Ankle arthrodesis using a modified Masquelet induced membrane technique for open ankle fracture with a substantial osteochondral defect: A case report of novel surgical technique

Reconstruction of a bone defect using the Masquelet induced membrane technique has been well described. However, there are few reports of arthrodesis using this technique. In this case report, we describe a modified Masquelet technique for ankle arthrodesis with nailing. The patient was a 32-year-old man who sustained an open fracture of the right ankle with a substantial osteochondral defect as a result of a fall. Immediately after the injury, a staged procedure using the Masquelet technique was planned. The bone defect was filled with bone cement in the acute stage, but replacement of the cement was needed 6 months after the injury because of a prolonged inflammatory reaction. Ten months after the injury, the bone cement was removed, and ankle arthrodesis was performed using an IM nail with a combination of autologous and artificial bone. As a modification of the Masquelet technique, the anterior surface of the transplant site was covered with a large but thin layer of cortical bone instead of suturing the incised membrane. At 1 year postoperatively, firm bony union was achieved and the implant was removed. At follow-up 3 years after his injury, the patient is able to walk, undertake physical work, and has no clinical signs of infection. Our experience suggests that a modified induced membrane technique may be useful when treating an open limb fracture with an extensive osteochondral defect where preservation of the joint is difficult and arthrodesis is considered.     

Rapid healing of femoral defects in rats with low dose sustained BMP2 expression from PEGDA hydrogel microspheres

Current strategies for bone regeneration after traumatic injury often fail to provide adequate healing and integration. Here, we combined the poly (ethylene glycol) diacrylate (PEGDA) hydrogel with allogeneic “carrier” cells transduced with an adenovirus expressing BMP2. The system is unique in that the biomaterial encapsulates the cells, shielding them and thus suppressing destructive inflammatory processes. Using this system, complete healing of a 5 mm‐long femur defect in a rat model occurs in under 3 weeks, through secretion of 100‐fold lower levels of protein as compared to doses of recombinant BMP2 protein used in studies which lead to healing in 2–3 months. New bone formation was evaluated radiographically, histologically, and biomechanically at 2, 3, 6, 9, and 12 weeks after surgery. Rapid bone formation bridged the defect area and reliably integrated into the adjacent skeletal bone as early as 2 weeks. At 3 weeks, biomechanical analysis showed the new bone to possess 79% of torsional strength of the intact contralateral femur. Histological evaluation showed normal bone healing, with no infiltration of inflammatory cells with the bone being stable approximately 1 year later. We propose that these osteoinductive microspheres offer a more efficacious and safer clinical option over the use of rhBMP2. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1597–1604, 2013     

Combination therapy with PTH and DBM cannot heal a critical sized murine femoral defect

Orthopaedic surgeons continue to search for cost‐effective bone graft substitutes to enhance bone repair. Teriparatide (PTH 1‐34) and demineralized bone matrix (DBM) have been used in patients to promote bone healing. We evaluated the efficacy of PTH and DBM in healing a critical sized femoral defect in three lineage‐specific transgenic mice expressing Col3.6GFPtopaz (pre‐osteoblastic marker), Col2.3GFPemerald (osteoblastic marker) and α‐SMA‐Cherry (pericyte/myofibroblast marker). Mid‐diaphyseal defects measuring 2 mm in length were created in the central 1/3 of mice femora using a circular saw and stabilized with an alveolar distractor device and cerclage wires. Three groups were evaluated: Group I, PTH 30 μg/kg injection daily, Group II, PTH 30 μg/kg injection daily + DBM, and Group III, DBM + 30μL saline injection. PTH was given for 28 days or until the time of sacrifice. Animals were sacrificed at 7, 14, 28, and 56 days. Radiographs at the time of sacrifice were evaluated using a 5‐point scaled scoring system. Radiographs showed a lack of healing across all treatment groups at all time points: Group I, 1.57 +/? 0.68; Group II, 3.00 +/? 1.29; and Group III, 2.90 +/? 1.03. Bone formation in the defect as measured by radiographic healing score was significantly better at 56 days in Groups II (p = 0.01) and III (p < 0.01) compared to Group I. Across all treatment groups and time points the defects were largely absent of osteoprogenitor cells based on gross observation of frozen histology and quantitation of cellular based histomorphometric parameters. Quantitation of frozen histologic slides showed a limited osteoprogenitor response to PTH and DBM. Our results suggest that the anabolic agent teriparatide is unable to induce healing in a critical sized mouse femoral defect when given alone or in combination with the DBM preparation we used as a local bone graft substitute. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1242–1249, 2015.

     

Alteration of Masquelet's induced membrane characteristics by different kinds of antibiotic enriched bone cement in a critical size defect model in the rat's femur

The Masquelet technique for the treatment of large bone defects consists of a 2-stage procedure. In the first stage, a polymethylmethacrylate (PMMA) cement spacer is inserted into the bony defect of a rat's femur and over a period of 2–4 weeks a membrane forms that encapsulates the defect/spacer. In a second operation the membrane is opened, the PMMA spacer is removed and the resulting cavity is filled with autologous bone. Different kinds of bone cements are available, with or without supplemental antibiotics. Both might influence the development and the characteristics of the induced membrane which might affect the bone healing response. Hence, this comparative study was performed to elucidate the effect of different bone cements with or without supplemental antibiotics on the development of an induced membrane in a critical size femur defect model in rats.A total of 72 male SD rats received a 10 mm critical size defect of the femur which was stabilised by a plate osteosynthesis and filled with either Palacos + Gentamycin, Copal Gentamycin + Vancomycin, Copal + Gentamycin + Clindamycin or Copal Spacem. The induced membranes were analysed after two, four and six weeks (wks) after insertion of the cement spacers (n = 6/group). Paraffin embedded histological sections of the membrane were microscopically analysed for membrane thickness, elastic fibres, vascularisation and proliferation by an independent observer blinded to the group setup.The thickness of the induced membrane increased significantly from 2 wks (553 μm) to 6 wks (774 μm) in group Palacos + Gentamycin whereas membrane thickness decreased significantly in groups Copal + Gentamycin + Clindamycin (682–329 μm) and Copal Spacem (916 μm to 371 μm). The comparison between the groups revealed significantly increased membrane thickness in group Palacos + Gentamycin and Copal Gentamycin + Vancomycin in comparison to group Copal + Gentamycin + Clindamycin six weeks after induction. However, the fraction of elastic fibres was significantly increased in groups Copal + Gentamycin + Clindamycin (71%, 80%) and Copal Spacem (82%, 81%) after 2 and 4 weeks in comparison to the groups Palacos + Gentamycin (56%, 57%) and Copal Gentamycin + Vancomycin (63%, 69%). Those differences however were partly diminished after 6 wks. The ratio of immature (vWF+) to more mature (CD31+) blood vessels increased significantly in groups Palacos + Gentamycin and Copal Gentamycin + Vancomycin whereas no significant alterations were noted in groups Copal + Gentamycin + Clindamycin and Copal Spacem.For the first time we demonstrated that thickness and proportion of elastic fibres in induced membranes were influenced by the type of cement and the kind of supplemental antibiotics being used. Whether these alterations of the induced membrane have an effect on bone healing remains to be proven in future studies.     

Enhancement of recombinant human BMP‐7 bone formation with bmp binding peptide in a rodent femoral defect model

Bone morphogenetic binding peptide (BBP) is an 18.5 kDa fragment of a bone matrix protein peptide. A rat femoral defect model was used to test the effect of BBP combined with recombinant human bone morphogenetic protein‐7 (rhBMP‐7) to induced bone healing. Two doses of BBP (500 and 1000 µg) were tested with two doses of rhBMP‐7 (2 and 5 µg), and the results were compared with a positive control (10 µg rhBMP‐7). Bone healing was evaluated by radiology, manual palpation, microcomputed tomography, and histology. The high dose of 10 µg of rhBMP‐7 resulted in a consistent 100% bone union rate and a mature histological appearance on histology, and was used as a positive control. When 1000 µg of BBP was combined with lower doses of BMP‐7 (2 µg rhBMP‐7 or 5 µg rhBMP‐7) significant differences were seen in radiographic scores, manual palpation, and bone volume, when compared to 2 µg rhBMP‐7 or 5 µg rhBMP‐7 alone. The combination of 1000 µg of BBP and 5 µg rhBMP‐7 also achieved 100% fusion rate, induced a larger amount of bone formation, and yielded similar maturity of bone marrow when compared with the high dosage 10 µg rhBMP‐7 group. This study demonstrated that when combined together, BBP can enhance the bone healing of rhBMP‐7. Improved healing imparted by the addition of BBP may result in lesser amounts of rhBMP‐7 needed to achieve union in the clinical setting. © 2010 OrthopaedicResearchSociety.PublishedbyWileyPeriodicals, Inc.JOrthopRes29:753–759,2011     

大鼠股骨缺损模型中BBP增强BMP-2的骨诱导作用

[目的]验证在大鼠节段性骨缺损模型中BBP对于rhBMP-2骨诱导作用的影响。[方法]70只缺损分别分成7组,每组不同剂量的rhBMP-2+/_1 000μg BBP,4、8周后分别摄片,动物8周后处死,股骨样本分别手工评估,采用uCT测量骨容积,随后分别采用组织学和生物力学分析。[结果]高剂量(10μg)rhBMP-2组术后8周可见骨愈合,骨缺损处骨的完全覆盖和桥接,但低剂量(5μg和2μg)rhBMP-2组术后8周骨愈合欠佳。与单独应用rhBMP-2相比,使用低剂量的rhBMP-2复合一定量的BBP可以取得更满意的骨形成量。BBP增强rhBMP-2的骨形成活性发生于4～8周时,而在术后早期并无明显作用。单纯应用BBP仅可见骨缺损处局部钙化,未见骨愈合。[结论]BBP能显著增强rhBMP-2的骨形成活性,这种增强作用需要一定时间来产生效果;其活性发生于术后4～8周时,在术后早期并无明显作用。而且BBP本身并没有骨诱导潜力,仅仅能增强rhBMP-2的骨形成活性。BBP起到缓释作用,与rhBMP-2紧密结合后,让rhBMP-2缓慢而持久的释放。     

Modified Masquelet technique using allogeneic umbilical cord-derived mesenchymal stem cells for infected non-union femoral shaft fracture with a 12 cm bone defect: A case report

IntroductionNon-union due to large bone loss often causes significant long-term morbidity. We incorporate the use of allogeneic umbilical cord-derived mesenchymal stem cells (UC-MSCs) as part of the diamond concept of regenerative medicine in a case of infected non-union fracture.Presentation of caseWe reported a 54-year-old female patient presenting with pain on the right thigh. She was previously diagnosed with a closed fracture of the right femoral shaft and underwent four surgeries before finally being referred to Dr. Cipto Mangunkusumo General Hospital with infected non-union of the right femoral shaft. The patient was treated with a combination of UC-MSCs, bone morphogenetic protein-2 (BMP-2), Hydroxyapatite (HA), and mechanical stabilization using Masquelet Technique. The combination of allogeneic MSCs, BMP2, HA, and Masquelet Technique was successful in creating new bone with no apparent side effects.DiscussionBone loss might be caused by external factors (true defects), or structural loss of the existing bone. The combination of allogeneic UC-MSCs, BMP-2, HA and an induced membrane technique pioneered by Masquelet allowed for faster regeneration process and more optimal bone healing. This paper aims to assess and compare the result of such procedures with the previous four surgeries done to the patient, which did not yield satisfactory results.ConclusionThe application of allogeneic UC-MSC, BMP-2, HA and Masquelet technique as proposed in the diamond concept is a viable method in treating critical-sized bone defect and provides an effective way to overcome non-union caused by large defect.     

Enhanced effects of BMP‐binding peptide combined with recombinant human BMP‐2 on the healing of a rodent segmental femoral defect

BMP‐binding peptide (BBP) enhances the osteogenic activity of recombinant human bone morphogenetic protein‐2 (rhBMP‐2), but the mechanism underlying the enhancement remains unclear. We aimed to elucidate the potential enhanced efficacy of BBP using critical‐sized segmental femoral bone defects in rats. Seventy defects in seven groups of rats were filled with various amounts (0, 2, 5, and 10 µg) of rhBMP‐2 with or without 1000 µg BBP. Radiographs were obtained after 4 and 8 weeks. The animals were euthanized at 8 weeks, and femoral specimens were assessed manually, evaluated for bone volume using microcomputed tomography, and subjected to histological or biomechanical analysis. Although 10 µg rhBMP‐2 yielded consistent results in terms of bone healing and quality of bone repair across the segmental defect, lower doses of rhBMP‐2 failed to induce satisfactory bone healing. However, the combined administration of lower doses of rhBMP‐2 and BBP induced the formation of significantly large amounts of bone. Our results suggest that the combined administration of rhBMP‐2 and BBP facilitates bone healing and has potential clinical applications. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:258–264, 2010     

Introduction of a new interlocked intramedullary nailing device for stabilization of critically sized femoral defects in the rat: A combined biomechanical and animal experimental study

The goals of this study were to develop a new intramedullary, rotation‐stable locking device and evaluate it biomechanically and in vivo for maintenance of a critical size osteotomy gap in a model of conscious pseudarthrosis. In standardized osteotomized rat femora (5 mm osteotomy gap) two different rotation‐ and axial‐stable locking devices (group pS + cS) were tested in vitro with respect to biomechanics and compared to a control group without an additional locking device (K; n = 6 for each group). For in vivo studies, 27 male Sprague Dawley rats (250–300 g) underwent a femoral defect osteotomy of critical size and were stabilized by one of the three methods (n = 9 for each group). All groups were examined radiologically postoperatively, after 14 days, and after 12 weeks. In vitro testing revealed higher compression and torsional rigidities for the two locking devices (p < 0.05) compared to the control group (compression rigidity: pS = 103.6 ± 13.2; cS = 91.3 ± 10.9; K = 52.8 ± 8.4 N/mm; torsional rigidity: pS = 5.9 ± 0.9; cS = 4.3 ± 1.4; K = 0.4 ± 0.1 Nmm/°). In vivo, group K and pS exhibited up to two thirds wire dislocation and reduction of the osteotomy gap, while dislocation was less frequent in the cS group. Thus, the locking device with compression of the wire showed advantages in rotational and axial stability for a critically sized defect, though the osteotomy gap could not be maintained in all cases over the 12‐week period. Nevertheless, our data corroborate the necessity of an internal fixation device with sufficient axial and rotational stability. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:184–189, 2008     

Management of a young patient with dextrocardia,atrial septal defect,and Eisenmenger syndrome with venous‐venous extracorporeal membrane oxygenation and heart‐lung transplantation

Dextrocardia is a rare congenital condition which presents important challenges for surgical management. We discuss a patient with dextrocardia, atrial septal defect, and Eisenmenger syndrome, which ultimately led to decompensated end‐stage lung disease and heart‐lung transplant. Venous‐venous extracorporeal membrane oxygenation was an important strategy to bridge the patient until donor organs became available. Transplantation of a heart‐lung block allowed for the treatment of the patient's underlying congenital heart defect, anatomic reversal of dextrocardia with appropriate venous and arterial connections, and management of pulmonary damage from pulmonary hypertension.     

How transplant surgeons can overcome the inevitable insufficiency of allograft size during adult living-donor liver transplantation: strategy for donor safety with a smaller-size graft and excellent recipient results

Small-for-size grafts are an issue in liver transplantation. Portal venous pressure (PVP) was monitored and intentionally controlled during living-donor liver transplantation (LDLT) in 155 adult recipients. The indocyanine green elimination rate (kICG) was simultaneously measured in 16 recipients and divided by the graft weight (g) to reflect portal venous flow (PVF). The target PVP was <20 mmHg. Patients were divided by the final PVP (mmHg): Group A, PVP < 12; Group B, 12 ≤ PVP < 15; Group C, 15 ≤ PVP < 20; and Group D, PVP ≥ 20. With intentional PVP control, we performed splenectomy and collateral ligation in 80 cases, splenectomy in 39 cases, and splenectomy, collateral ligation, and additional creation in five cases. Thirty-one cases received no modulation. Groups A and B showed good LDLT results, while Groups C and D did not. Final PVP was the most important factor for the LDLT results, and the PVP cutoffs for good outcomes and clinical courses were both 15.5 mmHg. The respective kICG/graft weight cutoffs were 3.5580 × 10(-4) /g and 4.0015 × 10(-4) /g. Intentional PVP modulation at <15 mmHg is a sure surgical strategy for small-for-size grafts, to establish greater donor safety with good LDLT results. The kICG/graft weight value may have potential as a parameter for optimal PVF and a predictor for LDLT results.