AOA Critical Issues Symposium: So, You Want to Be a Department Leader: Essentials for Success.

ABSTRACT: Most health systems are vertically integrated, and the leaders of orthopaedic surgery departments or service lines must have a comprehensive understanding of their role in the strategic plan of the health system. Orthopaedic surgery departments must be profitable while supporting the tripartite mission of excellence in clinical care, research, and education. This symposium had 4 specific objectives: to discuss how to (1) create synergy between the department or service line and the health system, (2) develop a strategy to enhance financial stability and revenue growth, (3) develop a comprehensive plan to enhance recruitment and retention of a diverse faculty, and (4) consider alternative strategies to foster education and research, even when the health system may be more focused on revenue generation.

Trends in the use of dual mobility bearings in hip arthroplasty.

AIMS: Dual mobility (DM) bearings are an attractive treatment option to obtain hip stability during challenging primary and revision total hip arthroplasty (THA) cases. The purpose of this study was to analyze data submitted to the American Joint Replacement Registry (AJRR) to characterize utilization trends of DM bearings in the USA. METHODS: All primary and revision THA procedures reported to AJRR from 2012 to 2018 were analyzed. Patients of all ages were included and subdivided into DM and traditional bearing surface cohorts. Patient demographics, geographical region, hospital size, and teaching affiliation were assessed. Associations were determined by chi-squared analysis and logistic regression was performed to assess outcome variables. RESULTS: A total of 406,900 primary and 34,745 revision THAs were identified, of which 35,455 (8.7%) and 8,031 (23.1%) received DM implants respectively. For primary THA, DM usage increased from 6.7% in 2012 to 12.0% in 2018. Among revision THA, DM use increased from 19.5% in 2012 to 30.6% in 2018. Patients < 50 years of age had the highest rates of DM implantation in every year examined. For each year of increase in age, there was a 0.4% decrease in the rate of DM utilization (odds ratio (OR) 0.996 (95% confidence interval (CI) 0.995 to 0.997); p < 0.001). Females were more likely to receive a DM implant compared to males (OR 1.077 (95% CI 1.054 to 1.100); p < 0.001). Major teaching institutions and smaller hospitals were associated with higher rates of utilization. DM articulations were used more commonly for dysplasia compared with osteoarthritis (OR 2.448 (95% CI 2.032 to 2.949); p < 0.001) during primary THA and for instability (OR 3.130 (95% CI 2.751 to 3.562) vs poly-wear; p < 0.001) in the revision setting. CONCLUSION: DM articulations showed a marked increase in utilization during the period examined. Younger patient age, female sex, and hospital characteristics such as teaching status, smaller size, and geographical location were associated with increased utilization. DM articulations were used more frequently for primary THA in patients with dysplasia and for revision THA in patients being treated for instability. Cite this article: Bone Joint J 2020;102-B(7 Supple B):27-32.

The role of transduced bone marrow cells overexpressing BMP-2 in healing critical-sized defects in a mouse femur.

The role that transduced mouse bone marrow stromal cells (mBMSCs) engineered to overexpress human bone morphogenetic protein 2 (BMP-2) play in healing critical-sized skeletal defects is largely unknown. We evaluated the interaction between host osteoprogenitor cells and donor mBMSCs transduced with either a lentiviral (LV) vector-expressing red fluorescent protein (RFP) with or without BMP-2 that were implanted into a critical-sized femoral defect. Radiographs taken at the time of killing were evaluated using a five-point scaled scoring system. Frozen histologic sections were analyzed to assess both the transduced cells' role in bone repair and the local osteoprogenitor response. There was complete radiographic bridging in 94% of group I (LV-RFPch-BMP-2-cmyc) and 100% of group III (recombinant human BMP-2) specimens. Radiographs demonstrated a lack of healing in group II (LV-RFPch). Mouse BMSCs transduced with an LV-RFPch-BMP-2 vector were able to induce host cells to differentiate down an osteoblastic lineage and heal a critical-sized defect. However, the donor cells appeared to be functioning as a delivery vehicle of BMP-2 rather than actually differentiating into osteoblasts capable of participating in bone repair as evidenced by a lack of colocalization of the transduced cells to the sites of skeletal repair where the host progenitor cells were found.

A comparison of the incidence of complications following total hip arthroplasty in patients with or without osteonecrosis.

Osteonecrosis (ON) is a common cause of hip arthritis requiring arthroplasty (THA). ON patients often have associated conditions that place them at a greater risk for complications. The aim of this study is to determine complication rates of ON versus other THA patients. Statewide hospital admissions for THA were identified (1995-2010). THA procedures and ON diagnosis were identified using ICD-9 codes. Logistic regression analysis was used to determine the role of ON as a predictor of complications. ON led to an increased risk of sepsis and readmission. There was no significant difference in mortality rate. This study demonstrates that patients with ON undergoing THA have increased rates of readmission and sepsis. These findings are helpful in allocating resources for treating this patient group.

Suicide gene approach using a dual-expression lentiviral vector to enhance the safety of ex vivo gene therapy for bone repair.

'Ex vivo' gene therapy using viral vectors to overexpress BMP-2 is shown to heal critical-sized bone defects in experimental animals. To increase its safety, we constructed a dual-expression lentiviral vector to overexpress BMP-2 or luciferase and an HSV1-tk analog, Δtk (LV-Δtk-T2A-BMP-2/Luc). We hypothesized that administering ganciclovir (GCV) will eliminate the transduced cells at the site of implantation. The vector-induced expression of BMP-2 and luciferase in a mouse stromal cell line (W-20-17 cells) and mouse bone marrow cells (MBMCs) was reduced by 50% compared with the single-gene vector. W-20-17 cells were more sensitive to GCV compared with MBMCs (90-95% cell death at 12 days with GCV at 1 µg ml(-1) in MBMCs vs 90-95% cell death at 5 days by 0.1 µg ml(-1) of GCV in W-20-17 cells). Implantation of LV-Δtk-T2A-BMP-2 transduced MBMCs healed a 2 mm femoral defect at 4 weeks. Early GCV treatment (days 0-14) postoperatively blocked bone formation confirming a biologic response. Delayed GCV treatment starting at day 14 for 2 or 4 weeks reduced the luciferase signal from LV-Δtk-T2A-Luc-transduced MBMCs, but the signal was not completely eliminated. These data suggest that this suicide gene strategy has potential for clinical use in the future, but will need to be optimized for increased efficiency.

Improving the clinical evidence of bone graft substitute technology in lumbar spine surgery.

Bone graft substitutes have been used routinely for spine fusion for decades, yet clinical evidence establishing comparative data remains sparse. With recent scrutiny paid to the outcomes, complications, and costs associated with osteobiologics, a need to improve available data guiding efficacious use exists. We review the currently available clinical literature, studying the outcomes of various biologics in posterolateral lumbar spine fusion, and establish the need for a multicenter, independent osteobiologics registry.

Development of quality of care indicators for patients undergoing total hip or total knee replacement.

OBJECTIVE: The objective of this study was to develop evidence-based quality indicators to measure key aspects of care that can be targeted to decrease variations in complication rates between surgeons performing total joint replacement. DESIGN: RAND/University of California, Los Angeles (UCLA) modified-Delphi expert panel method. To accomplish this objective, a proposed set of quality of care indicators was developed through a comprehensive literature search and structured interviews with expert clinicians. An expert panel of orthopaedic surgeons was then convened to rate the validity of these quality indicators using the RAND/UCLA Appropriateness Method. Indicators were classified as valid by the panel based on the median panel rating and the amount of dispersion of panel ratings. RESULTS: There were 101 candidate indicators of quality identified in the six domains of preoperative processes of care, intraoperative processes, postoperative processes, implant selection and the use of new technology, privileging of hospitals and surgeons, and outcomes and comorbidity assessment. A total of 68 of the 101 indicators were rated as valid with statistical agreement. CONCLUSIONS: This study identifies measures of structure, process and outcome rated as valid quality indicators for hip and knee replacement. This project provides tools to measure and improve quality of care for patients undergoing total joint replacement.

The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model.

PURPOSE: Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with (18)F-fluoride ion, which localizes in regions of high osteoblastic activity, and (18)F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. METHODS: Fractures were created in the femurs of immunocompetent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, (18)F-fluoride, and (18)F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. RESULTS: All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. (18)F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using (18)F-FDG PET imaging at any time point. CONCLUSION: This study suggests that (18)F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time point and may have a role in the assessment of longitudinal fracture healing. PET scans using (18)F-FDG were not helpful in differentiating metabolic activity between successful and delayed bone healing.

Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats.

The objective of the present study was to assess the ability of bone marrow cells expressing BMP-2 created via lentiviral gene transfer to heal a critical sized femoral defect in a rat model. Femoral defects in Lewis rats were implanted with 5x10(6) rat bone marrow stromal cells (RBMSC) transduced with a lentiviral vector containing either the BMP-2 gene (Group I), the enhanced green fluorescent protein (LV-GFP) gene (Group IV), or RBMSC alone (Group V). We also included femoral defects that were treated with BMP-2-producing RBMSC transduced with lentivirus, 8 weeks after infection (Group III), and a group with 1x10(6) RBMSC transduced with a lentiviral vector with the BMP-2 gene (Group II). All defects (10/10) treated in Group I healed at 8 weeks compared with none of the femora in the control groups (Groups IV and V). In Group II, only one out of 10 femora healed. In Group III, 5 out of 10 femora healed. Significantly higher amounts of in vitro BMP-2 protein production were detected in Groups I, II, and III when compared to that of the control groups (p<0.05). Histomorphometric analysis revealed significantly greater total bone volume in defects in Group I and III when compared to control specimens (p<0.003). Biomechanical testing revealed no significant differences in the healed defects in Groups I and III when compared to intact, nonoperated femora with respect to peak torque and torque to failure. Our results indicate that BMP-2-producing RBMSC created through lentiviral gene transfer have the capability of inducing long-term protein production in vitro and producing substantial new bone formation in vivo.

Effects of the proteasome inhibitor bortezomib on osteolytic human prostate cancer cell metastases.

Prostate adenocarcinoma is the most common malignancy diagnosed in males, and bone metastases remain a significant source of morbidity and mortality in this population. The ubiquitin-proteasome cascade is responsible for the degradation of intracellular proteins, and this pathway is thought to play an essential role in the development of malignancies by altering the levels of various proteins involved in the regulation of cell division. Proteasome inhibitors represent a class of chemotherapeutic agents that have been shown to inhibit tumor growth by a number of different mechanisms. Using a murine intratibial injection model, we examined the effects of the proteasome inhibitor bortezomib on the establishment and progression of osteolytic bone lesions induced by human CaP cells (PC-3 cell line). In this study, the intravenous administration of bortezomib (1 mg/kg) did not prevent the initial formation of osteolytic lesions but did appear to inhibit their growth in a time-dependent fashion. In contrast, bortezomib therapy effectively inhibited the establishment and progression of subcutaneous PC-3 tumors, which served as a positive control. These results suggest that proteasome inhibitors such as bortezomib may represent a novel adjunctive therapy for the treatment of osteolytic skeletal metastases, especially when treatment is initiated early during the disease process.

Healing of a critical-sized defect in the rat femur with use of a vascularized periosteal flap, a biodegradable matrix, and bone morphogenetic protein.

BACKGROUND: The purpose of this study was to evaluate the osseous healing of a critical-sized femoral defect in a rat model with use of recombinant human bone morphogenetic protein-2 (rhBMP-2), a matrix fabricated of D,D-L,L-polylactic and hyaluronan acid (OPLA-HY), and a vascularized periosteal flap. METHODS: The carrier matrix OPLA-HY with or without rhBMP-2 was implanted in a 1-cm-long femoral defect and secured with a plate and screws. In some groups, a vascularized periosteal flap was harvested from the medial surface of the tibia. In group 1, the femoral defects in the animals were filled with the OPLA-HY matrix alone; in group 2, the OPLA-HY matrix was covered by the vascularized periosteal flap; in group 3, 20 mug of rhBMP-2 was added to the OPLA-HY matrix; and in group 4, the femoral defect containing the OPLA-HY matrix and 20 mug of rhBMP-2 was wrapped circumferentially by the vascularized periosteal flap. The presence and density of new bone formation in the femoral defect were evaluated radiographically, histologically, and with histomorphometry at four and eight weeks postoperatively. RESULTS: Groups 1 and 2, which were not treated with rhBMP-2, showed no radiographic or histologic evidence of mature bone formation at four or eight weeks. Both groups 3 and 4, which were treated with rhBMP-2, demonstrated excellent bone formation. However, with the periosteal flap, group 4 demonstrated more bone formation on histomorphometric analysis at eight weeks (43.1%) than did group 3 (28.3%) (p < 0.01). Additionally, heterotopic bone formed outside the boundaries of the defect in eight of the fifteen animals in group 3, which had no periosteal flap. CONCLUSIONS: Bone-tissue engineering with use of the OPLA-HY matrix and rhBMP-2 produced good bone formation in the rat femoral defect model. However, the addition of a vascularized periosteal flap significantly increased bone formation within the boundaries of the defect and prevented heterotopic ossification.

Regional gene therapy to enhance bone repair.

Gene therapy presents a novel approach to the treatment of challenging bone loss problems. Recombinant, osteogenic growth factors are now available to enhance bone repair, particularly in those applications related to the treatment of fracture nonunions and the enhancement of fusion of the spine. However, there is concern that a single dose of an exogenous protein will not induce an adequate osteogenic signal in many patients, particularly in those cases where there is compromise of host bone and the surrounding soft tissue. Transfer of genes encoding osteogenic proteins has the potential to overcome the delivery problems associated with the use of the proteins themselves. Bone healing is an attractive application for gene therapy, because long-term protein production is not necessary for many bone repair problems. Therefore, the development of gene therapy strategies to treat bone repair problems promises to be easier than the application of gene therapy to treat chronic diseases. The purpose of this review is to highlight the advantages, disadvantages and clinical potential of various gene therapy strategies to enhance bone repair.

Comparison of ximelagatran, an oral direct thrombin inhibitor, with enoxaparin for the prevention of venous thromboembolism following total hip replacement. A randomized, double-blind study.

BACKGROUND: Prophylaxis is recommended following total joint replacement because of the high risk of venous thromboembolism (VTE). Postoperative low-molecular-weight heparin (LMWH) reduces the incidence of venographically detected deep vein thrombosis (DVT) to about 10-15% in total hip replacement (THR) patients. Ximelagatran is a novel, oral direct thrombin inhibitor that selectively and competitively inhibits both free and clot-bound thrombin. We compared the efficacy and safety of ximelagatran with those of enoxaparin for the prevention of VTE in patients undergoing THR. METHODS: This was a prospective, randomized, multicenter, double-blind study conducted principally in the USA and Canada. Patients received fixed-dose oral ximelagatran 24 mg bid or subcutaneous enoxaparin 30 mg bid and matched placebo for 7-12 days; both regimens were initiated the morning after surgery. The incidence of VTE (by postoperative day 12) included thrombosis determined by mandatory venography of the leg on which surgery was performed and symptomatic, objectively proven DVT or pulmonary embolism (PE). VTE and bleeding events were interpreted by an independent central adjudication committee for primary analysis. RESULTS: Of the 1838 patients randomized, 1557 had either adequate venography or symptomatic, proven VTE (efficacy population). Overall rate of venography acceptable for evaluation was 85.4%. Overall rates of total VTE were 7.9% (62 of 782 patients) in the ximelagatran group and 4.6% (36 of 775 patients) in the enoxaparin group, with an absolute difference of 3.3% and a 95% confidence interval for the difference of 0.9% to 5.7%. Proximal DVT and/or PE occurred in 3.6% (28 of 782 patients) in the ximelagatran group and 1.2% (nine of 774 patients) in the enoxaparin group. Major bleeding events were observed in 0.8% (seven of 906) of the ximelagatran-treated patients and in 0.9% (eight of 910) of the enoxaparin-treated patients (P > 0.95). Non-inferiority of ximelagatran 24 mg bid based on a prespecified margin of 5% was not met, resulting in superiority of the enoxaparin regimen. CONCLUSIONS: Both ximelagatran and enoxaparin decreased the overall rate of VTE compared with that reported historically. However, in this study, enoxaparin 30 mg bid was more effective than ximelagatran 24 mg bid for prevention of VTE in THR. Oral ximelagatran was used without coagulation monitoring, was well tolerated, and had bleeding rates comparable to those of enoxaparin. Further refinement by testing a higher dose of ximelagatran in the patients undergoing THR is warranted.

Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads.

Multipotential processed lipoaspirate (PLA) cells extracted from five human infrapatellar fat pads and embedded into fibrin glue nodules, were induced into the chondrogenic phenotype using chondrogenic media. The remaining cells were placed in osteogenic media and were transfected with an adenovirus carrying the cDNA for bone morphogenetic protein-2 (BMP-2). We evaluated the tissue-engineered cartilage and bone using in vitro techniques and by placing cells into the hind legs of five severe combined immunodeficient mice. After six weeks, radiological and histological analysis indicated that the PLA cells induced into the chondrogenic phenotype had the histological appearance of hyaline cartilage. Cells transfected with the BMP-2 gene media produced abundant bone, which was beginning to establish a marrow cavity. Tissue-engineered cartilage and bone from infrapatellar fat pads may prove to be useful for the treatment of osteochondral defects.

Differences in the cytokine profiles associated with prostate cancer cell induced osteoblastic and osteolytic lesions in bone.

Prostate adenocarcinoma is associated with the formation of osteoblastic metastases in bone. It is hypothesized that osteoclastogenesis is a critical component in the development of skeletal metastases. These findings, however, were generally noted in predominantly osteolytic lesions. The pathophysiology of osteoblastic lesions remains unknown but the type of bone lesion formed may be influenced by the cytokines produced by prostate tumors. To test this theory, we implanted PC-3 and LAPC-9 cells into the tibias of SCID mice. These mice were sacrificed at 1, 2, 4, 6, and 8 weeks after implantation and histologic analysis was performed on these tibias. PCR analysis was also performed on bulk tumors. The results showed that the PC-3 implanted tibias developed pure osteolytic lesions while the LAPC-9 implanted tibias developed pure osteoblastic lesions on radiographs. Analysis of tibias after injection with PC-3 cells revealed progressive osteolytic lesions with abundant osteoclast activity at 2 weeks and destruction of the proximal tibia at 6 weeks after cell implantation. In contrast, the LAPC-9 cells formed osteoblastic lesions six weeks after cell injection. There were rare osteoclasts prior to the establishment of the osteoblastic lesions but greater osteoclast activity was noted with remodeling of the osteoblastic lesion 8 weeks after implantation of the tumor cells. PCR analysis revealed that PC-3 cells produced RANKL, IL-1, and TNF-alpha, which are associated with osteoclastogenesis. In contrast, LAPC-9 cells produced osteoprotegerin, which blocks osteoclast production and no detectable levels of RANKL or IL-1 and only minimal amounts of TNF-alpha were noted. These cells secreted BMP-2, -4, -6, and IL-6, which are associated with bone formation. These results suggest that the role of the osteoclast in the development of a metastatic lesion is variable depending on the phenotype of the prostate cancer cells, and that tumor-induced osteolysis may not be required for osteoblastic metastases.

Prefabrication of bone by use of a vascularized periosteal flap and bone morphogenetic protein.

The purpose of this pilot study was to prefabricate a vascularized bone graft by using a vascularized periosteal flap containing osteoprogenitor cells, a structural matrix, and recombinant human bone morphogenetic protein-2 (rhBMP-2). In a rat model, a periosteal flap vascularized by the saphenous artery and vein was dissected off the medial surface of the tibia. This flap consisted of three layers-periosteum, muscle, and fascia-and was tubed on itself to form a watertight chamber that was then transferred on its vascular pedicle to the groin. A total of 78 vascularized periosteal chambers were constructed in 39 animals and divided into 10 groups. In group 1, the periosteal chamber was left empty. Groups 2, 3, and 4 consisted of the periosteal flap and rhBMP-2, but in group 3, the proximal vascular pedicle was ligated, and in group 4, the flap was harvested without the periosteal layer and turned inside out. Groups 5 through 10 consisted of the vascularized periosteal flap containing several different structural matrices (calcium alginate spheres, polylactic acid, or demineralized bone matrix) with or without rhBMP-2. Animals were killed at 2, 4, or 8 weeks in each group. The presence and density of any new bone formation was evaluated both radiologically and histologically. Significant bone formation was seen only in those periosteal flaps containing rhBMP-2 and either the calcium alginate or polylactic acid matrix. New bone formation increased both radiologically and histologically from 2 weeks to 8 weeks only in the periosteal flaps containing the polylactic acid matrix and rhBMP-2. This preliminary study therefore suggests that four factors-blood supply, osteoprogenitor cells in the periosteal layer, a biodegradable matrix, and rhBMP-2-are required for optimal prefabrication of a vascularized bone graft.

Hip function in patients >55 years old: population reference values.

The purpose of this study was to establish population values for hip function for patients of different ages using the validated WOMAC scoring system and the traditional Harris hip scoring system. A random sample of 184 individuals who had no prior history of hip or knee pain or pathology was evaluated. The average WOMAC scores for pain, function, and stiffness were 0.01, 1.8, and 0.4. The average Harris hip score was 94 +/- 8.2. No significant correlation was noted between the summary WOMAC score, the WOMAC stiffness or pain subscales, or the overall Harris hip score for any of the 3 age groups studied. Patients with complaints in other joints, such as the back and neck, had lower WOMAC and Harris hip scores. Adults who are healthy and do not have a prior history of hip or knee pathology do not show a significant decline in hip function as they grow older. A deterioration in the function of a total hip arthroplasty over time cannot be attributed solely to the aging process.

Development of an animal model for prostate cancer cell metastasis to adult human bone.

BACKGROUND: Prostate cancer metastases to bone are associated with significant morbidity and mortality. Presently, there is little known about the biological interaction between prostate cancer cells and bone. Development of an animal model using adult human bone will enhance our ability to study the biology of prostate cancer metastasis to bone. METHODS: Bone was harvested from patients undergoing total joint arthroplasty and implanted in the hindlimbs of pre-treated SCID mice. Two months after bone implantation 4 x 104 prostate cancer cells (PC-3 or LAPC-4) were injected near the bone implantation site. The animals were sacrificed approximately 8 to 12 weeks after the injections of the cells. Complete histological analysis including immunostaining was performed. RESULTS: Both the PC-3 and LAPC-4 prostate cancer cells homed to the human bone implant, specifically the reconstituted bone marrow cavity. Analysis of the bone-tumor interaction after injection of PC-3 cells revealed strong labeling for PTHrP, TNF alpha and IL-6, consistent with osteoclast recruitment and osteoclast activity. These cells also were positively stained for CK18. After cellular injection of LAPC-4 cells, there was strong labeling for TNF alpha, IL-6, and IL-1 (osteoclast recruitment and osteolytic activity). PTHrP staining was also noted. The bone cells were strongly stained for osteocalcin, and the tumor cells for PSA. CONCLUSIONS: These data suggest that the tumor cells may induce an osteolytic response to enhance their ability to metastasize to bone. This animal model allows us to study the biologic interaction between prostate cancer cells and human bone and may enhance our understanding of the events associated with prostate cancer metastasis to bone.

Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration.

Currently, functional treatment of fracture non-unions and bone loss remains a significant challenge in the field of orthopaedic surgery. Tissue engineering of bone has emerged as a new treatment alternative in bone repair and regeneration. Our approach is to combine a polymeric matrix with a cellular vehicle for delivery of bone morphogenetic protein-2 (BMP-2), constructed through retroviral gene transfer. The objective of this study is to develop an osteoinductive, tissue-engineered bone replacement system by culturing BMP-2-producing cells on an osteoconductive, biodegradable, polymeric-ceramic matrix. The hypothesis is that retroviral gene transfer can be used effectively in combination with a biodegradable matrix to promote bone formation. First, we examined the in vitro attachment and growth of transfected BMP-producing cells on a PLAGA-HA scaffold. Second, the bioactivity of the produced BMP in vitro was evaluated using a mouse model. It was found that the polymer-ceramic scaffold supported BMP-2 production, allowing the attachment and growth of retroviral transfected, BMP-2-producing cells. In vivo, the scaffold successfully functioned as a delivery vehicle for bioactive BMP-2, as it induced heterotopic bone formation in a SCID mouse model.

The Frank Stinchfield Award. Influence of cement technique on the interface strength of femoral components.

The optimal surface finish for polymethylmethacrylate cemented femoral components remains controversial. Concerns about early debonding of the prosthesis-cement interface have led surgeons to use roughened surfaces to enhance the cement-prosthesis bond. However, loosening of roughened stems is associated with the generation of excessive wear debris. The purpose of the current study was to determine whether the time to cementation influenced the cement-prosthesis bond of four roughened cobalt chrome surfaces (60 grit-blasted, 10 grit-blasted, 10 grit-blasted with polymethylmethacrylate precoating, glass bead-blasted) and one polished cobalt chrome surface. Fixation strength was assessed using mechanical pushout and tensile testing. Roughened and polymethylmethacrylate precoated surfaces had significantly greater tensile and shear strengths at early cementation times compared with polished surfaces. However, roughened components had significant decreases in tensile and shear strengths as cementation time increased from 2 to 4 minutes and 2 to 6 minutes. In contrast, tensile and shear strengths for the polished surface were significantly lower than for the roughened surfaces and did not change with longer cementation times. When using a roughened or precoated cemented femoral component, the surgeon should consider cementing earlier with wetter cement to maximize the cement-prosthesis bond. When implanting a polished femoral component, it is preferable that the cement is doughy, because the cement-prosthesis bond is not influenced by the wetness of the cement and it is easier to maintain the orientation of the femoral component.