Reconstruction Of Large Bony Defects Research Articles

Evaluation of the regenerative potential of decellularized skeletal muscle seeded with mesenchymal stromal cells in critical-sized bone defect of rat models

BackgroundThe morbidities and complications reported in the reconstruction of large bony defects have inspired progression in the field of bioengineering, with a recent breakthrough for the use of decellularized skeletal muscle grafts (DSMG). AimTo assess the osteogenic potentials of seeded DSMG in vitro and to investigate bone regeneration in critical size defect in vivo. Materials and MethodsAssessment of cell viability and characterization was carried out on seeded DSMG for different intervals in vitro. For in vivo experiments, histological analysis was performed for rat cranial defects for the following groups: (A) non-treated DSMG and (B) seeded DSMG after a period of 8 weeks. ResultsThe in vitro experiment demonstrated the lack of cytotoxicity and inert properties of seeded DSMG; these facilitated the osteogenic differentiation and significant gene expressions, particularly of COL1A1, RUNX2, and OPN (1.9174 ± 0.11673, 1.1806 ± 0.02383, and 1.1802 ± 0.00775, respectively). In the in vivo experiment, superior results were detected in the seeded DSMG group which showed highly vascularized and cellular dense connective tissue with deposited bone matrix and multiple scattered islets of newly formed bone. ConclusionOur results demonstrated the promising aspects of DSMG; however, there is a lack of studies to support further implications.

Prognostic factors associated with achieving total oral diet following osteocutaneous microvascular free tissue transfer reconstruction of the oral cavity

IntroductionOsteocutaneous microvascular free tissue transfer (OMFTT) is the current standard in reconstruction of large bony defects of the oral cavity. Although being able to swallow ranks as a top priority for patients undergoing OMFTT, factors associated with achieving an oral diet following surgery remain unclear. We sought to describe the rate of total oral diet achievement, and to identify possible pre-, intra-, and post-operative factors associated with achievement in patients undergoing OMFTT. MethodsRetrospective review between January 1, 2010 and March 31, 2018 at two tertiary academic centers. Results249 patients (67% male, mean age 58 years) met inclusion criteria, with a median follow up of 15 months. Overall, 142 (57%) of patients achieved a total PO diet post-operatively, with median time to achievement of 3.2 months. Multivariate analysis identified that lack of concurrent glossectomy (SHR 1.72 [1.09–2.70], p = 0.02), N0/1 disease (SHR 1.92 [1.16–3.13], p = 0.011), avoidance of post-operative fistula formation (SHR 1.96 [1.22–3.23], p = 0.005), pre-operative G-tube independence (SHR 3.33 [1.69–6.25], p < 0.001), and successful dental rehabilitation (SHR 2.08 [1.43–3.03], p < 0.001) are independently associated with total oral diet achievement. ConclusionsBony resections not requiring glossectomy, limited nodal disease burden, pre-operative gastrostomy-independence, avoidance of post-operative fistula, and dental rehabilitation are independently associated with achievement of total oral diet following OMFTT reconstruction of the oral cavity. Counseling patients on associated risk factors is important in guiding post-treatment expectations. Minimization of post-operative fistula, and maximization of dental rehabilitation may significantly improve total oral diet achievement in this patient population.

Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone.

Autologous bone grafts remain a standard of care for the reconstruction of large bony defects, but limitations persist. The authors explored the bone regenerative capacity of customized, three-dimensionally printed bioactive ceramic scaffolds with dipyridamole, an adenosine A2A receptor indirect agonist known to enhance bone formation. Critical-size bony defects (10-mm height, 10-mm length, full-thickness) were created at the mandibular rami of rabbits (n = 15). Defects were replaced by a custom-to-defect, three-dimensionally printed bioactive ceramic scaffold composed of β-tricalcium phosphate. Scaffolds were uncoated (control), collagen-coated, or immersed in 100 μM dipyridamole. At 8 weeks, animals were euthanized and the rami retrieved. Bone growth was assessed exclusively within scaffold pores, and evaluated by micro-computed tomography/advanced reconstruction software. Micro-computed tomographic quantification was calculated. Nondecalcified histology was performed. A general linear mixed model was performed to compare group means and 95 percent confidence intervals. Qualitative analysis did not show an inflammatory response. The control and collagen groups (12.3 ± 8.3 percent and 6.9 ± 8.3 percent bone occupancy of free space, respectively) had less bone growth, whereas the most bone growth was in the dipyridamole group (26.9 ± 10.7 percent); the difference was statistically significant (dipyridamole versus control, p < 0.03; dipyridamole versus collagen, p < 0.01 ). There was significantly more residual scaffold material for the collagen group relative to the dipyridamole group (p < 0.015), whereas the control group presented intermediate values (nonsignificant relative to both collagen and dipyridamole). Highly cellular and vascularized intramembranous-like bone healing was observed in all groups. Dipyridamole significantly increased the three-dimensionally printed bioactive ceramic scaffold's ability to regenerate bone in a thin bone defect environment.

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

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. 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. 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 13.6cm (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. 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.

Coculture of peripheral blood CD34+ cell and mesenchymal stem cell sheets increase the formation of bone in calvarial critical-size defects in rabbits

The reconstruction of large bony defects remains a clinical challenge, and angiogenesis and neovascularisation are being given more attention in bone tissue engineering. In this study we cocultured peripheral blood CD34+ cells (PB-CD34+ cells), an endothelial progenitor cell/haematopoietic stem cell-enriched population, with bone marrow-derived mesenchymal stem cells (MSC) to investigate their potential for bony regeneration. Cocultured cells showed better osteogenic differentiation than MSC alone in vitro. The cocultured cells and MSC sheets were also composited with hydroxyapatite and implanted in calvarial critical-size defects in rabbits. The rabbits were killed before microcomputed tomographic (MicroCT) and histological analysis. The results showed that cocultured cell composites had promoted bony regeneration more efficiently by 8 weeks after implantation. Our results indicate that the coculture of PB-CD34+ cells and MSC increases bony regeneration in calvarial critical-size defects in rabbits, and provide a new promising therapeutic strategy to aid skeletal healing.

The combination of a vascularized fibula with a massive allograft for reconstruction after intercalary resection of long bone tumor in extremities

Objective To investigate the effects of combined use of an allograft and vascularized fibular flap for the reconstruction of bone defects after intercalary resection of long bone malignancy.Methods From April 2006 to October 2009,19 patients that had intercalary resection of long bone malignancy (5 in humerus,7 in femur,7 in tibia)underwent reconstruction with an allograft and vascularized fibula construct,including 11 males and 8 females with an average age of 18.5 years.The average length of the defect was 13.2±4.3 cm.Free vascularized fibula flaps were used in 16 patients and ipsilateral pedicle vaseularized fibula grafts in 3.Time to union was recorded through evaluation of plain radiographs.Bone scan was used to evaluate the viability of the vascularized fibula.Patients were examined oncologically and radiographically and were assessed functionally with MSTS-93.Results The mean follow-up time was 27.5 months.The average length of the fibula flap was 17.9±5.2 cm.Viability of the fibular grafts was verified in all cases.The average time for bone union at allograft-host junction was 11.3±2.8 months in femur,14.1±3.3 in tibia,6.8±1.4 in humerus,respectively.The MSTS-93 average score at final follow-up was 95.2% in upper extremity and 91.8% in lower extremity.The oncology result in patients with follow-up more than 2 years was continuous disease free in 11 patients.no evidence of disease after recurrence following resection in 1,alive with tumor in 1,and died of lung metastasis in 1.Conclasion Vascularized fibular flap in combination with massive allograft provide an option for reconstruction of large bony defects after long bone malignancy extirpation.The viability of the fibula is a cornerstone in success of reconstruction that prevents allograft nonunion and result in decreased time to bone healing,leading to earlier patient's recovery of function. Key words: Fibula; Bone transplatation; Transplatation,homologous; Bone neoplasms; Extremities

Biological reconstruction using massive bone allograft with intramedullary vascularized fibular flap after intercalary resection of humeral malignancy

Reconstruction after excision of the humeral malignancy is a challenging issue for the reconstructive surgeon. The combined use of a fibular flap and allograft can provide a reliable reconstructive option. This article describes the authors' experience with this technique for the treatment of segmental bone defects after resection of humeral malignancy. From 2005 to 2008, seven patients that had intercalary resection of humeral malignancy underwent reconstruction with an allograft and vascularized fibula construct. Patients were examined clinically and radiographically. The average age at time of operation was 16.7 years. The mean follow-up time was 27.7 months. The average length of the resected humeral segment was 10.6 cm and that of the fibula flap was 13.1 cm. The average time of union of fibula was 20.7 weeks and for union of allograft was 26.3 weeks. Incorporation of the fibula into the allograft was seen in three patients. There were no allograft fractures and no infections. Three patients had surgery-related complications including a temporary radial nerve paralysis in 1, wound dehiscence in 1, and clawed toes in 1. The MSTS average score was 95.2% at final follow-up. Intramedullary fibular flaps in combination with massive allografts provide an excellent option for reconstruction of large bony defects after humeral malignancy extirpation. The viability of the fibula is a cornerstone in success of reconstruction that prevents allograft nonunion and result in decreased time to bone healing, leading to earlier patient recovery and return of function.

In Situ Cranioplasty for Hyperostosing Meningiomas of the Cranial Vault

Hyperostosis of the bone overlying meningiomas has been reported in up to 50% of cases. The skull becomes infiltrated by meningothelial tumor cells, necessitating removal of the hypertrophied bone to achieve a complete tumor resection. Unfortunately, aesthetic reconstruction of large bony defects can pose a significant challenge intra-operatively. Custom cranioplasty implants are very expensive and can only be fabricated after the bony defect exists, requiring a second surgery for implantation. Although numerous composite materials exist to repair the defects at the time of tumor resection, the challenge is to create an implant that fits appropriately without shifting and approximates the natural curvature of the skull. We have developed a technique for an "in situ cranioplasty" using a composite construct with strength in compression and tension. After the skull is reshaped by shaving down part of the hyperostotic bone, titanium mesh is molded to the surface of the skull and screwed into the surrounding normal bone. The bone flap is then removed by drilling a trough at the outer margin of the tumor-involved skull and removing a ring of normal surrounding bone. The central portion of tumor involved skull is then craniectomized. The mesh can be reapplied and the full thickness of the central bone can be reconstructed with polymethylmethacrylate, yielding a solid construct perfectly matched to the patient's natural head shape. This novel technique yields a sturdy, aesthetic, and cost-effective result which can be used to address any cranial vault defect at the time of tumor resection.

The Use of Massive Allograft with Intramedullary Fibular Graft for Intercalary Reconstruction after Resection of Tibial Malignancy

Reconstruction after intercalary excision of tibia malignancy is challenging. The combined use of a vascularized fibular flap and allograft can provide a reliable reconstructive option. Eight patients underwent reconstruction with an allograft and vascularized fibula following tibia malignancy resection. Patients were examined clinically and radiographically. The average age of patients was 16.5 years. The mean follow-up time was 38.4 months. Contralateral free fibula flap was used in three patients and ipsilateral pedicle fibula in five. The average length of defect was 11.8 cm and of fibula flap was 15.9 cm. Primary union was achieved in seven patients. The average time for bone union was 5.8 months at fibula-tibia junction and 14.1 months at allograft-tibia junction. Five patients had 10 complications. The Musculoskeletal Tumor Society average score was 90.8% at final follow-up. Intramedullary fibular flap in combination with massive allografts provide an excellent option for reconstruction of large bony defects after tibial malignancy extirpation. Ipsilateral pedicle fibula transportation had the advantages of short operation time and avoidance of donor site complications compared with the contralateral free fibula transfer.

Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells

Microvascular reconstruction is the state-of-the-art in many fields of defect surgery today. Currently, reconstruction of large bony defects involves harvesting of autologous bone causing donor site morbidity and risk of infection. Specifically, utilizing autologous adipose stem cells (autoASCs), large quantities of cells can be retrieved for cell therapy applications and the risk of tissue rejection is diminished. The authors describe the first case report of a microvascular custom-made ectopic bone flap employing good manufacturing practice (GMP) level ASCs. The patient underwent a hemimaxillectomy due to a large keratocyst. After 36 months of follow-up, the defect was reconstructed with a microvascular flap using autoASCs, beta-tricalcium phosphate and bone morphogenetic protein-2. ASCs were isolated and expanded in clean room facilities according to GMP standards and were characterized in vitro. After 8 months of follow-up, the flap had developed mature bone structures and vasculature and was transplanted into the defect area. Postoperative healing has been uneventful, and further rehabilitation with dental implants has been started. The in vitro characterization demonstrated multipotentiality and mesenchymal stem cell characteristics in ASCs. This is the first clinical case where ectopic bone was produced using autoASCs in microvascular reconstruction surgery and it will pave way for new clinical trials in the field.

The Use of Massive Bone Allograft with Intramedullary Free Fibular Flap for Limb Salvage in a Pediatric and Adolescent Population

Long segmental bony defects after tumor extirpation can pose difficult problems for the reconstructive surgeon. Capanna and colleagues have described a technique that places a free fibular flap within the intramedullary canal of an allograft for reconstruction of large intercalary bony defects. This article describes the authors' long-term follow-up with this technique for the treatment of large segmental bone defects in a pediatric population. Over a 6-year period, seven patients underwent bony reconstruction with an allograft and vascularized fibular construct. All reconstructions were performed for lower extremity salvage after tumor extirpation. Grafts were evaluated for viability with bone scans 10 days postoperatively. Radiologic and clinical evaluations were performed on all patients. Time to union was recorded through evaluation of plain radiographs. Patients' charts were evaluated for postoperative complications. There were two female and five male patients with an average age of 10.5 years. The average follow-up time was 36 months (range, up to 72 months). Limb salvage was 100 percent, with all bone scans positive at 10 days. Two nonunions at the allograft interface were treated successfully with a secondary bone graft. The average time to complete bony union of the fibula and allograft to the native bone was 9 months. There were no allograft fractures and no infections. One patient developed nonunion at the donor leg syndesmosis site. Average final knee motion was 110 degrees. All patients returned to ambulation. Intramedullary free fibular flaps in combination with massive bony allografts provide an excellent option in the pediatric population for reconstruction of large bony defects after tumor extirpation.

Long-term behaviour of the free vascularised fibula following reconstruction of large bony defects

Thirty-two free vascularised fibula grafts performed at our unit have been assessed retrospectively with respect to success, bony union and percentage graft hypertrophy. Between 1981 and 1998, there were 21 males and 11 females (aged 8–61 years) with follow-up of 5 months to 14.6 years. The mean bony defect bridged was 12.0 cm (standard deviation 4.8; range 5.0–21.0 cm). Bony union and hypertrophy were assessed radiographically. Time to bony union was compared using the log-rank, Wilcoxon or likelihood ratio tests. Kaplan–Meier survival curves were constructed. Hypertrophy was compared with Wilcoxon's rank sum test. Three flaps failed. Seventy-four percent of patients healed primarily at a median time of 4.75 months; five patients required further surgery to heal by 18 months (interquartile range 14–20 months). Complication rate and donor site morbidity were low. The stress fracture rate was 21%. Ninety percent of patients regained a functional limb by 12 months. Hypertrophy was measured in 22 patients and ranged from 0 to 316% (median 71%; interquartile range 10–145%). Median hypertrophy in the lower limb was 76.5% (interquartile range 26.5–165%) compared to 33.5% in the upper limb (0–88%); p=0.16. Median hypertrophy in trauma cases was 80% (interquartile range 10–167%) compared to 70% in tumour cases (33–105%); p=0.62. Our findings confirm that the fibula responds physiologically to biomechanical loading. Our results compare well with other series and alternative reconstructive modalities. We conclude that the free fibula flap can provide excellent results in the salvage of limbs with large bony defects.

Dacron-Urethane Composite for Reconstructive Surgery

AbstractA composite biocompatible material made of polyethyleneterephalate (Dacron) and polyetherurethane was fabricated as an aid to bone grafting for the reconstruction of large bony defects of the craniomaxillofacial regions. Bone graft material is placed within the confines of the Dacron-urethane implant and new bone forms to the shape imposed by the implant.The principle application of this material has been for the reconstruction of defects of the neurocranium and of the mandible [1–5]. A number of other applications have been studied including reconstruction of long bone discontinuity defects [6], reconstruction of an infant's anterior chest wall [19], the prosthetic replacement of large defects of the cervical trachea [7] and as a potential material for a thrombo-resistant small diameter vascular prosthesis [8].

The Use of Allografts to Reconstruct Intercalary Defects of Long Bones

The problems involved in the use of freeze-dried and fresh frozen allografts in the reconstruction of large bony defects were caused by the treatment of a variety of conditions. Twenty-four patients served as a basis for the review with an average of 34.7 months of follow-up study. Fifteen of these patients had, in addition, massive supplemental autografts. Rigid internal fixation consisting of either an intramedullary fluted rod or some combination of AO plate fixation was used in most cases, except in one instance in which no internal fixation was used. There was no difference in the time to incorporation of the freeze-dried and fresh frozen allografts into the host bone bed. No appreciable differences were noted in the group that had massive supplemental autografts, except that there was improvement in the quality of the union. The average time to radiographic union was 14 months. The complication rate in this series of patients was 54%. Most of the complications were minor and resolved with little residual. The overall results produced nine excellent, eight good, three fair, and four poor results. Considering the magnitude of the procedures involved, allografts appeared to have a distinctive place in the surgeon's armamentarium for reconstruction of large bony defects.