injection of 1 mg OP-1 with collagenous carrier material, and injection of carrier material alone. Twenty-one animals were sacri"ced after 2 weeks and 19 after 4 weeks. Biomechanical testing was perfomed on both explanted tibiae. Four longitudinal samples of the fracture were sawn, processed for histology, and examined by two observers. Biomechanical evaluation showed a higher sti!ness and strength at 2 weeks after injection of OP-1. Histological evaluation showed normal fracture healing patterns in all animals without adverse e!ects of the given injections. These data show that fracture healing can be accelerated with a single injection of OP-1, eventually resulting in normally healed bone.

Experimental Animals, 2011

To clarify the distribution of bone-marrow-derived cells in fractures treated by plate fixation, fracture models were created using the green fluorescent protein (GFP) chimeric mouse. We observed 2 types of fracture healing processes with different types of callus formation and cellular events by using Mouse Fix™, a device allowing plate fixation on the mouse femur, and differences in the distribution of bone-marrow-derived cells between the 2 types. The GFP chimeric mice were created by bone marrow transplantation. Fractures were created on the left femurs of mice and stabilized with either rigid (Group R) or flexible (Group F) plates to prepare undecalcified fresh-frozen sections. In Group F, a large external callus and a large intramedullary callus were formed mostly by endochondral ossification. The cells that made up the intramedullary callus and callus in the fracture gap were GFP positive, but most cells of the external callus were not. In Group R, bone union was achieved mostly without external callus formation, bone apposition occurred directly in the gap, and a small intramedullary callus was formed. As observed in Group F, this group had GFP-positive cells in the callus within the fracture gap and in the intramedullary calluses. The results of this study provided direct evidence of the distribution of bone-marrow-derived cells in the callus of fractures treated by plate fixation under different stability conditions.