Tommaso Frisoni

Factors affecting outcome of massive intercalary bone allografts in the treatment of tumours of the femur

We retrospectively reviewed 101 consecutive patients with 114 femoral tumours treated by massive bone allograft at our institution between 1986 and 2005. There were 49 females and 52 males with a mean age of 20 years (4 to 74). At a median follow-up of 9.3 years (2 to 19.8), 36 reconstructions (31.5%) had failed. The allograft itself failed in 27 reconstructions (24%). Mechanical complications such as delayed union, fracture and failure of fixation were studied. The most adverse factor on the outcome was the use of intramedullary nails, followed by post-operative chemotherapy, resection length > 17 cm and age > 18 years at the time of intervention. The simultaneous use of a vascularised fibular graft to protect the allograft from mechanical complications improved the outcome, but the use of intramedullary cementing was not as successful. In order to improve the strength of the reconstruction and to advance the biology of host-graft integration, we suggest avoiding the use of intramedullary nails and titanium plates, but instead using stainless steel plates, as these gave better results. The use of a supplementary vascularised fibular graft should be strongly considered in adult patients with resection > 17 cm and in those who require post-operative chemotherapy.

The Posterior Iliac Crest Outperforms the Anterior Iliac Crest When Obtaining Mesenchymal Stem Cells from Bone Marrow

BACKGROUND The clinical application of freshly isolated connective-tissue progenitors, as well as the potential preparation of culture-expanded mesenchymal stem cell populations for therapeutic applications, will benefit from clinical methods that maximize the yield of the starting population. We compared the number of cells, concentration, and prevalence of colony-founding connective-tissue progenitors from the anterior and posterior iliac crest. In addition, we compared the expansion kinetics and multilineage differentiation potential of their culture-expanded progeny when processed to form mesenchymal stem cells. METHODS Marrow aspirate was collected from both the anterior and posterior iliac crest of twenty-two patients. The concentration and prevalence of colony-founding connective-tissue progenitors were estimated with use of a colony formation assay. The expansion kinetics and multilineage differentiation potential of the culture-expanded mesenchymal stem cell populations derived from these starting samples were compared. RESULTS The yield of colony-founding connective-tissue progenitors was 1.6 times greater in the posterior compared with the anterior iliac crest. No differences were found with respect to the viability, phenotype, expansion kinetics, or multilineage differentiation potential of mesenchymal stem cell populations derived from these two sites. CONCLUSIONS The concentration and yield of colony-founding connective-tissue progenitors were greater when aspirate was obtained from the posterior compared with the anterior iliac crest, whereas the biological potential of the cells derived from these sites appeared comparable. CLINICAL RELEVANCE The harvesting of bone marrow from the posterior iliac crest appears to be preferred, as it provided a modestly higher concentration of colony-founding connective-tissue progenitors than comparable aspirate from the anterior iliac crest.

OP-1 application in bone allograft integration: preliminary results in sheep experimental surgery.

UNLABELLED Massive bone allografts are frequently used in orthopaedic reconstructive surgery. However the failure rate at long term follow-up is around 25%. AIM Stimulation of allograft incorporation. MATERIALS AND METHODS In order to stimulate bone remodeling of an allograft we applied recombinant human osteogenic protein-1 (rh-OP-1, also know as bone morphogenetic protein-7, BMP-7) to a long bone critical size defect sheep model. In nine sheep we created a 3 cm osteoperiosteal metatarsal defect replaced with a structural allograft alone (control group, 4 animals), or an allograft added with rh-BMP-7 (BMP group, 5 animals). Radiographic, mechanical, histological and histomorphometric analysis were performed. RESULTS X-rays in the BMP group showed a better and faster callus formation, compared to the control group within the first 8 weeks after surgery. After 16 weeks there was a higher evidence of bone remodeling in the BMP group. Radiographic healing at junction sites was more evident in the BMP group at 4, 8 and 16 weeks. Mechanical testing on screw extraction showed no statistical differences between the two groups and histomorphometry showed no difference in terms of newly formed bone inside the allograft as well. The resorption rate of the graft was higher in the BMP group in comparison to the control group. The penetration of newly formed vessels was significantly higher in the BMP group. CONCLUSIONS These findings indicate that BMP-7 added to a structural bone allograft inducing early remodeling of the graft through stimulation of neo-angiogenesis and osteoclastic activity, without negative effects in mechanical strength and clinical outcome.

Alloprosthetic Composite is a Suitable Reconstruction After Periacetabular Tumor Resection

BackgroundResection of a tumor of the pelvis is most disabling when the acetabulum is excised and a durable reconstruction of the defect is hard to achieve. All available methods are associated with frequent complications. Few large series have been published, and fewer have focused entirely on complete resections of the acetabulum. The use of an allograft-prosthetic composite allows customization on the operating table. However, while such composites restore anatomy and function of the pelvis the use of pelvic allografts is controversial and the durability is unknown.Questions/purposesWe therefore examined (1) the frequency of allograft and prosthetic failure, (2) positive and negative factors influencing the survival of the allograft prosthetic composite, and (3) function of patients with this reconstruction.Patients and MethodsWe retrospectively evaluated 35 patients who had resection of the entire acetabulum and reconstruction with an allograft-prosthetic composite. Function was scored by the Musculoskeletal Tumor Society system. Followup in 24 survivors averaged 120 months (range, 61–188 months).ResultsGreater than 75% of the allografts were still in place at last followup, and the original prosthetic reconstruction was still in place in 56%. Infection was an important negative factor for allograft survival. The average functional score was 72%, with better mean scores for patients who had reconstruction with a stemmed cup and an artificial ligament (average 89%).ConclusionsAn allograft-prosthetic composite provides a versatile substitution of the pelvis and hip, with functional scores approximately 75% of normal.Level of EvidenceLevel IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Osteogenic Protein-1 Associated with Mesenchymal Stem Cells Promote Bone Allograft Integration

Limited incorporation and modest bone remodeling can cause allograft failure. We investigated whether mesenchymal stem cells (MSCs) and osteogenic protein-1 (OP-1) can improve allograft integration. A 3-cm full-size intercalary bone defect was created in the mid-diaphysis of the metatarsal bone of the sheep and it was replaced with an allograft alone (control group), or with MSCs (MSC group), OP-1 (OP-1 group), or MSCs and OP-1 (MSC + OP-1 group). Radiographic results showed a faster and complete integration of the allograft in the MSC + OP-1 group. Histology demonstrated that the amount of new bone was significantly greater inside the graft and a longer vessel penetration in the MSC + OP-1 group than in others. Mechanical strength of the allograft was not compromised by the high rate of bone remodeling. These results demonstrated that the association of MSCs and OP-1 improve bone allograft integration promoting an almost complete bone restoring.

Advance in the treatment of aneurysmal bone cyst of the sacrum

ObjectiveThe objective of this study was the review of 11 patients with two different treatment methods used historically for aneurysmal bone cyst in the sacrum. The outcome of both procedures is reported. In addition, the treatment technique of CT-guided percutaneous injections of demineralized bone matrix mixed with bone marrow concentrate is described.Materials and methodsFrom 1997 to 2008, 11 patients with sacral aneurysmal bone cyst were treated at the Rizzoli Institute, Bologna, Italy. The first seven patients had surgical curettage without bone grafting, chemical adjuvants, or arterial embolization. The last four patients had arterial embolization. The last patient did not respond to arterial embolization and was treated by CT-guided injection of demineralized bone matrix mixed with bone marrow concentrate.ResultsCurettage was successful in five out of seven patients. Two patients suffered complications, and two cases had recurrence. Arterial embolization was successful in three of four patients. The patient treated with injection had a good clinical and radiographic result.ConclusionBoth surgical and arterial embolization are effective for aneurysmal bone cyst in the sacrum. However, these treatments may lead to complications and recurrence. The use of CT-guided injections of demineralized bone matrix mixed with bone marrow concentrate may be a safe and effective alternative for treatment of these destructive and problematic lesions.

Fresh osteochondral allograft is a suitable alternative for wide cartilage defect in the knee

INTRODUCTION There are several surgical options to restore a wide osteochondral defect in the knee. Fresh osteochondral allografts are usually considered a poor alternative due to their difficulties in surgical application. The aim of this work is first to present our experience including the surgical technique and the functional results of patients receiving fresh osteochondral allograft to restore major knee lesions, then, to compare our results with other results presented in literature. METHODS Between 2006 and 2011, we treated 11 patients with osteochondral lesion of the knee (Outerbridge IV°). The average lesion size was 10.3 cm(2) (range 3-20 cm(2)). The average age was 34 years (range 18-66). Patients were followed from 12 to 55 months (average of 26.5) through clinical examination, X-ray film and MRI every 3 months for the first year, then every 6 months. RESULTS The treatment was successful in 10 patients showing pain regression and mean IKDC subjective score improvements from 27.3 to 58.7. The IKDC objective score also improved of at least one class for each patient except the who failed. The radiographs show good osteointegration in all cases but one. CONCLUSIONS Fresh allograft is an effective therapy for osteochondral defects repair because it allows functional recovery in a considerable number of patients. This technique obtains better results in lesion smaller than 8 cm(2). However larger lesion show good results. LEVEL OF EVIDENCE Therapeutic study, Level IV.

A rapid method for obtaining mesenchymal stem cells and platelets from bone marrow aspirate

Mesenchymal stem cells (MSCs) and platelet‐rich plasma (PRP) are currently used alone or in combination for therapeutic applications especially for bone repair. We tested whether MSCs can be isolated from bone marrow (BM) aspirate using a commercially available kit commonly used to obtain PRP from peripheral blood (PB). Results revealed that mononuclear cells and platelets from both PB and BM could be efficiently isolated by obtaining a mononuclear and platelet rich fraction (PB‐MPRF and BM‐MPRF, respectively). Starting with comparable volumes, the number of platelets increased 1.5‐fold in BM‐MPRF compared to PB‐MPRF. The number of clonogenic cells in BM‐MPRF samples was significantly higher than whole BM samples as revealed by CFU‐F assay (54.92 ± 8.55 CFU‐F/1.5 x 105 nucleated cells and 32.50 ± 12.43 CFU‐F/1.5 x 105 nucleated cells, respectively). Cells isolated from BM‐MPRF after in vitro expansion fulfilled the definition of MSCs by phenotypic criteria, and differentiated along osteogenic, adipogenic and chondrogenic lineages following induction. Results showed that the kit isolated MSCs and platelets from BM aspirate. Isolated MSCs were further expanded in a laboratory and BM‐MPRF was used clinically following BM withdrawal for rapid intra‐operative cell therapy for the treatment of bone defects. Copyright