Dose-Dependent Resorption of Allograft by rhBMP-2 Uncompensated by New Bone Formation-A Canine Study With Implants and Zoledronate.

BACKGROUND: Impacted bone allograft is used to restore lost bone in total joint arthroplasties. Bone morphogenetic proteins (BMPs) can induce new bone formation to improve allograft incorporation, but they simultaneously invoke a seemingly dose-dependent allograft resorption mediated by osteoclasts. Bisphosphonates effectively inhibit osteoclast activity. Predicting allograft resorption when augmented with bone morphogenetic protein 2 (BMP-2), we intended to investigate whether a balanced bone metabolism was achievable within a range of BMP-2 doses with systemic zoledronate treatment. METHODS: Implants were coated with 1 of 3 BMP-2 doses (15 µg, 60 µg, and 240 µg) or left untreated. Implants were surrounded by a 2.5-mm gap filled with impacted morselized allograft. Each of the 12 dogs included received 1 of each implant (15 µg, 60 µg, 240 µg, and untreated), 2 in each proximal humerus. During the 4-week observation period, zoledronate intravenous (0.1 mg/kg) was administered to all animals 10 days after surgery as anticatabolic treatment. Implant osseointegration was evaluated by histomorphometry and mechanical push-out tests. RESULTS: Untreated implants had the best mechanical fixation and superior retention of allograft as compared to any of the BMP-2 implants. Both mechanical implant fixation and retention of allograft decreased significantly with BMP-2 dose increments. Surprisingly, there was no difference among the treatment groups in the amount of new bone. CONCLUSION: The use of BMP-2 to augment impaction-grafted implants cannot be recommended even when combined with systemic zoledronate.

Topical zoledronic acid decreases micromotion induced bone resorption in a sheep arthroplasty model.

BACKGROUND: Initial micromotion of a total hip replacement is associated with aseptic loosening. The use of bisphosphonates could be one way to reduce peri-implant bone resorption induced by micromotion. Bisphosphonates compounds are inhibitors of bone resorption. The aim of this study was to investigate whether local treatment with bisphosphonate would reduce bone resorption and fibrous tissue around an experimental implant subjected to micromotion. METHODS: One micromotion implant were inserted into each medial femoral condyle in ten sheep. During each gait cycle the implant axially piston 0.5 mm. During surgery one of the femoral condyles were locally treated with 0.8 mg zoledronate. The other condyle served as control. Observation period was 12 weeks. RESULTS: Histological evaluation showed a fibrous capsule around both the control and bisphosphonate implants. Histomorphometrical analysis showed that 97% of the surface on both control and bisphosphonate implants were covered by fibrous tissue. However, the bisphosphonate was able to preserve bone in a 1 mm zone around the implants. CONCLUSION: This study indicates that local treatment with bisphosphonate cannot prevent the formation of a fibrous capsule around an implant subjected to micromotion, but bisphosphonate is able to reduce resorption of peri-prosthetic bone.

Incorporation of raloxifene-impregnated allograft around orthopedic titanium implants impairs early fixation but improves new bone formation.

BACKGROUND: The anti-osteoporotic drug raloxifene reduces the risk of vertebral fractures by increasing bone mass density. We investigated whether raloxifene offers any benefits in augmenting early fixation of orthopedic implants in the setting of impaction bone grafting. METHODS: 24 non-weight-bearing grafted gap implants were inserted bilaterally into the tibia of 12 dogs. The 2.5-mm peri-implant gap was filled with either raloxifene-impregnated or untreated bone allograft. Implants were harvested after 28 days. Implant fixation was assessed by mechanical testing and histomorphometric evaluation. RESULTS: Raloxifene-treated allograft reduced early implant fixation compared to untreated allograft, as measured by inferior maximum shear strength (p < 0.001) and apparent shear stiffness (p = 0.001). We found that the raloxifene group had more newly formed bone in the gap around the implant (p = 0.02), but also less allograft (p = 0.03). INTERPRETATION: The accelerated allograft resorption in the raloxifene group explained the impaired early fixation, despite its stimulation of new bone formation. Our results with local and possible high-dose treatment are not consistent with current theory regarding the mechanism of how systemic raloxifene administration counteracts the decrease in BMD in postmenopausal women. Instead of being solely anti-resorptive as generally held, our results indicate a possible anabolic side of raloxifene.

Rinsing of allograft bone does not improve implant fixation: a study in 12 dogs.

BACKGROUND AND PURPOSE: Impacted morselized allograft bone is a well-established method for reconstructing bone defects at revision surgery. However, the incorporation of bone graft is not always complete, and a substantial volume of fibrous tissue has been found around grafted implants. We hypothesized that rinsing the bone graft may improve graft incorporation by removing the majority of immunogenic factors present in blood, marrow, and fat. METHODS: We implanted a cylindrical (10- × 6-mm) porous-coated Ti implant into each proximal tibia of 12 dogs. The implants were surrounded by a 2.5-mm gap into which morselized fresh frozen allograft bone was impacted. The bone graft was either (1) untreated or (2) rinsed in 37°C saline for 3 × 1 min. After 4 weeks, the animals were killed and implant fixation was evaluated by mechanical push-out and histomorphometry. RESULTS: The groups (rinsed vs. control) were similar regarding mechanical implant fixation (mean (SD)): shear strength (MPa) 2.7 (1.0) vs. 2.9 (1.2), stiffness (MPa/mm) 15 (6.7) vs. 15 (5.6), and energy absorption (kJ/m(2)) 0.5 (0.2) vs. 0.6 (0.4), The same was evident for the new bone formation on the implant surface and around the implant: ongrowth (%) 6 vs. 7 and ingrowth (%) 9 vs. 9. Although not statistically significant, a 61% reduction in fibrous tissue ongrowth and 50% reduction in ingrowth were found in the rinsed group. INTERPRETATION: Within the limits of this experimental model, we did not detect any benefits of rinsing morselized allograft bone prior to impaction grafting.

Strontium doping of bone graft extender.

BACKGROUND AND PURPOSE: Allografts are often used during revision hip replacement surgery for stabilization of the implant. Resorption of the allograft may exceed new bone formation, and instability of the prosthesis can develop. We investigated whether strontium could regulate the imbalance of fast resorption of allograft and slower formation of new bone, because it is both an anabolic and an anticatabolic agent. METHOD: Strontium was added to the implant interface environment by doping a hydroxyapatite bone graft extender. 10 dogs each received 2 experimental titanium implants. The implants were inserted within a 2.7-mm concentric gap in cancellous bone. The gap was filled with 50% (v/v) allograft mixed with 50% bone graft extender. The extender either had 5% strontium doping (SrHA) or was undoped (HA). After 4 weeks, osseointegration and mechanical fixation were evaluated by histomorphometry and by push-out test. RESULTS: SrHA bone graft extender induced a 1.2-fold increase in volume of new bone, a 1.2-fold increase in allograft remaining in the gap, and a 1.4-fold increase in surface area of the bone graft extender material in contact with new bone compared to HA bone graft extender. All these increases were statistically significant. SrHA bone graft extender did not significantly improve ongrowth of bone onto the implants or improve any of the mechanical push-out parameters compared to HA bone graft extender. INTERPRETATION: Doping of the HA bone graft extender with 5% strontium increased gap healing, preserved more of the allograft in the gap, and increased the ongrowth of bone onto the bone graft extender material, but did not improve mechanical fixation.

Augmentation of implant surfaces with BMP-2 in a revision setting : effects of local and systemic bisphosphonate.

AIMS: We wanted to evaluate the effects of a bone anabolic agent (bone morphogenetic protein 2 (BMP-2)) on an anti-catabolic background (systemic or local zoledronate) on fixation of allografted revision implants. METHODS: An established allografted revision protocol was implemented bilaterally into the stifle joints of 24 canines. At revision surgery, each animal received one BMP-2 (5 µg) functionalized implant, and one raw implant. One group (12 animals) received bone graft impregnated with zoledronate (0.005 mg/ml) before impaction. The other group (12 animals) received untreated bone graft and systemic zoledronate (0.1 mg/kg) ten and 20 days after revision surgery. Animals were observed for an additional four weeks before euthanasia. RESULTS: No difference was detected on mechanical implant fixation (load to failure, stiffness, energy) between local or systemic zoledronate. Addition of BMP-2 had no effect on implant fixation. In the histomorphometric evaluation, implants with local zoledronate had more area of new bone on the implant surface (53%, p = 0.025) and higher volume of allograft (65%, p = 0.007), whereas implants in animals with systemic zoledronate had the highest volume of new bone (34%, p = 0.003). Systemic zoledronate with BMP-2 decreased volume of allograft by 47% (p = 0.017). CONCLUSION: Local and systemic zoledronate treatment protects bone at different stages of maturity; local zoledronate protects the allograft from resorption and systemic zoledronate protects newly formed bone from resorption. BMP-2 in the dose evaluated with experimental revision implants was not beneficial, since it significantly increased allograft resorption without a significant compensating anabolic effect. Cite this article: Bone Joint Res 2021;10(8):488-497.

The effect of soaking allograft in bisphosphonate: a pilot dose-response study.

BACKGROUND: Long-term survival of uncemented total joint replacements relies on osseointegration. With reduced bone stock impacted morselized allograft enhances early implant fixation but is subject to resorption. PURPOSE: We therefore asked whether soaking morselized allograft in different concentrations of bisphosphonate before impaction would enhance fixation. METHODS: In each of 10 dogs, we implanted four unloaded titanium implants surrounded by a 2.5-mm gap into the proximal humerus, two implants in each humerus. The gap was filled with impacted morselized allograft soaked in saline or a low-, middle-, or high-dose bisphosphonate solution (0.005, 0.05, or 0.5 mg zoledronate/mL). At 4 weeks, the implants were evaluated by histomorphometric analysis and mechanical pushout test. RESULTS: The low dose of zoledronate increased new bone formation in the allograft but the high dose decreased new bone formation. The high dose of zoledronate resulted in the greatest inhibition of allograft resorption, whereas the low dose of zoledronate resulted in the lowest inhibition of allograft resorption. Implants surrounded allograft soaked in the low dose of zoledronate or saline had better fixation for all three mechanical parameters compared with implants surrounded by allograft soaked in the middle or high dose of zoledronate. CONCLUSIONS: These data suggest bisphosphonate may enhance osseointegration of allografted implants and emphasize the need for preclinical testing of antiresorptive therapies.

Crack revision improves fixation of uncemented HA-coated implants compared with reaming: an experiment in dogs.

The crack procedure is a surgical technique for preparing the implant cavity at revision of loose joint replacement components. It disrupts the neocortical bone shell that typically forms around the cavity. Using an animal model, we compared the crack technique with reaming. Twenty micromotion implants were inserted bilaterally into the knees of 10 dogs according to our revision protocol, allowing formation of a standardized revision cavity (loose implant, fibrous tissue, and sclerotic bone rim). Eight weeks later we performed revision surgery. On the control side, in which the neocortex was removed, the cavity was reamed. On the intervention side, in which the neocortex was perforated but left in situ, the cavity was cracked. For revision we used non-motioning hydroxyapatite (HA)-coated, plasma-sprayed titanium implants. Observation after revision was 4 weeks. The implants revised by the crack technique had better mechanical fixation in all mechanical parameters by the push-out test. The crack revisions also provided more new bone formation around the implants compared with the reamed revisions but had no effect on new bone ongrowth. The data suggest using this bone-sparing technique may be superior to reaming in terms of achieving improved early implant fixation of uncemented HA-coated revision implants.

The effect of pretreating morselized allograft bone with rhBMP-2 and/or pamidronate on the fixation of porous Ti and HA-coated implants.

BMPs stimulate new bone formation, but may also accelerate bone resorption. We added rhBMP-2 and pamidronate to morselized bone allograft packed around uncemented HA-coated and non-coated porous Ti implants in sixteen dogs. Each dog received four implants where the allograft was added (1) nothing, (2) BMP, (3) BP, and (4) BMP+BP. After four weeks, the untreated control implants had better mechanical fixation than all other treatment groups. The rhBMP-2-treated group had abundant formation of new bone on and around the implant. However, almost all allografts were resorbed, rendering the implant mechanically unstable. In the pamidronate-treated group the allograft was preserved, but the implants were covered by fibrous tissue and there was almost no new bone formation. This was also the case for the combined BMP+BP group, although fibrous tissue was absent on these implants. The HA-coated implants had more than twice as good mechanical fixation and improved osseointegration compared to the corresponding Ti implants. RhBMP-2 raised the total metabolic turnover of bone within the allograft with a net negative result on implant fixation. Pamidronate virtually blocked bone metabolism, also when combined with rhBMP-2. The results warrant a conservative approach and emphasize the importance of identifying a therapeutic window for these substances prior to clinical use.

Ceramic bone graft substitute with equine bone protein extract is comparable to allograft in terms of implant fixation: a study in dogs.

BACKGROUND AND PURPOSE: We studied whether osseointegration and fixation of plasma-sprayed titanium implants grafted with beta-TCP granules (Ossaplast) can be improved by adding an osteogenic signal (Colloss E). The results were compared to implants grafted with fresh frozen morselized allograft with and without the Colloss E device. METHODS: 4 porous-coated Ti implants were placed in the proximal humeri in each of 10 dogs. All implants were surrounded by a 2.5-mm defect, which was grafted with: (A) beta-TCP, (B) beta-TCP+20 mg Colloss E, (C) allograft, or (D) allograft+20 mg Colloss E. The observation time was 4 weeks. RESULTS: Mechanical testing showed that the beta-TCP group with Colloss E was twice as well fixed as the control group grafted with beta-TCP granules alone, and comparable to both allograft groups. We found that every control implant in the beta-TCP grafted group was covered by a dense fibrous membrane. No fibrous tissue was seen in the beta-TCP group augmented with Colloss. These implants were well osseointegrated, with new bone covering 10-25% of the implant surface. Both treated groups had increased graft resorption compared to their respective control groups. Colloss E had no effect on new bone formation or fibrous tissue reduction around the allografted implants. INTERPRETATION: The Colloss E device improved early osseointegration of implants grafted with beta-TCP granules and increased their mechanical implant fixation to the level of allografted implants. The experiment indicates that ceramic bone substitutes may be a viable alternative to allograft when combined with an osteogenic signal such as Colloss E.

Healing in peri-implant gap with BMP-2 and systemic bisphosphonate is dependent on BMP-2 dose-A canine study.

The bone-implant interface of cementless orthopedic implants can be described as a series of uneven sized gaps with discontinuous areas of direct bone-implant contact. Bridging these voids and crevices by addition of an anabolic stimulus to increase new bone formation can potentially improve osseointegration of implants. Bone morphogenetic protein 2 (BMP-2) stimulates osteoblast formation to increase new bone formation but also indirectly stimulates osteoclast activity. In this experiment, we investigate the hypothesis that osseointegration, defined as mechanical push-out and histomorphometry, depends on the dose of BMP-2 when delivered as an anabolic agent with systemic administration of the anti-resorptive agent zoledronate to curb an increase in osteoclast activity. Four porous coated titanium implants (one with each of three doses of surface-applied BMP-2 (15 µg; 60 µg; 240 µg) and untreated) surrounded by a 0.75 mm empty gap, were inserted into the distal femurs of each of twelve canines. Zoledronate IV (0.1 mg/kg) was administered 10 days into the observation period of 4 weeks. Bone-implant specimens were evaluated by mechanical push-out test and histomorphometry. The 15 µg implants had the best fixation on all mechanical parameters and largest surface area covered with new bone compared to the untreated, 60 and 240 µg implants, as well as the highest volume of new bone in the implant gap compared to 60 and 240 µg implants. The results in a canine implant model demonstrated that a narrow range of BMP-2 doses have opposite effects in bridging an empty peri-implant gap with bone, when combined with systemic zoledronate. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1406-1414, 2018.

The Importance of the Saphenous Nerve Block for Analgesia Following Major Ankle Surgery: A Randomized, Controlled, Double-Blind Study.

BACKGROUND AND OBJECTIVES: Major ankle surgery causes intense postoperative pain, and whereas the importance of a sciatic nerve block is well established, the clinical significance of a supplemental saphenous nerve block has never been determined in a prospective, randomized, double-blind, placebo-controlled trial. We hypothesized that a saphenous nerve block reduces the proportion of patients experiencing significant clinical pain after major ankle surgery. METHODS: Eighteen patients were enrolled and received a popliteal sciatic nerve block. Patients were randomized to single-injection saphenous nerve block with 10 mL 0.5% bupivacaine with 1:200,000 epinephrine or 10 mL saline (Fig. 1). Primary outcome was the proportion of patients reporting significant clinical pain, defined as a score greater than 3 on the numerical rating scale. Secondary outcomes were maximal pain and analgesia of the cutaneous territory of the infrapatellar branch of the saphenous nerve. RESULTS: Eight of 9 patients in the placebo group reported significant clinical pain versus 1 of 9 patients in the bupivacaine-epinephrine group (P = 0.003). Maximal pain was significantly lower in the active compared with the placebo group (median, 0 [0-0] vs 5 [4-6]; P = 0.001). Breakthrough pain from the saphenous territory began within 30 minutes after surgery in all cases. Sensory testing of the cutaneous territory of the infrapatellar branch of the saphenous nerve showed correlation between pain reported in the anteromedial ankle region and the intensity of cutaneous sensory block in the anteromedial knee region. CONCLUSIONS: The saphenous nerve is an important contributor to postoperative pain after major ankle surgery, with significant clinical pain appearing within 30 minutes after surgery. CLINICAL TRIALS REGISTRATION: This study has been registered at ClinicalTrials.gov, identifier NCT02697955.

Topical bisphosphonate augments fixation of bone-grafted hydroxyapatite coated implants, BMP-2 causes resorption-based decrease in bone.

Bone allograft is used in total joint arthroplasties in order to enhance implant fixation. BMPs are known to stimulate new bone formation within allograft, but also known to accelerate graft resorption. Bisphosphonates are strong inhibitor of bone resorption. The aim of this study was to investigate whether the bisphosphonate zoledronate was able to counteract the accelerated graft resorption without interfering with the BMP induced bone formation. In the present study the two drugs alone and in combination were studied in our canine model of impaction bone grafting. We included 10 dogs in this study. Cancellous allograft bone grafts were soaked in either saline or zoledronate solution (0.005mg/mL) and then vehicle or BMP2 (0.15mg rhBMP2) was added. This produced four treatment groups: A) control, B) BMP2, C) zoledronate and D) BMP2+zoledronate. The allograft treated with A, B, C or D was impacted into a circumferential defect of 2.5mm around HA-coated porous Ti implants. Each dog received all four treatment groups with two implants in the distal part of each femur. The group with allograft soaked in zoledronate (C) showed better biomechanical fixation than all other groups (p<0.05). It had less allograft resorption compared to all other groups (p<0.005) without any statistically significant change in new bone formation. The addition of BMP2 to the allograft did not increase new bone formation significantly, but did accelerate allograft resorption. This was also the case where the allograft was treated with BMP2 and zoledronate in combination (D). This caused a decrease in mechanical implant fixation in both these groups compared to the control group, however only statistically significant for the BMP2 group compared to control. The study shows that topical zoledronate can be a valuable tool for augmenting bone grafts when administered optimally. The use of BMP2 in bone grafting procedures seems associated with a high risk of bone resorption and mechanical weakening.

Local delivery of zoledronate from a poly (d,l-lactide)-coating increases fixation of hydroxy-coated implants.

Initial secure implant fixation predicts long-term survival. Bisphosphonates are anti-resorptive agents. They have been shown to increase implant fixation. We investigated whether local delivery of zoledronate from a poly-d,l-lactide (PDLLA)-coating could improve fixation and osseointegration of hydroxy-apatite coated implants. Cylindrical hydroxy-apatite coated implants were bilaterally inserted press-fit into the proximal tibiae of 10 dogs. On one side the implant was coated with PDLLA containing zoledronate. The PDLLA coating was applied upon the hydroxy-apatite coating. We used the contralateral implant as control. This implant was not coated with a poly-d,l-lactide. Observation period was 12 weeks. We evaluated implant fixation with histomorphometry and biomechanical push-out test. Zoledronate resulted in an approximately threefold increase in all biomechanical parameters when comparing data with their respective controls. We found that zoledronate increased preservation of old lamellar bone and increased formation of new woven bone. This study indicates that local delivery of zoledronate from a PDDLA coating has the potential to increase implant fixation. Studies investigating different doses of zoledronate and longer follow-up are needed. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:974-979, 2017.

Local delivery of zoledronate from a poly (D,L-lactide)-Coating increases fixation of press-fit implants.

Early secure fixation of total joint replacements is crucial for long-term survival. Antiresorptive agents such as bisphosphonates have been shown to increase implant fixation. We investigated whether local delivery of zoledronate from poly-D, L-lactide (PDLLA)-coated implants could improve implant fixation and osseointegration. Experimental titanium implants were bilaterally inserted press-fit into the proximal tibiae of 10 dogs. On one side the implant was coated with PDLLA containing zoledronate. The contralateral implant was uncoated and used as control. Observation period was 12 weeks. Implant fixation was evaluated with histomorphometry and biomechanical push-out test. We found an approximately twofold increase in all biomechanical parameters when comparing data from the zoledronate group with their respective controls. Histomorphometry showed increased amount of preserved bone and increased bone formation around the zoledronate implants. This study indicates that local delivery of zoledronate from a PDDLA coating has the potential to increase implant fixation.

Dental pulp-derived stromal cells exhibit a higher osteogenic potency than bone marrow-derived stromal cells in vitro and in a porcine critical-size bone defect model.

INTRODUCTION: The osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSCs) was compared with that of dental pulp-derived stromal cells (DPSCs) in vitro and in a pig calvaria critical-size bone defect model. METHODS: BMSCs and DPSCs were extracted from the tibia bone marrow and the molar teeth of each pig, respectively. BMSCs and DPSCs were cultured in monolayer and on a three-dimensional (3D) polycaprolactone (PCL) - hyaluronic acid - tricalcium phosphate (HT-PCL) scaffold. Population doubling (PD), alkaline phosphatase (ALP) activity, and calcium deposition were measured in monolayer. In the 3D culture ALP activity, DNA content, and calcium deposition were evaluated. Six non-penetrating critical-size defects were made in each calvarium of 14 pigs. Three paired sub-studies were conducted: (1) empty defects vs. HT-PCL scaffolds; (2) PCL scaffolds vs. HT-PCL scaffolds; and (3) autologous BMSCs on HT-PCL scaffolds vs. autologous DPSCs on HT-PCL scaffolds. The observation time was five weeks. Bone volume fractions (BV/TV) were assessed with micro-computed tomography (µCT) and histomorphometry. RESULTS AND DISCUSSION: The results from the in vitro study revealed a higher ALP activity and calcium deposition of the DPSC cultures compared with BMSC cultures. Significantly more bone was present in the HT-PCL group than in both the pure PCL scaffold group and the empty defect group in vivo. DPSCs generated more bone than BMSCs when seeded on HT-PCL. In conclusion, DPSCs exhibited a higher osteogenic potential compared with BMSCs both in vitro and in vivo, making it a potential cell source for future bone tissue engineering.

Sheep Hip Arthroplasty Model of Failed Implant Osseointegration.

Early secure stability of an implant is important for long-term survival. We examined whether micromotion of implants consistently would induce bone resorption and formation of a fibrous membrane and thereby prevent osseointegration. One micromotion implant was inserted into one of the medial femoral condyles in ten sheep. The micromotion device consists of an anchor bearing a PMMA implant and a PE plug. During each gait cycle the PE plug will make the PMMA implant axially piston 0.5 mm. After 12 weeks of observation the bone specimens were harvested and a post-mortem control implant was inserted into the contra-lateral medial femoral condyle. Histomorphometrical evaluation showed that the surface on the implant observed for 12 weeks was covered by fibrous tissue. The control implants were covered by lamellar bone. No difference was found with respect to the volume fraction of lamellar bone in a 1 mm zone around the implants. This study indicates that implant micromotion is sufficient to induce bone resorption and formation of a fibrous membrane.

Does tobramycin impregnation of allograft bone affect implant fixation? - an experimental study in 12 dogs.

Clinical trials have used antibiotic impregnated impacted bone allograft in revisions of infected arthroplasties. By this method high local antibiotic concentration and good control of infection was achieved. Toxicity studies, however, suggest that high local antibiotic concentration can impair osteoblast replication. We therefore asked whether impregnating morselized allograft bone with different quantities of tobramycin before impaction would impair implant fixation. We implanted three cylindrical (10 mm × 6 mm) porous-coated titanium implants into the distal femurs of 12 dogs. The implants were surrounded by a circumferential gap of 2.5 mm into which a standardized volume of morselized allograft bone, with or without tobramycin, was impacted. In each animal, the bone graft was impregnated with either 0 mg (control), 50 mg (low dose), or 200 mg (high dose) of tobramycin per 1 mL of bone graft. At the end of the 4 weeks experimental period, the implants with surrounding bone were evaluated by histomorphometric analysis and mechanical push-out test. We found no difference between the treatment groups regarding new bone formation, bone graft resorption, or implant fixation. There was, however, a tendency toward a decrease in implant fixation with higher tobramycin dose. The present study is unable to provide evidence on whether the use of topical tobramycin with allograft is safe or whether it indeed can impair implant fixation. The tendency toward an impaired implant fixation warrants further preclinical studies. Its current clinical use should be weighed against its possible positive effects on preventing infection in complicated revisions.

Comparative biomechanical and microstructural analysis of native versus peracetic acid-ethanol treated cancellous bone graft.

Bone transplantation is frequently used for the treatment of large osseous defects. The availability of autologous bone grafts as the current biological gold standard is limited and there is a risk of donor site morbidity. Allogenic bone grafts are an appealing alternative, but disinfection should be considered to reduce transmission of infection disorders. Peracetic acid-ethanol (PE) treatment has been proven reliable and effective for disinfection of human bone allografts. The purpose of this study was to evaluate the effects of PE treatment on the biomechanical properties and microstructure of cancellous bone grafts (CBG). Forty-eight human CBG cylinders were either treated by PE or frozen at -20 °C and subjected to compression testing and histological and scanning electron microscopy (SEM) analysis. The levels of compressive strength, stiffness (Young's modulus), and fracture energy were significantly decreased upon PE treatment by 54%, 59%, and 36%, respectively. Furthermore, PE-treated CBG demonstrated a 42% increase in ultimate strain. SEM revealed a modified microstructure of CBG with an exposed collagen fiber network after PE treatment. We conclude that the observed reduced compressive strength and reduced stiffness may be beneficial during tissue remodeling thereby explaining the excellent clinical performance of PE-treated CBG.