Structural Bone Allografts Research Articles

Clinical and Radiographic Outcomes and Graft Incorporation Rate Assessed by CT Scan After Reverse Shoulder Arthroplasty With Glenoid Structural Bone Graft Reconstruction.

Reverse total shoulder arthroplasty (RTSA) with structural bone graft has been described as a technique in addressing glenoid bony defects. Studies have demonstrated acceptable outcomes with structural autograft or allograft. However, most of these studies are relatively small and rarely evaluate bone graft incorporation with CT scan. The aim of this study was to assess clinical and radiographic outcomes and report graft incorporation assessed on CT scan after RTSA where structural bone autograft or allograft was used to reconstruct the glenoid. From May 2011 through June 2016, 38 patients underwent RTSA with structural bone graft. Of these, 35 were available for a minimum 2-year follow-up and retrospectively enrolled. From July 2016 through February 2019, 32 patients undergoing RTSA with structural bone graft were prospectively enrolled. Preoperative and postoperative American Shoulder and Elbow Surgeons and visual analog scale (for pain) scores and radiographs were obtained. CT scan was obtained at least 1 year postoperatively. Thirty-five patients were enrolled retrospectively (52.2%) and 32 prospectively (47.8%). Autograft was used in 46 cases (68.7%) and allograft in 21 cases. The mean American Shoulder and Elbow Surgeons score improved from 33.1 (SD 18.5) to 78.2 (SD 22.4), with P < 0.0001. On postoperative radiographs, 63 cases (94.0%) showed stable RTSA constructs while four cases (6.0%) developed glenoid baseplate subsidence. Postoperative CT scan demonstrated complete graft incorporation in 45 cases (90.0%) while partial incorporation was noted in 4 cases (8.0%), and in 1 case (2.0%), there was no graft incorporation. No correlation was observed between baseplate subsidence and graft type (autograft versus allograft) or primary versus revision surgery. Reverse shoulder arthroplasty with structural bone autograft and allograft is reliable for glenoid augmentation in patients undergoing RTSA in both primary and revision settings. Bony incorporation of autograft and allograft as evaluated on CT scan is predictably high.

Glenoid structural bone grafting in reverse total shoulder arthroplasty: clinical and radiographic outcomes

IntroductionCurrent options for reconstruction of large glenoid defects in reverse total shoulder arthroplasty (RTSA) include structural bone grafting, utilization of augmented components, or 3D printed custom implants. Given the paucity in the literature on structural bone grafts in RTSA, this study reflects our experience on clinical and radiographic outcomes of structural bone grafts utilized for glenoid defects in RTSA. MethodsWe identified 33 consecutive patients who underwent RTSA utilizing structural bone grafts for glenoid bone loss between 2008 and 2019. Twenty-six patients with mean clinical follow-up of 4.4 ± 3.9 years and mean radiographic follow-up of 2.7 ± 3.2 years were included. Patient demographic data, peri-operative functional outcomes, radiographic outcomes, complications, and re-operation rates were determined. ResultsBetween 2008 and 2019, 26 RTSAs were performed utilizing structural autograft or allograft for glenoid defects. There were 20 females (77%) and 6 males (23%), with mean presenting age of 68 years (range 41-86), mean BMI of 29 (range 21-44) and mean Charlson Comorbidity Index of 3 (range 0-8). There were 19 cases of central glenoid defects, and 7 were combined central and peripheral defects. Structural grafts included humeral head autograft (7), proximal humerus autograft (7), iliac crest autograft (7), distal clavicle autograft (2), and femoral head allograft (3). All eighteen revision RTSA cases had simultaneous humeral-sided revision. There was significant postoperative improvement in ASES scores (27.0 ± 12.6 preop vs. 59.8 ± 24.1 postop; p<0.001) and VAS scores (8.1 ± 3.6 preop vs. 3.0 ± 3.2 postop; p<0.001). Range of motion improved significantly for active forward elevation (63 ± 36º preop vs. 104 ± 36º postop; p<0.001) and external rotation (21 ± 20º preop vs. 32 ± 23º postop, p=0.036). Eighty-eight percent (23/26) of cases had successful reconstruction of the glenoid, defined as no visible radiolucent lines nor glenoid component migration at final follow-up. Re-operation rate was 19% (5/26) Postoperative complications included 2 cases of acromial stress fractures that were treated non-operatively, for a total complication rate (including re-operation) of 27% (7/26 cases). ConclusionsThe use of structural bone autografts and allografts in RTSA was associated with improved outcome scores and range of motion. A reoperation rate of 19% and total complication rate of 27% were reported for these challenging cases. However, 86% of these complications were not related to structural glenoid reconstruction failure. Structural grafts are a reasonable option for glenoid reconstruction in RTSA cases with glenoid bone loss.

Impact of NaOH based perfusion-decellularization protocol on mechanical resistance of structural bone allografts

ABSTRACT Introduction To mitigate the post-operative complication rates associated with massive bone allografts, tissue engineering techniques have been employed to decellularize entire bones through perfusion with a sequence of solvents. Mechanical assessment was performed in order to compare conventional massive bone allografts and perfusion/decellularized massive bone allografts. Material and methods Ten porcine femurs were included. Five were decellularized by perfusion. The remaining 5 were left untreated as the “control” group. Biomechanical testing was conducted on each bone, encompassing five different assessments: screw pull-out, 3-points bending, torsion, compression and Vickers indentation. Results Under the experimental conditions of this study, all five destructive tested variables (maximum force until screw pull-out, maximum elongation until screw pull-out, energy to pull out the screw, fracture resistance in flexion and maximum constrain of compression) were statistically significantly superior in the control group. All seven nondestructive variables (Young’s modulus in flexion, Young’s modulus in shear stress, Young’s modulus in compression, Elastic conventional limit in compression, lengthening to rupture in compression, resilience in compression and Vickers Hardness) showed no significant difference. Discussion Descriptive statistical results suggest a tendency for the biomechanical characteristics of decellularized bone to decrease compared with the control group. However, statistical inferences demonstrated a slight significant superiority of the control group with destructive mechanical stresses. Nondestructive mechanical tests (within the elastic phase of Young’s modulus) were not significantly different.

Clinical, Radiographic, and Patient-Reported Outcomes of First Metatarsophalangeal Interposition Arthrodesis Using Porous Titanium Wedges.

First metatarsophalangeal (MTP) arthrodesis is a common surgical procedure for addressing hallux MTP pathology. In the setting of revision procedures with significant bone loss, porous titanium wedges may provide an alternative to structural bone autograft or allograft. The purpose of this study is to report the clinical and radiographic outcomes achieved in first MTP interposition arthrodesis using porous titanium wedges. A retrospective analysis of 9 patients with a mean age 65.4 years (45-82 years) who underwent first MTP interposition arthrodesis with the use of porous titanium wedges from February 2014 to September 2017 was performed. Outcomes were assessed using both plain-film radiographs and computed tomography (CT) scans, as well as patient-reported outcome measures, including Foot and Ankle Ability Measure (FAAM) (Sports and Activities of Daily Living), pain Visual Analogue Scale (VAS), and 36-Item Short Form Survey (SF-36). Average follow-up time was 34.2 months (14-72 months). At final follow-up, the average FAAM score was 91.1 ± 14.7 (75.1 ± 5.3 FAAM Activities of Daily Living; 17.9 ± 9.9 FAAM Sports). Average pain VAS score was 1.9 ± 1.7. Postoperative computed tomography (CT) imaging was obtained for 5 patients, all of which demonstrated good bony apposition or osseous integration of the wedge. Four patients underwent subsequent surgical procedures, including 3 isolated dorsal fixation revisions, and 1 complete MTP arthrodesis revision. To our knowledge, this study represents the first reported clinical and radiographic outcomes in patients undergoing first MTP interposition arthrodesis with use of porous titanium wedges. While we found this technique to be a viable alternative to bone grafting for this difficult problem, further research should focus on comparative data with other commonly performed operative techniques. Level IV: Case series.

Effect of gamma irradiation and supercritical carbon dioxide sterilization with Novakill™ or ethanol on the fracture toughness of cortical bone.

Sterilization of structural bone allografts is a critical process prior to their clinical use in large cortical bone defects. Gamma irradiation protocols are known to affect tissue integrity in a dose dependent manner. Alternative sterilization treatments, such as supercritical carbon dioxide (SCCO2 ), are gaining popularity due to advantages such as minimal exposure to denaturants, the lack of toxic residues, superior tissue penetration, and minor impacts on mechanical properties including strength and stiffness. The impact of SCCO2 on the fracture toughness of bone tissue, however, remains unknown. Here, we evaluate crack initiation and growth toughness after 2, 6, and 24 h SCCO2 -treatment using Novakill™ and ethanol as additives on ~11 samples per group obtained from a pair of femur diaphyses of a canine. All mechanical testing was performed at ambient air after 24 h soaking in Hanks' balanced salt solution (HBSS). Results show no statistically significant difference in the failure characteristics of the Novakill™-treated groups whereas crack growth toughness after 6 and 24 h of treatment with ethanol significantly increases by 37% (p = .010) and 34% (p = .038), respectively, compared to an untreated control group. In contrast, standard 25 kGy gamma irradiation causes significantly reduced crack growth resistance by 40% (p = .007) compared to untreated bone. FTIR vibrational spectroscopy, conducted after testing, reveals a consistent trend of statistically significant differences (p < .001) with fracture toughness. These trends align with variations in the ratios of enzymatic mature to immature crosslinks in the collagen structure, suggesting a potential association with fracture toughness. Additional Raman spectroscopy after testing shows a similar trend with statistically significant differences (p < .005), which further supports that collagen structural changes occur in the SCF-treated groups with ethanol after 6 and 24 h. Our work reveals the benefits of SCCO2 sterilization compared to gamma irradiation.

Clinical results of periacetabular osteotomy with structural bone allograft for the treatment of severe hip dysplasia.

To clarify the mid-term results of transposition osteotomy of the acetabulum (TOA), a type of spherical periacetabular osteotomy, combined with structural allograft bone grafting for severe hip dysplasia. We reviewed patients with severe hip dysplasia, defined as Severin IVb or V (lateral centre-edge angle (LCEA) < 0°), who underwent TOA with a structural bone allograft between 1998 and 2019. A medical chart review was conducted to extract demographic data, complications related to the osteotomy, and modified Harris Hip Score (mHHS). Radiological parameters of hip dysplasia were measured on pre- and postoperative radiographs. The cumulative probability of TOA failure (progression to Tönnis grade 3 or conversion to total hip arthroplasty) was estimated using the Kaplan-Meier product-limited method, and a multivariate Cox proportional hazard model was used to identify predictors for failure. A total of 64 patients (76 hips) were included in this study. The median follow-up period was ten years (interquartile range (IQR) five to 14). The median mHHS improved from 67 (IQR 56 to 80) preoperatively to 96 (IQR 85 to 97) at the latest follow-up (p < 0.001). The radiological parameters improved postoperatively (p < 0.001), with the resulting parameters falling within the normal range in 42% to 95% of hips. The survival rate was 95% at ten years and 80% at 15 years. Preoperative Tönnis grade 2 was an independent risk factor for TOA failure. Our findings suggest that TOA with structural bone allografting is a viable surgical option for correcting severely dysplastic acetabulum in adolescents and young adults without advanced osteoarthritis, with favourable mid-term outcomes.

Impacted bone allograft personalised by a novel 3D printed customization kit produces high surgical accuracy in medial opening wedge high tibial osteotomy: a pilot study

PurposeContemporary medial opening wedge high tibial osteotomy (MOWHTO) still seems to struggle with inconsistent accuracy outcomes. Our objective was to assess surgical accuracy and short-term clinical outcomes when using 3D planning and a patient-specific instrumentation (PSI) kit to prepare customized bone allografts.MethodsThirty subjects (age 48y ± 13) were included in a double-center prospective case series. A low-dose CT-scan was performed to generate 3D bone models, a MOWHTO was simulated, and PSI was designed and 3D printed based on the complementary negative of the planned osteotomy gap. Clinical outcome was assessed at two, four, 12 weeks and one year using NRS, KOOS, UCLA activity score, EQ-5D and anchor questions. A linear-mixed model approach was implemented for data analysis.ResultsPreoperative 3D values were 175.0° ± 2.2 mechanical tibiofemoral angle (mTFA), 85.0° ± 3.0 medial proximal tibial angle (MPTA), and 94.1° ± 3.4 medial posterior tibial slope (MPTS). Target planning ranged from slight varus to the lateral tibial spine (slight valgus). Postoperative 3D analysis showed an accuracy of 1.1° ± 0.7 ΔMPTA (p = 0.04) and 1.2° ± 1.2 ΔMPTS (p = 0.11). NRS decreased from baseline 6.1 ± 1.9 to 2.7 ± 1.9 at four weeks (p < 0.001) and 1.7 ± 1.9 at one year (p < 0.001). KOOS increased from 31.4 ± 17.6 to 50.6 ± 20.6 at 12 weeks (p < 0.001) and to 71.8 ± 15.6 at one year (p < 0.001).ConclusionThe study suggests that 3D printed instrumentation to personalize structural bone allograft is a viable alternative method in MOWHTO that has the benefit of optimizing surgical accuracy while providing early and consistent pain relief after surgery.

Vasculogenic gene therapy: No role for revitalization of structural bone allografts.

Segmental bone defects are often performed with cryopreserved allografts. They provide immediate stability, but risk nonunion, infection and late stress fracture. Improving the rate and extent of bone revitalization may improve results. Angiogenesis from surgically placed arteriovenous (AV) bundles improves bone blood flow and vitality in cryopreserved rat femora, augmented by vasculogenic growth factors. This study tests the same principal in Yucatan mini-pigs with a tibial diaphyseal defect, combining surgical angiogenesis with angiogenic gene therapy within cryopreserved orthotopically-placed allografts. Tibial diaphyseal defects were reconstructed with cryopreserved allografts and rigid internal fixation in 16 mini pigs. Half of the cranial tibial AV bundles placed within the allograft medullary canal were transfected with an adeno-associated virus containing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) genes (AAV9.VEGF.PDGF). Bone remodeling, angiogenesis, and allograft healing were assessed. During the postoperative survival period 5 of 8 transfected animals developed cutaneous benign vascular lesions at sites remote from the operated hindlimb, causing excessive bleeding. Within the allograft, both medullary (p = 0.013) and cortical (p = 0.009) vascular volumes were higher and vessels more mature than nontransfected allografts. Bone turnover (p = 0.013), bone mineralization (p = 0.018), bone healing (p = 0.008) and graft incorporation (p = 0.006) were all significantly higher in the gene therapy group. In a large animal tibial defect model, gene therapy of implanted AV bundles improved revascularization, remodeling and healing of cryopreserved allografts used for limb reconstruction. However, benign vascular lesions causing excessive bleeding developed in 5 out of 8 pigs transfected with AAV containing genes for VEGF and PDGF. This unforeseen complication makes vasculogenic gene therapy unacceptable for clinical use.

227. Prospective, randomized, blinded clinical trial comparing PEEK and allograft spacers in patients undergoing ACDF surgeries

BACKGROUND CONTEXT The biomechanical qualities as well as osteoconductive, osteogenic and osteoinductive properties of various graft materials have been previously evaluated. There remain questions, however as to whether there are any clinical and/or radiographic outcome differences in the selection of interbody graft types for ACDF. PURPOSE The main objective of the study was to examine clinical and radiological outcomes in patients undergoing ACDF surgeries randomized to receive either PEEK or structural bone allografts. STUDY DESIGN/SETTING A prospective, randomized, blinded clinical trial was initiated at a single center. PATIENT SAMPLE A total of 120 patients were enrolled and randomized. OUTCOME MEASURES All patients were followed for 2 years ± 2 months; radiographic and clinical outcomes were assessed at 3, 6, 12 and 24 months with an additional follow-up at 3 weeks for radiographic assessment. METHODS Patients undergoing one- to three-level ACDF with single anterior plate fixation were randomized (1:1 ratio) to receive either cortical allograft or PEEK interbody spacers. RESULTS Comparing clinical outcomes, no differences in arm or neck pain scores were noted, however there was a statistically significant (< 0.041) improvement in SF-36 PCS scores for the allograft group at all follow-up time points and a tendency towards lower disability scores. Overall, evidence of radiographic fusion was achieved in 87 (91.6%) patients: five (10.2%) and three (6.5%) patients had pseudoarthrosis (p=0.72) in the PEEK and allograft groups, respectively. At 24 months follow-up time, any cervical or segmental alignment restoration achieved with surgery was lost and no statistically significant changes were detected when all levels of surgery were included. Likewise, there were no statistically significant differences between the groups for anterior or posterior body height measurements at the 24 months follow-up. Approximately 20% of patients had anterior and posterior subsidence, all grade 0 regardless of the group assignment. CONCLUSIONS Comparable radiographic outcomes were observed for patients undergoing one- to three-level PEEK vs allograft-assisted ACDF surgeries. There was a tendency for improved clinical outcomes in the allograft patient group. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs. The biomechanical qualities as well as osteoconductive, osteogenic and osteoinductive properties of various graft materials have been previously evaluated. There remain questions, however as to whether there are any clinical and/or radiographic outcome differences in the selection of interbody graft types for ACDF. The main objective of the study was to examine clinical and radiological outcomes in patients undergoing ACDF surgeries randomized to receive either PEEK or structural bone allografts. A prospective, randomized, blinded clinical trial was initiated at a single center. A total of 120 patients were enrolled and randomized. All patients were followed for 2 years ± 2 months; radiographic and clinical outcomes were assessed at 3, 6, 12 and 24 months with an additional follow-up at 3 weeks for radiographic assessment. Patients undergoing one- to three-level ACDF with single anterior plate fixation were randomized (1:1 ratio) to receive either cortical allograft or PEEK interbody spacers. Comparing clinical outcomes, no differences in arm or neck pain scores were noted, however there was a statistically significant (< 0.041) improvement in SF-36 PCS scores for the allograft group at all follow-up time points and a tendency towards lower disability scores. Overall, evidence of radiographic fusion was achieved in 87 (91.6%) patients: five (10.2%) and three (6.5%) patients had pseudoarthrosis (p=0.72) in the PEEK and allograft groups, respectively. At 24 months follow-up time, any cervical or segmental alignment restoration achieved with surgery was lost and no statistically significant changes were detected when all levels of surgery were included. Likewise, there were no statistically significant differences between the groups for anterior or posterior body height measurements at the 24 months follow-up. Approximately 20% of patients had anterior and posterior subsidence, all grade 0 regardless of the group assignment. Comparable radiographic outcomes were observed for patients undergoing one- to three-level PEEK vs allograft-assisted ACDF surgeries. There was a tendency for improved clinical outcomes in the allograft patient group.

The effect of surgical revascularization on the mechanical properties of cryopreserved bone allograft in a porcine tibia model.

Cryopreserved bone allografts(CBA) are susceptible to infection, nonunion, and late stress fracture. Althoughsurgical revascularization by intramedullary implantation of an arteriovenous bundle (AV bundle) generates a neoangiogenic blood supply, there is potential for vascular ingrowth-mediated bone resorption to weaken the graft. For this reason, we have evaluated changes in CBA mechanical properties of structural tibial allografts with and without surgically induced angiogenesis. Cryopreserved tibia bone allografts were transplanted to reconstruct a 3.5 cm segmental tibial defect in 16 Yucatan mini pigs. Surgical revascularization was performed in half by implantation of a cranial tibial AVbundle, (revascularization group). A control group of identical size had a ligated AV bundle implanted, (ligated group). At 20 weeks micro-computed tomography (CT) measured bone mineral density (BMD) as well as bone union. Reference point indentation (RPI) compared cortex material properties, and axial compression determined the allotransplant compressive modulus. Seven of eighttibiae in the angiogenesis group were healed at both junction points at 20 weeks. Only fourof eighttibiae healed in the ligated control group. There was no significant difference between the revascularization and ligated control groups in BMDand axial compression test. Similarly, RPI parameters were statistically equal. In paired comparisons with contralateral tibias, however, some RPI values were significantly worse in the ligated control group tibiae. This study demonstrates no adverse effect of surgical angiogenesis on cryopreserved structural bone allograft biomechanical properties in a large animal orthotopic segmental tibial defect model. These data suggest the potential value of surgical angiogenesis in clinical limb-sparing reconstructive surgery.

Application of structural allogenous bone graft in two-stage exchange arthroplasty for knee periprosthetic joint infection: a case control study

BackgroundKnee prosthetic joint infection (PJI) is a common but devastating complication after knee arthroplasty. The revision surgeries for knee PJI may become more challenging when it is associated with large bone defects. The application of structural bone allograft in knee revision surgeries with large bone defects is not a new technique. However, there is a lack of literature reporting its efficacy in PJI cases. This study aimed to investigate the outcome of structural fresh frozen allogenous bone grafts in treating patients in knee PJI with large bone defects.MethodsWe performed a retrospective cohort analysis of knee PJI cases treated with two-stage exchange arthroplasty at our institution from 2010 to 2016. 12 patients with structural allogenous bone graft reconstructions were identified as the study group. 24 patients without structural allograft reconstructions matched with the study group by age, gender, and Charlson comorbidity index were enrolled as the control group. The functional outcome of the study group was evaluated with the Knee Society Score (KSS). Treatment success was assessed according to the Delphi-based consensus definition. The infection relapse rate and implant survivorship were compared between groups.ResultsRevision knees with structural allograft presented excellent improvement in the KSS (33.1 to 75.4). There was no significant difference between infection relapse-free survival rate and prosthesis survival rate in the two groups. The 8-year prosthesis survival rate was 90.9% in the study group and 91% in the control group (p = 0.913). The 8-year infection relapse-free survival rate was 80 and 83.3% in the study group and control group, respectively (p = 0.377).ConclusionThe structural fresh frozen allogenous bone graft provided an effective way for bone defect reconstruction in knee PJI with an accountable survival rate. Meanwhile, using structural allografts did not increase the relapse rate of infection.

Personalized 3D-printed guide in malignant bone tumor resection and following reconstruction – 17 cases in pelvic and extremities

IntroductionCustomized accurate tumor resection and individualized reconstruction is a challenging in treatment of malignant bone tumor. Three-dimensional (3D)-printing technique is now widely used in the resection and following reconstruction of malignant bone tumor, which included but not limited to tumor model, osteotomy guide and customized implant. MethodsWe retrospectively reviewed 17 patients, who underwent limb salvage surgery by using 3D-printed guide at a single center between August 2014 and October 2019. The median duration of follow-up was 26.5 months. Osteosarcoma (41.2%) were the predominant diagnoses. The functional outcomes were assessed by Musculoskeletal Tumor Society (MSTS) functional score. We also analyzed survival status, intraoperative data (blood loss, operation time and resection length), reconstruction method, margin outcomes and complications. ResultsWe totally performed 93 guided osteotomies on affected bone and allograft bone in 17 patients. Reconstruction in 12 cases was performed with biological technique: allograft combined with autograft was used in 7 cases. 11 of 12 (91.7%) cases showed a good bone healing in both allograft and autograft. 1 of 12 (8.3%) cases had allograft necrosis. Additional intra-operative extracorporeal radiation was performed in 3 pelvic cases for reconstruction. 63 of 64 (98%) osteotomies achieved wide resection and negative margin. All the cases had successful limb salvage result without amputation. At the latest follow up, the mean MSTS Score was 24 (range: 13–30), 12 patients alive with no evidence of disease, 1 patient alive with disease, 5 patients had died of disease and 5 years overall survival is 73.3%. The most common complications are wound healing disorder in 4 cases (23.5%) and infection in 3 cases (17.6%). ConclusionThe 3D-printed resection guide was easy to use and showed promise in the field of orthopedic oncology. It can not only used in primary malignant bone tumor personalized resection but also in shaping structural bone allograft in biological reconstruction, which can achieve a safety surgical margin and individualized resection at the same time.

The High-cycle Fatigue Life of Cortical Bone Allografts Is Radiation Sterilization Dose-dependent: An In Vitro Study.

Structural cortical bone allografts are a reasonable treatment option for patients with large cortical bone defects caused by trauma, tumors, or complications of arthroplasty. Although structural cortical bone allografts provide the benefit of an osteoconductive material, they are susceptible to fatigue failure (fracture) and carry a risk of disease transmission. Radiation-sterilization at the recommended dose of 25 kGy decreases the risk of disease transmission. However, previous studies demonstrated that radiation sterilization at this dose can negatively impact the high cycle-fatigue life of cortical bone. Although the effects of higher doses of radiation on cortical bone allografts are well described, the effects of lower doses of radiation on a high-cycle fatigue life of cortical bone are poorly understood. (1) Does the cycle-fatigue life of human cortical allograft bone vary with gamma radiation dose levels of 0 (control), 10 kGy, 17.5 kGy, and 25 kGy? (2) What differences in Raman spectral biomarkers are observed following varying doses of gamma radiation exposure? The high-cycle fatigue behavior of human cortical bone specimens was examined at different radiation sterilization doses under physiologic stress levels (35 MPa) and in a 37° C phosphate-buffered saline bath using a custom-designed rotating-bending fatigue device. Six human femora from three donors were obtained for this study (two male, 63 and 61 years old, respectively, and one female, 48 years old). Test specimens were allocated among four treatment groups (0 kGy [control], 10 kGy, 17.5 kGy, and 25 kGy) based on donor and anatomic location of harvest site (both length and cross-sectional quadrant of femoral diaphysis) to ensure equal variation (n = 13 per group). Specimens underwent high-cycle fatigue testing to failure. The number of cycles to failure was recorded. Raman spectroscopy (a noninvasive vibrational spectroscopy used to qualitatively assess bone quality) was used to detect whether any changes in Raman spectral biomarkers occurred after varying doses of gamma radiation exposure. There was a decrease in the log-transformed mean high-cycle fatigue life in specimens irradiated at 25 kGy (5.39 ± 0.32) compared with all other groups (0 kGy: 6.20 ± 0.50; 10k Gy: 6.35 ± 0.79; 17.5 kGy: 6.01 ± 0.53; p = 0.001). Specimens irradiated at 25 kGy were also more likely to exhibit a more brittle fracture surface pattern than specimens with more ductile fracture surface patterns irradiated at 0 kGy, 10 kGy, and 17.5 kGy (p = 0.04). The Raman biomarker for the ratio of the relative amount of disordered collagen to ordered collagen showed a decrease at the 10 kGy radiation level from 1.522 ± 0.025 preirradiation to 1.489 ± 0.024 postirradiation (p = 0.01); no other detectable changes in Raman biomarkers were observed. The high-cycle fatigue life of cortical bone undergoes a nonlinear, dose-dependent decrease with an increase in gamma radiation sterilization in a clinically relevant dose range (0-25 kGy). Importantly, a notable drop-off in the high-cycle fatigue life of cortical bone appeared to occur between 17.5 kGy and 25 kGy, correlating to a sixfold decrease in mean cycles to failure. We speculate that the decrease in the Raman biomarker for disordered collagen at 10 kGy with no loss in high-cycle fatigue life may be caused by an increased amount of nonenzymatic crosslinking of the collagen backbone relative to collagen chain-scission (whereas the benefits of crosslinking may be outweighed by excess scission of the collagen backbone at higher radiation doses), but future studies will need to ascertain whether this in fact is the case. Radiation sterilization at the industry standard of 25 kGy has a substantial negative impact on the high-cycle fatigue life of cortical bone. Given these findings, it is possible to provide a meaningful increase in the high-cycle fatigue life and improve the overall functional lifetime of cortical bone allografts by lowering the radiation-sterilization dose below 25 kGy. Future work on radiation-sterilization methods at these clinically relevant doses is warranted to aid in preserving the high cycle fatigue life of cortical bone allografts while maintaining sterility.

MSLA-based 3D printing of acrylated epoxidized soybean oil - nano-hydroxyapatite composites for bone repair

Structural bone allografts are used to treat critically sized segmental bone defects (CSBDs) as such defects are too large to heal naturally. Development of biomaterials with competent mechanical properties that can also facilitate new bone formation is a major challenge for CSBD repair. 3D printed synthetic bone grafts are a possible alternative to structural allografts if engineered to provide appropriate structure with sufficient mechanical properties. In this work, we fabricated a set of novel nanocomposite biomaterials consisting of acrylated epoxidized soybean oil (AESO), polyethylene glycol diacrylate (PEGDA) and nanohydroxyapatite (nHA) by using masked stereolithography (mSLA)-based 3D printing.The nanocomposite inks possess suitable rheological properties and good printability to print complex, anatomically-precise, ‘by design’ grafts. The addition of nHA to the AESO/PEGDA resin improved the tensile strength and fracture toughness of the mSLA printed nanocomposites, presumably due to small-scale reinforcement. By adding 10 vol% nHA, tensile strength, modulus and fracture toughness (KIc) were increased to 30.8 ± 1.2 MPa (58% increase), 1984.4 ± 126.7 MPa (144% increase) and 0.6 ± 0.1 MPa·m1/2 (42% increase), respectively (relative to the pure resin). The nanocomposites did not demonstrate significant hydrolytic, enzymatic or oxidative degradation when incubated for 28 days, assuring chemical and mechanical stability at early stages of implantation. Apatite nucleated and covered the nanocomposite surfaces within 7 days of incubation in simulated body fluid. Good viability and proliferation of differentiated MC3T3-E1 osteoblasts were also observed on the nanocomposites. Taken all together, our nanocomposites demonstrate excellent bone-bioactivity and potential for bone defect repair.

CORR Insights®: Deep-freezing Temperatures During Irradiation Preserves the Compressive Strength of Human Cortical Bone Allografts: A Cadaver Study.

CORR Insights®: Deep-freezing Temperatures During Irradiation Preserves the Compressive Strength of Human Cortical Bone Allografts: A Cadaver Study.

Prospective, randomized, double-blinded clinical trial comparing PEEK and allograft spacers in patients undergoing transforaminal lumbar interbody fusion surgeries

Allograft and polyether-ether-ketone (PEEK) radiographic, biomechanical, histological properties have been extensively studied and both spacers have their advantages and shortcomings. There are no comparative randomized or double-blinded spinal fusion clinical trials reported to date. The study's primary objective was to prospectively investigate clinical and radiological outcomes in patients undergoing lumbar interbody fusions and randomized to receive either PEEK or structural bone allografts. A prospective, randomized, double-blinded clinical trial was initiated at a single center. A total of 138 patients were enrolled, randomized and 121 patients completed the study. The primary clinical outcome parameters were scored from standardized patient-reported questionnaires. The severity of lower back and leg pain was evaluated using the 11-point Visual Analog Scale (VAS). The Oswestry Disability Questionnaire was used to evaluate chronic disability and activities of daily living. Health-related quality of life and functional outcomes were assessed using Health-related Quality of Life Questionnaire (SF-36 v2). Two scores within the scoring algorithm were analyzed: Physical Component (PCS) and Mental Component Summary (MCS). The primary radiological outcomes included restoration and maintenance of vertebral body height, lumbar sagittal and segmental alignment, and fusion status. All patients were followed for 2 years ± 2 months; radiographic and clinical outcomes were assessed at 3, 6, 12 and 24 months with an additional follow-up at 3 weeks for radiographic assessment. A total of 138 patients undergoing transforaminal lumbar interbody fusions (TLIF) were randomized (1:1) to receive either cortical allograft or PEEK interbody lordotic spacers. Although no differences were detected between the allograft and PEEK patient groups at any of the follow-up time points, there was a highly significant (p<.0001) improvement in all clinical outcome measures. Overall, evidence of radiographic fusion was achieved in 118 (97.5%) patients at the 24 months follow-up. Three patients, all in the allograft group, had pseudoarthrosis and underwent revision surgeries. Postoperative improvement of sagittal alignment, anterior (ABH) or posterior body height (PBH) was initially achieved, but it was mainly lost or reduced at the final follow-up and there were no statistically significant differences between the groups. At the end of the study, improvement and maintenance of lumbar lordosis were achieved in 43.3% and 49.2% patients and segmental alignment in 38.3% and 36.1% for the allograft and PEEK patient groups, respectively. Similarly, ABH was improved and maintained in 28.3% and 36.1% patients and PBH in 28.3% and 44.3% for the allograft and PEEK groups, respectively. Although allograft-assisted surgeries may have reduced fusion rates, the study findings demonstrated that TLIF surgery with two different types of cages and in conjunction with rhBMP-2 resulted in similar radiological or clinical outcomes and a highly statistically significant improvement in all clinical outcome measures at the end of the study regardless of the randomization group.

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.

Modular endoprosthetic replacement for proximal tibia tumor patients

The major method of malignant bone tumors treatment is surgery. The most important task of an orthopedic surgeon is to preserve an adjacent joint. Currently, there are a large number of various reconstructive surgeries, including structural bone allograft, allocomposite and modular endoprosthetics replacement. The aim: to analyze the results of surgical treatment for proximal tibia malignant tumors using modular endoprosthesis. Materials and methods. The results of proximal tibia (PT) modular endoprosthetic replacement in 48 patients with PT tumor lesions were evaluated. The patients were divided into two groups: I (n = 36) – tumor resection and primary modular endoprosthesis, II (n = 12) – revision modular endoprosthetic replacement due to complications. Complications were divided into oncological, mechanical and non-mechanical. The functional outcomes were measured using the MSTS and TESS scores. Results. During the treatment, 10 (21.2 %) patients underwent myofascioplastic amputation at the middle third of the thigh: due to periprosthetic infection – 8 people and tumor recurrence – 2. It was found that the patients got back to regular way of life on average in 2.0–2.5 months. Functional results on the MSTS score were 73 ± 12 %, on the TESS score – 74 ± 16 %, which corresponds to good functional results. Among the patients, who underwent limb salvage surgery, no tumor recurrence was detected during a follow-up period from 6 months up to 11 years. Conclusions. The choice of surgical treatment depends on the size of tumor, its location, pathohistomorphological picture, age, presence of pathological fractures, vascular and nerve tumor invasion. The use of modern designs of PT modular tumor endoprostheses and perfect surgeries makes it possible to minimize complications.

Combined Surgical and Medical Treatment for Vancouver B1 and C Periprosthetic Femoral Fractures: A Proposal of a Therapeutic Algorithm While Retaining the Original Stable Stem.

IntroductionThere is lack of consensus regarding best operative fixation strategy for periprosthetic femoral fractures (PFFs) around a stable stem. Evidence exists that some patterns of fracture around a stable stem are better treated with revision surgery than with standard fixation. Anyway, a more aggressive surgical procedure together with medical treatment could allow for stem retention, and reduced risk of nonunion/hardware failure, even in these cases.SignificanceThis paper is placed in a broader context of lack of studies on the matter, and its aim is to shed some light on the management of PFFs around a stable stem, when peculiar mechanical and biological aspects are present.ResultsBased on our casuistry in the treatment of nonunions after PFF successfully treated with original stem retention, and on review of Literature about risk factors for fixation failure, an algorithm is proposed that can guide in choosing the ideal surgical technique even for first-time PFFs with a stable stem, without resorting to revision. Mechanical (major and minor) and biological (local and systemic) factors that may influence fracture healing, leading to nonunion and hardware failure, and subsequent need for re-operation, are considered. The proposed surgical technique consists of rigid fixation with absolute stability (using a plate and structural allograft) plus local biological support (structural allograft and autologous bone marrow concentrate over a platelet-rich plasma-based scaffold) at fracture site. Systemic anabolic treatment (Teriparatide) is also administered in the post-operative period.ConclusionMechanical factors are not the only issues to be considered when choosing the surgical approach to PFFs over a stable stem. Systemic and local biological conditions should be taken into account, as well. A therapeutic algorithm is proposed, given the prosthetic stem to be stable, considering mechanical and biological criteria.

Periosteum Mimetic Coating on Structural Bone Allografts via Electrospray Deposition Enhances Repair and Reconstruction of Segmental Defects.

Structural bone allograft transplantation remains one of the common strategies for repair and reconstruction of large bone defects. Due to the loss of periosteum that covers the outer surface of the cortical bone, the healing and incorporation of allografts is extremely slow and limited. To enhance the biological performance of allografts, herein, we report a novel and simple approach for engineering a periosteum mimetic coating on the surface of structural bone allografts via polymer-mediated electrospray deposition. This approach enables the coating on allografts with precisely controlled composition and thickness. In addition, the periosteum mimetic coating can be tailored to achieve desired drug release profiles by making use of an appropriate biodegradable polymer or polymer blend. The efficacy study in a murine segmental femoral bone defect model demonstrates that the allograft coating composed of poly(lactic-co-glycolic acid) and bone morphogenetic protein-2 mimicking peptide significantly improves allograft healing as evidenced by decreased fibrotic tissue formation, increased periosteal bone formation, and enhanced osseointegration. Taken together, this study provides a platform technology for engineering a periosteum mimetic coating which can greatly promote bone allograft healing. This technology could eventually result in an off-the-shelf and multifunctional structural bone allograft for highly effective repair and reconstruction of large segmental bone defects. The technology can also be used to ameliorate the performance of other medical implants by modifying their surfaces.