Reconstruction Of Large Skeletal Defects Research Articles

Effect of Angiogenesis in Bone Tissue Engineering.

The reconstruction of large skeletal defects is still a tricky challenge in orthopedics. The newly formed bone tissue migrates sluggishly from the periphery to the center of the scaffold due to the restrictions of exchange of oxygen and nutrition impotent cells osteogenic differentiation. Angiogenesis plays an important role in bone reconstruction and more and more studies on angiogenesis in bone tissue engineering had been published. Promising advances of angiogenesis in bone tissue engineering by scaffold designs, angiogenic factor delivery, in vivo prevascularization and in vitro prevascularization are discussed in detail. Among all the angiogenesis mode, angiogenic factor delivery is the common methods of angiogenesis in bone tissue engineering and possible research directions in the future.

Large Animal Models of an In Vivo Bioreactor for Engineering Vascularized Bone.

Reconstruction of large skeletal defects is challenging due to the requirement for large volumes of donor tissue and the often complex surgical procedures. Tissue engineering has the potential to serve as a new source of tissue for bone reconstruction, but current techniques are often limited in regards to the size and complexity of tissue that can be formed. Building tissue using an in vivo bioreactor approach may enable the production of appropriate amounts of specialized tissue, while reducing issues of donor site morbidity and infection. Large animals are required to screen and optimize new strategies for growing clinically appropriate volumes of tissues in vivo. In this article, we review both ovine and porcine models that serve as models of the technique proposed for clinical engineering of bone tissue in vivo. Recent findings are discussed with these systems, as well as description of next steps required for using these models, to develop clinically applicable tissue engineering applications.

The effect of ribose pre-treatment of cortical bone on γ-irradiation sterilization effectiveness.

Reconstruction of large skeletal defects is a significant and challenging issue. Tissue banks often use γ-irradiation (15-35kGy) to sterilize bone allografts, which, however, drastically impairs the post-yield mechanical properties. In previous studies, we reported the development of a method that protects human bone collagen connectivity through ribose crosslinking while still undergoing γ-irradiation. Given these promising results, the next step was to determine if the presence of ribose within the bone tissue would interfere with the effectiveness of the γ-irradiation sterilization against bacteria. This study had two stages. The aim of the first stage was to assess the protective effect of ribose in solution using a Bacillus pumilus spore strip model. The aim of the second stage was to assess the protective effect of ribose (R) on spores within a human cortical bone model in comparison to conventionally irradiated bone (I). Treatment of B. pumilus spore strips with ribose in solution led to temperature-dependent effects on spore viability versus spore strips treated with PBS alone. Ribose solution at 60°C led to a notable two logs decrease in spore count relative to PBS at 60°C. In the human bone model, the number of spores in the I and R groups were greatly decreased in comparison to the non-irradiated N group. No spore colonies were detected in the R group (n=4) whereas two of the four plates of group I formed colonies. This study provides evidence that the method of pre-treating bone with ribose crosslinking prior to irradiation sterilization, while improving irradiation sterilized bone allograft quality, also may improve the effectiveness of the sterilization process.

Development of a novel method for the strengthening and toughening of irradiation-sterilized bone allografts.

Reconstruction of large skeletal defects is a significant and challenging issue. Bone allografts are often used for such reconstructions. However, sterilizing bone allografts by using γ-irradiation, damages collagen and causes the bone to become weak, brittle and less fatigue resistant. In a previous study, we successfully protected the mechanical properties of human cortical bone by conducting a pre-treatment with ribose, a natural and biocompatible agent. This study focuses on examining possible mechanisms by which ribose might protect the bone. We examined the mechanical properties, crosslinking, connectivity and free radical scavenging potentials of the ribose treatment. Human cortical bone beams were treated with varying concentration of ribose (0.06-1.2M) and γ-irradiation before testing them in 3-point bending. The connectivity and amounts of crosslinking were determined with Hydrothermal-Isometric-Tension testing and High-Performance-Liquid-Chromatography, respectively. The free radical content was measured using Electron Paramagnetic Resonance. Ribose pre-treatment improved the mechanical properties of irradiation sterilized human bone in a pre-treatment concentration-dependent manner. The 1.2M pre-treatment provided >100% of ultimate strength of normal controls and protected 76% of the work-to-fracture (toughness) lost in the irradiated controls. Similarly, the ribose pre-treatment improved the thermo-mechanical properties of irradiation-sterilized human bone collagen in a concentration-dependent manner. Greater free radical content and pentosidine content were modified in the ribose treated bone. This study shows that the mechanical properties of irradiation-sterilized cortical bone allografts can be protected by incubating the bone in a ribose solution prior to irradiation.

Reconstruction with modular megaprostheses for sarcomas of the lower extremity.

Limb-preserving surgery using modular megaprostheses for the reconstruction of large skeletal defects is currently the preferred treatment for sarcomas. The authors report the postoperative outcomes after skeletal resection for lower extremity sarcomas and the use of the METS cemented modular implant system (Stanmore Implants, Hertfordshire, United Kingdom) for reconstruction. They retrospectively studied 52 consecutive patients operated on from 2003 to 2012. There were 27 distal femur prostheses, 13 proximal femur, 11 proximal tibia, and 1 total femur implants. Patients were followed for a mean of 4.3 years. Overall patient survival, prosthesis survival, limb salvage rate, and secondary complications were documented. Five years postoperatively, prosthesis survival was 79%. Complications warranting implant revision surgery were documented in 15% of patients, whereas complications warranting surgery of any kind were observed in 27% of the patients. Nonmechanical complications, namely local relapse of the tumor and prosthetic infection, were the most common cause of prosthetic failure, accounting for 88% of major revision surgeries and 100% of amputations. Mechanical complications were rare, observed in only 6% of patients. No patients required secondary revision surgery. The limb salvage rate was 89%. Overall patient survival was 79% at 5 years and 71% at 10 years. The low risk for mechanical complications and the high limb salvage rate support the use of the METS modular megaprostheses for the reconstruction of skeletal defects following lower limb sarcoma surgery.

Clinical Results of Using a Vascularized Bone Graft Combined with a Locking Compression Plate for Reconstruction of Large Skeletal Defects in the Upper and Lower Extremities

Clinical Results of Using a Vascularized Bone Graft Combined with a Locking Compression Plate for Reconstruction of Large Skeletal Defects in the Upper and Lower Extremities

The use of megaprostheses for reconstruction of large skeletal defects in the extremities: a critical review.

In the case of primary malignant tumors, extensive metastatic disease, major trauma or end-stage revision arthroplasty, the orthopaedic surgeon often has to deal with the need to reconstruct large skeletal defects, or replace bone of low quality. In the past years this was frequently impossible, and the only solution was amputation of the extremity. Later, the introduction of custom-made endoprostheses capable of reconstructing large skeletal defects, also known as megaprostheses, allowed for sparing of the extremity. This was especially valuable in the case of oncologic orthopaedic surgery, as advances in the medical treatment of sarcoma patients improved prognosis and limb-preserving surgery proved to have comparable patient survival rates to amputation. However, custom-made designs were implicated in frequent mechanical failures. Furthermore, they were extremely difficult to revise.The introduction of modular endoprostheses in the 1980s marked a new era in orthopaedic oncologic surgery. Modular megaprostheses consist of a number of different components in readily available sets, which can be assembled in various combinations to best address the specific bone defect. Moreover, they proved to have considerably lower rate of mechanical failures, which were also much easier to address during revision surgery by replacing only the parts that failed. The functional outcome after reconstruction with megasprostheses is often very satisfactory and the patient can enjoy a good quality of life. Nowadays, the major challenge is to eliminate the rate of non-mechanical complications associated with surgery of that magnitude, namely the risk for wound dehiscence and necrosis, deep infection, as well as local recurrence of the tumor.In our present mini-review, we attempt to make a critical approach of the available literature, focusing on the multiple aspects of reconstructive surgery using megaprostheses. We present the evolution of megasprosthetic implants, the indications for their use, and describe the outcome of surgery, so that the non-specialized orthopedic surgeon also becomes familiar with that kind of surgery which is usually performed in tertiary centers. A special interest lays in the recent developments that promise for even better results and fewer complications.

Vascularized fibula transfer for lower limb reconstruction

Massive bony defects of the lower extremity are usually the result of high-energy trauma, tumor resection, or severe sepsis. Vascularized fibular grafts are useful in the reconstruction of large skeletal defects, especially in cases of scarred and avascular recipient sites, or in patients with combined bone and soft-tissue defects. Microvascular free fibula transfer is considered the most suitable autograft for reconstruction of the middle tibia because of its long cylindrical straight shape, mechanical strength, predictable vascular pedicle, and hypertrophy potential. The ability to fold the free fibula into two segments or to combine it with massive allografts is a useful technique for reconstruction of massive bone defects of the femur or proximal tibia. It can also be transferred with skin, fascia, or muscle as a composite flap. Proximal epiphyseal fibula transfer has the potential for longitudinal growth and can be used in the hip joint remodeling procedures. Complications can be minimized by careful preoperative planning of the procedure, meticulous intraoperative microsurgical techniques, and strict postoperative rehabilitation protocols. This literature review highlights the different surgical techniques, indications, results, factors influencing the outcome, and major complications of free vascularized fibular graft for management of skeletal or composite defects of the lower limb.

Free Vascularized Fibular Graft Reconstruction of Large Skeletal Defects after Tumor Resection

Skeletal reconstruction of large tumor resection defects is challenging. Free vascularized fibular transfer offers the potential for rapid autograft incorporation in limbs compromised by adjuvant chemotherapy or radiation. We retrospectively reviewed 30 patients treated with free vascularized fibular graft reconstruction of large skeletal defects after tumor resections (mean defect length, 14.8 cm). The minimum followup was 2 years (mean, 4.9 years; range, 2-15 years). One patient died with liver and lung metastases at 3 years postoperatively. Loss of limb occurred in one patient. Five patients either had metastatic disease (one patient) or had metastatic disease (four patients) develop after treatment, with a mean time to metastasis of 18 months. The overall complication rate was 16 of 30 (53%), with a reoperation rate of 12 of 30 (40%). Union was attained in all 30 grafts. Primary union was attained in 23 (77%) at a mean of 6 months. Secondary union was achieved in seven (23%) after revision fixation and bone grafting; the mean subsequent time to union was 9.2 months, with an index of 1.33 additional operations per patient. Graft fracture (20%) and infection (10%) were other common complications. Despite a high complication rate, free vascularized fibular graft reconstruction offers a reliable treatment of large skeletal defects after tumor resection without increased risk of limb loss, local recurrence, or tumor metastasis. Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.

Osteomyelitis - Rekonstruktion von großen Knochendefekten bei Kindern

Reconstruction of Large Skeletal Defects Due to Osteomyelitis with the Vascularized Fibular Graft in Children. J Bone Joint Surg Am. 2007;89:2233-2240

Pasteurized autograft–prosthesis composite for distal femoral osteosarcoma

BackgroundWe examined the survivorship and functional outcome of the pasteurized autograft–prosthesis composite for distal femoral osteosarcoma. We also evaluated complications including nonunion, loosening, bony resorption, infection, and fracture. MethodsWe retrospectively reviewed 15 distal femoral osteosarcoma patients who underwent reconstructions using pasteurized autograft–prosthesis composite between 1993 and 2003. ResultsNo patient required graft removal during a minimum follow-up of 35 months (average 56 months; range 35–78 months). The average Musculoskeletal Tumor Society System (MTSS) functional score was 86%. Nonunion developed in five patients, and three of them subsequently showed loosening of the stem. No patient experienced infection or fracture. ConclusionsOur data suggest that the pasteurized autograft–prosthesis composite could be an easily accessible alternative for the reconstruction of large skeletal defects in the distal femur because of the satisfactory functional outcome with a low rate of ultimate failure and complications in this study.

Reconstruction of Large Skeletal Defects Due to Osteomyelitis with the Vascularized Fibular Graft in Children

Reconstruction of large skeletal defects secondary to osteomyelitis is a challenging problem. The purpose of this study was to evaluate the outcome of the use of a vascularized fibular graft to treat such defects in children. Eight patients with a mean age of seven years and a skeletal defect with a mean length of 11.8 cm (range, 6 to 17 cm) were treated with a vascularized fibular graft. A staged protocol was used for the five patients with an active infection at the time of presentation. The first procedure consisted of radical débridement, and at the second stage a free (seven patients) or pedicled (one patient) vascularized fibular graft was used. The mean follow-up time was 5.7 years. Union of the graft occurred primarily in seven of the eight patients, at a mean of 3.5 months, and after iliac crest bone-grafting in the remaining patient. There was no recurrence of deep infection. Complications developed in two patients. The mean time to full weight-bearing by the seven patients with a lower-extremity reconstruction was 8.4 months, and all patients were pain-free and able to walk without supportive devices. A vascularized fibular graft is a viable option for the management of large skeletal defects resulting from osteomyelitis in children.

The Use of Free Vascularized Fibular Grafts in Skeletal Reconstruction for Bone Tumors in Children

The reconstruction of large skeletal defects in children following resection of a bone tumor presents a unique challenge to the orthopaedic surgeon. Issues in this population that are not present in the adult population include significant remaining growth potential, the desire for biologic preservation of the joint surface, and the need for a long-term viable reconstruction in patients who are anticipated to survive for decades. The use of a free vascularized fibular graft, supplied by the peroneal vessels in intercalary fibular grafts and the anterior tibial vessels in proximal fibular grafts, has been shown to provide biologic reconstruction that successfully addresses these issues in the pediatric population. Specific techniques are applied in the upper and lower extremity to provide long-term excellent functional results. Experience in microvascular surgery and careful postoperative care are required for the success of these procedures.

Reconstruction of Large Skeletal Defects Due to Osteomyelitis with the Vascularized Fibular Graft in Children

Reconstruction of Large Skeletal Defects Due to Osteomyelitis with the Vascularized Fibular Graft in Children

Sequential Treatment with Intermittent Low-Dose Human Parathyroid Hormone (1-34) and Bisphosphonate Enhances Large-Size Skeletal Reconstruction by Vascularized Bone Transplantation

Vascularized bone transplantation enables reconstruction of large skeletal defects, but this process needs a long time. Since short-term intermittent parathyroid hormone (PTH) enhances rat fracture healing, we investigated the effects of 4-week intermittent low-dose (10 microg/kg/day) or high-dose (100 microg/kg/day) PTH followed by 4-week vehicle, low-dose or high-dose intermittent PTH, or zoledronic acid (ZOL, 2 micro/kg/week), a potent bisphosphonate, on large skeletal reconstruction by vascularized tibial grafting in rats. Compared to 8-week vehicle, 8-week low-dose PTH did not significantly increase the serum osteocalcin level as well as the urinary deoxypyridinoline level, while 4-week low-dose or high-dose PTH followed by 4-week ZOL decreased both of these levels. Eight-week PTH increased the bone mass of the graft and strength of the reconstructed skeleton in a dose-dependent manner; notably, the reconstructed skeleton showed an obviously higher response to PTH compared to the contralateral nonoperated femur. In contrast, 4-week PTH followed by 4-week vehicle reduced these effects and caused local bone loss at the host-graft junctions. Four-week PTH followed by 4-week ZOL did not induce such bone loss; however, 4-week high-dose PTH followed by 4-week ZOL caused a large callus in the distal cortical junction. Four-week PTH followed by 4-week ZOL increased the bone mass and strength similarly to 8-week PTH. These preliminary findings suggest, for the first time, that sequential treatment with short-term intermittent low-dose PTH and bisphosphonate as well as long-term intermittent low-dose PTH treatment enhance large skeletal reconstruction by vascularized bone transplantation, though early timing of sequential antiresorptive treatment could result in delay of bone repair.

Free vascularized fibular grafting for reconstruction after tumor resection in the upper extremity

Limb salvage is viable in the majority of patients with malignant bone tumors, but especially in case of extensive tumors and bad soft tissue conditions, it is challenging in upper extremity. The clinical and radiological results of 21 patients, who had free vascularized fibular grafts (VFG), for diaphyseal (14), and epipyseal (7) defect reconstruction of the upper extremity, are presented. The indications for VFG were resection after osteosarcoma (9 cases), Ewings sarcoma (9 cases), chondrosarcoma (1 case), rhabdomyosarcoma (1 case), and 1 case of fibrous dysplasia. The 20 malignant tumors were staged as follows: 2a (1), 2b (18), 3 (1). The mean follow-up was 43.6 months (min 6.0-max 131.9). Functional results were described and graded quantitatively according to the MSTS-score. Results were satisfactory with regard to pain, emotional acceptance, manual dexterity, and function. Lifting ability was decreased in two patients. Hypertrophy index was 31% (min 13%-max 71%). Main complications were fracture (5), pseudoarthrosis (4), prolonged wound healing (4), temporary nerve irritation (2), and deep infection (1). Re-operation was required in eight patients (12 operations). VFG offers a good possibility for biological reconstruction of large skeletal defects, with an acceptable complication and re-operation rate. When conservative treatment of complications was not successful, further surgery led to recovery in the majority of cases.

Osteoinductive Properties of Micro Macroporous Biphasic Calcium Phosphate Bioceramics

Abstract. We have developed 17 years ago, with the collaboration of Lynch, Nery, and Legeros in USA, a bioactive concept based on biphasic calcium phosphate ceramics (BCP). The concept is determined by an optimum balance of the more stable phase of HA and more soluble TCP. The material is soluble and gradually dissolves in the body, seeding new bone formation as it releases calcium and phosphate ions into the biological medium. The bioactive concept based on the dissolution/transformation processes of HA and TCP with a specific microstructure (micropore) and macrostructure (mesopores and macropores) represents a dynamic process, including physico-chemical processes, crystal/proteins interactions, cells and tissue colonization, bone remodelling, finally contributing to ingrowth at the expense of the MBCP. The microstructure of such material is achieved with low temperature sintering conditions preserving the microstructure. The material has shown osteoconductive properties largely reported in the literature, but its osteionductive properties have not been explored and documented for such bioceramics (Triosite O Zimmer). This paper presents retrospectives series of animal data (rats, rabbits, dogs, cats) demonstrating that promotion of the mineralization into micropores occurred simultaneously with osteoid and bone ingrowth into mesopores and macropores in non bony sites. Introduction Synthetic calcium phosphate bioceramics are attracting more interest in bone reconstruction due to their unlimited availability, excellent biocompatibilty, osteo-conductivity and even more recently reported osteo-inductivity. Macroporous biphasic calcium phosphate MBCP, a mixture of hydroxyapatite (HA) and beta tricalcium phosphate ( b-TCP) was developed 20 years ago by Lynch, Nery, Legeros and Daculsi [1]. MBCP bioceramics have been largely used as bone substitutes and represent the largest bibliography on this concept of bioceramics. However, data on its potential osteoinductive properties have not been reported to date. The mechanism of osteoinduction by biomaterials is not understood and the amount of induced bone might be too limited for the reconstruction of large skeletal defects. It has been shown recently that some calcium phosphate bioceramics and coatings on metal implants can induce ectopic bone formation after implantation in muscles of different animals.[2-10] These biomaterials have demonstrated the ability to induce bone intramuscularly within their porosity in 6-12 weeks without the addition of osteogenic cells or growth factors prior to implantation. Implanted in critical size osseous defects, these osteoinductive biomaterials have demonstrated superior bone healing capacities than conventional bioceramics and coatings. Previous investigations from our group and others laboratories have shown that the implants should exhibit two features to induce ectopic bone: (i) a calcium phosphate surface with micropores and (ii) a macroporous structure.

An innovative method of reconstruction of large skeletal chest wall defects.

The reconstruction of large skeletal defects of the chest wall is considered complex and difficult. A simple technique for this repair, using polymethylmethacrylate ribs that are prefabricated in a prosthodontic laboratory using heat cure polymer, is presented. These ribs are used as bone substitutes while reconstructing the chest wall defect. The prefabricated polymethylmethacrylate ribs have been used to reconstruct the large chest wall defects after resection of chest wall tumors in three patients. There was risk of severe paradoxical movement of the chest wall without the skeletal defect reconstruction. In all of the cases, there was no need for postoperative mechanical ventilation and there was no paradoxical movement. Cosmetically, it was highly satisfactory. In one patient, the stainless steel wire caused a sinus after 1 year of reconstruction, requiring removal of the wire and the rib, but it did not compromise the stability of the chest wall. We conclude that reconstruction of large chest wall defects with prefabricated polymethylmethacrylate ribs is simple, cost-effective, and easy to plan and execute.

Vascularized bone transfer.

We evaluated the results of reconstruction of a skeletal defect with use of a vascularized bone graft from the iliac crest or fibula in 160 patients who had been managed consecutively between 1979 and 1989. The indications for the procedure were a skeletal defect including non-union, resulting from resection of a tumor; traumatic bone loss; osteomyelitis; or a congenital anomaly. The average duration of follow-up was forty-two months (range, twelve to 112 months). For the entire series, the rate of union after the primary procedure was 61 per cent and the over-all rate at the latest follow-up examination (including the patients who had a secondary procedure) was 81 per cent. In a subgroup of seventy-six patients who had union after the primary procedure and did not have additional treatment, the average interval until union was six months and the average interval until full activity was sixteen months. The results were more favorable for the patients who had had reconstruction for resection of a tumor (of sixty-nine patients, fifty-six had union), for a congenital anomaly (of six patients, five had union), or for a non-union without infection (of twenty-five patients, twenty-three had union). The results were less satisfactory for patients who had had the reconstruction for bone loss due to osteomyelitis (of sixty patients, forty-six had union). Our data suggest that vascularized bone transfer for the reconstruction of large skeletal defects is a valuable procedure in appropriately selected patients.

Reconstruction of large skeletal defects by vascularized fibula transfer

We have studied the results of reconstruction of a large skeletal defect using a vascularized fibula graft in 62 consecutive cases. We were particularly interested in factors that may significantly influence the outcome of union. In at least 90% of cases, eventual union can be expected in the reconstruction of large skeletal defects resulting from tumour resection, traumatic bone loss, or nonunion. The results of reconstruction for osteomyelitis were less favorable. Statistical analysis of the influences of bone graft polarity, internal fixation, additional bone graft polarity, internal fixation, additional bone graft material, and the length of the graft on the outcome of union revealed that the use of stable fixation and additional bone graft material significantly enhanced bone union, whereas the length or polarity of the graft had no influence.