Immunohistochemical analysis revealed the expression of bone morphogenetic proteins-4, 6, 7, and 9 in human induced membrane samples treated with the Masquelet technique

Background Induced membrane (IM) is the key component of Masquelet reconstruction surgery for the treatment of bone defects. IM is formed around the cement spacer and is known to secrete growth factors and osteoinductive factors. However, there is limited evidence available concerning the presence of osteoinductive factors in IM. This study aimed to investigate the existence of bone morphogenetic proteins (BMPs) in IM harvested from patients during the treatment of bone defects using the Masquelet technique. Methods This study involved six patients whose bone defects had been treated using the Masquelet technique. The affected sites were the femur (n = 3) and the tibia (n = 3). During the second-stage surgery, 1 cm2 pieces of IM were harvested. Histological sections of IM were immunostained with anti-BMP-4, 6, 7, and 9 antibodies. Human bone tissue served as the positive control. Results The presence of BMP-4, 6, 7, and 9 was observed in all IM samples. Further, immunolocalization of BMP-4, 6, 7, and 9 was observed in blood vessels and fibroblasts in all IM samples. Immunolocalization of BMP-4, 6, 7, and 9 was also observed in bone tissue within the IM in one sample, in which osteogenesis inside the IM was observed. Conclusions This study showed that osteoinductive factors BMP-4, 6, 7, and 9 were present in the IM harvested from patients, providing evidence indicating that the Masquelet technique effectively contributes to healing large bone defects. Therefore, it may be possible for surgeons to omit the addition of BMPs to bone grafts, given the endogenous secretion of BMPs from the IM.

Implant Survival, Clinical Outcome and Complications of Megaprosthetic Reconstructions Following Sarcoma Resection

Megaprosthetic reconstruction of segmental bone defects following sarcoma resection is a frequently chosen surgical approach in orthopedic oncology. While the use of megaprostheses has gained popularity over the last decades and such implants are increasingly used for metastatic reconstructions and in non-tumor cases, there still is a high risk of long-term complications leading to revision surgery. This article investigates current implant survivorship, frequency and types of complications as well as functional outcomes of upper and lower limb megaprosthetic reconstructions.

Local Application of Mineral-Coated Microparticles Loaded With VEGF and BMP-2 Induces the Healing of Murine Atrophic Non-Unions

Deficient angiogenesis and disturbed osteogenesis are key factors for the development of nonunions. Mineral-coated microparticles (MCM) represent a sophisticated carrier system for the delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2. In this study, we investigated whether a combination of VEGF- and BMP-2-loaded MCM (MCM + VB) with a ratio of 1:2 improves bone repair in non-unions. For this purpose, we applied MCM + VB or unloaded MCM in a murine non-union model and studied the process of bone healing by means of radiological, biomechanical, histomorphometric, immunohistochemical and Western blot techniques after 14 and 70 days. MCM-free non-unions served as controls. Bone defects treated with MCM + VB exhibited osseous bridging, an improved biomechanical stiffness, an increased bone volume within the callus including ongoing mineralization, increased vascularization, and a histologically larger total periosteal callus area consisting predominantly of osseous tissue when compared to defects of the other groups. Western blot analyses on day 14 revealed a higher expression of osteoprotegerin (OPG) and vice versa reduced expression of receptor activator of NF-κB ligand (RANKL) in bone defects treated with MCM + VB. On day 70, these defects exhibited an increased expression of erythropoietin (EPO), EPO-receptor and BMP-4. These findings indicate that the use of MCM for spatiotemporal controlled delivery of VEGF and BMP-2 shows great potential to improve bone healing in atrophic non-unions by promoting angiogenesis and osteogenesis as well as reducing early osteoclast activity.

Evaluation of the Efficacy of Mineralized Dentin Graft in the Treatment of Intraosseous Defects: An Experimental In Vivo Study

Background and Objectives: Dentin grafts have osteoinductive and osteoconductive properties and are considered as an alternative to autogenous graft. This study evaluates the efficacy of autogenous mineralized dentin graft (AMDG) alone or with xenograft and compares it with those of various graft materials used in the treatment of intraosseous bone defects. Materials and Methods: The third incisor teeth of six sheep (2–3 years old) were extracted and AMDG was obtained. Six defects were prepared on each tibia of these six sheep: empty defect (group E); autogenous graft (group A), dentin graft (group D), xenograft (group X), autogenous + xenograft (group A + X) and dentin + xenograft (group D + X). Three sheep in each group were sacrificed in the post-operative 3rd and 6th week and the histologic analyses were performed. Results: The D and D + X groups showed histological features similar to the other groups in the 3rd and 6th weeks. No statistically significant difference was found regarding the rates of new bone formation between the D and D + X groups (p = 1.0) and the other groups at both time intervals (p > 0.05). Conclusions: Similar results observed in this study between groups A, D, X, A + X and D + X demonstrate that AMDG can be successfully used in the treatment of intraosseous bone defects. Further experimental and clinical studies are needed to be able to evaluate the effectiveness of dentin grafts in different types of indications.

Safety and efficacy of a novel retrograde route for femoral bone graft harvesting by Reamer-Irrigator-Aspirator: a pilot study on 24 patients

Background The Reamer–Irrigator–Aspirator system was initially developed to reduce fat embolism and thermic necrosis during reamed intramedullary nail fixation of femoral shaft fractures. Currently, this system is used in extended applications including accessing large volume of autologous bone graft, as alternative for iliac crest harvesting. Antegrade femoral bone graft harvesting using the Reamer-Irrigator-Aspirator system is considered the standard technique. The aim of our study is to evaluate the efficacy (bone graft volume) and the complications (blood loss, postoperative pain, and incidence of iatrogenic fractures) of the Reamer–Irrigator–Aspirator system through the retrograde femoral route in a series of patients with post-traumatic bone defects or nonunions. Methods A non-controlled single center retrospective observational cohort study was conducted in a level1 trauma center to evaluate all patients who were treated using the RIA system. Between November 2015 and May 2019, 24 patients (8 women and 16 men; mean age: 41 years [range 27–55 years]) with bone defects or nonunions underwent bone graft harvesting using the Reamer–Irrigator–Aspirator system through retrograde femoral route. Postoperative pain, complications, and bone graft volume were analyzed. Inclusion criteria was patients older than 18 years with a diagnosis of post-traumatic bone defect or associated tibial or femoral nonunion, with minimum 6-months follow, treated using the RIA. We hypothesized that the retrograde route of the RIA system is a safe and efficacious method for bone harvesting. Results The average volume of collected graft was 45 cc (range 30–60 cc). In 83% of the cases, bone grafting was sufficient, while in 17% it was necessary to add iliac crest bone graft to completely fill the bone defect. A mean drop in postoperative hemoglobin of 4.1 g / dL (range 0.5–6.0 g / dL) was evidenced. In 4 cases (33%), a unit of packed red blood cells was required. Regarding postoperative pain, visual analogue scale after 3 months postoperatively was 1.6 in average. After 6 months, the value has decreased to 0.4. There were no perioperative or postoperative complications at 6-month follow-up. Conclusion In this limited case series, large volumes of bone graft were harvested using the retrograde route of the RIA system and there were no intra-/ postoperative complications observed at 6-month follow-up. Therefore this novel technique appears safe and efficacious. However, it’s important to highlight that future prospective controlled studies are necessary to validate the insights from this pilot study.

Muscle and Bone Impairment in Infantile Nephropathic Cystinosis: New Concepts

Cystinosis Metabolic Bone Disease (CMBD) has emerged during the last decade as a well-recognized, long-term complication in patients suffering from infantile nephropathic cystinosis (INC), resulting in significant morbidity and impaired quality of life in teenagers and adults with INC. Its underlying pathophysiology is complex and multifactorial, associating complementary, albeit distinct entities, in addition to ordinary mineral and bone disorders observed in other types of chronic kidney disease. Amongst these long-term consequences are renal Fanconi syndrome, hypophosphatemic rickets, malnutrition, hormonal abnormalities, muscular impairment, and intrinsic cellular bone defects in bone cells, due to CTNS mutations. Recent research data in the field have demonstrated abnormal mineral regulation, intrinsic bone defects, cysteamine toxicity, muscle wasting and, likely interleukin-1-driven inflammation in the setting of CMBD. Here we summarize these new pathophysiological deregulations and discuss the crucial interplay between bone and muscle in INC. In future, vitamin D and/or biotherapies targeting the IL1β pathway may improve muscle wasting and subsequently CMBD, but this remains to be proven.

A Narrative Review of Cell-Based Approaches for Cranial Bone Regeneration

Current cranial repair techniques combine the use of autologous bone grafts and biomaterials. In addition to their association with harvesting morbidity, autografts are often limited by insufficient quantity of bone stock. Biomaterials lead to better outcomes, but their effectiveness is often compromised by the unpredictable lack of integration and structural failure. Bone tissue engineering offers the promising alternative of generating constructs composed of instructive biomaterials including cells or cell-secreted products, which could enhance the outcome of reconstructive treatments. This review focuses on cell-based approaches with potential to regenerate calvarial bone defects, including human studies and preclinical research. Further, we discuss strategies to deliver extracellular matrix, conditioned media and extracellular vesicles derived from cell cultures. Recent advances in 3D printing and bioprinting techniques that appear to be promising for cranial reconstruction are also discussed. Finally, we review cell-based gene therapy approaches, covering both unregulated and regulated gene switches that can create spatiotemporal patterns of transgenic therapeutic molecules. In summary, this review provides an overview of the current developments in cell-based strategies with potential to enhance the surgical armamentarium for regenerating cranial vault defects.

Positive Osteocalcin Expressions in Periodontium Regenerated by Nano Bioceramics after Orthodontic Tooth Movement

The research is to analyse the immunohistochemical reaction of orthodontic force on the periodontium reformed by nanobiphasic calcium phosphate ceramics (nBCP). Two third incisors were selected randomly and operated as experimental groups in 2 Beagle dogs. In the labial aspects of the third incisors, alveolar bone defects were surgically made and implanted with NBCP. The contralateral teeth in the same jaw did not receive any treatment as control. After 24 weeks, all the third incisors were moved labially. The dogs were euthanized 4 weeks later. The expression levels of osteocalcin were detected by immunohistochemical staining. Positive osteocalcin expressions in regenerated periodontium were observed and compared with the normal periodontium in the control groups. There were no significant differences within and between them. It means the periodontium regenerated by nBCP can bear orthodontic forces with a normal function. Based on these findings, we concluded that nBCP may offer a new bone graft choice for periodontic disease patients who have demands for orthodontic treatment.