Does joint-sparing tumor resection jeopardize oncologic and functional outcomes in non-metastatic high-grade osteosarcoma around the knee?

BACKGROUND: We previously reported joint-sparing tumor resection for osteosarcoma with epiphyseal involvement in which transepiphyseal osteotomy went through the in situ ablated epiphysis. However, we do not know whether this is a safe approach when compared with joint-sacrificed tumor resection. Our objective was to compare oncologic and functional outcomes between patients who underwent joint preservation (JP) and joint replacement (JR) tumor resection. Furthermore, we identified the risk factors of local recurrence, metastasis and survival. METHODS: Eighty-nine patients with non-metastatic high-grade osteosarcoma around the knee were treated with limb-salvage surgery (JP in 47 and JR in 42). Age, gender, tumor location, pathologic fracture, plain radiographic pattern, limb diameter change, perivascular space alteration, surgical margin, local recurrence, metastasis, death, and the Musculoskeletal Tumor Society (MSTS)-93 scores were extracted from the records. Univariate analysis was performed to compare oncologic and functional outcomes. Binary logistic and cox regression models were used to identify predicted factors for local recurrence, metastasis, and survival. RESULTS: Local recurrence, metastasis and overall survival were similar in the JP and JR group (p = 0.3; p = 0.211; p = 0.143). Major complications and limb survival were also similar in the JR and JP group (p = 0.14; p = 0.181). The MSTS score of 27.06 ± 1.77 in the JP group was higher than that of 25.88 ± 1.79 in the JR group (p = 0.005). The marginal margin of soft tissue compared with a wide margin was the only independent predictor of local recurrence (p = 0.006). Limb diameter increase and perivascular fat plane disappearance during neoadjuvant chemotherapy were independent predictors for metastasis (p = 0.002; p = 0.000) and worse survival (p = 0.000; p = 0.001). CONCLUSIONS: Joint-sparing tumor resection with the ablative bone margin offers advantage of native joint preservation with favorable functional outcomes while not jeopardizing oncologic outcomes compared with joint-sacrificed tumor resection. Surgeon should strive to obtain adequate soft tissue surgical margin decreasing risk of local recurrence. Novel drug regimens might be reasonable options for patients with obvious limb diameter increase and perivascular fat disappearance during chemotherapy.

Is the Capanna Technique a Reliable Method for Revision Surgery after Failure of Previous Limb-Salvage Surgery?

BACKGROUND: Reconstruction of a massive bone defect caused by previous failed limb-salvage surgery in patients with bone sarcoma is challenging. Many procedures have been used, but they all have their inherent disadvantages. The Capanna technique has demonstrated good functional outcomes and a low incidence of complications in primary reconstructive surgery of massive bone defect. However, few studies have focused on its usage in revision surgery after failed primary limb-salvage surgery. METHODS: Between June 2011 and January 2017, 13 patients underwent revision surgery with the Capanna technique for reconstruction of a secondary segmental bone defect caused by a previous failed surgical procedure. The demographics, operating procedures, graft union, functional outcomes, oncologic outcomes, and postoperative complications of each patient were recorded. RESULTS: The current study investigated 13 patients. The rate of limb salvage was 100 %. Bone union was achieved for all patients during a mean time of 8.54 ± 2.15 months (range 4-11 months) at the fibula-host bone junction and 14.92 ± 2.33 months (range 12-21 months) at the allograft-host bone junction. The postoperative complications included wound healing issues and internal fixation loosening. Allograft fracture, nonunion, and infection were not observed. All the patients achieved good functional outcomes, with a Musculoskeletal Tumor Society (MSTS) score of 0.86 ± 0.03 at the latest follow-up visit. CONCLUSIONS: The Capanna technique is a reliable alternative method for revision reconstruction of a segmental bone defect caused by a previous failed surgical procedure. LEVEL OF EVIDENCE: Level IV, therapeutic study.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. LEVEL OF EVIDENCE: Therapeutic Level IV.

What are the Oncologic and Functional Outcomes After Joint Salvage Resections for Juxtaarticular Osteosarcoma About the Knee?

BACKGROUND: Joint salvage surgery for patients with juxtaarticular osteosarcoma remains challenging, especially when the tumor invades the epiphysis. Because patients are surviving longer with current chemotherapy regimens, it is advantageous to retain native joints if possible, especially in young patients. However, the results using joint-preserving tumor resections in this context have not been well characterized. QUESTIONS/PURPOSES: (1) What are the functional outcomes after limb salvage surgery at a minimum of 3 years? (2) What are the oncologic outcomes? (3) Is joint salvage surgery for epiphyseal tumors associated with an increased risk of local recurrence compared with metaphyseal tumors not invading the epiphysis? (4) What are the complications associated with joint salvage surgery? METHODS: Between 2004 and 2013, we treated 117 patients with juxtaarticular osteosarcoma; of those, 43 (38%) were treated with joint salvage surgery, and 41 (95%) of the 43 patients are included in our study. The other two (5%) were lost to followup before 3 years (mean, 4.4 years; range, 3-11 years,). During the period in question, we generally performed joint salvage surgery in these patients when they had a favorable response to chemotherapy, did not have a pathologic fracture or extrusion of the tumor into the joint, and did not have a whole-epiphyseal osteolytic lesion, a large mass, or obvious neurovascular involvement. This report is a followup of an earlier study; the current study includes an additional nine patients, and additional followup of a mean of 19 months for the patients included in the earlier report. We ascertained overall survival and survival free from local recurrence which was estimated using the Kaplan-Meier method, functional status of the limb which was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 scoring system, and recorded reconstructive complications including infection, fracture, skin necrosis, and nonunion. We compared oncologic and functional outcomes between patients with (n = 28) and without tumor extension to epiphysis (n =13). We also compared oncologic and functional outcomes among patients with different adjuvant treatments including microwave ablation (n = 11), cryoablation (n = 12), and navigation-assisted osteotomy (n = 5). Complications were tallied using records from our institutional database. RESULTS: The overall Kaplan-Mayer survival rate was 82% (95% CI, 104-128 months) at 5 years. The overall Kaplan-Meier survivorship from local recurrence was 91% at 5 years (95% CI, 115-133 months). Three patients had a local recurrence, but none had local recurrence in or close to the remaining epiphysis. The MSTS scores ranged from 22 to 30 points, with a median of 28. There were no differences in survival rate, local recurrence, or MSTS scores between patients with a tumor that did not invade the epiphysis and those in whom the tumor did invade the epiphysis. There were differences in MSTS scores among patients with epiphyseal tumor extension in which different adjuvant techniques, including microwave ablation, cryoablation, and navigation-assisted osteotomy, were used. Additional surgical procedures were recorded for 10 patients (24%). Osteonecrosis of the residual epiphysis was detected 13 patients (31%). CONCLUSIONS: Our findings suggest it is possible to salvage joints in selected patients with juxtaarticular osteosarcoma around the knee. The patients who have a favorable response to chemotherapy are the best candidates for this approach. Future studies might explore the role of adjuvant techniques of microwave ablation and cryoablation, particularly when the tumor invades the epiphysis, and whether resections can be facilitated with navigation. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Adjuvant argon-based cryoablation for joint-preserving tumor resection in patients with juxta-articular osteosarcoma around the knee.

BACKGROUNDS: Opinion remains controversial as to whether joint-saving surgery could be safely performed in patients with juxta-articular osteosarcoma. The aim of this study was to assess the validity of adjuvant cryosurgery in joint salvage surgery. METHODS: We evaluated the oncological and functional outcomes of patients who underwent joint-sparing surgery in which argon-based cryoablation was employed to aid partial epiphysis-preserved tumor resection for osteosarcoma around the knee (7 in proximal tibia, 5 in distal femur). RESULTS: The study included 12 patients (5 male, 7 female, mean age 15.8 years (11-24). At a mean follow-up of 48.4 months (38-61), lung metastasis occurred in three patients. Among these, one patient had died, one was alive with disease, and one had no evidence of disease after lobectomy. Histological examination of the resected specimens revealed no viable tumor at the osteotomy plane. There was no local recurrence in the residual epiphysis except one in soft tissue. The mean Musculoskeletal Tumor Society functional score was 92.7%. CONCLUSIONS: Argon-based cryosurgery is a reliable method of sterilizing the tumor in the epiphysis thus allowing safe joint-saving tumor resection possible in patients with juxta-articular osteosarcoma.

A classification system of joint-salvage tumor resection in osteosarcoma of the knee: A retrospective cohort study.

BACKGROUND: Joint-preserving surgery is possible for patients with juxta-articular osteosarcoma of the knee, even when the tumor invades the epiphysis. Oncologic and functional outcomes may vary due to the extent of tumor invasion, the amount of epiphysis preservation, and reconstruction methods. We aimed to introduce a novel classification facilitating clinical evaluation of different surgical treatments. METHODS: We identified 52 patients with osteosarcoma of the knee undergoing joint-preserving tumor resection and intercalary reconstruction. We classified procedures into two types and six subtypes based on the tumor location and adjuvant treatment employed. Oncologic outcomes, limb function and complications were compared among different types. RESULTS: None of the patients had a local recurrence in the preserved epiphysis apart from three (5.7 %) who had local recurrence in soft tissue. Overall survival rate of the patients was 82.7 % at 5 and 10 years. There was no difference in survival rate (P = 0.909), local recurrence (P = 0.642) between type I (tumor not invading epiphysis) and type II (tumor invading epiphysis). In addition to one skin necrosis in the 3D-printed prosthesis reconstruction and one infection in Capanna reconstruction, all complications necessitating additional surgery occurred in allograft. The Musculoskeletal Tumor Society (MSTS) scores ranged from 21 to 30 with a median of 26. There were differences in the MSTS scores among six subgroups (P = 0.015), with the highest in type Ia and the lowest in type IIc. The less of the viable epiphysis retained, the worse the knee function was at long-term follow up. CONCLUSIONS: The suggested classification can guide surgical strategy and is convenient for comparison of the functional results.

Predicting chemosensitivity based on mini patient-derived xenografts in osteosarcoma patients: A retrospective study.

Context: The survival of patients diagnosed with osteosarcoma has not improved in the past three decades because of chemoresistance. Aim: This study aimed to improve the prognosis of patients with osteosarcoma. Settings and Design: From January 1, 2018, to June 30, 2019, a total of 14 patients with osteosarcoma were enrolled who underwent mini patient-derived xenograft (mini-PDX) assay in our hospital. Methods and Materials: We recruited 14 patients with osteosarcoma having acquirable lesions to establish PDX models and examine the sensitivity of nine drugs, including methotrexate (MTX), ifosfamide (IFO), epirubicin, and etoposide. Drug sensitivity was evaluated using the tumor relative proliferation rate (TRPR), and the patients' responses were assessed according to the RECIST 1.1 guidelines. Statistical Analysis Used: The difference in TRPR was analyzed using a paired t-test, while progression-free survival (PFS) was analyzed using the Kaplan-Meier method. Results: The mini-PDX results revealed that IFO had a lower tumor proliferation rate than MTX, indicating that IFO was more sensitive in patients with osteosarcoma (38.3% vs. 84.3%, P = 0.031). Thus, the regimen where IFO alternates with doxorubicin and cisplatin was recommended as adjuvant chemotherapy. MTX could replace IFO if the TRPR was better. Finally, 11 patients received adjuvant chemotherapy. A comparison of PFS revealed that sensitive patients with TRPR of <40% had a better prognosis (9.4 months vs. 3.7 months, P = 0.0324). Conclusions: Chemotherapy based on mini-PDX can improve the survival of patients with osteosarcoma whose TRPR was <40%, and that chemotherapy without MTX could be an alternative for osteosarcoma.

Reconstructing avascular necrotic femoral head through a bioactive ß-TCP system: From design to application.

A variety of techniques have been used for treating avascular necrosis of the femoral head (ANFH), but have frequently failed. In this study, we proposed a ß-TCP system for the treatment of ANFH by boosting revascularization and bone regeneration. The angio-conductive properties and concurrent osteogenesis of the highly interconnected porous ß-TCP scaffold were revealed and quantified through an in vivo model that simulated the ischemic environment of ANFH. Mechanical test and finite element analysis showed that the mechanical loss caused by tissue necrosis and surgery was immediately partially compensated after implantation, and the strength of the operated femoral head was adaptively increased and eventually returned to normal bone, along with continuous material degradation and bone regeneration. For translational application, we further conducted a multi-center open-label clinical trial to assess the efficacy of the ß-TCP system in treating ANFH. Two hundred fourteen patients with 246 hips were enrolled for evaluation, and 82.1% of the operated hips survived at a 42.79-month median follow-up. The imaging results, hip function, and pain scores were dramatically improved compared to preoperative levels. ARCO stage Ⅱ disease outperformed stage Ⅲ in terms of clinical effectiveness. Thus, bio-adaptive reconstruction using the ß-TCP system is a promising hip-preserving strategy for the treatment of ANFH.

Establishment of a rabbit's model for modified Capanna technique.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Combined allograft and intramedullary vascularized fibula transfer in rabbit's tibia represent an ideal model that accurately simulates the Capanna technique for CSD reconstruction.

Intercalary tibial reconstruction with frozen tumor-bearing autograft in combination with ipsilateral fibula in limb-salvage surgery.

PURPOSE: The purpose of this study was to examine whether the results of a reconstruction using frozen autograft in combination with vascularized fibula are comparable to other reconstructive methods in limb-salvage surgery for tibial sarcoma with regard to the functional outcome and complications. METHODS: Between 2008 and 2012, nine patients with bone sarcoma of the tibia underwent excision of the affected segment that was then frozen and reimplanted with an ipsilateral vascularized fibular graft within it. Patients were examined clinically and radiographically. RESULTS: The mean follow-up was 48.8 months. The mean time to full weight-bearing was 6.2 months and to complete radiological union 6.8 months at the conjunction. One patient required a mid-thigh amputation due to local recurrence in soft tissue. No local recurrence arising from the frozen autograft was detected. Complications included wound dehiscence in 1, clawed toes in 1, temporary peroneal nerve palsy in 1, and stress fracture in 1. The average musculoskeletal tumor society functional score was 94.5%. CONCLUSIONS: Combination of a frozen tumor-bearing autograft and ipsilateral pedicled fibula is an effective reconstruction for massive bone defect arising from resection of bone sarcoma in tibia. This approach has the advantage of combining the biological properties offered by the vascularized bone graft with the mechanical endurance of the frozen autograft. The method is best indicated for intercalary defects of the tibia for selected patients. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Cryoablation-aided joint retention surgery for epiphysis involvement in osteosarcoma compared with endoprosthetic replacement.

AIMS: We have previously reported cryoablation-assisted joint-sparing surgery for osteosarcoma with epiphyseal involvement. However, it is not clear whether this is a comparable alternative to conventional joint arthroplasty in terms of oncological and functional outcomes. METHODS: A total of 22 patients who had localized osteosarcoma with epiphyseal involvement around the knee and underwent limb salvage surgery were allocated to joint preservation (JP) group and joint arthroplasty (JA) group. Subjects were followed with radiographs, Musculoskeletal Tumor Society (MSTS) score, and clinical evaluations at one, three, and five years postoperatively. RESULTS: Patients in both groups (ten in JP and 12 in JA) did not differ in local recurrence (p ≥ 0.999) and occurrence of metastases (p ≥ 0.999). Overall survival was similar in both groups (p = 0.858). Patients in the JP group had less range of motion (ROM) of the knee (p < 0.001) and lower MSTS scores (p = 0.010) compared with those of the JA group only at one year postoperatively. There was no difference between groups either at three years for ROM (p = 0.185) and MSTS score (p = 0.678) or at five years for ROM (p = 0.687) and MSTS score (p = 0.536), postoperatively. Patients in the JA group tended to have more complications (p = 0.074). Survival of primary reconstruction in the JP group was better than that of the JA group (p = 0.030). CONCLUSION: Cryoablation-aided joint-sparing surgery offers native joint preservation with comparable functional recovery and more durable reconstruction without jeopardizing oncological outcomes compared with conventional limb salvage surgery. Cite this article: Bone Joint J 2021;103-B(8):1421-1427.

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?

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Salvianolic Acid B-Loaded Chitosan/hydroxyapatite Scaffolds Promotes The Repair Of Segmental Bone Defect By Angiogenesis And Osteogenesis.

BACKGROUND: Salvianolic acid B has been proven as an effective drug to promote osteogenesis and angiogenesis which could be beneficial for bone repair. PURPOSE: The objective of this study was to construct a salvianolic acid B-loaded chitosan/hydroxyapatite (Sal B-CS/HA) bone scaffold with controlled release and effective bioactivity. METHODS: The characteristics, controlled release behavior and bioactivity of Sal B-CS/HA scaffold were evaluated in vitro. The bone repair effect was evaluated in the rabbit radius defect model. RESULTS: The results showed that chemical and physical characteristics of salvianolic acid B and chitosan/hydroxyapatite (CS/HA) material did not obviously change after the drug loading procedure; the drug release of salvianolic acid B was stable and continuous from the Sal B-CS/HA scaffold for 8 weeks in vitro; the biocompatibility of the Sal B-CS/HA was favorable by evaluation of cell morphology and proliferation; the osteogenic and angiogenic bioactivities of the Sal B-CS/HA scaffold were proved to be effective by in vivo and in vitro tests. CONCLUSION: Our results suggest that this salvianolic acid B-loaded bone scaffold has potential to be used for bone defect repair with both osteogenic and angiogenic bioactivities.

Factors Influencing Osseous Union Following Surgical Treatment of Bone Tumors with Use of the Capanna Technique.

BACKGROUND: The Capanna technique involves the use of a vascularized fibular graft inlaid in a massive bone graft in intercalary reconstruction for diaphyseal long-bone defects caused by tumor resection. Allograft-host union time varies in different reports, and few studies have focused on the underlying factors affecting union time. The purpose of the present study was to analyze factors relevant to union time and to report complications of the Capanna technique. METHODS: We identified 60 patients who underwent segmental reconstruction with use of the Capanna technique following tumor resection (in the humerus in 10 patients, the femur in 33 patients, and the tibia in 17 patients). Multivariable linear multiple regression model analysis was performed with allograft-host osseous union time as the dependent variable. Union time was evaluated on radiographs. Independent variables included age, tumor site, adjuvant treatment, a previous surgical procedure, defect length, fixation method, and fibular viability. A retrieved specimen of the composite was histologically assessed. RESULTS: The mean defect length was 16 cm. All allografts and host bone united, with the mean time to union of 13 months (range, 6 to 27 months). Prolonged union time was associated with devitalization of the fibular graft (p < 0.001), use of chemotherapy (p = 0.031), and a previous surgical procedure (p = 0.048). Patient age (p = 0.742), amount of resection (p = 0.907), operative site (p = 0.508), and fixation method (p = 0.105) were not associated with union time. On histological analysis, we found that the allograft-host cortical junction was united by callus from both periosteum of the host bone and the fibula. CONCLUSIONS: The Capanna technique appears to be a reliable method for intercalary reconstruction with a low rate of complications. Devitalization of the transplanted fibula, chemotherapy, and a previous surgical procedure are adverse factors leading to prolonged union time. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Novel 3D-printed prosthetic composite for reconstruction of massive bone defects in lower extremities after malignant tumor resection.

OBJECTIVE: To introduce a novel 3D-printed prosthetic composite for reconstruction of massive bone defects after resection for bone malignancy of lower extremities. The design concept, surgical technique, and the preliminary outcomes were elaborated. METHODS: Patients with primary malignant tumors of lower extremities requiring tumor resection and reconstruction were recruited between Jun 2015 and Nov 2018. Patient-specific 3D-printed prostheses were designed according to preoperative imaging data. After tumor resection, reconstruction was performed with composites consisting of 3D- printed prosthesis, beta-tricalcium phosphate (ß-TCP) bioceramics and/or vascularized fibula. All patients underwent regular follow-up postoperatively. The functional outcomes were assessed by the Musculoskeletal Tumor Society score (MSTS). Oncological outcomes, imaging results, and complications were recorded and analyzed. RESULTS: Ten cases averaging 12.90 years of age participated in this study. There were five femur and five tibia reconstructions. The mean follow-up period was 16.90 months. At last follow-up, all patients were alive without tumor recurrence. Average MSTS functional score was 80.33 ± 11.05%. All prostheses were intact and stable without failure or systemic breakage. No serious complications occurred after the operation. Postoperative X-ray, computed tomography (CT) and single-photon emission computed tomography (SPECT) showed an ideal integration between the bone and the prosthetic composite. Moreover, vascularized fibula and implanted ß-TCP bioceramics indicated relatively high metabolic activity in vivo. CONCLUSIONS: Patient-specific 3D-printed prostheses combined with ß-TCP bioceramics and/or vascularized fibula provide an excellent option for reconstruction of massive bone defects after lower extremity malignant tumor extirpation. Short-term follow up showed promising clinical results in recovering lower limb function, promoting osseointegration and reducing complications.

Preparation, physicochemical properties and biocompatibility of PBLG/PLGA/bioglass composite scaffolds.

In this study, novel poly(γ-benzyl l-glutamate)/poly(lactic-co-glycolic acid)/bioglass (PBLG/PLGA/BG) composite scaffolds with different weight ratios were fabricated using a negative NaCl-templating method. The morphology, compression modulus and degradation kinetics of the scaffolds were characterized. The results showed that the PBLG/PLGA/BG composite scaffolds with a weight ratio of 5:5:1, namely PBLG5PLGA5BG composite scaffolds, displayed a pore size range of 50-500µm, high compressive modulus (566.6±8.8kPa), suitable glass transition temperature (46.8±0.2°C) and low degradation rate (>8weeks). The in vitro biocompatibility of the scaffolds was evaluated with MC3T3-E1 cells by live-dead staining, MTT and ALP activity assays. The obtained results indicated that the PBLG5PLGA5BG composite scaffolds were more conducive to the adhesion, proliferation and osteoblastic differentiation of MC3T3-E1 cells than PBLG and PBLG/PLGA composite scaffolds. The in vivo biocompatibility of the scaffolds was evaluated in both SD rat subcutaneous model and rabbit tibia defect model. The results of H&E, Masson's trichrome and CD34 staining assays demonstrated that the PBLG5PLGA5BG composite scaffolds allowed the ingrowth of tissue and microvessels more effectively than PBLG/PLGA composite scaffolds. The results of digital radiography confirmed that the PBLG5PLGA5BG composite scaffolds significantly improved in vivo osteogenesis. Collectively, the PBLG5PLGA5BG composite scaffolds could be a promising candidate for tissue engineering applications.

CD31hiEmcnhi Vessels Support New Trabecular Bone Formation at the Frontier Growth Area in the Bone Defect Repair Process.

CD31hiEmcnhi vessels were a subtype of vessels in the murine skeletal system, with high levels of platelet and endothelial cell adhesion molecule-1 (PECAM-1/CD31) and endomucin (Emcn). They were reported coupling angiogenesis and osteogenesis during bone development. We investigated the distribution of these vessels in rat tibiae and their temporal and spatial distribution during the bone defect repair process to improve our understanding of the importance of these vessels. We confirmed that CD31hiEmcnhi vessels were specially distributed around the trabecular bones near metaphysis and endosteum in rat tibiae. At 3 days post bone injury, CD31hiEmcnhi vessels proliferated and were extensively distributed across the entire repair area. At 7 and 14 days post-injury, these vessels decreased but were specially distributed around the growing trabecular bones near the frontier growth area, suggesting that these vessels support new bone formation. The distribution of CD31hiEmcnhi vessels and the transcriptions of Hif-1α and VEGFA, as well as BMP2 and Osterix decreased at 7 and 14 days post-injury under osteoporotic conditions, in combination with insufficient osteogenesis. Our research is of great significance to help understand the important role of CD31hiEmcnhi vessels in supporting new trabecular bones formation during bone defect repair process.

Extracorporeally frozen tumour-bearing bone combined with free vascularised fibula for the intercalary reconstruction of femoral defect after resection of bony sarcoma.

BACKGROUND: With the improved survival for patients with bone sarcomas, there is a trend to reconstruct intercalary femur defects using biologic techniques. This study examined whether the results of a frozen femur autograft with vascularised fibula are comparable to other reconstructive options in terms of the functional outcomes and the complications. MATERIALS AND METHODS: Between 2008 and 2012, eight patients with bony sarcoma of the femur were subjected to reconstruction with a recycled frozen autograft combined with a vascularised fibula flap inside. The oncologic and functional results were analysed retrospectively. RESULTS: The mean follow-up was 48.7 months (37-71). The oncologic results were continuously disease free in five patients; there was no evidence of disease in one, one patient was alive with disease and another died of the disease. The average length of defect was 13.6 cm (9-21). Bone union was achieved in all cases. The mean time to bone union was 7.9 months (5-19) and to full weight bearing was 7.8 months (6-11). There was no infection or construct fracture in this series. Two complications were observed. One tumour recurrence in soft tissue was treated with reresection. One tibia fracture was successfully managed with cast immobilisation. The average Musculoskeletal Tumor Society functional score was 95% (27-30). The construct was intact in all patients. CONCLUSIONS: Vascularised fibular flap combined with frozen autografts is a dependable and durable option for the reconstruction of large bony defects after femoral sarcoma resection. It had the merits of reliable bone union and low complications, which compare well with other biological reconstructions. Evidence Rating Scale for Therapeutic Studies Level IV, therapeutic study.