The SGLT2i Dapagliflozin Reduces RV Mass Independent of Changes in RV Pressure Induced by Pulmonary Artery Banding.

BACKGROUND: Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class is efficacious in the treatment and prevention of right heart failure has not been explored. HYPOTHESIS: We hypothesized that SGLT2 inhibition would reduce the structural, functional, and molecular responses to pressure overload of the right ventricle. METHODS: Thirteen-week-old Fischer F344 rats underwent pulmonary artery banding (PAB) or sham surgery prior to being randomized to receive either the SGLT2 inhibitor: dapagliflozin (0.5 mg/kg/day) or vehicle by oral gavage. After 6 weeks of treatment, animals underwent transthoracic echocardiography and invasive hemodynamic studies. Animals were then terminated, and their hearts harvested for structural and molecular analyses. RESULTS: PAB induced features consistent with a compensatory response to increased right ventricular (RV) afterload with elevated mass, end systolic pressure, collagen content, and alteration in calcium handling protein expression (all p < 0.05 when compared to sham + vehicle). Dapagliflozin reduced RV mass, including both wet and dry weight as well as normalizing the protein expression of SERCA 2A, phospho-AMPK and LC3I/II ratio expression (all p < 0.05). SIGNIFICANCE: Dapagliflozin reduces the structural, functional, and molecular manifestations of right ventricular pressure overload. Whether amelioration of these early changes in the RV may ultimately lead to a reduction in RV failure remains to be determined.

Single and reciprocal friction testing of micropatterned surfaces for orthopedic device design.

The use of micropatterning to create uniform surface morphologies has been cited as yielding improvements in the coefficient of friction during high velocity sliding contact. Studies have not been preformed to determine if these micropatterns could also be useful in biomedical applications, such as total joint replacement surfaces, where the lower sliding velocities are used. In addition, other factors such as lubricant viscosities and materials used are more tightly constrained. In this study, the effect of pattern geometry, feature size and lubricant on contact friction and surface damage was investigated using 316L steel in sliding contact with a stainless steel and polyethylene pins. Using a novel proprietary forming process that creates millions of microstructures in parallel, a variety of micropatterned surfaces were fabricated to study the influence of shape (oval, circular, square), geometry (depressions, pillars) and feature size (10, 50 and 100 mm) on both contact friction and surface damage. All samples were 316L stainless steel and the static and dynamic coefficients of friction when in contact with either a stainless steel or polyethylene counterface were measured in dry and lubricated conditions. All samples were characterized for surface uniformity and pattern aspect ratio using white light interferometry and optical microscope image analysis, and the coefficients of friction were measured for each surface/lubricant/pin system using a CETR scratch testing system. Results showed that round depressions with diameters of 10 µm had a significantly lower steady state coefficient of friction than the non-patterned substrates or substrates with greater diameter depression patterns. In addition, our results showed that the single-pass coefficient of friction measurements were not good predictors of the steady state coefficient of friction values measured.

Single flexion-axis selection influences femoral component alignment and kinematics during knee simulation.

The objective of this paper is to investigate the effect of the implant geometry and alignment on its surface displacement, and to show that the proposed method of alignment can be used to improve the consistency of total knee replacement alignment for knee simulation. Poor femoral flexion-axis selection in the alignment process can possibly alter the intended design's functionality and introduce significant anterior/posterior (A/P), and proximal/distal (P/D) displacements. In the study, four multi-axis femoral components from each of two different manufacturers, NKII and 3DKnee, were used. A custom-built femoral alignment and surface measurement instrument was used to adjust and locate the single femoral axis position for each implant, which would optimally minimize their P/D displacements and A/P translations. The aligned NKII implants yielded a mean implant maximum P/D and A/P contact point shifts of 0.577 +/- 0.078 mm (+/- std. dev.) and of 2.325 +/- 0.243 mm between 0 and 60 degrees of flexion, which was significantly different from the aligned 3DKnee, 0.415 +/- 0.157 mm and 0.800 +/- 0.1512mm (p<0.0001, p<0.0001). Future work is needed to quantify the effect of femoral flexion axis selection on resulting long-term wear, damage areas, and soft tissue loading during simulation.

Reduction of total knee replacement wear with vitamin E blended highly cross-linked ultra-high molecular weight polyethylene.

Ultra-high molecular weight polyethylene (UHMWPE) is a common bearing component in total knee replacement (TKR) implants, and its susceptibility to wear continues to be the long-term limiting factor in the life of these implants. This study hypothesized that in TKR systems, a highly cross-linked (HXL) UHMWPE blended with vitamin E will result in reduced wear as compared to a direct compression-moulded (DCM) UHMWPE. A wear simulation study was conducted using an asymmetric lateral pivoting '3D Knee' design to compare the two inserts. The highly cross-linked UHMWPE was aged prior to the testing and force-controlled wear testing was carried out for 5 million cycles using a load-controlled ISO-14243 standard at a frequency of 1 Hz on both groups. Gravimetric measurements of DCM UHMWPE (4.4 +/- 3.0 mg/million cycles) and HXL UHMWPE with vitamin E (1.9 +/- 1.9 mg/million cycles) showed significant statistical differences (p < 0.01) between the wear rates. Wear modes and surface roughness for both groups revealed no significant dissimilarities.

Bi-unicondylar knee prosthesis functional assessment utilizing force-control wear testing.

Recent in vivo studies have identified variations in knee prosthesis function depending on prosthesis geometry, kinematic conditions, and the absence/presence of soft-tissue constraints after knee replacement surgery. In particular, unicondylar knee replacements (UKR) are highly sensitive to such variations. However, rigorous descriptions of UKR function through experimental simulation studies, performed under physiological force-controlled conditions, are lacking. The current study evaluated the long-term functional performance of a widely used fixed-bearing unicompartmental knee replacement, mounted in a bi-unicondylar configuration (Bi-UKR), utilizing a force-controlled knee simulator during a simulated (ISO 14243) walking cycle. The wear behaviour, the femoral-tibial kinematics, and the incurred damage scars were analysed. The wear rates for the medial and the lateral compartments were 10.27 +/- 1.83 mg/million cycles and 4.49 +/- 0.53 mg/million cycles, respectively. Although constant-input force-controlled loading conditions were maintained throughout the simulation, femoral-tibial contact point kinematics decreased by 65 to 68 per cent for average anterior/posterior travel and by 58 to 74 per cent for average medial/lateral travel with increasing cycling time up to 2 million cycles. There were no significant differences in damage area or damage extent between the medial and the lateral compartments. Focal damage scars representing the working region of the femoral component on the articular surface extended over a range of 16-21 mm in the anterior-posterior direction. Kinematics on the shear plane showed slight variations with increasing cycling time, and the platform exhibited medial pivoting over the entire test. These measures provide valuable experimental insight into the effect of the prosthesis design on wear, kinematics, and working area. These functional assessments of Bi-UKR under force-controlled knee joint wear simulation show that accumulated changes in the UKR articular conformity manifested as altered kinematics both for anterior/posterior translations and internal/external rotations.

S100B interaction with the receptor for advanced glycation end products (RAGE): a novel receptor-mediated mechanism for myocyte apoptosis postinfarction.

RATIONALE: Post-myocardial infarction ventricular remodeling is associated with the expression of a variety of factors including S100B that can potentially modulate myocyte apoptosis. OBJECTIVE: This study was undertaken to investigate the expression and function of S100B and its receptor, the receptor for advanced glycation end products (RAGE) in both postinfarction myocardium and in a rat neonatal myocyte culture model. METHODS AND RESULTS: In a rat model of myocardial infarction following coronary artery ligation, we demonstrate in periinfarct myocytes, upregulation of RAGE, induction of S100B, and release into plasma with consequent myocyte apoptosis. Using a coimmunoprecipitation strategy, we demonstrate a direct interaction between S100B and RAGE. In rat neonatal cardiac myocyte cultures, S100B at concentrations > or = 50 nmol/L induced myocyte apoptosis, as evidenced by increased terminal DNA fragmentation, TUNEL, cytochrome c release from mitochondria to cytoplasm, phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p53, increased expression and activity of proapoptotic caspase-3, and decreased expression of antiapoptotic Bcl-2. Transfection of a full-length cDNA of RAGE or a dominant-negative mutant of RAGE resulted in increased or attenuated S100B-induced myocyte apoptosis, respectively. Inhibition of ERK1/2 by U0126/PD-98059 or overexpression of a dominant negative p53 comparably inhibited S100B-induced myocyte apoptosis. CONCLUSIONS: These results suggest that interaction of RAGE and its ligand S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53 signaling. This receptor-mediated mechanism is uniquely amenable to therapeutic intervention.

Mixed parentage in Neolamprologus pulcher groups.

Genetic data collected on co-operatively breeding Neolamprologus pulcher groups from Lake Tanganyika revealed mixed parentage in 80% of the groups examined. A case (1/11) of shared maternity was detected where a subordinate female bred alongside the dominant female in a social group. Extra-pair paternity was assigned to other dominant males who held their own social groups, but subordinate males were not found to father young in any group (0/9).

Liver size reveals social status in the African cichlid Neolamprologus pulcher.

Wild groups (n = 167) of the cooperatively breeding Lake Tanganyika cichlid, Neolamprologus pulcher, were used to investigate how social status and sex influence liver investment. In contrast to expectations, males and females (controlling for body size) had similar liver investment and subordinates (both sexes) had relatively larger livers compared with dominants. Three hypotheses were considered for why social status results in liver size disparity: liver mass might reflect status-dependent differences in (1) energy expenditure, (2) energy storage and (3) energy acquisition. First, dominants performed more energetically costly behaviours (e.g. social policing and care) compared with subordinates, supporting the notion that energy expenditure drives liver investment. Moreover, dominants in large groups (with many subordinates to monitor) and those holding multiple territories (with large areas to patrol), tended to have smaller livers. Second, subordinates did not appear to use the liver as a strategic energy storage organ. In laboratory and field experiments, subordinates ascending in rank had similar or larger livers during periods of rapid growth compared with non-ascending controls. Third, although subordinates fed more frequently than dominants, a negative relationship was found between feeding rates and liver size. Hence, these results contrast with previous liver studies and suggest that liver investment patterns were linked to status-driven differences in energy expenditure but not to energy intake or storage in N. pulcher.

Female-mediated causes and consequences of status change in a social fish.

In highly social species, dominant individuals often monopolize reproduction, resulting in reproductive investment that is status dependent. Yet, for subordinates, who typically invest less in reproduction, social status can change and opportunities to ascend to dominant social positions are presented suddenly, requiring abrupt changes in behaviour and physiology. In this study, we examined male reproductive anatomy, physiology and behaviour following experimental manipulations of social status in the cooperatively breeding cichlid fish, Neolamprologus pulcher. This unusual fish species lives in permanent social groups composed of a dominant breeding pair and 1-20 subordinates that form a linear social dominance hierarchy. By removing male breeders, we created 18 breeding vacancies and thus provided an opportunity for subordinate males to ascend in status. Dominant females play an important role in regulating status change, as males successfully ascended to breeder status only when they were slightly larger than the female breeder in their social group. Ascending males rapidly assumed behavioural dominance, demonstrated elevated gonadal investment and androgen concentrations compared with males remaining socially subordinate. Interestingly, to increase gonadal investment ascending males appeared to temporarily restrain somatic growth. These results highlight the complex interactions between social status, reproductive physiology and group dynamics, and underscore a convergent pattern of reproductive investment among highly social, cooperative species.

Evidence for size and sex-specific dispersal in a cooperatively breeding cichlid fish.

African Great Lake cichlid populations are divided into thousands of genetic subpopulations. The low gene flow between these subpopulations is thought to result from high degrees of natal philopatry, heavy predation pressure, and a patchy distribution of preferred habitats. While predation pressure and habitat distribution are fairly straightforward to assess, data on dispersal distances and rates are scarce. In fishes, direct observations of dispersal events are unlikely, but dispersal can be studied using molecular markers. Using seven microsatellite loci, we examined dispersal in the cooperatively breeding cichlid fish, Neolamprologus pulcher. As this species is found in well-defined groups clustered into subpopulations, we could assess dispersal on a narrow (within subpopulation) and broad (between subpopulation) scale. While fish were generally more related to others in their own subpopulation than they were to fish from other subpopulations, large males diverged from this pattern. Large males were more related to other large males from different subpopulations than they were to large males from their own subpopulation, suggesting more frequent dispersal by large males. Across subpopulations, relatedness between large males was higher than the relatedness among large females; this pattern was not detected in small males and small females. Within a subpopulation, individuals appeared to be preferentially moving away from relatives, and movement was unrestricted by the physical distance between groups. Our results highlight the importance of examining multiple spatial scales when studying individual dispersal biases.

Reproductive-tactic-specific variation in sperm swimming speeds in a shell-brooding cichlid.

Theory predicts that males experiencing elevated levels of sperm competition will invest more in gonads and produce faster-swimming sperm. Although there is ample evidence in support of the first prediction, few studies have examined sperm swimming speed in relation to sperm competition. In this study, we tested these predictions from sperm competition theory by examining sperm characteristics in Telmatochromis vittatus, a small shell-brooding cichlid fish endemic to Lake Tanganyika. Males exhibit four different reproductive tactics: pirate, territorial, satellite, and sneaker. Pirate males temporarily displace all other competing males from a shell nest, whereas sneaker males always release sperm in the presence of territorial and satellite males. Due to the fact that sneakers spawn in the presence of another male, sneakers face the highest levels of sperm competition and pirates the lowest, whereas satellites and territorials experience intermediate levels. In accordance with predictions, sperm from sneakers swam faster than sperm from males adopting the other reproductive tactics, whereas sperm from pirates was slowest. Interestingly, we were unable to detect any variation in sperm tail length among these reproductive tactics. Thus, sperm competition appears to have influenced sperm energetics in this species without having any influence on sperm size.

Increased total knee arthroplasty ultra-high molecular weight polyethylene wear using a clinically relevant hyaluronic acid simulator lubricant.

In this study, osteoarthritic and periprosthetic synovial fluid samples were rheologically and biochemically compared to develop a hyaluronic acid (HA) supplemented bovine serum (BS) lubricant that mimicked the properties of human joint synovial fluid. The effect of this BS + HA lubricant (50 per cent bovine calf serum + 1.5 g/l HA) on the wear rate of ultra-high molecular weight polyethylene (UHMWPE) during a total knee replacement wear test was then investigated. In conjunction with biochemical similarities, the rheological analysis showed that the BS + HA lubricant viscosity was not statistically different to aspirated total knee arthroplasty (TKA) revision joint fluid viscosity over a range of physiologic shear rates. Gravimetric results at 5 million wear testing cycles showed that the BS + HA lubricant produced an average of 6.88 times more UHMWPE wear than 50 per cent bovine serum lubricant alone. The BS + HA lubricated CoCr femoral component surfaces revealed pitting and surface roughening that was not observed using standard bovine serum only lubricants, but that was similar to the metallic surface corrosion observed on in vivo CoCr femoral component retrievals. These findings support the hypothesis that the addition of HA to simulator lubricant is capable of producing CoCr femoral component surface damage similar to that observed in vivo.

Effect of lubricant composition on the fatigue properties of ultra-high molecular weight polyethylene for total knee replacement.

Ultrahigh molecular weight polyethylene (UHMWPE) fatigue is a critical factor affecting the longevity of total knee replacement (TKR) bearings. With the increased need for laboratory studies to mimic near in vivo conditions for accurate characterization of material performance, the present study investigated the role of hyaluronic acid (HA) in testing lubricant on the crack growth response of UHMWPE. It was hypothesized that the change in lubricant viscosity as a result of HA would affect the fatigue life of the polymer. A fracture mechanics approach as per ASTM E 647 was adopted for this study. Surface micrograph and surface chemistry analyses were employed to study the micromechanisms of fatigue failure and protein adsorption of the specimen surfaces. Rheological analysis indicated that the addition of HA to diluted bovine serum increased testing lubricant viscosity. HA concentrations of 2.22, 0.55, and 1.5 g/l closely matched the viscosity ranges reported for osteoarthritis, rheumatoid arthritic diseased joint fluid, and periprosthetic fluids respectively. Results showed that the addition of HA to standard diluted bovine serum lubricants, in concentrations similar to that of periprosthetic fluid, delayed crack initiation and crack growth during fatigue testing.

Effect of stair descent loading on ultra-high molecular weight polyethylene wear in a force-controlled knee simulator.

A loading protocol approximating forces, torques and motions at the knee during stair descent was developed from previously published data for input into a force-controlled knee simulator. A set of total knee replacements (TKRs) was subjected to standard walking cycles and stair descent cycles at a ratio of 70: 1 for 5 million cycles. Another set of implants with similar articular geometry and the same ultra-high molecular weight polyethylene (UHMWPE) resin (GUR 415), sterilization and packaging was tested with standard walking cycles only. Implant kinematics, gravimetric wear and surface roughness of the UHMWPE inserts were analysed for both sets of implants. Contact stresses were calculated for both loading protocols using a Hertzian line contact model. Significantly greater weight loss (p < 0.05) and more severe surface damage of UHMWPE inserts resulted with the walking + stair descent loading protocol compared to walking cycles only. Anterior-posterior (AP) tibiofemoral contact point displacements were lower during stair descent than walking, but not significantly different (p = 0.05). Contact stresses were significantly higher during stair descent than walking, owing to higher axial loads and the smaller radius of curvature of the femoral components at higher flexion angles. High contact stresses on UHMWPE components are likely to accelerate the fatigue of the material, resulting in more severe wear, similar to what is observed in retrieved implants. Thus the inclusion of loading protocols for activities of daily living in addition to walking is warranted for more realistic in vitro testing of TKRs.

Effects of in vitro wear of machined and molded UHMWPE tibial inserts on TKR kinematics.

The effect of manufacturing process on the wear and mechanical performance of a total knee replacement (TKR) design was investigated with the use of a force-controlled knee joint simulator. Ultra-high molecular weight polyethylene (UHMWPE) tibial inserts processed by direct compression molding from 1900H resin were compared to UHMWPE tibial inserts machined from a compression-molded sheet of GUR 1050. Both sets of components had the same posterior-cruciate-retaining geometry, and were identically aligned with cobalt-chromium-molybdenum alloy femoral components. Wear tests were conducted at a frequency of 1 Hz for 4 million cycles with the use of a standard walking cycle pattern. Implant kinematics, including anterior-posterior (AP) displacement and internal-external (IE) rotation in response to applied loads were monitored. Gravimetric wear, surface roughness, and surface morphology were used to characterize the wear process of the UHMWPE inserts. Results showed that the molded UHMWPE inserts exhibited less gravimetric wear over time than the machined inserts of the same design. Both the machined and molded components exhibited scratching, pitting, and burnishing over their wear areas. The AP displacement distance per cycle of the molded tibial inserts decreased over the course of testing, resulting in a shorter total testing displacement for this group compared to machined tibial inserts. Although AP displacement distance per cycle for machined tibial inserts did not change significantly over the course of testing, their position relative to the femoral components shifted posteriorly over time, resulting in an elongated wear track.

Biodistribution of NX211, liposomal lurtotecan, in tumor-bearing mice.

Prolonging tumor exposure to topoisomerase I inhibitors has been correlated to enhance the efficacy of those agents. Lurtotecan, a water-soluble camptothecin analog, was formulated as a liposomal drug, NX211, to enhance the delivery of drug to tumors. Tumor-bearing mice were treated with either [14C]NX211 containing [14C]lurtotecan, [3H]NX211 containing [3H]phosphatidylcholine or [14C]lurtotecan, euthanized at selected times post-injection, and tissues, plasma, urine and feces were collected. These studies demonstrated that KB tumors of [14C]NX211-treated mice had approximately 70-fold greater concentrations of [14C]lurtotecan at 24 h, respectively, compared to concentrations of [14C]lurtotecan of the KB tumors of [14C]lurtotecan-treated mice. The area under curve (AUC) from 0 to 48 h of [14C]lurtotecan for the KB tumors of [14C]NX211-treated animals was over 17-fold greater than the AUC of [14C]lurtotecan for the tumors of [14C]lurtotecan-treated animals. Treatment with [3H]NX211 demonstrated that the lipid component continually accumulated over 24 h in the tissues. HPLC analysis of extracted material from tumors of [14C]NX211-treated mice showed that more than 95% of the radioactive material was intact [14C]lurtotecan. These findings are one of the keys justifying the development of a liposomal formulation of lurtotecan, which has the intent to increase tumor exposure and increase antitumor efficacy.

The use of a force-controlled dynamic knee simulator to quantify the mechanical performance of total knee replacement designs during functional activity.

The experimental evaluation of any total knee replacement (TKR) design should include the pre-implantation quantification of its mechanical performance during tests that simulate the common activities of daily living. To date, few dynamic TKR simulation studies have been conducted before implantation. Once in vivo, the accurate and reproducible assessment of TKR design mechanics is exceedingly difficult, with the secondary variables of the patient and the surgical technique hindering research. The current study utilizes a 6-degree-of-freedom force-controlled knee simulator to quantify the effect of TKR design alone on TKR mechanics during a simulated walking cycle. Results show that all eight TKR designs tested elicited statistically different measures of tibial/femoral kinematics, simulated soft tissue loading, and implant geometric restraint loading during an identical simulated gait cycle, and that these differences were a direct result of TKR design alone. Maximum ranges of tibial kinematics over the eight designs tested were from 0.8mm anterior to 6.4mm posterior tibial displacement, and 14.1 degrees internal to 6.0 degrees external tibial rotation during the walking cycle. Soft tissue and implant reaction forces ranged from 106 and 222N anteriorly to 19 and 127N posteriorly, and from 1.6 and 1.8Nm internally to 3.5 and 5.9Nm externally, respectively. These measures provide valuable experimental insight into the effect of TKR design alone on simulated in vivo TKR kinematics, bone interface loading and soft tissue loading. Future studies utilizing this methodology should investigate the effect of experimentally controlled variations in surgical and patient factors on TKR performance during simulated dynamic activity.

Antitumor efficacy, pharmacokinetics, and biodistribution of NX 211: a low-clearance liposomal formulation of lurtotecan.

Lurtotecan is a clinically active water-soluble camptothecin analogue that has been formulated into a low-clearance unilamellar liposome, NX 211. Comparative studies between free drug and NX 211 have been performed assessing pharmacokinetics in nude mice, tissue distribution in tumor-bearing mice, and antitumor efficacy in xenografts. Compared with lurtotecan, NX 211 demonstrated a significant increase in plasma residence time and a subsequent 1500-fold increase in the plasma area under the drug concentration curve. The volume of distribution was also greatly restricted, suggesting altered tissue distribution. Evaluation of tissues 24 h after administration of either [14C]NX 211 or [14C]lurtotecan to ES-2 tumor-bearing mice demonstrated a 40-fold increase in radiolabeled compound in the tumors of NX 211-treated mice compared with mice treated with lurtotecan. In single-dose efficacy studies, NX 211 produced a consistent 3-fold or greater increase in therapeutic index compared with lurtotecan in both the KB and ES-2 xenograft models. When compared at equitoxic levels in repeat-dose efficacy studies, NX 211 generated durable cures lasting >60 days and a 2-8-fold increase in log10 cell kill, compared with lurtotecan and topotecan, respectively. Together, these data demonstrate that NX 211 has significant therapeutic advantage over lurtotecan and that the improved antitumor activity is consistent with increased exposure and enhanced drug delivery to tumor sites.

Size and position of a single condyle allograft influence knee kinematics.

An optimal match for size and shape between the donor femur and the host knee is considered a critical factor influencing the outcome of a knee allograft implantation. An in vitro allograft model was developed to determine the influence of the size and position of a lateral distal femoral condylar allograft on knee kinematics. Functional knee motion was simulated in a cadaver host knee in the intact state after removing and reimplanting the native lateral condyle of the distal femur and after serially replacing the native condyle with eight donor allografts. Each allograft was first tested in an optimal position and subsequently shifted 3 mm proximal and 3 mm distal to the joint line to quantify changes in joint kinematics due to the position of the allograft. The intact knee and the knee with the ideally implanted native allograft followed similar kinematic trends. Decreasing the width of the allograft increased the valgus knee orientation at full flexion, translated the tibia posteriorly at full extension, and externally rotated the tibia throughout knee flexion. The proximal shift in allograft position increased the valgus orientation at full extension, translated the tibia posteriorly at mid-flexion, and externally rotated the tibia throughout flexion. The distal shift in position had the opposite effect on the kinematics of the proximal shift. These results indicate that improving techniques for preoperative size-matching and intraoperative allograft placement may help to reduce biomechanical complications following implantation of the allograft.