Treatment Of Large Segmental Defects Research Articles

Scaffold Guided Bone Regeneration for the Treatment of Large Segmental Defects in Long Bones.

Bone generally displays a high intrinsic capacity to regenerate. Nonetheless, large osseous defects sometimes fail to heal. The treatment of such large segmental defects still represents a considerable clinical challenge. The regeneration of large bone defects often proves difficult, since it relies on the formation of large amounts of bone within an environment impedimental to osteogenesis, characterized by soft tissue damage and hampered vascularization. Consequently, research efforts have concentrated on tissue engineering and regenerative medical strategies to resolve this multifaceted challenge. In this review, we summarize, critically evaluate, and discuss present approaches in light of their clinical relevance; we also present future advanced techniques for bone tissue engineering, outlining the steps to realize for their translation from bench to bedside. The discussion includes the physiology of bone healing, requirements and properties of natural and synthetic biomaterials for bone reconstruction, their use in conjunction with cellular components and suitable growth factors, and strategies to improve vascularization and the translation of these regenerative concepts to in vivo applications. We conclude that the ideal all-purpose material for scaffold-guided bone regeneration is currently not available. It seems that a variety of different solutions will be employed, according to the clinical treatment necessary.

PTH1-34 improves devitalized allogenic bone graft healing in a murine femoral critical size defect

The treatment of large segmental defects of long bones resulting from trauma, infection, or bone tumor resections is a major challenge for orthopedic surgeons. The reconstruction of bone defects with acellular allografts can be used as an osteoconductive approach. However, devitalized allografts are associated with high rates of clinical failure as a result of poor intrinsic osteoinduction properties and a lack of further remodeling. Nevertheless, evidence suggests that due to its anabolic properties, teriparatide (PTH1-34) could be effective as an adjuvant therapy for massive allograft healing. Therefore, our goal was to investigate in a murine critical-sized defect model whether the intermittent administration of PTH1-34 improves the incorporation and revitalization of acellular structural bone allografts. Thus, a 2.5-mm critical-sized defect was established in the right femur of C57BL/6 mice, followed by the reconstruction with a devitalized cortical structural allograft. A titanium micro locking plate was applied to the anterior femoral surface and secured in place with self-tapping locking screws. Subsequently, daily doses of PTH1–34 (30, and 40 µg/kg) or saline were administered to the mice for 14 days after surgery. The mice were maintained without PTH1–34 therapy for an additional 7 days before being euthanized at 3 weeks post-surgery. Bone graft consolidation was assessed on radiographic images and by histomorphometric analysis. Additionally, to determine the frequency of osteoprogenitor cells in the bone marrow and their in vitro osteogenic capacity, stromal cells were isolated from the bone marrow of animals treated with 30 or 40 µg/kg/day of PTH1-34 following the same protocol used for the experimental animals. Our results suggest that intermittent PTH1-34 treatment at 30 µg/kg/day after femoral allograft reconstruction surgery accelerated the healing process as evidenced by new bone formation induced on endosteal and periosteal surfaces, enhanced revitalization of allogeneic graft, and increased frequency and osteogenic capacity of bone marrow stromal cells (BMSC). These findings should encourage further studies aimed at investigating the potential therapeutic use of intermittent PTH1-34, specifically with regards to the optimal dosing regimen in clinically challenging orthopedic scenarios.

Parathyroid hormone for bone regeneration.

Delayed healing and/or non-union occur in approximately 5-10% of the fractures that occur annually in the United States. Segmental bone loss increases the probability of non-union. Though grafting can be an effective treatment for segmental bone loss, autografting is limited for large defects since a limited amount of bone is available for harvest. Parathyroid hormone (PTH) is a key regulator of calcium homeostasis in the body and plays an important role in bone metabolism. Presently PTH is FDA approved for use as an anabolic treatment for osteoporosis. The anabolic effect PTH has on bone has led to research on its use for bone regeneration applications. Numerous studies in animal models have indicated enhanced fracture healing as a result of once daily injections of PTH. Similarly, in a human case study, non-union persisted despite treatment attempts with internal fixation, external fixation, and autograft in combination with BMP-7, until off label use of PTH1-84 was utilized. Use of a biomaterial scaffold to locally deliver PTH to a defect site has also been shown to improve bone formation and healing around dental implants in dogs and drill defects in sheep. Thus, PTH may be used to promote bone regeneration and provide an alternative to autograft and BMP for the treatment of large segmental defects and non-unions. This review briefly summarizes the unmet clinical need for improved bone regeneration techniques and how PTH may help fill that void by both systemically and locally delivered PTH for bone regeneration applications. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2586-2594, 2018.

Repair of large segmental bone defects with fascial flap-wrapped allogeneic bone.

BackgroundThe objective of this study was to investigate the therapeutic effects of the application of fascial flap-wrapped allogeneic bone for repair of large segmental tibial defects in rabbits and provide a theoretical basis for treatment of large segmental defects in weight-bearing bones.MethodsForty-eight healthy adult New Zealand White (NZW) rabbits were randomized into two groups to establish 15-mm bone defects in the proximal tibia. Bone defects in test and control groups were repaired using allogeneic bone with and without a vascularized fascial flap from the rabbit proximal tibia, respectively. The differences in repair of bone defects between the two groups were assessed with postoperative X-ray examination, new bone quantity assessment, serum bone Gla protein (BGP) level, and biomechanical testing.ResultsThe therapeutic effect in the test group was superior to that in the control group.ConclusionsFascial flap-wrapped allogeneic bone is superior to allogeneic bone alone, and is ideal for the treatment of large segmental bone defects.

Chondrosarcoma of the Proximal Humerus Secondary to Ollier Disease: An 8-Year Follow-Up of Successful Resection of the Tumor With Endoprosthetic Replacement of the Proximal Humerus

We present a 25-year-old male patient with a diagnosis of multiple enchondromatosis, who developed chondrosarcoma on the proximal humerus of the right upper limb. The patient had the pre-existing lesions of Ollier’s disease discovered during his childhood. The patient underwent wide resection of the sarcoma with a prosthetic replacement of the proximal humerus. So far we have followed up the patient for 8 years with no evidence of local recurrence and/or metastasis. The therapeutic results have been satisfied with a good functional recovery of the treated limb, enabling the patient to return to the pre-disease daily living and occupational activities. The reconstructive procedures represent an effective surgical strategy for limb salvage in the treatment of large segmental defects after resection of humeral tumors, substantially solving the functional and esthetic problems due to such a wide resection, and significantly improving the quality of life for the patient.

Histological and immunohistochemical analysis of an allogenic bone graft engineered with autologous bone marrow mononuclear cells in the treatment of a large segmental defect of the ulna. A case report

The treatment of large (6 cm) segmental bone defects, especially in areas associated with soft tissue damages and exposure, is challenging. Massive bone allografts are widely used in reconstructive surgery to replace missing bone parts such as critical size defects, nevertheless, early vascular invasion is a critical factor in bone allograft incorporation and in the consequent success of the surgery. Unfortunately, it has been proven that only slow and incomplete bone integration is possible by using frozen allografts in the treatment of large bone defects. An allogenic frozen bone graft was engineered with bone marrow mononuclear cells (BMMCs) to repair a large ulna defect in a male patient. When infection and sinus developed at the graft site 4 months after implantation, the partially reabsorbed graft was removed and send to the lab for examination. The histological and immunohistochemical analysis performed on a graft removed from the central zone of the defect demonstrated areas of neo-vascularisation, indicating that a remodelling process was actively occurring even in an area not usually repopulated with the conventional techniques. For these reasons, we may hypothesise that the use of BMMCs has a role in the re-building of large segmental defects.

Functional results of patients treated with modular prosthetic replacement for bone tumors of the extremities

We evaluated functional results of patients who were treated with cemented modular prosthetic replacement for bone tumors of the extremities. The study included 23 patients (12 males, 11 females; mean age 49 years; range 14 to 81 years) who underwent wide resection and cemented endoprosthetic replacement with the TMTS (Turkish Musculoskeletal Tumor Society) prosthesis for bone tumors. Twelve patients (52.2%; mean age 63.5 years) had metastatic, 11 patients (47.8%; mean age 38 years) had primary tumors. The most common site of involvement was the femur (n=17), followed by the humerus (n=5). Functional evaluations were made with the Musculoskeletal Tumor Society (MSTS) scoring system. The mean follow-up period was 24 months (range 1 to 108 months), being 30 months for primary, and 3 months for metastatic tumors. Postoperative complications were seen in seven patients (30.4%), being local recurrences in three patients. During the follow-up period, 11 patients died due to tumoral causes, distant metastasis developed in three patients, and nine patients were tumor-free. Survival was significantly better in patients with primary tumors (p<0.001). All the patients were able to walk without crutches in the postoperative period. The mean MSTS score was 58.9% (range 40% to 90%) in survivors, which was 71.5% (range 60% to 90%) for primary tumors, and 47.4% (range 40% to 73%) for metastatic tumors (p<0.001). Reconstruction with cemented modular endoprostheses is an appropriate surgical alternative in the treatment of large segmental defects after resection of extremity tumors, with satisfactory functional results particularly in primary tumors.

Repair of Segmental Defects of the Tibia with Cancellous Bone Grafts Augmented with Human Bone Morphogenetic Protein

Human bone morphogenetic protein (hBMP) is a bone cell differentiation-inducing factor. Six patients with traumatic segmental three- to 17-cm tibial defects developed solid union by implantation of hBMP and autogeneic cancellous grafts and stabilization. There were no allergic, infectious, or surgical complications. If hBMP augmentation in biodegradable delivery systems can be established by a prospective, randomized, double-blind investigation, the incidence of successful bone graft operations for treatment of large segmental defects would be measurably improved.