Massive Bone Allografts Research Articles

Enhancing the biological integration of massive bone allografts: A porcine preclinical in vivo pilot-study

Critical bone loss can have several origins: infections, tumors or trauma. Therefore, massive bone allograft can be a solution for limb salvage. Such a biological reconstruction should have the ideal biomechanical qualities. However, their complication rate remains too high. Perfusion-decellularization of massive allografts could promote the vitality of these grafts, thereby improving their integration and bone remodeling.Three perfusion-decellularized massive bone allografts were compared to 3 fresh frozen massive bone allografts in a preclinical in vivo porcine study using an orthopedic surgery model. Three pigs each underwent a critical diaphyseal femoral defects followed by an allogeneic intercalary femoral graft on their both femurs (one decellularized and one conventional fresh frozen as “native”) to reconstruct the defect. Clinical imaging was performed over 3 months of follow-up. The grafts were then explanted and examined by non-decalcified histology, fluoroscopic microscopy and immunohistochemistry.Bone consolidation was achieved in both groups at the same time. However, the volume of bone callus appeared to be greater in the decellularized group. Histology demonstrated a superior bone remodeling in the decellularized group, with a higher number of osteoclasts (p < 0.001) and larger areas of osteoid matrix and newly formed bone as compared to the “native” group. Immunohistochemistry showed a superior vitality and remodeling in both the cortical and medullary cavities for osteocalcin (p < 0.001), Ki67 (p < 0.001), CD3 (p < 0.001) and α-SMA (p < 0.001) as compared the “native” group. Three months after implantation, the decellularized grafts were proven to be biologically more active compared to native grafts. Fluoroscopic microscopy revealed more ossification fronts in the depth of the decellularized grafts (p = 0.021).This pilot study provides the first in vivo demonstration on the enhanced biological capacities of massive bone allograft decellularized by perfusion as compared to conventional massive bone allografts.

Impact of NaOH based perfusion-decellularization protocol on mechanical resistance of structural bone allografts

ABSTRACT Introduction To mitigate the post-operative complication rates associated with massive bone allografts, tissue engineering techniques have been employed to decellularize entire bones through perfusion with a sequence of solvents. Mechanical assessment was performed in order to compare conventional massive bone allografts and perfusion/decellularized massive bone allografts. Material and methods Ten porcine femurs were included. Five were decellularized by perfusion. The remaining 5 were left untreated as the “control” group. Biomechanical testing was conducted on each bone, encompassing five different assessments: screw pull-out, 3-points bending, torsion, compression and Vickers indentation. Results Under the experimental conditions of this study, all five destructive tested variables (maximum force until screw pull-out, maximum elongation until screw pull-out, energy to pull out the screw, fracture resistance in flexion and maximum constrain of compression) were statistically significantly superior in the control group. All seven nondestructive variables (Young’s modulus in flexion, Young’s modulus in shear stress, Young’s modulus in compression, Elastic conventional limit in compression, lengthening to rupture in compression, resilience in compression and Vickers Hardness) showed no significant difference. Discussion Descriptive statistical results suggest a tendency for the biomechanical characteristics of decellularized bone to decrease compared with the control group. However, statistical inferences demonstrated a slight significant superiority of the control group with destructive mechanical stresses. Nondestructive mechanical tests (within the elastic phase of Young’s modulus) were not significantly different.

Vascular study of decellularized porcine long bones: Characterization of a tissue engineering model

IntroductionMassive bone allografts enable the reconstruction of critical bone defects in numerous conditions (e.g. tumoral, infection or trauma). Unfortunately, their biological integration remains insufficient and the reconstruction may suffer from several postoperative complications. Perfusion-decellularization emerges as a tissue engineering potential solution to enhance osseointegration. Therefore, an intrinsic vascular study of this novel tissue engineering tool becomes essential to understand its efficacy and applicability. Material and methods32 porcine long bones (humeri and femurs) were used to assess the quality of their vascular network prior and after undergoing a perfusion-decellularization protocol. 12 paired bones were used to assess the vascular matrix prior (N = 6) and after our protocol (N = 6) by immunohistochemistry. Collagen IV, Von Willebrand factor and CD31 were targeted then quantified. The medullary macroscopic vascular network was evaluated with 12 bones: 6 were decellularized and the other 6 were, as control, not treated. All 12 underwent a contrast-agent injection through the nutrient artery prior an angio CT-scan acquisition. The images were processed and the length of medullary vessels filled with contrast agent were measured on angiographic cT images obtained in control and decellularized bones by 4 independent observers to evaluate the vascular network preservation. The microscopic cortical vascular network was evaluated on 8 bones: 4 control and 4 decellularized. After injection of gelatinous fluorochrome mixture (calcein green), non-decalcified fluoroscopic microscopy was performed in order to assess the perfusion quality of cortical vascular lacunae. ResultsThe continuity of the microscopic vascular network was assessed with Collagen IV immunohistochemistry (p-value = 0.805) while the decellularization quality was observed through CD31 and Von Willebrand factor immunohistochemistry (p-values <0.001). The macroscopic vascular network was severely impaired after perfusion-decellularization; nutrient arteries were still patent but the amount of medullary vascular channels measured was significantly higher in the control group compared to the decellularized group (p-value <0.001). On average, the observers show good agreement on these results, except in the decellularized group where more inter-observer discrepancies were observed. The microscopic vascular network was observed with green fluoroscopic signal in almost every canals and lacunae of the bone cortices, in three different bone locations (proximal metaphysis, diaphysis and distal metaphysis). ConclusionDespite the aggressiveness of the decellularization protocol on medullary vessels, total porcine long bones decellularized by perfusion retain an acellular cortical microvascular network. By injection through the intact nutrient arteries, this latter vascular network can still be used as a total bone infusion access for bone tissue engineering in order to enhance massive bone allografts prior implantation.

An algorithm for surgical treatment of children with bone sarcomas of the extremities.

Limb salvage surgery in children following bone sarcoma resection is a challenging problem because of the small size of the bones, the lack of appropriate size-matched implants, and the risk of limb-length discrepancy once skeletal growth is complete, secondary to the loss of the epiphyseal plate. Although several reconstruction options are available in children with bone sarcomas, such as vascularized fibula, massive bone allograft, extracorporeal devitalized autograft, endoprosthesis, and allograft-prosthesis composite, a consensus has not been reached on the best reconstruction method. The purpose of the present study is to propose an algorithm for reconstruction after resection of bone sarcomas in children. In this review, we analyzed reports on limb reconstruction in children following treatment for bone sarcoma, to provide a comprehensive overview of the different reconstruction options in children with bone sarcomas, the outcomes, and the risks and benefits of the different surgical approaches. Despite a high risk of complications and the necessity for limb-lengthening procedures, prosthetic or biological reconstructions seem to achieve good functional outcomes in children with bone sarcoma. The use of massive bone graft seems to be recommended for intercalary reconstructions, with a free vascularized fibular graft for long defects, while for osteoarticular reconstruction a modular or expandable prosthesis or an allograft-prosthesis composite seems to have good results. For reconstruction of the proximal humerus, modular prosthesis or allograft-prosthesis composite are more commonly used than expandable prosthesis since there are fewer functional constraints related to possible limb-length discrepancy on the upper limb compared to the lower limb. We discuss the advantages and limitations of the different available surgical options for bone reconstruction following tumor resection in children and propose an algorithm of potential surgical treatments for children with bone sarcomas of the extremities.

Decellularization of Massive Bone Allografts By Perfusion: A New Protocol for Tissue Engineering.

In terms of large bone defect reconstructions, massive bone allografts may sometimes be the only solution. However, they are still burdened with a high postoperative complication rate. Our hypothesis is that the immunogenicity of residual cells in the graft is involved in this issue. Decellularization by perfusion might therefore be the answer to process and create more biologically effective massive bone allografts. Seventy-two porcine bones were used to characterize the efficiency of our sodium hydroxide-based decellularization protocol. A sequence of solvent perfusion through each nutrient artery was set up to ensure the complete decellularization of whole long bones. Qualitative (histology and immunohistochemistry [IHC]) and quantitative (fluoroscopic absorbance and enzyme-linked immunosorbent assay) evaluations were performed to assess the decellularization and the preservation of the extracellular matrix in the bone grafts. Cytotoxicity and compatibility were also tested. Comparatively to nontreated bones, our experiments showed a very high decellularization quality, demonstrating that perfusion is mandatory to achieve an entire decellularization. Moreover, results showed a good preservation of the bone composition and microarchitecture, Haversian systems and vascular network included. This protocol reduces the human leukocyte antigen antigenic load of the graft by >50%. The majority of measured growth factors is still present in the same amount in the decellularized bones compared to the nontreated bones. Histology and IHC show that the bones were cell compatible, noncytotoxic, and capable of inducing osteoblastic differentiation of mesenchymal stem cells. Our decellularization/perfusion protocol allowed to create decellularized long bone graft models, thanks to their inner vascular network, ready for in vivo implantation or to be further used as seeding matrices.

A quantitative CT analysis of fibula inlayed in a massive allograft for femoral diaphysis reconstruction

IntroductionIn diaphyseal reconstructions for bone tumor resection, massive bone allografts (MBA) are historically regarded as the gold standard. However, these are not without complications, and they present an elevated risk of infection, nonunion and structural failure that increases over time as the graft remains largely avascular. To counteract this disadvantage, a combination of allograft with a vascularized fibula has been proposed. The aim of our study was to objectively review the results of combined vascularized fibula-allograft constructs compared to plain allograft reconstruction for bone defects in tumor patients and to assess fibular vitality predictive factors from imaging studies. Materials and methodsOur data was retrospectively reviewed for patients with femoral diaphysis reconstructions in the past ten years. Ten patients (six males and four females) with a mean average follow-up time of 43.80 months (range 20–83, SD 18.17) with combined graft (Group A) were included in the study. As a control group 11 patients (six males and five females) with a mean average follow-up of 56.91 months (range 7–118, SD 41.33) with a simple allograft reconstruction were analyzed (Group B). Demographic and surgical data, adjuvant therapy as well as complications were analyzed in both groups. Both groups were assessed with plain radiographs for bony fusion at the osteotomy sites. Patients in “Group A” had consecutive CT scans at 6 months and then annually to check for potential bone stock and bone density changes. We analyzed total bone density as well as incremental changes in three different areas of the reconstruction. This was done at two defined levels for each patient. Only patients with at least two consecutive CT scans were included in the study. ResultsThere were no statistical differences between the groups in terms of demographics, diagnosis or adjuvant therapy (p = 1.0). The mean average surgical time (599.44 vs 229.09) and mean average blood loss (1855.56 ml vs. 804.55 ml) were significantly higher in the combined graft group A (p < 0.001 and p = 0.01, respectively). The mean average length of resection (19.95 cm vs. 15.50 cm) was higher in the combined graft group (p = 0.04). The risk for non-union and infectious complication was higher in the allograft group, however, the difference was not significant (p = 0.09 and p = 0.66, respectively). The mean average time to union at junction sites was 4.71 months (range 2.5–6.0, SD 1.19) for cases of successful fibula transfer, 19.50 months (range 5.5–29.5, SD 12.49) for the three cases where we presumed the fibula was not viable and 18.85 months (range 9–60, SD 11.99) for the allograft group. The difference in healing time was statistically significant (p = 0.009). There were four cases of non-union in the allograft group.Seven out of ten patients in Group A exhibited incremental changes in all CT scan measured values. This difference was statistically significant already at 18 months from the index surgery (p = 0.008). The patients with a non-viable fibula had a smaller increase in the percentage of total bone density area measured in the CT scan compared to those patients with a successful fibula transfer (4.33, SD 2.52 vs. 52.29, SD 22.74, p = 0.008). The average bone density incremental increase in-between the fibula and allograft was different among patients with an unsuccessful fibula transfer (32.22, SD 10.41) and the ones with a viable fibula (288.00, SD123.74, p = 0.009). Bony bridges were observed in six cases of viable fibula and in none of the tree presumably dead fibulas (p = 0.03). The mean average MSTS score was higher for the subgroup of successful fibular transfer (26.7/30, SD 2.87) when compared to the group of non-viable fibular graft (17.00/30, SD 6.08) and this was also statistically significant (p = 0–007). ConclusionA viable fibula enhances incorporation of the allograft and decreases the risk for both structural failure as well as infectious complications. Viable fibula also contributes to better functional status of the recipient. Consecutive CT scans proved to be a reliable method for assessing fibular vitality. When no measurable changes are present at 18-month follow-up, we can declare the transfer unsuccessful with a good amount of certainty. These reconstructions behave as simple allograft reconstructions with analogue risk factors. The presence of either axial bridges between the fibula and allograft or newly formed bone on the inner surface of the allograft is indicative of a successful fibular transfer. The success rate of fibular transfer in our study was only 70% and skeletally mature and taller patients seem to be at increased risk for failure. The longer surgical times and donor site morbidity therefore warrant stricter indications for this procedure.

MASSIVE BONE ALLOGRAFT DECELLULARIZATION BY A PERFUSION PROTOCOL SET UP FOR A BIOCOMPATIBLE MODEL

The purpose of this study is to enhance massive bone allografts osseointegration used to reconstruct large bone defects. These allografts show &gt;50% complication rate requiring surgical revision in 20% cases. A new protocol for total bone decellularisation exploiting the vasculature can offer a reduction of postoperative complication by annihilating immune response and improving cellular colonization/ osseointegration.The nutrient artery of 18 porcine bones - humerus/femur/radius/ulna - was cannulated. The decellularization process involved immersion and sequential perfusion with specific solvents over a course of one week. Perfusion was realized by a peristaltic pump (mean flow rate: 6ml/min). The benefit of arterial perfusion was compared to a control group kept in immersion baths without perfusion.Bone samples were processed for histology (HE, Masson's trichrome and DAPI for cell detection), immunohistochemistry (IHC : Collagen IV/elastin for intraosseous vascular system evaluation, Swine Leukocyte Antigen – SLA for immunogenicity in addition to cellular clearance) and DNA quantification. Sterility and solvent residues in the graft were also evaluated with thioglycolate test and pH test respectively.Compared to native bones, no cells could be detected and residual DNA was &lt;50ng/mg dry weight. Intramedullary spaces were completely cleaned. IHC showed the preservation of intracortical vasculature with channels bounded by Collagen IV and elastin within Haversian systems. IHC also showed a significant decrease in SLA signaling. All grafts were sterile at the last decellularization step and showed no solvent residue. The control group kept in immersion baths, paired with 6 perfused radii/ulnae, showed that the perfusion is mandatory to ensure complete decellularisation.Our results prove the effectiveness of a new concept of total bone decellularisation by perfusion. These promising results could lead to a new technique of Vascularized Composite Allograft transposable to pre-clinical and clinical models.

Current Concepts in the Resection of Bone Tumors Using a Patient-Specific Three-Dimensional Printed Cutting Guide

Orthopedic oncology has begun to use three-dimensional-printing technology, which is expected to improve the accuracy of osteotomies, ensure a safe margin, and facilitate precise surgery. However, several difficulties should be considered. Cadaver and clinical studies have reported more accurate osteotomies for bone-tumor resection using patient-specific cutting guides, especially in challenging areas such as the sacrum and pelvis, compared to manual osteotomies. Patient-specific cutting guides can help surgeons achieve resection with negative margins and reduce blood loss and operating time. Furthermore, this patient-specific cutting guide could be combined with more precise reconstruction using patient-specific implants or massive bone allografts. This review provides an overview of the basic technologies used in the production of patient-specific cutting guides and discusses their current status, advantages, and limitations. Moreover, we summarize cadaveric and clinical studies on the use of these guides in orthopedic oncology.

A New Osteogenic Membrane to Enhance Bone Healing: At the Crossroads between the Periosteum, the Induced Membrane, and the Diamond Concept

The lack of viability of massive bone allografts for critical-size bone defect treatment remains a challenge in orthopedic surgery. The literature has reviewed the advantages of a multi-combined treatment with the synergy of an osteoconductive extracellular matrix (ECM), osteogenic stem cells, and growth factors (GFs). Questions are still open about the need for ECM components, the influence of the decellularization process on the latter, the related potential loss of function, and the necessity of using pre-differentiated cells. In order to fill in this gap, a bone allograft surrounded by an osteogenic membrane made of a decellularized collagen matrix from human fascia lata and seeded with periosteal mesenchymal stem cells (PMSCs) was analyzed in terms of de-/recellularization, osteogenic properties, PMSC self-differentiation, and angiogenic potential. While the decellularization processes altered the ECM content differently, the main GF content was decreased in soft tissues but relatively increased in hard bone tissues. The spontaneous osteogenic differentiation was necessarily obtained through contact with a mineralized bone matrix. Trying to deepen the knowledge on the complex matrix-cell interplay could further propel these tissue engineering concepts and lead us to provide the biological elements that allow bone integration in vivo.

The role of conventional radiography to assess the outcome of oncologic skeletal reconstructions of lower limbs aided by vascularized fibular autograft

IntroductionVascularized fibular autografts (VFA) are used in the oncologic skeletal reconstructions of long bones, alone or combined with massive bone allografts (MBA). Data regarding the role of imaging in assessing these complex skeletal reconstructions are lacking, and have mainly focused on Computed Tomography (CT). Our aim was to evaluate if early conventional radiography (CR) findings are correlated with the outcome of these skeletal reconstructions. Materials and methodsAll consecutive patients who underwent oncologic resection of lower limbs long bones followed by VFA reconstruction were included in this single-center retrospective study. We compared the CR obtained immediately after surgery with the CR at the 6-month control, as well as the CR at 6 months with the CT at 6 months when available. The following scores were assigned to the VFA: 0 (unchanged), 1 (osteopenia-cortical bone thinning), 2 (increase in bone density-cortical thickening). We then investigated whether this score correlated with the implant outcome within 12 months (optimal integration, suboptimal integration, integration requiring further surgery or lack of integration) using Kaplan-Meier and Cox regression analyses, considering the occurrence of integration and the duration time before the surgical removal of the whole bone reconstruction. ResultsForty-five patients were included (32 men [71.1%], mean age 14.6 years), 26 affected by osteosarcoma, 14 by Ewing sarcoma, 3 by adamantinoma and 2 operated for the failure of previous reconstructions for bone sarcoma. VFA changes on 6-month CR were significantly associated with optimal integration of the implants (log-rank P = 0.0137, multivariate Hazard ratio = 7.62, 95% confidence interval = 1.13–51.25). None of the other clinical and surgical features were associated with the implant outcome. The findings on 6-month CR and CT follow-up were not significantly different. CT at 6 months was available in 36 patients (80.0%). ConclusionThe assessment of VFA morphological changes on CR performed at 6 months can predict the outcome of the skeletal implant. This data should be considered for clinical decision-making, selecting patients requiring additional images (CT), and possible subsequent revision surgical procedures.

What's New in Musculoskeletal Tumor Surgery.

What's New in Musculoskeletal Tumor Surgery.

Total calcaneal reconstruction using a massive bone allograft and a distally pedicled osteocutaneous fibula flap: A novel technique to prevent amputation after calcaneal malignancy

In patients with primary calcaneal malignancies, such as Ewing's sarcoma, radical treatment with amputation of the foot can result in serious functional impairment and chronic pain. Total calcanectomy followed by the reconstruction of the calcaneal defect offers an alternative treatment to amputation. Capanna etal. described a technique for successfully reconstructing long limb segmental bone defects using a free fibula flap placed within the intramedullary canal of an allograft. We present both a review of the literature on calcaneal reconstruction and describe how the principles of Capanna can be adapted to reconstruct the calcaneus. Total calcanectomy due to Ewing's sarcoma and the subsequent application of this novel reconstructive technique was performed in two young patients aged 5 and 16 years. The reconstruction was achieved by inserting a distally pedicled osteocutaneous fibula flap within the reamed canal of an allograft and placing the composite in the calcaneal defect. Reconstruction was successful with complete bone union between the allograft and the adjacent bone. There were no fractures or infections and both flaps survived. Functional outcome was assessed with a physiotherapist at a follow-up period of 2 years postoperatively, showing near-normal ambulance. This novel technique proved excellent as a limb salvage procedure, avoiding amputation, and offering a satisfactory oncological and functional outcome.

Gorham Stout disease: 3 additional cases with 2 very rare polyostotic diseases.

Gorham Stout disease is a very rare monostotic or polyostotic osteolysis and physiopathology of the osteolysis is not yet fully understood. Three new cases are reported with their evolution and treatment. Among these 3 cases, two are very rare cases of polyostotic involvement. One patient finally deceased from respiratory complications despite limb amputation. The two others are alive. Both needed final reconstruction with massive bone allograft for one and with a prosthesis for the other. Monostotic osteolysis is the most frequent presentation of Gorham Stout disease and extensive polyostotic osteolysis is very rare. Treatment methods vary from one clinic to another, from drug treatment to surgical treatment with or without radiotherapy. Sometimes, as a last solution, an amputation of the affected limb is performed. The prognosis depends on the affected region and the reponse to various treatments. Chylothorax seems to be a factor of poor prognosis.

Custom Massive Allograft in a Case of Pelvic Bone Tumour: Simulation of Processing with Computerised Numerical Control vs. Robotic Machining.

The use of massive bone allografts after the resection of bone tumours is still a challenging process. However, to overcome some issues related to the processing procedures and guarantee the best three-dimensional matching between donor and recipient, some tissue banks have developed a virtual tissue database based on the scanning of the available allografts for using their 3D shape during virtual surgical planning (VSP) procedures. To promote the use of future VSP bone-shaping protocols useful for machining applications within a cleanroom environment, in our work, we simulate a massive bone allograft machining with two different machines: a four-axes (computer numerical control, CNC) vs. a five-axes (robot) milling machine. The allograft design was based on a real case of allograft reconstruction after pelvic tumour resection and obtained with 3D Slicer and Rhinoceros software. Machining simulations were performed with RhinoCAM and graphically and mathematically analysed with CloudCompare and R, respectively. In this case, the geometrical differences of the allograft design are not clinically relevant; however, the mathematical analysis showed that the robot performed better than the four-axes machine. The proof-of-concept presented here paves the way towards massive bone allograft cleanroom machining. Nevertheless, further studies, such as the simulation of different types of allografts and real machining on massive bone allografts, are needed.

Establishment of a rabbit's model for modified Capanna technique

Massive bone allograft with an intramedullary vascularized fibula (Capanna technique) represents one of the most widely used methods for the reconstruction of massive bone defect. However, the mechanisms, healing process, and underlying influential factors were poorly understood due to the lack of suitable experimental animal models. Critical-sized defects (CSD) in bone were constructed in the proximal tibia of 24 rabbits and randomly divided into two groups. Allogeneic bone segments of the same size as CSDs were obtained from another 12 rabbits and then inactivated. In group Ⅰ, an ipsilateral pedicled vascularized fibula was dissociated and transferred into the intramedullary cavity of allograft to assemble a composite for CSD reconstruction (Capanna technique), while group Ⅱ received a reconstruction with allogeneic bone alone. Radiographic evaluation was performed every week after the operation to assess union status. All animals were sacrificed at 16th week, and the specimens were histologically analyzed. All animals survived without severe intraoperative complications. There was one rabbit (8.33%) in group Ⅰ developed a postoperative infection and died, while three rabbits (25%) had postoperative complications in group Ⅱ (two died of infection and one died of internal fixation fracture). Radiographically, the mean time to union at the allograft-host junction in group Ⅰ was 12.8±1.80 weeks, significantly shorter than in group II (>15.18±1.12 weeks; p<0.001). The grade of graft union of group Ⅰ was significantly higher than that of group Ⅱ both at 8th and 16th week (8th week: p=0.035; 16th week: p=0.033). Fully bone union at the junctions was histologically confirmed in all specimens in group Ⅰ and 66.67% (8/12) in group Ⅱ. Combined allograft and intramedullary vascularized fibula transfer in rabbit's tibia represent an ideal model that accurately simulates the Capanna technique for CSD reconstruction.

Use of Vascularized Fibular Epiphyseal Transfer with Massive Bone Allograft for Proximal Humeral Reconstruction in Children with Bone Sarcoma.

The vascularized fibula epiphyseal transfer provides a reconstructive option for longitudinal growth after oncologic resection of the proximal humerus in pediatric patients. However, postoperative fractures and poor shoulder function are common. The purpose of this review was to introduce a composite approach in oncologic reconstruction of the proximal humerus and assess its clinical outcomes. We retrospectively investigated five children (3 osteosarcoma and 2 Ewing's sarcoma) who underwent biological reconstruction with combination of vascularized fibula epiphyseal transfer and massive bone allograft after oncologic resection of the proximal humerus. The mean follow-up was 46.8 months. All patients were alive at the last follow-up. There was no graft fracture, hardware failure, or infection. The mean time of osseous union was 2.9 months at fibula-humerus junction and 6.2 months at allograft-humerus junction. Hypertrophy and axial growth were evident in all, except one patient who has avascular necrosis of the fibula head. The mean hypertrophy index was 51.5%, and the mean growth was 4.4 mm per annum. The mean arm discrepancy was 4.6 cm. All reconstruction was in situ with the average abduction of 113° and forward flexion of 69°. The mean Musculoskeletal Tumor Society (MSTS) score was 85.4% at the final follow-up. All patients experienced dropped foot and resolved spontaneously. The combination of vascularized fibula epiphyseal transfer with massive allograft bone provides a reliable oncologic reconstruction of proximal humerus in children. It not only offers the ability of longitudinal growth, hypertrophy, and osseous union but also diminishes reconstructive complications and improves shoulder function. Therapeutic Level IV.

Intercalary reconstruction following resection of diaphyseal bone tumors: A systematic review

IntroductionThe options for the reconstruction of diaphyseal defects following the resection of bone tumors include biological or prosthetic implants. The purpose of our study was to evaluate different types of intercalary reconstruction techniques, including massive bone allograft, extracorporeal devitalized autograft, vascularized free fibula, and modular prosthesis. MethodsWe performed a systematic review of articles using the terms diaphyseal bone tumor and intercalary reconstruction. All the studies reporting the non-oncological complications such as infection, nonunion and fracture of the intercalary reconstructions were included. We excluded articles published before 2000 or did not involve humans in the study. Case reports, reviews, technique notes and opinion articles were also excluded based on the abstracts. Thirty-three articles included in this review were then studied to evaluate failure rates, complications and functional outcome of different surgical intercalary reconstruction techniques. ResultsNonunion rates of allograft ranged 6%–43%, while aseptic loosening rates of modular prosthesis ranged 0%–33%. Nonunion rates of allograft alone and allograft with a vascularized fibula graft ranged 6%–43% and 0%–33%, respectively. Fracture rates of allograft alone and allograft with a vascularized fibula graft ranged 7%–45% and 0%–44%, respectively. Infection rates of allograft alone and allograft with a vascularized fibula graft ranged 0%–28% and 0%–17%, respectively. All of the allograft (range: 67%–92%), extracorporeal devitalized autograft including irradiation (87%), autoclaving (70%), pasteurization (88%), low-heat (90%) or freezing with liquid nitrogen (90%), and modular prosthesis (range: 77%–93%) had similar Musculoskeletal Tumor Society functional scores. Addition of a vascularized fibula graft to allograft did not affect functional outcome [allograft with a vascularized fibula graft (range: 86%–94%) vs. allograft alone (range: 67%–92%)]. ConclusionAseptic loosening rates of modular prosthesis seem to be less than nonunion rates of allograft. Adding a vascularized fibula graft to allograft seems to increase bone union rate and reduce the risk of fractures and infections, though a vascularized fibula graft needs longer surgical time and has the disadvantage of donor site morbidity. These various intercalary reconstruction techniques with or without a vascularized fibula autograft had similar functional outcome.

CORR Insights®: Does the Addition of a Vascularized Fibula Improve the Results of a Massive Bone Allograft Alone for Intercalary Femur Reconstruction of Malignant Bone Tumors in Children?

CORR Insights®: Does the Addition of a Vascularized Fibula Improve the Results of a Massive Bone Allograft Alone for Intercalary Femur Reconstruction of Malignant Bone Tumors in Children?

Effect of vascularized periosteum on revitalization of massive bone isografts: An experimental study in a rabbit model.

In the last years, limb salvage has become the gold standard treatment over amputation. Today, 90% of extremity osteogenic sarcomas can be treated with limb salvage surgery. However, these reconstructions are not exempt from complications. Massive allografts have been associated to high risk of nonunion (12-57%), fracture (7-30%) and infection (5-21%). Association of vascularized periosteum flap to a massive bone allograft (MBA) has shown to halve the average time of allograft union in clinical series, even compared to vascularized fibular flap. Creeping substitution process has been reported in massive allograft when periosteum flap was associated. However, we have little data about whether it results into allograft revitalization. We hypothesize that the association of a periosteum flap to a bone isograft promotes isograft revitalization, defined as the colonization of the devitalized bone by new-form vessels and viable osteocytes, turning it vital. Forty-four New Zealand white male rabbits underwent a 10 mm segmental radial bone defect. In 24 rabbits the bone excision included the periosteum (controls); in 20 rabbits (periosteum group) bone excision was performed carefully detaching periosteum in order to preserve it. Cryopreserved bone isograft from another rabbit was trimmed and placed to the defect gap and was fixed with a retrograde intramedullar 0.6 mm Kirschner wire. Rabbits were randomized and distributed in 3 subgroups depending on the follow-up (control group: 5 rabbits in 5-week follow up group, 8 rabbits in 10-week follow-up group, 7 rabbits in 20-week follow-up group; periosteum group: 5 rabbits in 5-week follow up group, 7 rabbits in 10-week follow-up group, 7 rabbits in 20-week follow-up group). Fluoroscopic images of rabbit forelimb were taken after sacrifice to address union. Each specimen was blindly evaluated in optical microscope (magnification, ×4) after hematoxylin and eosin staining to qualitative record: presence of new vessels and osteocytes in bone graft lacunae (yes/no) to address revitalization, presence of callus (yes/no) and woven bone and cartilage tissue area (mm2 ) to address remodeling (osteoclast resorption of old bone and substitution by osteoblastic new bone formation). No isograft revitalization occurred in any group, but it was observed bone graft resorption and substitution by new-formed bone in periosteum group. This phenomenon was accelerated in 5-week periosteum group (control group: 49.5 ± 9.6 mm2 vs. periosteum group: 34.9 ± 10.4 mm2 ; p = .07). Remodeled lamellar bone was observed in both 20-week groups (control group: 6.1 ± 6.3 mm2 vs. periosteum group: 5.8 ± 3.0 mm2 , p = .67). Periosteum group showed complete integration and graft substitution, whereas devitalized osteons were still observed in 20-week controls. All periosteum group samples showed radiographic union through a bone callus, whereas controls showed nonunion in eight specimens (Union rate: control group 60% vs. periosteum group 100%, p = .003). Association of vascularized periosteum to a massive bone isograft has shown to accelerate bone graft substitution into a newly formed bone, thus, no bone graft revitalization occurs.

Microsurgical reconstruction with vascularized fibula and massive bone allograft for bone tumors.

Combining massive bone allograft and vascularized fibula in intercalary reconstruction following resection of bone tumors represents a complex reconstructive procedure that requires specialists in microvascular surgery as well as orthopedic surgery. The purpose of our study was to examine the outcomes using this surgical technique in patients with bone tumors in terms of oncologic results, complications related to surgery, Musculoskeletal Tumor Society (MSTS) scores and duration of surgery. We analyzed 81 patients with femoral or tibial sarcomas who underwent intercalary resection and microsurgical reconstruction with massive bone allograft and vascularized fibula. There were 56 boys and 25 girls with a mean age of 13.4years at the time of surgery. The patients' medical records were reviewed for clinical and functional outcomes as well as postoperative complications. The study group was comprised of 33 patients who underwent reconstruction of the femur with massive bone allograft and free vascularized fibula and 48 patients who underwent reconstruction of the tibia with massive bone allograft and free or pedicle vascularized fibula. The mean length of resection was 15.9cm (8-31cm). The functional evaluation of the patients was done at the end of the follow-up using MSTS score for the lower limb. All patients had at least a 2-year follow-up. The overall limb salvage rate was 94%, although many patients required re-operation after the procedure. Complications occurred in 24 patients, 18 of which underwent additional surgical procedures. They included fractures of the massive bone allograft-vascularized fibula construct with or without implant failure (19) and deep infection (5). After surgical or conservative treatment, all the fractures successfully healed. The overall MSTS functional score was good to excellent in 91% of patients. The combination of massive bone allograft and vascularized fibula seems to be a reasonable option for reconstruction of diaphyseal defects following intercalary resection of bone tumors. Although there was a high rate of complications and therefore re-operations, the biology of vascularized fibula was able to save the reconstruction in most of the cases that had complications.