Massive Bone Defects Research Articles

Deformity correction (upper tibial bone defect due to osteomyelitis) in lower limb using Ilizarov technique

Here we are presenting a massive bone defect of upper tibia and 7 cm limb length discrepancy due to long standing osteomyelitis, which was treated successfully using Ilizarov technique and frame.

Effects of VEGF on Prefabricated Vascularized Bone Allografts in Rats

Massive bone defects after wide resection of malignant bone tumors or a serious injury require treatment using vascularized bone grafts. Although cadaveric bone allografts combined with vascularized bone autografts are currently thought to be ideal in terms of size and durability, this treatment requires the scarification of healthy bone tissue. In a previous study, we attempted to improve this situation by prefabricating a vascularized bone allograft in recipient rats. In this study, we added vascular endothelial growth factor (VEGF)-containing hydroxyapatite/collagen composite (HAp/Col) to a prefabricated vascularized bone allograft to stimulate angiogenesis, which is known to be important for bone formation. Sprague Dawley rats (n = 50) were used as donors and Wistar rats (n = 50) as recipients. All rats were 9 weeks old. The recipient rats were divided into five groups according to the use of vascular bundles, HAp/Col, and an additive substance (VEGF). The bone allografts collected from the donors were transplanted into the thigh region of the recipients, and a saphenous vein and 10 μg HAp/Col with VEGF were inserted into the bone allografts through the slit. After 4 weeks, the transplanted bone allografts were harvested, and histologic and genetic evaluations were performed in relation to bone formation and resorption. The results showed that, compared with the control group, the implantation of the vascular bundles and VEGF-containing HAp/Col significantly stimulated angiogenesis and bone formation in the rats with the bone allografts. However, histological and genetic evaluations of bone resorption revealed that resorption was not observed in any group. These results suggest that VEGF-containing HAp/Col effectively stimulates angiogenesis and bone formation, but not bone resorption, in prefabricated vascularized bone allografts. This method could therefore become a useful tool for treating large bone defects.

Bone Union Enhancement by bFGF-Containing HAp/Col in Prefabricated Vascularized Allo-Bone Grafts.

We have developed a prefabricated vascularized allo-bone graft (PVAG) by implanting the saphenous vascular bundles of recipient rats into transplanted donor bones in a flow-through manner. We previously demonstrated that the angiogenetic and bone formative abilities of the PVAG are stimulated by the addition of a basic fibroblast growth factor (bFGF)-containing hydroxyapatite/collagen (HAp/Col). This study aimed to demonstrate that the bone union ability of the PVAG is similarly stimulated by the bFGF-containing HAp/Col composite. Sprague-Dawley donor rats (n = 32) and Wistar recipient rats (n = 32) were used in this study. The PVAG was fixed to the femur of the recipient rat using K-wire (dimeter: 0.7 mm) pinning, followed by suturing with a 4-0 nylon suture. Recipients were divided into four groups: with or without vascular bundles, and with or without bFGF-containing HAp/Col. Rats were sacrificed 6 weeks after transplantation, and bone union, bone resorption, and angiogenesis were radiologically and histologically evaluated. Radiological analysis revealed a significant increase in callus formation and union rate, while histological analysis showed a significant increase in bone formation and angiogenesis in the group treated with both vascular bundles and bFGF. Bone resorption did not significantly increase in any of the evaluated groups. Osteogenic cells, osteoconductive scaffolds, growth factors, and mechanical environment are known to be important factors in the process of fracture healing. The PVAG developed herein contains osteogenic cells, osteoconductive scaffolds, and growth factors. In addition, the PVAG is rigidly fixed to the fracture site, providing a stable mechanical environment. Together, these four factors contributed to a good bone union. Furthermore, this method did not promote bone resorption. Thus, the addition of a vascular bundle and bFGF-containing HAp/Col makes it possible to create an ideal vascularized allo-bone graft for the reconstruction of massive bone defects.

Survival Analysis of Allografting and Antiprotrusio Cage in Treating Massive Acetabular Bone Defects

BackgroundMassive acetabular bone defects reconstructed with allografting and antiprotrusio cage in revision hip arthroplasty is less reported in the literature. We here report a series of 84 antiprotrusio cages and analyze the risk factors associated with failure. MethodsAll instances of use of an antiprotrusio cage for massive acetabular defect (Paprosky type IIc, III, and pelvic discontinuity) between 2002 and 2017 in the authors’ institute were reviewed after institutional review board’s approval. Survival analyses based on clinical data, bone defect (Paprosky system), type of allograft, size of cage, fixation quality, and position of cage were performed. Failure was defined as cage loosening or breakage, poor hip function, or cage revision for any reason. ResultsA total of 84 cages in 77 patients (mean age, 62.9 years), with a mean follow-up period of 6.2 years, had a survival rate of 82.1%. Failure was noted in 15 hips, including mechanical failure in 8 hips, recurrent dislocation in 1 hip, poor hip function in 1 hip, and periprosthetic joint infection in 5 hips. Pelvic discontinuity, reconstruction with morselized allograft alone, and fewer than 4 fixation points to the host bone were associated with higher failure rates (hazard ratios, 4.02, 3.42, and 9.9, respectively). ConclusionWe found that an antiprotrusio cage combined with strut allografts, fixed securely to the host bone (>4 fixation points), are beneficial for the management of massive acetabular bone defects. However, pelvic discontinuity remains a challenge that warrants the further study of technical or prosthetic innovations, such as triflange implants, cup cage, and 3D-printed implants.

Management of the bone loss by metaphyseal sleeves in primary and revision knee arthroplasty: clinical experience and outcome after forty three cases.

Management of metaphyseal bone loss in complex primary and revision TKA is a challenge for surgeons. Out of various types of bony defects, large metaphyseal bone loss (AORI types IIB and III) requires special augments in the form of cones or sleeves. The aim of this study is to assess the reliability of metaphyseal sleeves, in dealing with massive bone defects to provide stability for immediate weight bearing and also to check short to mid-term survivorship of metaphyseal sleeves in Asian population by assessing various parameters and complications. This is a retrospective study that includes 36 patients (43 knees), operated from 2011 to 2019. Patients with AORI type IIB (large metaphyseal bone defect) and AORI type III (metaphyseal defect with compromised collateral ligaments) were included. We included both the primary and revision knee arthroplasties in our study. Our interest in this study was to look for incidence of intra-operative iatrogenic fracture on the one hand, and post-operative complications in the form of peri-prosthetic joint infection and aseptic loosening on the other hand. Knee Society Score (KSS) was used to assess improvement in patient's clinical outcome. SPSS version 23 was used to process data. The average age of patients in our study was 59.4 (SD 9.78) years. Male to female ratio was 21:15. The average follow-up was 5.42 (SD 2.24) years with the longest follow up of nineyears. Metaphyseal sleeves were used in 12 primary TKA and 31 revision TKA. During surgery, iatrogenic fracture of tibial condyle was encountered in three patients (6.9%), all were managed without any intervention and union was achieved in all cases. There was not a single case with aseptic loosening as per radiological criteria in our study. Peri-prosthetic joint infection (PJI) was encountered in a single case (2.3%). Pre-op Knee Society Score (KSS) was 36.21 (SD 7.43) where as it improved to 92.00 (SD 5.66),sixmonths after surgery. Also the range of flexion was increased from 76.83o (SD 14.07o) to 122.91o (SD 4.84o). In our study, metaphyseal sleeves showed excellent short to mid-term survivorship in AORI types IIB and III boneloss in Asian population. These results are comparable to various studies conducted on North American and European population. Metaphyseal sleeve is a reliable tool in the armamentarium ofthe arthroplasty surgeon. It is user friendly implant and provides immediate stability to allow full weight-bearing mobilization.

Management of Massive Tibial Bone Defect Using Unifocal Bone Transport with Ilizarov Apparatus: A case study

Introduction: Ilizarov technique is one of the excellent methods used for bony lengthening. The current literature states that the maximum possible amount of tibial lengthening by bifocal transport of an Ilizarov apparatus was 22 cm, while the maximum amount of tibial lengthening by unifocal transport of an Ilizarov apparatus was 14.5 cm.Case report: 40 years old Saudi teacher was presented with an open fracture at the right tibia of type 3B. The second debridement was done and ended up with 21.49 cm bone loss of the middle Tibial segment. Local flap plastic surgery was done to cover the skin defect and the bone transport was done at a rate of 1mm/day. The overall healing was excellent, and the patient returned to his pre-injury functional activity and rejoined his job as a teacher.Conclusion: Thus, the current case report is a unique new record of 21.49 cm of tibial lengthening achieved by the Ilizarov apparatus using unifocal transport. This will be a treatment hope for patients with excessive bone loss.

Cup-Cage Solution for Massive Acetabular Defects: A Systematic Review and Meta-Analysis.

Our systematic review compiled multiple studies and evaluated survivorship and clinical outcomes of cup‐cage construct usage in the management of massive acetabular bone defects. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Various combinations of “acetabular”, “pelvis”, “cup cage” and their corresponding synonyms were used to search relevant articles in the Cochrane, EMBASE, and PubMed databases. Basic information of the functional scores, implant revision rate, and complication rate were selected as outcomes for analysis. Finally, a total of 11 articles published between 1999 and 2019 were selected, which include 232 patients with an average age of 68.5 years (range, 30–90). The mean follow‐up period was 48.85 months (range, 1–140). Our study shows that the cup‐cage construct has a good clinical outcome with a low revision rate and a low complication rate. Improved clinical outcomes of cup‐cage constructs were seen with a revision rate of 8% and an all‐cause complication rate of 20%. The most commonly reported complication was dislocation, followed by aseptic loosening, infection, and nerve injuries. In summary, it is a promising method for managing large acetabular bone defects in total hip revision.

The ‘apple core’ cement spacer for the management of massive bone loss in two-stage revision knee arthroplasty for infection

Antibiotic-loaded cement spacers are used in two-stage revision knee arthroplasty for infection, but commercially available spacers may not always be suitable for significant bone loss or soft tissue failure in multiply revised cases. We describe a technique for producing an on-table, static, reinforced cement spacer – the ‘apple core’ spacer – with the intended outcome of providing joint stability in such patients, prior to undertaking a second-stage procedure. Following a radical debridement, the spacer is made of three components: (1) a ‘central bar’ of external fixator connecting rods, combined using cerclage wires as needed; (2) a standard polymethylmethacrylate cement ‘apple core’; and (3) a covering ‘skin’ of high dose antibiotic-loaded cement, which is stippled as it sets, to increase the surface area and facilitate antibiotic elution. This technique was performed in nine patients who underwent two-stage salvage revision for complex, recurrent infected total knee arthroplasty at a single institution. All patients successfully went on to definitive second-stage reimplantation and have retained their limbs. The ‘apple core’ cement spacer allows massive bone defects to be effectively managed between staged revision procedures.

Repair of Massive Bone Defects of the Proximal Femur Using Iliac Bone Flaps of the Ascending Branch of the Lateral Circumflex Femoral Artery: A Retrospective Report.

The management of bone defects is still a difficult problem. Local vascularized bone grafts represent an efficient and widely used method. In this retrospective report, iliac bone flaps of the ascending branch of the lateral circumflex femoral artery were used for the management of proximal femur bone defects. The hospital information system and clinical data collected by surgeons were retrospectively reviewed. Patients with massive bone defects of the proximal femur reconstructed with iliac bone flaps of the ascending branch of the lateral circumflex femoral artery were included. Relevant data, including general information, perioperative treatment, and imaging data during follow-up, were retrieved for analysis. Five patients (4 males and 1 female) aged 18 to 42 years were included in this report. All patients were diagnosed with proximal femoral bone defects. The sizes of the bone defects ranged from 5 ×4 cm to 8 × 5 cm. Harris hip score was adopted to evaluate the functional outcomes. The adverse events were recorded. The mean follow-up time was 6.3 years. Iliac bone flaps of the ascending branch of the lateral circumflex femoral artery were transferred locally for the 5 patients. Bone flaps were fixed with plates in 4 cases and Kirschner wires in 1 case. The hospital stay was 12 to 27 days, with an average of 19.4 days. All cases achieved bony healing after 3 to 6 months postoperatively. The Harris hip scores ranged from 87 to 95 at final follow-up. All patients achieved good to excellent functional outcomes. One superficial infection occurred. No other adverse events or serious adverse events were noted. Local transfer of iliac bone flaps of the ascending branch of the lateral circumflex femoral artery represents a safe and effective method for the reconstruction of massive bone defects of the proximal femur.

Is frozen tumour-bearing autograft with concurrent vascularized fibula an alternative to the Capanna technique for the intercalary reconstruction after resection of osteosarcoma in the lower limb?

The use of frozen tumour-bearing autograft combined with a vascularized fibular graft (VFG) represents a new technique for biological reconstruction of massive bone defect. We have compared the clinical outcomes between this technique and Capanna reconstruction. From June 2011 to January 2016 a retrospective study was carried out of patients with primary osteosarcoma of lower limbs who underwent combined biological intercalary reconstruction. Patients were categorized into two groups based on the reconstructive technique: frozen tumour-bearing autograft combined with concurrent VFG (Group 1) and the Capanna method (Group 2). Demographics, operating procedures, oncological outcomes, graft union, limb function, and postoperative complications were compared. A total of 23 patients were identified for analysis: eight in Group 1 and 15 in Group 2. There was no difference in the demographics (age, sex, and affected site) and operating procedures (resection length, duration of surgery, and blood loss) between the two groups. No significant difference was found in local recurrence in Group 1 versus Group 2 (p = 0.585). Mean union time for the frozen autograft-host junction was 8.4 months (7.0 to 11.0), significantly earlier than for the allograft-host junction in Group 2 (mean 14.1 months (10.0 to 28.0); p < 0.001). Mean Musculoskeletal Tumor Society scores in groups 1 and 2 were 90.3% (SD 7.4%) and 88.0% (SD 9.0%), respectively, with no significant statistical difference (p = 0.535). In terms of complications, infection (n = 1, 6.7%) and delayed union (n = 2, 13.3%) occurred in Group 2, but no such complications were observed in Group 1. Frozen tumour-bearing autograft in combination with VFG can be used as an alternative to the Capanna reconstruction in properly selected patients with osteosarcoma. Cite this article: Bone Joint J 2020;102-B(5):646-652.

Bifunctional effect of Zoledronic Acid (ZA) on human mesenchymal stem cells (hMSCs) based on the concentration level

BackgroundTreatment of massive bone defects is a great challenge. Mesenchymal stem cells (MSCs) enhance bone regeneration by differentiating into osteoblasts. Bisphosphonates (BPs) are antiresorptives reducing bone resorption. Despite Medication-related osteonecrosis of the jaw (MRONJ) is a known side effect of antiresorptives, evidences suggest that BPs have positive effect on bone formation. The aims of this study were to investigate the effect of zoledronic acid (ZA) and geranylgeraniol (GGOH) on human mesenchymal stem cells (hMSCs) being a part of the bone microenvironment and evaluate whether low dose of bisphosphonate has enhanced osteogenic differentiation of hMSCs. Materials and methodsThe effect of ZA and GGOH on MSCs was investigated in addition to the effect of low doses of ZA on osteogenic differentiation of MSCs and analysed by WST-1, Live/Dead staining and coefficient of drug index (CDI). The osteogenic differentiation of the cells was confirmed by ALP activity, xylenol orange and alizarin red staining, microarray and PCR with levels of statistical significance indicated at *P<0.05, **P<0.01 and ***P<0.0001. Main findingsAlthough, high concentration of ZA had significantly decreased the cell viability in MSCs, GGOH reversed the action of ZA on the cells while at very high concentration; it caused severe reduction in the cell viability. CDI showed antagonism or synergism depending on the concentrations of ZA and GGOH. ConclusionThe treatment of cells with ZA has increased the mineralization and osteogenic differentiation of MSCs. Our study supported the hypothesis that zoledronic acid plays a bifunctional role depending on the concentration.

Analysis of principles inspiring design of three-dimensional-printed custom-made prostheses in two referral centres.

Three-dimensional (3D) printing is an emerging technology used in numerous medical fields. Reconstruction of large bone defects after tumor resections or complex revision surgeries is challenging especially in specific sites where modular prostheses are not available. The possibility to realize custom-made 3D-printed prostheses improves their application in surgical field despite the complication rate, gaining a lot of attention for potential benefits. We asked: (1) What are the emerging indications and designs of 3D-printed prostheses for complex bone reconstructions? (2) What complications occur with the use of custom implants considering site? We performed a retrospective analysis of every patient in whom a custom-made 3D-printed prosthesis was used to reconstruct a bone defect after resection for a bone tumour or challenging revision surgery from 2009 to 2018 in two referral centres. Forty-one patients (11 males [27%], 30 females [73%]) with a mean age of 41years (range, 10-78years) were included. Our general indications for using these implants were complex reconstructions of massive bone defects, in the absence of available modular prostheses. Seven were non-oncologic patients, whereas 24 patients were mainly treated for their malignant bone tumours. Custom-made 3D-printed prostheses were used in pelvis (29), forearm (6), scapula (2), distal tibia (2), calcaneus (1), and femoral diaphysis (1). The reconstruction included complete articular replacement in 24 cases (58%) whereas a combined spinopelvic implant has been used in two cases. Flaps were used in 25 cases (61%). Statistical analyses include Kaplan-Meier curves of survival. The mean follow-up was 20months. In the oncologic group, overall survival was 89% at fiveyear follow-up and only three patients died of disease. Only one patient required implant removal due to deep infection. Overall major and minor complication rate was 22% (14 complications in 9/41 patients), mainly wound-related problems. One patient reported a periprosthetic fracture, one had hip dislocation, and four (12% [4/34 cases]) had local recurrence. Mean MSTS functional outcome score at follow-up was 73% (range, 23-100%), with a full weight bearing at an average time of 73days from surgery of lower limbs. Custom-made 3D-printed prostheses represent at today a promising reconstructive technique, maintaining however the correct indications for their use in musculoskeletal oncology and challenging revision surgery. Complication rate is acceptable, with infection and wound healing problems relatively common after complex pelvic reconstructions. We will continue to follow our patients over the longer term to ascertain the role of these implants; however, larger studies will need to confirm indications and control for prognostic factors.

Efficacy comparison of double-level and single-level bone transport with Orthofix fixator for treatment of tibia fracture with massive bone defects.

The aim of this study was to evaluate the clinical and functional outcomes of patients with large post-traumatic tibial bone defects managed by double-level bone transport using the Ilizarov technique and compare it with one-level bone transport technique. A retrospective cohort study was conducted on 26 patients with open tibial fracture from January 2010 to January 2017. All cases were Gustilo III. Depending on the site of osteotomy, the patients were divided into single-level (n= 13) and double-level groups (n= 13). The bone transport time, consolidation time of the distraction gap, docking site healing time, external fixation time, external fixation index, soft tissue defect area, soft tissue growth index, operating time, and surgical bleeding volume were recorded and compared between the two groups. Bone and functional results were evaluated according to the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria. The mean duration of follow-up was 28.5 ± 5.8months (range 13-38months) since the Orthofix fixator was removed, all patients achieved complete union in the docking site and consolidation in the regenerate bone; moreover, the wound was closed The mean bone defect length after debridement was 7.2cm (range 5.8-9.0cm) in single-level group vs. 10.7cm (range 7.5-15.0cm) in the double-level group (P< 0.05). The mean docking site healing time was 10.85 ± 1.52months in the single-level group vs. 8.93 ± 2.29months in the double-level group (P< 0.05); external frame time was 18.06months (range 15-20months) in single-level group vs. 12.71months (range 9.5-16.0months) in the double-level group (P< 0.05); external fixation index was 2.52months/cm (range 2.15-2.94months/cm) versus 1.22months/cm (range 0.96-1.67months/cm) in double-level group (P< 0.01); and soft tissue growth index was 0.29months/cm2 (range 0.21-0.45months/cm2) in the single-level group versus 0.62months/cm2 (range 0.47-0.86months/cm2) in the double-level group (P< 0.01). According to the ASAMI classification, the clinical and functional results in the double-level group were better than in the single-level group. The Ilizarov technique of double-level bone transport with Orthofix external fixator can be used successfully to repair and reconstruct the tibial bone loss and accompanying soft tissue defect.

Enhancement of osteoblast cells osteogenic differentiation and bone regeneration by hydroxyapatite/phosphoester modified poly(amino acid).

Hydroxyapatite/poly(amino acid) (HA/PAA) has been used to treat a variety of long bone and vertebral bony defects, and a further biocompatibility improvement is a key for better application. Phosphoester (PE) contained materials are highly biocompatible but could hardly treat massive bone defects due to its fast-degradation-derived mechanical instability. To address the problems of the two materials, we have incorporated PE molecule into the main chain of PAA by chemical bonding. As a result, the compressive strength of HA/PAA with 1wt% and 2.5wt% PE maintained in the range of 80-150MPa after soaking in PBS for 12weeks, which could be attributed to the amplified hydrogen-bonding inside composites. Besides, the PE-containing HA/PAAs with increased hydrophilic function groups (O=P-O bonds and O=P-N), created a more favourable surface for cell adhesion. Meanwhile, compared with HA/PAA, the PE-containing HA/PAAs had a fast minerlization speed and promoted cell osteogenic differentiation. Furthermore, the in vivo study indicated that PE-containing HA/PAAs could facilitate bone formation (4weeks), and form a complete bone bridging (12weeks) in a rabbit cranial bone defect. In summary, the HA/PE-m-PAAs possessed good mechanical stability, improved cytocompatibility and osteoconductivity, so the composites have a great potential for massive bone defect treatment.

Application of pasteurized tumor-bearing bone replantation for primary malignant bone tumor of extremities

To assess the effectiveness of the pasteurized tumor-bearing bone replantation in treatment of primary malignant bone tumor of extremities. Between February 2012 and June 2016, 13 patients with primary malignant bone tumor of extremities were treated with pasteurized tumor-bearing bone replantation after extensive excision. There were 8 males and 5 females, aged from 11 to 27 years, with an average of 17.4 years. Tumors were located at the mid-upper humerus in 2 cases, the mid-upper femur in 2 cases, the mid-lower femur in 6 cases, the mid-upper tibia in 2 cases, and the middle tibia in 1 case. According to Enneking staging system, 3 patients were classified as stage ⅠB, 5 patients as stage ⅡA, and 5 patients as stage ⅡB. There were 11 cases of osteosarcoma and 2 cases of chondrosarcoma. The disease duration ranged from 3 to 8 months, with an average of 4.8 months. The length of the tumor-bearing bone ranged from 8 to 16 cm, with an average of 12.5 cm. Postoperative follow-up was conducted regularly to evaluate the status of inactivated bone and complications. The limb function was assessed by the Musculoskeletal Tumor Society 93 (MSTS-93) scoring system. All 13 patients were followed up 26-79 months, with an average of 50.5 months. Eleven patients survived without tumors. Two patients had local soft tissue recurrence and underwent amputation, 1 had lung metastasis after amputation and died. All patients had no complications of bone resorption, shortening, and internal fixation disorder. The nonunion of osteotomy occurred in 4 cases. Among them, 3 cases were successfully healed after autologous iliac bone grafting, and 1 case was treated conservatively. The healing time of metaphyseal osteotomy end was 10-15 months (mean, 12.6 months), the healing rate was 90.9% (10/11); the healing time of diaphyseal osteotomy end was 12-21 months (mean, 17.0 months), the healing rate was 72.7% (8/11); and the total healing rate of osteotomy end was 81.8% (18/22). One case had inactivated bone fracture and 1 case had incision dehiscence and infection after operation. At last follow-up, the MSTS-93 score of affected limb ranged from 21 to 28, with an average of 25.3. The procedure of the pasteurized tumor-bearing bone replantation is an effective, simple, and economic way in repair of massive segmental bone defect to save limb function for primary malignant bone tumor of extremities.

The combinatory effect of sinusoidal electromagnetic field and VEGF promotes osteogenesis and angiogenesis of mesenchymal stem cell-laden PCL/HA implants in a rat subcritical cranial defect

BackgroundRestoration of massive bone defects remains a huge challenge for orthopedic surgeons. Insufficient vascularization and slow bone regeneration limited the application of tissue engineering in bone defect. The effect of electromagnetic field (EMF) on bone defect has been reported for many years. However, sinusoidal EMF (SEMF) combined with tissue engineering in bone regeneration remains poorly investigated.MethodsIn the present study, we investigated the effect of SEMF and vascular endothelial growth factor (VEGF) on osteogenic and vasculogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Furthermore, pretreated rBMSC- laden polycaprolactone-hydroxyapatite (PCL/HA) scaffold was constructed and implanted into the subcritical cranial defect of rats. The bone formation and vascularization were evaluated 4 and 12 weeks after implantation.ResultsIt was shown that SEMF and VEGF could enhance the protein and mRNA expression levels of osteoblast- and endothelial cell-related markers, respectively. The combinatory effect of SEMF and VEGF slightly promoted the angiogenic differentiation of rBMSCs. The proteins of Wnt1, low-density lipoprotein receptor-related protein 6 (LRP-6), and β-catenin increased in all inducted groups, especially in SEMF + VEGF group. The results indicated that Wnt/β-catenin pathway might participate in the osteogenic and angiogenic differentiation of rBMSCs. Histological evaluation and reconstructed 3D graphs revealed that tissue-engineered constructs significantly promoted the new bone formation and angiogenesis compared to other groups.ConclusionThe combinatory effect of SEMF and VEGF raised an efficient approach to enhance the osteogenesis and vascularization of tissue-engineered constructs, which provided a useful guide for regeneration of bone defects.

A new biarticular cement spacer technique for infected total hip and knee arthroplasty with massive bone loss.

The management of massive femoral bone defects following prosthetic infection remains a surgical challenge, particularly when the entire femur is affected. We present the first results of a new biarticular cement spacer with antibiotic technique using a cephalomedullary nail for the treatment of infected hip arthroplasty involving complete femoral bone loss. 5 patients with a minimum follow-up of 1 year were included. In all cases 2-stage replacement due to hip periprosthetic infection was carried out, with the need for a biarticular complete femoral spacer in view of the magnitude of the bone defect. The infection was resolved in all patients, with no complications (spacer fracture or dislocation) associated to spacer use, and the patients were all able to maintain the sitting position with active knee movements between the 2 surgical stages. Improvement with respect to preoperative functional status was observed in all cases, as evidenced by the Harris Hip Score (HHS) (from 24.2 to 73; p < 0.001) and 12-Item Short-Form Health Survey (SF-12) (from 16.8 to 33.2; p = 0.001), with a lessened need for walking aids. The described technique offers a possible solution to a number of complications observed with the use of spacers in massive defects, affording greater patient comfort and autonomy while waiting to receive total femoral replacement.

Various Dosages of BMP-2 for Management of Massive Bone Defect in Sprague Dawley Rat.

BMP-2 has a crucial role in the treatment of extensive bone defect. However, data about the optimal dosage of BMP-2 in the massive bone defect casesis rare. Twenty-five SD rats were randomly allocated into a control group of hydroxyapatite (HA) alone (Group I), HA+BMP-2 1µg/mL (Group II), HA+BMP-2 5 ug/mL (Group III), HA+BMP-2 10 µg/mL (Group IV), and HA+BMP-2 20 ug/mL (Group V). Osteotomies were performed in each group with 10 mm bone defect in the right femur, followed by fixation and filling the defect. The fracture healing was evaluated by histomorphometry, and radiographs using RUST score. We found there were significant differences in the mean total area of callus between the treatment groups (P<0.001); there were significant differences in the mean area of woven bone between group II, III, IV, and V with the control group (respectively P=0.009, P=0.016, P=0.009 and P=0.016), the area of the cartilage between the treatment groups and control group (respectively P=0.009, P=0.009, P=0.009 and P=0.028). A statistically significant difference was found in the average area of fibrosis between group II and control group, group IV and control group (respectively P=0.047 and P=0.009). RUST scores showed significant differences between the control group and group II, III, IV, V (respectively P=0.005, P=0.006, P=0.005 and P=0.006). The administration of BMP-2 stimulates the formation of bone bridging in a massive bone defect. The bone bridging filling massive bone defect depends on the dose or concentration of BMP-2. Administration of an optimal dose (10 µg/mL) of BMP-2 demonstrates better result than lower or higher dose for massive bone defect healing in SD rate.

A Tetra-PEG Hydrogel Based Aspirin Sustained Release System Exerts Beneficial Effects on Periodontal Ligament Stem Cells Mediated Bone Regeneration.

Bone defects, massive bone defects in particular, is still an issue clinically. Acetylsalicylic acid (ASA), also known as aspirin, has been proven to be conducive for mesenchymal stem cells osteogenic differentiation, which may be benefited for bone regeneration. In order to achieve a more appealing prognosis of bone defect, here we develop a well-defined tetra-PEG hydrogel sealant with rapid gelation speed, strong tissue adhesion, and high mechanical strength. After in-situ encapsulation of aspirin, this drug-loaded tetra-PEG hydrogel possessed a sustained release, anti-inflammation, and osteoinductive properties. In vitro experiments showed that the cell proliferation was slightly facilitated, and the osteogenic differentiation was notably augmented when periodontal ligament stem cells (PDLSCs) were co-incubating with the hydrogel materials. Moreover, in vivo study manifested that the aspirin sustained release system significantly facilitated the PDLSCs mediated bone defect regeneration. Overall, tetra-PEG hydrogel-based aspirin sustained release system is applicable not only for enhancing the osteogenesis capacity of PDLSC but also providing a new thought of bone regenerative therapy.

Biomimetic Nanosilica-Collagen Scaffolds for In Situ Bone Regeneration: Toward a Cell-Free, One-Step Surgery.

Current approaches to fabrication of nSC composites for bone tissue engineering (BTE) have limited capacity to achieve uniform surface functionalization while replicating the complex architecture and bioactivity of native bone, compromising application of these nanocomposites for in situ bone regeneration. A robust biosilicification strategy is reported to impart a uniform and stable osteoinductive surface to porous collagen scaffolds. The resultant nSC composites possess a native-bone-like porous structure and a nanosilica coating. The osteoinductivity of the nSC scaffolds is strongly dependent on the surface roughness and silicon content in the silica coating. Notably, without the use of exogenous cells and growth factors (GFs), the nSC scaffolds induce successful repair of a critical-sized calvarium defect in a rabbit model. It is revealed that topographic and chemical cues presented by nSC scaffolds could synergistically activate multiple signaling pathways related to mesenchymal stem cell recruitment and bone regeneration. Thus, this facile surface biosilicification approach could be valuable by enabling production of BTE scaffolds with large sizes, complex porous structures, and varied osteoinductivity. The nanosilica-functionalized scaffolds can be implanted via a cell/GF-free, one-step surgery for in situ bone regeneration, thus demonstrating high potential for clinical translation in treatment of massive bone defects.