Cryopreserved, Thin, Laser-Etched Osteochondral Allograft maintains the functional components of articular cartilage after 2 years of storage.

BACKGROUND: Despite improvements in treatment options and techniques, articular cartilage repair continues to be a challenge for orthopedic surgeons. This study provides data to support that the 2-year Cryopreserved, Thin, Laser-Etched Osteochondral Allograft (T-LE Allograft) embodies the necessary viable cells, protein signaling, and extracellular matrix (ECM) scaffold found in fresh cartilage in order to facilitate a positive clinical outcome for cartilage defect replacement and repair. METHODS: Viability testing was performed by digestion of the graft, and cells were counted using a trypan blue assay. Growth factor and ECM protein content was quantified using biochemical assays. A fixation model was introduced to assess tissue outgrowth capability and cellular metabolic activity in vitro. Histological and immunofluorescence staining were employed to confirm tissue architecture, cellular outgrowth, and presence of ECM. The effects of the T-LE Allograft to signal bone marrow-derived mesenchymal stem cell (BM-MSC) migration and chondrogenic differentiation were evaluated using in vitro co-culture assays. Immunogenicity testing was completed using flow cytometry analysis of cells obtained from digested T-LE Allografts and fresh articular cartilage. RESULTS: Average viability of the T-LE Allograft post-thaw was found to be 94.97 ± 3.38%, compared to 98.83 ± 0.43% for fresh articular cartilage. Explant studies from the in vitro fixation model confirmed the long-term viability and proliferative capacity of these chondrocytes. Growth factor and ECM proteins were quantified for the T-LE Allograft revealing similar profiles to fresh articular cartilage. Cellular signaling of the T-LE Allograft and fresh articular cartilage both exhibited similar outcomes in co-culture for migration and differentiation of BM-MSCs. Flow cytometry testing confirmed the T-LE Allograft is immune-privileged as it is negative for immunogenic markers and positive for chondrogenic markers. CONCLUSIONS: Using our novel, proprietary cryopreservation method, the T-LE Allograft, retains excellent cellular viability, with native-like growth factor and ECM composition of healthy cartilage after 2 years of storage at - 80 °C. The successful cryopreservation of the T-LE Allograft alleviates the limited availably of conventionally used fresh osteochondral allograft (OCA), by providing a readily available and simple to use allograft solution. The results presented in this paper supports clinical data that the T-LE Allograft can be a successful option for repairing chondral defects.

Cross talk from pets to people: translational osteosarcoma treatments.

Osteosarcoma is almost identical in companion animals and in people, so research in basic cancer biology and treatment is readily translational across the species. In this article the authors (one DVM and one MD) present examples of species "cross talk" based on their parallel careers in musculoskeletal oncology surgery. Dogs in particular provide a relevant osteosarcoma model that is 10 times more prevalent than the corresponding human condition and offers a unique opportunity to answer questions related to local tumor control and metastasis. Advantages of the dog model include spontaneous development of the disease; the animal's large size, intact immune system, shared genetic aberrations, and response to traditional chemotherapies; and owners' acceptance and compliance with clinical trials for their pets. We describe several cross-species treatment strategies for osteosarcoma--chemotherapy, limb-sparing techniques, and radiation--as well as surprising impacts of infection and immunology. We conclude with some discussion of areas for further discovery and development to advance species cross talk in support of One Health.

Osteochondral lesions of the talus treated with fresh talar allografts.

BACKGROUND: Osteochondral lesions of the talar dome (OLT) can be devastating injuries. Many of these problems occur in younger adult patients and can cause permanent joint pain and stiffness. Several treatment methods have been used to treat the symptomatic lesion, including arthroscopic debridement and microfracture, transfer of autologous osteoarticular tissue from the knee or talus (OATS), autologous chondrocyte implantation (ACI), frozen and fresh allograft transplantation. MATERIALS AND METHODS: Eighteen patients underwent fresh talar allograft transplantation with internal fixation for an OLT. Fresh talar allograft transplantation involved arthrotomy of the ankle, often with malleolar osteotomy, and replacement of the talar dome defect with fresh talar allograft tissue and internal fixation. Thirteen of the 18 patients returned for clinical and radiographic examination in addition to completing two validated questionnaires. The other five patients did not return for followup evaluation. The 13 patients who were seen in followup had an average age of 30 (range, 15 to 44) years with a mean followup of 48 months. RESULTS: There was a significant difference (p < 0.01) between the patients' preoperative and postoperative pain and activity abilities as measured with the Foot Function Index and AOFAS Ankle-Hindfoot questionnaires. Clinical examination and X-rays confirmed healing of the graft. CONCLUSION: Based on these results, we conclude that this is a reasonable procedure for younger adult patients with focal osteochondral talar defects that cannot be corrected with curettage and microfracture.

Case report: Osteochondritis dissecans in twins: treatment with fresh osteochondral grafts.

Osteochondritis dissecans is a lesion of subchondral bone with subsequent involvement of the overlying cartilage. Although the etiology of the disease is unknown, mechanical, traumatic, and ischemic etiologies have been suggested, in addition to developmental and genetic factors. There are several treatment options depending on the stage of the disease and surgeon preference. The use of a fresh osteochondral allograft for treatment of a lesion of the femoral condyle is relatively new, and we report its use in a unique situation involving identical twins who both presented with osteochondritis dissecans of the same anatomic location within 2 years of each other. Since these were identical lesions in identical twins, this commonality supports the suggestion that some genetic component may be present in the etiology, especially in this situation where a genetic connection existed. We recommend genetic studies to determine the extent of genetic influence on the disease.

Bread mold osteomyelitis in the femur.

Rhizopus osteomyelitis is an uncommon and often fatal infection that usually occurs in immunocompromised patients. The infection is commonly referred to as "bread mold." The usual course of treatment is Amphotericin B, debridement, and, if needed, amputation of the affected limb. This article details a rare case of postoperative Rhizopus osteomyelitis in an otherwise healthy patient. The patient originally presented at another institution for anterior cruciate ligament repair after a ski injury. Postoperatively, he developed clinical evidence of infection. He was referred to our institution with stiffness and swelling in the knee as well as weight loss and decreased range of motion. Fluid collection was visible on magnetic resonance imaging. Arthroscentesis was cultured for fungus and bacteria, and the fungal cultures were positive for Rhizopus species. An attempt at limb salvage was made. Debridement, use of a cement spacer loaded with Amphotericin B, systemic antifungal therapy, and 23 hyperbaric oxygen treatments were used to eradicate the disease. Four surgeries were needed to eradicate the disease, and 10 months after initial presentation, the patient had a distal femoral endoprosthesis placed in his leg. Laboratory tests returned to normal and frozen sections were negative for fungus. At 3-year follow-up, the patient reported a musculoskeletal functional score of 50% and had no evidence of recurrent infection.

Intraarterial chemotherapy for extremity osteosarcoma and MFH in adults.

UNLABELLED: The neoadjuvant treatment of osteosarcoma using intravenous agents has resulted in survival rates of 55% to 77% [3, 5, 6, 20, 22, 35]. We designed a neoadjuvant chemotherapy protocol using combined intraarterial and intravenous agents to treat high-grade osteosarcoma and malignant fibrous histiocytoma of bone in an attempt to improve survival. We report the results of treating 53 adults (age 18-77 years) diagnosed with nonmetastatic extremity osteosarcoma or malignant fibrous histiocytoma. Preoperative chemotherapy consisted of intravenous doxorubicin followed by intraarterial cisplatinum administered repetitively every 3 weeks for three to five cycles, depending on tumor response assessed by serial arteriography. Dose and duration of cisplatin were adjusted for tumor size. After resection, good responders (90% or greater necrosis) underwent treatment with the same agents and poor responders were treated with alternative agents for longer duration. Minimum followup was 24 months (mean, 111 months; range, 24-235 months). Estimated Kaplan-Meier survival at 10 years was 82% and event-free survival was 79%. Forty-one patients (77%) had a good histologic response and 92% (49 of 53) underwent limb-sparing procedures. Local recurrence occurred in two patients (4%). These results compared favorably with those reported in the current literature. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Reconstruction options for pediatric bone tumors about the knee.

The surgical decisions involved with high-grade sarcoma surgery about the knee in pediatric patients are complicated. The orthopedic oncologist must have experience as well as a great deal of insight into the intricacies of each procedure and the wishes and demands of patients--not only while they are young but in into their adult life. It is difficult to predict the interests and vocation young patients will choose as their lives progress. However, if the patient qualifies as a candidate for limb preservation, the functional and cosmetic results obtained by limb preservation seem to be preferred. Amputation and rotationplasty should be reserved for patients who are not candidates for limb preservation or who are in an otherwise salvage situation. The prognosis for quality of life and limb after treatment for bone sarcomas has increased dramatically during the past decade. Survival approaching the 70% to 90% range can be expected, with >90% of those patients having limb preservation surgery. With further advancements in the biologic control of tissue healing, bioengineering, and prosthetic design and implantation, the future of these patients continues to be optimistic.

The value of serial arteriography in osteosarcoma: delivery of chemotherapy, determination of therapy duration, and prediction of necrosis.

PURPOSE: To investigate the value of serial arteriography to assess tumor response, predict necrosis, and individualize the duration of a combined intravenous (IV) and intraarterial (IA) neoadjuvant chemotherapy protocol in patients with biopsy-proven high-grade osteosarcoma or malignant fibrohistiocytoma of bone. MATERIALS AND METHODS: Between July 1987 and March 2003, 109 patients completed a chemotherapy protocol of neoadjuvant IV doxorubicin and IA cisplatin. Patients were eligible regardless of age, disease stage, or disease site. A minimum of three IA cycles followed by definitive surgery was required for inclusion in the final analysis. IA dose and duration were increased for tumors larger than 10 cm. Initial arteriograms were scored as indicating mild, moderate, or marked tumor neovascularity (TNV). Subsequent arteriograms were prospectively compared with the baseline image for percent change in TNV. Treatment continued until a maximum of five cycles were administered or one of three criteria were met: (i) at least 90% decrease in TNV, (ii) plateau of effect, or (iii) no response. RESULTS: Of 408 IA procedures, 42 patients underwent three cycles, 53 underwent four, and 14 required five cycles of neoadjuvant therapy. There was a 2.5% minor complication rate. Eighty-six percent of patients exhibited at least 90% decrease in TNV and 82% exhibited good histologic response (> or =90% tumor necrosis). Serial arteriography predicted a good histologic response with an accuracy of 90% and a sensitivity of 97%. CONCLUSIONS: Serial arteriography was highly sensitive and accurately predicted good responses. This individually modified, dose-intensified neoadjuvant protocol yielded an excellent histologic response rate with minimal complications. Future endeavors should involve a multiinstitutional study of this unique approach.

Treatment of benign bone lesions with an injectable calcium sulfate-based bone graft substitute.

The treatment of benign bone lesions can be challenging due to the limited quantity of autogenous graft available for harvest and grafting of the defect. The use of an injectable calcium bone graft substitute, Minimally-Invasive Injectable Graft (MIIG) (Wright Medical Technology, Inc, Arlington, Tenn), material for treatment of these bone lesions is advantageous. Calcium sulfate has a long-standing history in the treatment of bone voids secondary to trauma, infection, or neoplastic processes. Minimally-Invasive Injectable Graft injectable calcium sulfate graft may be injected into surgically created osseous defects or bone defects secondary to traumatic injury. After hardening, the paste acts as a temporary intraosseous support through which internal fixation may be placed. Fifteen patients with benign space-occupying lesions were treated with curettage and grafting with an injectable, surgical-grade, calcium sulfate bone graft substitute. Bone healing was assessed postoperatively and defined as resorption of the bone graft substitute material and replacement with new bone formation. The grafted defects in 14 of the 15 patients showed complete incorporation of the graft material at an average of 8 weeks. One patient required incision and drainage for a deep infection 5 weeks postoperatively. The average follow-up was 6 months (range: 3-15 months), and Musculoskeletal Tumor Society functional outcome scores averaged 83%. This injectable, minimally invasive graft material is easy to use, provides a temporary structural support when grafting bone defects, and results in predictable rapid bone healing.

Early multicenter experience with a noninvasive expandable prosthesis.

A noninvasive expandable prosthesis for skeletally immature children after limb salvage surgery has been developed. Between 1998 and 2001, 18 Phenix prostheses were implanted in 15 pediatric patients who had been diagnosed and treated for osteosarcoma about the knee. Of the 15 original prostheses, 10 were implanted at the time of primary tumor resection and five were revisions from an endoprosthetic modular knee system. Sixty expansions of the 18 prostheses were done, with all but two done as outpatient procedures. An average 8.5 mm was obtained per lengthening (range, 1-30 mm). The average followup was 21.5 months (range, 12-33 months) and the latest Musculoskeletal Tumor Society functional scores averaged 90%. Eight revisions were required for stem fracture or loosening. There was one amputation because of a postoperative arterial thrombosis. The principle of the Phenix prosthesis involves storage of energy in a spring compressed by a locking system. Lengthening is achieved via exposure to an electromagnetic field that allows controlled release of the spring. This is a unique expandable custom prosthesis that offers many benefits in maintaining limb length equality in growing patients. Although the early experience is promising, additional data are required regarding the long-term structural integrity of the prosthesis. We are optimistic that this technology will prove beneficial, not only for patients with malignant bone tumors but in applications requiring serial limb length equalizations or for spinal deformities.

Treatment of metastatic disease of the tibia.

Metastatic lesions to bone outnumber primary bone malignancies. Osseous metastases to the tibia tend to be less common than osseous metastases to other long bones. This study examined the treatment options for a population of patients with metastatic disease to the tibia, with surgical intervention being the cornerstone of treatment for the osseous lesion. A multicenter study had 592 patients with metastatic disease to the bone, with 26 lesions occurring in the tibia (4.4%) during a 13-year period. No patient had concurrent metastases distal to the elbow. After confirmation of metastatic disease, treatment consisted of surgical intervention in all patients, including plate osteosynthesis, intramedullary rodding and cementation, endoprosthetic replacement, and in most patients, postoperative radiation therapy. In 96% of patients, the reconstruction outlasted their life expectancy. All patients were satisfied with their reconstruction. Four complications were encountered in the postoperative period, all requiring additional surgery. Aggressive treatment of osseous metastasis is justified in patients with metastatic disease despite a limited life expectancy. Intervention by an orthopaedic oncologist may result in fewer reconstructive failures. Surgical intervention contributes to an improved quality of life and limb function, ease of nursing care, and may help in maintaining patient independence.

Reoperation after limb preservation surgery for sarcomas of the knee in children.

Limb preservation surgery compares favorably with amputation in oncologic and functional outcomes. However, an increased incidence of complications and reoperations is associated with limb preservation. This study compared the outcome of a group of young patients who required at least one reoperation after limb preservation surgery because of a complication or need for prosthetic lengthening with the outcome of a similar group who did not require additional surgery. The functional scores before and after reoperation are compared to determine the impact on reported function and patient satisfaction. Forty-four consecutive patients younger than 19 years were treated for a malignancy of the distal femur or proximal tibia. Six of these patients required an amputation because of extensive disease or inadequate response to chemotherapy. The Musculoskeletal Tumor Society functional evaluation scores of 26 patients who required at least one reoperation (Group A) were compared with the scores of 10 patients who have not required additional surgery (Group B). Average before and after reoperation functional scores were compared to discern a decline in function with time. The minimum followup was 2 years. Patients in Group A required 54 reoperations. No difference in mean functional scores between Group A and Group B was detected. Likewise, after isolating Group A scores, no significant difference was detected between the average functional scores before (67%) and after (68%) reoperation or lengthening. Despite relatively small numbers, the current study suggests that adequate function is maintained despite reoperation or revision in young patients with malignancies of the knee who have limb preservation surgery.

Superior survival in treatment of primary nonmetastatic pediatric osteosarcoma of the extremity.

BACKGROUND: A protocol to treat osteosarcoma of the extremity was developed at two local institutions. METHODS: The study involved a dose-intensified neoadjuvant protocol of intravenous doxorubicin and intra-arterial cisplatin administered repetitively until maximum angiographic response was noted. Definitive surgery was delayed until > or =90% reduction in tumor neovascularity was documented. Prospective assessment of serial arteriograms was highly accurate (94%) in predicting histological response and assisted in surgical planning. After resection, if patients were determined to be good responders (> or =90% tumor necrosis), they underwent a 4-month postoperative course with the same agents. Poor responders (<90% necrosis) were treated with alternative agents for 12 months from diagnosis. Forty-seven assessable patients with primary, high-grade, nonmetastatic osteosarcoma of the extremity were included in this analysis. The median age was 15 years (range, 7-21 years). RESULTS: Patients underwent an average of four preoperative intra-arterial courses. Forty-three patients underwent limb-preservation procedures, and 41 had >90% tumor necrosis. With an average follow-up of 92 months (range, 20-178 months), 39 patients were continuously disease free, 3 died of disease, 1 died of other causes, and 4 have no evidence of disease 11 to 51 months after relapse (all pulmonary metastases). There were no local recurrences. Kaplan-Meier analysis demonstrated a 10-year overall survival of 92% and an event-free survival of 84%. CONCLUSIONS: This study demonstrates excellent survival with a dose-intensified neoadjuvant protocol. Future endeavors should involve a multi-institutional randomized study comparing this approach with another multiagent intravenous neoadjuvant protocol.

Percutaneous treatment of long bone nonunions: the use of autologous bone marrow and allograft bone matrix.

Sixty-six patients with 69 "stiff" nonunions (no gross motion) of long bones were entered into a prospective study. The only therapeutic intervention was the percutaneous administration of a mixture of autologous bone marrow and allograft demineralized bone matrix on an outpatient basis. Sixty-one of the percutaneous treatments (88%) resulted in union at an average of 8.1 months (range: 2 months to 3 years). This method of treating nonunions is as successful as standard iliac crest autologous bone grafting and offers the distinct advantages of decreased morbidity, reduced costs, and shorter hospital stay.

The effect of allomatrix injectable putty on the outcome of long bone applications.

Long bone defects due to nonunion or surgical excision of benign bone tumors result in areas that require rapid regeneration of local bone. This clinical and radiographic article details the results of a commercially prepared allograft demineralized bone matrix in patients with long bone voids or gaps. Of the 76 patients included for study, 41 (54%) patients were undergoing surgical intervention for removal of benign tumors or space-occupying lesions and 35 (46%) patients had long bone nonunions. AlloMatrix Injectable Putty (Wright Medical Technology, Inc, Arlington, Tenn) was used alone in 74 (97%) patients and in combination with bone marrow aspirate in two (3%) patients with tibial nonunion. Adjunctive strut allografts were used in three patients with humeral nonunion. The average time to follow-up for the combined population was 7 months (nonunion group 6 months; benign tumor group 7 months). At the most recent follow-up, radiographic evidence of the average percent of bone healing was 85.1% for the nonunion patient group and 93% for the benign tumor patient group. From this study, AlloMatrix Injectable Putty used as a bone void filler in long bone nonunions and benign tumors shows results equal to those historically reported for autograft and other materials.

Revision of the failed distal femoral replacement to allograft prosthetic composite.

Orthopaedic oncologists often prefer a modular prosthetic cemented prosthesis for reconstruction after tumor excision in the distal femur. However, these frequently young patients face the prospect of either mechanical failure or loosening during their lifetime. Between 1993 and 2000, 41 patients (18 males, 23 females) with a malignancy of the distal femur had distal femoral replacement. Eight revisions and one amputation were required. Of these, four patients had revision to an allograft-prosthetic composite because of prosthetic fracture or loosening. These patients comprise the study population. Revisions were required at an average of 4 years after distal femoral replacement and the average age of the patients at revision was 17 years. The average time to achieve healing at the allograft-host junction was approximately 3 months and patients were fully weightbearing by that time. Followup from revision surgery to the last visit averaged 59 months, with average Musculoskeletal Tumor Society and Hospital for Special Surgery scores of 62% and 72%, respectively. There have been no mechanical problems, fractures, or osteolysis to signify loosening in the allograft or host bone. It is anticipated that this type of revision will survive longer than a conventional cemented revision and obviate the need for multiple reoperations in young patients who have difficulty with the biologic features of a cemented prosthesis construct.