-
Open Veterinary Journal Apr 2024The bone regeneration potential of erythropoietin (EPO) is not yet fully investigated, but some previous experimental studies demonstrated that its application activated...
BACKGROUND
The bone regeneration potential of erythropoietin (EPO) is not yet fully investigated, but some previous experimental studies demonstrated that its application activated the differentiation of osteoblasts and promoted bone formation.
AIM
The aim of the present study was to evaluate the effects of recombinant human erythropoietin (rhEpo) on bone healing in cats with fragmented long bone fractures.
METHODS
Twelve cats were divided into two groups-control ( = 6) in which physiological saline was applied at the fracture gap site and EPO ( = 6) with the application of 1,000 IU rhEpo. The effects of EPO on blood erythrocyte counts, hemoglobin content, and hematocrit were monitored by serial complete blood cell tests, whereas bone formation was evaluated by clinical and radiographic examinations on post-operative weeks 1, 2, 3, 4, 6, and 8.
RESULTS
All tested blood parameters were within the reference range. A faster fracture healing and full limb weight-bearing were observed in the EPO group, with statistically significant differences with respect to the control group.
CONCLUSION
The obtained results confirmed that the local application of rhEpo promoted bone healing in cats with fragmented femoral fractures and increased bone callus strength without having significant systemic effects.
Topics: Animals; Cats; Erythropoietin; Recombinant Proteins; Fracture Healing; Femoral Fractures; Male; Female; Cat Diseases; Humans
PubMed: 38808286
DOI: 10.5455/OVJ.2024.v14.i4.8 -
Journal of Clinical Medicine May 2024The controlled dynamization of fractures can promote natural fracture healing by callus formation, while overly rigid fixation can suppress healing. The advent of locked... (Review)
Review
The controlled dynamization of fractures can promote natural fracture healing by callus formation, while overly rigid fixation can suppress healing. The advent of locked plating technology enabled new strategies for the controlled dynamization of fractures, such as far cortical locking (FCL) screws or active plates with elastically suspended screw holes. However, these strategies did not allow for the use of non-locking screws, which are typically used to reduce bone fragments to the plate. This study documents the first in vivo study on the healing of ovine tibia osteotomies stabilized with an advanced active plate (AAP). This AAP allowed plate application using any combination of locking and non-locking screws to support a wide range of plate application techniques. At week 9 post-surgery, tibiae were harvested and tested in torsion to failure to assess the healing strength. The five tibiae stabilized with an AAP regained 54% of their native strength and failed by spiral fracture through a screw hole, which did not involve the healed osteotomy. In comparison, tibiae stabilized with a standard locking plate recovered 17% of their strength and sustained failure through the osteotomy. These results further support the stimulatory effect of controlled motion on fracture healing. As such, the controlled dynamization of locked plating constructs may hold the potential to reduce healing complications and may shorten the time to return to function. Integrating controlled dynamization into fracture plates that support a standard fixation technique may facilitate the clinical adoption of dynamic plating.
PubMed: 38792446
DOI: 10.3390/jcm13102905 -
Journal of Orthopaedic Case Reports May 2024The masquelet technique is a two-stage procedure used by orthopedic surgeons to treat large segmental bone defects secondary to infection, trauma, and tumor resection....
INTRODUCTION
The masquelet technique is a two-stage procedure used by orthopedic surgeons to treat large segmental bone defects secondary to infection, trauma, and tumor resection. This technique characteristically requires the placement of a temporary cement spacer and subsequent bone grafting for complete reconstruction. We describe a unique case of segmental bone loss reconstruction in which a patient successfully achieved fracture union after the first step of the masquelet technique without bone grafting.
CASE REPORT
This is a case of a 21-year-old male who presented with an open femur fracture with 10 cm of segmental bone loss after a motorcycle collision. An antibiotic cement spacer was inserted according to the first stage of the masquelet technique. Due to considerable callus formation around the spacer, normal alignment, and pain-free ambulation at follow-up, further surgical intervention was not pursued, and the poly-methyl-methacrylate spacer was left in place. The fracture healed without infection, and the patient remained weight-bearing without pain.
CONCLUSION
This case identifies a unique instance of successful fracture union of a 10 cm segmental bone defect despite the completion of only the first step in the masquelet procedure. While the masquelet technique is believed to be a mandatory two-step procedure, this unique case of rapid bone growth and fracture union warrants further research on the possibilities of masquelet-induced regeneration without bone grafting.
PubMed: 38784867
DOI: 10.13107/jocr.2024.v14.i05.4446 -
Medical Journal of the Islamic Republic... 2024In extra-articular distal femoral fractures (EDFFs), nonunion is a serious complication that occurs rarely. In this study, we examined how longer preservation of initial...
BACKGROUND
In extra-articular distal femoral fractures (EDFFs), nonunion is a serious complication that occurs rarely. In this study, we examined how longer preservation of initial fracture hematoma by delaying the osteosynthesis (OS) affects the fracture union.
METHODS
In a retrospective cohort study, 98 EDFF patients were included. The OS was done within 2 days of injury in 50 patients (early OS group) and after 2 days of injury in 48 patients (late OS group). Time to callus formation and fracture union, bleeding amount, surgical duration, pain, knee range of motion, knee function, and postoperative complications, including the nonunion, knee deformity, infection, and revision, were compared between the 2 groups. Statistical analyses were done with SPSS. A comparison of the mean between the 2 groups was made with an independent t test or its nonparametric counterpart. A comparison of categorical variables between the 2 groups was made using a chi-square or the Fisher's exact test. ˂ 0.05 was considered statistically significant.
RESULTS
The mean time to callus formation was 47.1 ± 17.3 days in the early OS group and 46.9 ± 19.7 in the late OS group ( = 0.950). The mean time to fracture union was 114.9 ± 21 in the early OS group and 117.4 ± 28.8 days in the late OS group ( = 0.630). The mean operation time and bleeding amount between the 2 groups did not differ significantly ( = 0.230 and = 0.340, respectively). The knee range of motion, pain, and function were not notably different ( = 0.620, = 0.790, and = 0.770, respectively). Nonunion occurred in 3 patients of early OS and 2 patients of the late OS group. Other complications were also comparable in the 2 study groups.
CONCLUSION
Delayed OA in EDFF patients has no significant effect on bone healing and fracture union. Future standard studies are required to confirm these results.
PubMed: 38783980
DOI: 10.47176/mjiri.38.25 -
Journal of Orthopaedic Surgery and... May 2024Elderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic...
BACKGROUND
Elderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic inflammation with decreased antioxidant capacity. Tanshinone IIA is widely used in treating cardiovascular and cerebrovascular diseases in China and has anti-inflammatory and antioxidant effects. We aimed to observe the antioxidant effects of Tanshinone IIA on mesenchymal stem cells (MSCs), which play important roles in bone repair, and the effects of local application of Tanshinone IIA using an injectable biodegradable hydrogel on osteoporotic fracture healing.
METHODS
MSCs were pretreated with or without different concentrations of Tanshinone IIA followed by HO treatment. Ovariectomized (OVX) C57BL/6 mice received a mid-shaft transverse osteotomy fracture on the left tibia, and Tanshinone IIA was applied to the fracture site using an injectable hydrogel.
RESULTS
Tanshinone IIA pretreatment promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes, and inhibited HO-induced reactive oxygen species accumulation in MSCs. Furthermore, Tanshinone IIA reversed HO-induced apoptosis and decrease in osteogenic differentiation in MSCs. After 4 weeks of treatment with Tanshinone IIA in OVX mice, the bone mineral density of the callus was significantly increased and the biomechanical properties of the healed tibias were improved. Cell apoptosis was decreased and Nrf2 expression was increased in the early stage of callus formation.
CONCLUSIONS
Taken together, these results indicate that Tanshinone IIA can activate antioxidant enzymes to protect MSCs from HO-induced cell apoptosis and osteogenic differentiation inhibition. Local application of Tanshinone IIA accelerates fracture healing in ovariectomized mice.
Topics: Animals; Abietanes; Female; Mesenchymal Stem Cells; Apoptosis; Mice, Inbred C57BL; Fracture Healing; Ovariectomy; Mice; Antioxidants; Hydrogen Peroxide; Osteogenesis; Osteoporotic Fractures
PubMed: 38783358
DOI: 10.1186/s13018-024-04793-x -
JCI Insight May 2024We present a transcriptomic analysis that provides a better understanding of regulatory mechanisms within the healthy and injured periosteum. The focus of this work is...
We present a transcriptomic analysis that provides a better understanding of regulatory mechanisms within the healthy and injured periosteum. The focus of this work is on characterizing early events controlling bone healing during formation of periosteal callus on day 3 post fracture. Building upon our previous findings showing that induced Notch1 signaling in osteoprogenitors leads to better healing, we compared samples in which Notch 1 intracellular domain is overexpressed by periosteal stem/progenitor cells with control intact and fractured periosteum. Molecular mechanisms and changes in skeletal stem/progenitor cells (SSPCs) and other cell populations within the callus, including hematopoietic lineages were determined. Notably, Notch ligands were differentially expressed in endothelial and mesenchymal populations, with Dll4 restricted to endothelial cells, whereas Jag1 was expressed by mesenchymal populations. Targeted deletion of Dll4 in endothelial cells using Cdh5CreER resulted in negative effects on early fracture healing, while deletion in SSPCs using α-smooth muscle actin-CreER did not impact bone healing. Translating these observations into clinically relevant model of bone healing revealed the beneficial effects of delivering Notch ligands alongside osteogenic inducer, BMP2. These findings provide insights into the regulatory mechanisms within the healthy and injured periosteum, paving the way for novel translational approaches to bone healing.
PubMed: 38781018
DOI: 10.1172/jci.insight.181073 -
Stem Cell Research & Therapy May 2024The aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low...
BACKGROUND
The aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low dose of recombinant human rhBMP-2 to promote the regeneration of a metaphyseal femoral defect in an osteoporotic rat model.
METHODS
6 weeks after induction of osteoporosis by bilateral ventral ovariectomy and administration of a special diet, a total of 64 rats underwent a distal femoral metaphyseal osteotomy using a manual Gigli wire saw. Defects were stabilized with an adapted Y-shaped mini-locking plate and were subsequently treated with alginate only, or alginate loaded with hUC-MSC-sEVs (2 × 10), rhBMP-2 (1.5 µg), or a combination of sEVs and rhBMP-2 (n = 16 for each group). 6 weeks post-surgery, femora were evaluated by µCT, descriptive histology, and biomechanical testing.
RESULTS
Native radiographs and µCT analysis confirmed superior bony union with callus formation after treatment with hUC-MSC-sEVs in combination with a low dose of rhBMP-2. This finding was further substantiated by histology, showing robust defect consolidation 6 weeks after treatment. Torsion testing of the explanted femora revealed increased stiffness after application of both, rhBMP-2 alone, or in combination with sEVs, whereas torque was only significantly increased after treatment with rhBMP-2 together with sEVs.
CONCLUSION
The present study demonstrates that the co-application of hUC-MSC-sEVs can improve the efficacy of rhBMP-2 to promote the regeneration of osteoporotic bone defects.
Topics: Animals; Bone Morphogenetic Protein 2; Recombinant Proteins; Osteoporosis; Rats; Female; Humans; Femur; Umbilical Cord; Extracellular Vesicles; Bone Regeneration; Rats, Sprague-Dawley; Transforming Growth Factor beta; Disease Models, Animal; X-Ray Microtomography; Mesenchymal Stem Cells
PubMed: 38764077
DOI: 10.1186/s13287-024-03755-8 -
Frontiers in Surgery 2024Delayed 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... (Review)
Review
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.
PubMed: 38756355
DOI: 10.3389/fsurg.2024.1376441 -
PloS One 2024First metatarsophalangeal joint arthrodesis is a typical medical treatment performed in cases of arthritis or joint deformity. The gold standard for this procedure is... (Comparative Study)
Comparative Study
Comparative analysis of mechanical conditions in bone union following first metatarsophalangeal joint arthrodesis with varied locking plate positions: A finite element analysis.
BACKGROUND
First metatarsophalangeal joint arthrodesis is a typical medical treatment performed in cases of arthritis or joint deformity. The gold standard for this procedure is arthrodesis stabilisation with the dorsally positioned plate. However, according to the authors' previous studies, medially positioned plate provides greater bending stiffness. It is worth to compare the mechanical conditions for bone formation in the fracture callus for both placements of the locking plate.
METHODS
Two finite element models of the first metatarsophalangeal joint with the dorsally and medially positioned plate were defined in the Abaqus software to simulate differentiation of the fracture callus. A simplified load application, i.e. one single step per each day and the diffusion of the mesenchymal stem cells into the fracture region were assumed in an iterative hardening process. The changes of the mesenchymal stem cells into different phenotypes during the callus stiffening were governed by the octahedral shear strain and interstitial fluid velocity according to Prendergast mechanoregulation theory. Basing on the obtained results the progress of the cartilage and bone tissues formation and their distribution within the callus were compared between two models.
FINDINGS
The obtained results suggest that after 6 weeks of simulation the healing progress is in general comparable for both plates. However, earlier closing of external callus was observed for the medially positioned plate which had greater vertical bending stiffness. This process enables faster internal callus hardening and promotes symmetrical bridging.
Topics: Finite Element Analysis; Arthrodesis; Bone Plates; Humans; Metatarsophalangeal Joint; Biomechanical Phenomena; Bony Callus; Fracture Healing
PubMed: 38753866
DOI: 10.1371/journal.pone.0303752 -
The Journal of Clinical Investigation May 2024Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they...
Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21+ cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21+ cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21+ cell clearance did not alter bone loss due to aging; conversely, p16+ cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21+ neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21+ OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell-like OCH subset that was p21+ and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells were key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings established contextual roles of p21+ vs p16+ senescent/senescent-like cells that may be leveraged for therapeutic opportunities.
PubMed: 38753433
DOI: 10.1172/JCI179834