The purpose of this study is to enhance massive bone allografts osseointegration used to reconstruct large bone defects. These allografts show >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 <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

Paediatric musculoskeletal (MSK) disorders often produce severe limb deformities, that may require surgical correction. This may be challenging, especially in case of multiplanar, multifocal and/or multilevel deformities. The increasing implementation of novel technologies, such as virtual surgical planning (VSP), computer aided surgical simulation (CASS) and 3D-printing is rapidly gaining traction for a range of surgical applications in paediatric orthopaedics, allowing for extreme personalization and accuracy of the correction, by also reducing operative times and complications. However, prompt availability and accessible costs of this technology remain a concern. Here, we report our experience using an in-hospital low-cost desk workstation for VSP and rapid prototyping in the field of paediatric orthopaedic surgery. From April 2018 to September 2022 20 children presenting with congenital or post-traumatic deformities of the limbs requiring corrective osteotomies were included in the study. A conversion procedure was applied to transform the CT scan into a 3D model. The surgery was planned using the 3D generated model. The simulation consisted of a virtual process of correction of the alignment, rotation, lengthening of the bones and choosing the level, shape and direction of the osteotomies. We also simulated and calculated the size and position of hardware and customized massive allografts that were shaped in clean room at the hospital bone bank. Sterilizable 3D models and PSI were printed in high-temperature poly-lactic acid (HTPLA), using a low-cost 3D-printer. Twenty-three operations in twenty patients were performed by using VSP and CASS. The sites of correction were: leg (9 cases) hip (5 cases) elbow/forearm (5 cases) foot (5 cases) The 3D printed sterilizable models were used in 21 cases while HTPLA-PSI were used in five cases. customized massive bone allografts were implanted in 4 cases. No complications related to the use of 3D printed models or cutting guides within the surgical field were observed. Post-operative good or excellent radiographic correction was achieved in 21 cases. In conclusion, the application of VSP, CASS and 3D-printing technology can improve the surgical correction of complex limb deformities in children, helping the surgeon to identify the correct landmarks for the osteotomy, to achieve the desired degree of correction, accurately modelling and positioning hardware and bone grafts when required. The implementation of in-hospital low-cost desk workstations for VSP, CASS and 3D-Printing is an effective and cost-advantageous solution for facilitating the use of these technologies in daily clinical and surgical practice

Primary malignant bone tumor often requires a surgical treatment to remove the tumor and sometimes restore the anatomy using a frozen allograft. During the removal, there is a need for a highest possible accuracy to obtain a wide safe margin from the bone tumour. In case of reconstruction using a bone allograft, an intimate and precise contact at each host-graft junction must be obtained (Enneking 2001). The conventional freehand technique does not guarantee a wide safe margin nor a satisfying reconstruction (Cartiaux 2008). The emergence of navigation systems has procured a significant improvement in accuracy (Cartiaux 2010). However, their use implies some constraints that overcome their benefits, specifically for long bones. Patient-specific cutting guides become now available for a clinical use and drastically simplify the intra-operative set-up. We present the use of pre-operative assistances to produce patient-specific cutting guides for tumor resection and allograft adjustment. We also report their use in the operative room. We have developed technical tools to assist the surgeon during both pre-operative planning and surgery. First, the tumor extension is delineated on MRI images. These MRI images are then merged with Computed Tomography scans of the patient. The tumor and the CTscan are loaded in custom software that enables the surgeon to define target (desired) cutting planes around the tumor (Paul 2009) including a user-defined safe margin. Finally, cutting guides are designed on the virtual model of the patient as a mould of the bone surface surrounding the tumor, materialising the desired cutting planes. When required, a massive bone allograft is selected by comparing shapes of the considered patient's bone and available allografts. The resection planes are transferred onto the selected allograft and a second guide is designed for the allograft cutting. The virtually-designed cutting guides are then manufactured by a rapid prototyping machine using biocompatible material. This procedure has been used to excise a local recurrence of a tibial sarcoma and reconstruct the anatomy using a frozen tibial allograft. The pre-operative planning using virtual models of the patient's bone, tumor and the available allografts enabled the surgeon to localise the tumor, define the desired cutting planes and select the optimal allograft. Patient- and allograft-specific guides have been designed and manufactured. A stable and accurate positioning of guide onto the patient's tibia was made easier thanks to the plate formerly put in place during the previous surgery. An accurate positioning of the allograft cutting guide has been obtained thanks to its design. The obtained reconstruction was optimal with a adjusted allograft that was perfectly fitting the bone defect. The leg alignment was also optimally restored. Computer assistances for tumor surgery are progressively appearing. We have presented at CAOS 2010 an optical navigation system for tumor resection in the pelvis that was promising. However, such a tool is not well adapted for long bones. We have used patient-specific guides on a clinical case to assess the feasibility of the technique and check its accuracy in the resection and reconstruction. The surgeon has benefited from the 3D planning to define his strategy. He had the opportunity to select the optimal transplant for his patient and plan the same cuttings for the allograft and the patient. During the surgery, guide positioning was straightforward and accurate. The bone cuttings were very easy to perform. The use of custom guides decreases the operating time when compared to the conventional procedure since there is no need for measurements between cutting trajectories and anatomical landmarks. Furthermore, the same cutting planes were performed around the tumor and onto the allograft to obtain a transplant that optimally fills the defect. We recommend the use of such an intra-operative assistance for tumor surgery

We retrospectively reviewed 101 consecutive patients with 114 femoral tumours treated by massive bone allograft at our institution between 1986 and 2005. There were 49 females and 52 males with a mean age of 20 years (4 to 74). At a median follow-up of 9.3 years (2 to 19.8), 36 reconstructions (31.5%) had failed. The allograft itself failed in 27 reconstructions (24%). Mechanical complications such as delayed union, fracture and failure of fixation were studied. The most adverse factor on the outcome was the use of intramedullary nails, followed by post-operative chemotherapy, resection length > 17 cm and age > 18 years at the time of intervention. The simultaneous use of a vascularised fibular graft to protect the allograft from mechanical complications improved the outcome, but the use of intramedullary cementing was not as successful. In order to improve the strength of the reconstruction and to advance the biology of host–graft integration, we suggest avoiding the use of intramedullary nails and titanium plates, but instead using stainless steel plates, as these gave better results. The use of a supplementary vascularised fibular graft should be strongly considered in adult patients with resection > 17 cm and in those who require post-operative chemotherapy

Reconstruction following internal hemipelvectomy for bone tumors remains a major surgical challenge. Most of the cases are considered not suitable for reconstruction because of high complication occurrence. Allografts coupled with standard prosthesis is a reliable method of reconstruction. 26 patients received a McMinn stemmed cup (Link, Germany) after periacetabular tumor resection from February 1999 to 2006. In 18 patients the reconstruction followed resection of the acetabular area while in other 8 an extrarticular resection of the proximal femur was performed. In 21 cases a stemmed acetabular cup were associated with massive bone allograft. There were 13 female and 13 male with a mean age of 41 years (13 to 70). Average follow-up was 45 months (7 to 105). Six patients were affected by local recurrence of the tumour and five underwent hindquarter amputation. In 4 of them the index surgery followed a previous recurrence of the tumour. Finally 6 patients died for related causes within 2 years. All the other 20 have been followed clinically and radiographically for a minimum of 24 months. Deep infection occurred in one case, there were no cases of dislocation. Radiolucency at the prosthesis-bone interface was observed in 3 cases, 2 patients had proximal migration < of 20 mm. Only one patient was treated for aseptic loosening because of incorrect initial position of the implant. The iliac osteotomy was consolidated in all cases, while a delayed union was frequently observed in the pubic osteotomy, however without compromise the stability of implant. Functional result were evaluated according to the MSTS system and this showed 65% of excellent or good clinical results. The procedure requires appropriate patient selection, accurate preoperative planning, meticulous selection and preparation of allograft. Usually artificial ligaments are applied to reduce hip instability, however, this type of reconstruction do not require complex fixation, thus reducing surgical time and early complications

We reviewed 25 patients who had undergone resection of a primary bone sarcoma which extended to within 5 cm of the knee with reconstruction by a combination of a free vascularised fibular graft and a massive allograft bone shell. The distal femur was affected in four patients and the proximal tibia in 21. Their mean age at the time of operation was 19.7 years (5 to 52) and the mean follow-up period 140 months (28 to 213). Three vascularised transfers failed. The mean time to union of the fibula was 5.6 months (3 to 10) and of the allograft 19.6 months (10 to 34). Full weight-bearing was allowed at a mean of 21.4 months (14 to 36). The mean functional score at final follow-up was 27.4 (18 to 30) using a modfied 30-point Musculoskeletal Tumour Society rating system. The overall limb-salvage rate was 88%. The results of our study suggest that the combined use of a vascularised fibular graft and allograft is of value as a limb-salvage procedure for intercalary reconstruction after resection of bone tumours around the knee, especially in skeletally immature patients

The mean way to fill bone loss, to fix loss of continuity or to correct severe dysplasia in pelvis and in the femur during replacement or revision arthroplasty is the augmentation of the bone stock by mean of bulky or morcellized bone allograft. In order to treat these problems, limiting the possible complications connected to the use of massive bone allograft (bulky or morcellized), and to simplify the surgical procedure we thought to apply in selected cases the platelet’s derived autologous growth factors (AGF), alone or added to Granular Hydroxyapatite. From january 2001 to june 2003 we have applied-autologous growth factors in 10 cases. The diagnosis was: 5 acetabula in primary THR, 2 acetabular and 1 femoral revision after THR, 1 femoral and 1tibial revision after TKR. We applied the pure AGF in 2 cases and AGF plus Granular Hydroxyapatite in 8 cases. We used emispherical, HA coated, uncemented acetabular cup plus screws (6 cases), uncemented revision cup plus screws (1 case), straight HA coated uncemented femoral stem (1 cases), semi-constrained cemented TKR prosthesis (1 cases). The mean age atoperation was 45 years (21–69). The mean follow-up time was 12,5 months (28–6). At the last follow up in all the implants there were no signs of loosening; all the graft seems to be well osteo integrated except in 1 case in which we have had fracture and partial reabsorption of the granular HA, without failure of the implant. We haven’t had any inflammatory reaction or signs of intollerance to the graft. The short term results of our experience seems to be encouraging. If these results will be confirmed in the future the application of AGF should reduce the utilization of massive bone allograft

Bone allografts can be used in any kind of surgery involving bone from minor defects to major bone loss after tumour resection. This review describes the various types of bone grafts and the current knowledge on bone allografts, from procurement and preparation to implantation. The surgical conditions for optimising the incorporation of bone are outlined, and surgeon expectations from a bone allograft discussed.

We have carried out in 24 patients, a two-stage revision arthroplasty of the hip for infection with massive bone loss. We used a custom-made, antibiotic-loaded cement prosthesis as an interim spacer. Fifteen patients had acetabular deficiencies, eight had segmental femoral bone loss and one had a combined defect.

There was no recurrence of infection at a mean follow-up of 4.2 years (2 to 7). A total of 21 patients remained mobile in the interim period. The mean Merle D’Aubigné and Postel hip score improved from 7.3 points before operation to 13.2 between stages and to 15.8 at the final follow-up. The allograft appeared to have incorporated into the host bone in all patients. Complications included two fractures and one dislocation of the cement prosthesis.

The use of a temporary spacer maintains the function of the joint between stages even when there is extensive loss of bone. Allograft used in revision surgery after septic conditions restores bone stock without the risk of recurrent infection.

We reviewed 29 patients who had undergone intercalary resection for malignant tumours. Of these, 14 had received segmental allograft reconstruction and 15 extracorporeally-irradiated autograft.

At a mean follow-up of 71 months (24 to 132), 20 were free from disease, five had died and four were alive with pulmonary metastases. Two patients, one with an allograft and one with an irradiated autograft, had a local recurrence. Reconstruction with extracorporeally-irradiated autograft has a significantly lower rate of nonunion (7% vs 43%, p = 0.031) but an insignificantly higher rate of fracture (20% vs 14%, p = 0.535) than that with segmental allograft. Using the Enneking functional evaluation system, the mean postoperative score for the patients without local recurrence was 87% (80% to 96%) and was similar in both groups.

Extracorporeally-irradiated autograft could be an acceptable alternative for reconstruction after intercalary resection, especially in countries where it is difficult to obtain allografts.

In order to investigate the efficacy of free vascularised fibular graft (VFG) after bone intercalary tumour resection in tibia, we present our results with a minimum follow-up of 2 years. From 1988 to 2001, 47 patients affected by high-grade tibial sarcoma in 31 cases (66%), and low-grade diesease in 16 cases (34%) were treated in our department. Average age was 19 years (range 5–60 years), with a male/female ratio of 1.35. The average length of tibial resection was 15 cm, while the average length of the fibular graft was 19 cm. In 11 cases (21%) VFG was assembled alone, while in 36 cases (79%) a massive bone allograft was associated to the fibula. Three patients developed a deep infection, treated by amputation in two cases and by graft removal and an Ilizarov device in one case. Minor complications occurred in 28 cases (55%) (stress fractures, wound slough, osteosynthesis breakage), all healed by minor surgery or conservative treatment. At an average follow-up of 108 months (range 24 to 185 months), four patients had died of disease and three were lost to follow-up. Regarding the overall results, the combined group of fibula plus massive allograft showed to be more effective than the group of fibula alone in terms of early weight bearing (6 versus 12 months), while VFG showed intrinsic efficacy in achieving early bony fusion at the osteotomy lines and hypertrophy of the graft in both groups. Furthermore, using the combined assembly the articular surface could be spared in all the trans-epiphyseal resections, while VFG alone appeared to be electively indicated for infected or irradiated fields. In conclusion, despite the demanding surgical technique, VFG appears to be a long-lasting and definitive biological reconstruction procedure after intercalary tibial resection

The reconstruction of a skeletal defect after resection of a bone tumour represents a challenge for the orthopaedic surgeon. Age, site of the lesion and extension of the disease often limit the choice of surgical technique for a conservative procedure, but several options are available, mainly modular, composite or custom prostheses, massive bone allografts with or without autologous vascularised fibular grafts (AVF), and arthrodeses. An interesting reconstructive technique uses the AVF graft, with microsurgical technique, alone or associated with a massive allograft. The association of a fibular transplant with an allograft increases the mechanical strength of the reconstruction, also promoting more rapid integration. The fibula is a cortical bone and it may provide mechanical strength in the reconstruction of a large segmental bony defect if employed as a viable biological rod. In the present paper the authors discuss their experience with 17 patients treated at the Oncological Orthopaedic Unit of the G.Pini Orthopaedic Institute, for bone tumour resection and reconstruction using AVF graft, almost always combined with a bone allograft. No treatments were performed as augmentation in osteoarticular massive allografts. Subjects’ ages ranged from 7 to 66 years (mean 25.2 years). Most of the patients were referred for a diagnosis of malignancy (15 of 17 cases) and in only two patients were the tumours not aggressive. In 11 patients the AVF was transplanted immediately after tumour resection, while in the others it was used after problems of previous reconstruction. The authors report two cases of deep infection and four mechanical fractures (all healed after a period of cast immobilisation with or without bone bridging). All the AVF survived and healed with a good functional result for the patients except for two recurrences that required an amputation

Purpose: Revision total knee arthroplasty (RTKA) is particularly difficult and results more variable than primary total knee arthroplasty due to the added problem of bone loss. Massive bone allografts have been proposed to restore bone stock and mechanical conditions as close to the physiological situation as possible. The purpose of this retrospective analysis was to assess clinical and radiological results after knee reconstruction with massive allografts in patients undergoing revision total knee arthroplasty. Materials and method: This series included 14 patients who underwent a revision procedure between February 1990 and August 1998 for RTKA with segmentary bone loss and bone defects. This group included seven patients with mechanical failure and seven others with septic loosening. Reconstruction was achieved with a massive allograft sealed around a long stem cemented implant. The composite assembly was impacted into the patient’s bony segment. The allografts were used to reconstruct the distal femur in nine cases, the proximal tibia in one, and both in the others. The IKS score and radiographic homogenisation of the host-graft junction were assessment criteria. Results: Mean follow-up was 50 months (24–110). Mean IKS score was significantly improved from 43 (11–70) pre-operatively to 75 (40–100) at last follow-up (Wilcoxon test, p = 0.002). At last follow-up, the flexion-extension amplitude was 91±10°. Radiographic integration of the allografts was achieved in 14 out of 18 grafts. Three allografts were resorbed leading to fracture with subsequent implant failure and a new revision in two. There were no infections. Discussion and conclusion: Bone grafts may be a solution to the difficult problem of bone loss during RTKA. Massive grafts combined with long stem implants have given encouraging early and mid-term results. The duration of these results is under evaluation

We analysed the cellular immune response in ten transplantations of different massive bone allografts, of which five had a poor clinical outcome. Cytotoxic T lymphocytes (CTL) and T helper lymphocytes (TH) against mismatched donor antigens were found in all patients. More importantly, CTL with a high affinity for donor antigens were found in five cases. High-affinity CTL need no CD8 molecule to stabilise the antigen binding and are strongly associated with rejection of heart and corneal transplants. Even after removal of most of the bone-marrow cells, we found high-affinity CTL and high TH frequencies. This T-cell response could be detected over a period of years. We conclude that frozen bone allografts can induce high-affinity donor-specific CTL. The present assay allows qualification and quantification of the levels of CTL and TH in the blood. This approach may be helpful in studying the effect of the immune response on the outcome of the graft

We performed biopsies during reoperation for minor complications in two active young patients 9 and 19 months after massive bone allograft implantation for bone tumour. The grafts were dead and resorption-apposition activity, when present, was predominantly in subperiosteal areas. Inflammatory infiltration was very seldom found. Features considered as ‘microfractures’ or ‘microcracks’ were noted in the cortical ring together with the formation of woven bone, in areas with remodelling. Such cracks are likely to be of mechanical origin and do not inevitably lead to complications