Legacy Research and Technology Center

Portland, OR, United States

Legacy Research and Technology Center

Portland, OR, United States
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Bahney C.S.,Oregon Health And Science University | Lujan T.J.,Legacy Research and Technology Center | Hsu C.W.,Rice University | Bottlang M.,Legacy Research and Technology Center | And 2 more authors.
European Cells and Materials | Year: 2011

Biological activity can be added to synthetic scaffolds by incorporating functional peptide sequences that provide enzyme-mediated degradation sites, facilitate cellular adhesion or stimulate signaling pathways. Poly(ethylene glycol) diacrylate is a popular synthetic base for tissue engineering scaffolds because it creates a hydrophilic environment that can be chemically manipulated to add this biological functionality. Furthermore, the acrylate groups allow for encapsulation of cells using photopolymerization under physiological conditions. One complication with the addition of these peptides is that aromatic amino acids absorb light at 285nm and compete with the ultraviolet (UV)-sensitive photoinitiators such as IrgacureTM 2959 (I2959), the most commonly used initiator for cytocompatible photoencapsulation of cells into synthetic scaffolds. In this study we define non-toxic conditions for photoencapsulation of human mesenchymal stem cells (hMSC) in PEGDA scaffolds using a visible light photoinitiator system composed of eosin Y, triethanolamine and 1-vinyl-2-pyrrolidinone. This visible light photoinitiator produced hydrogel scaffolds with an increased viability of encapsulated hMSCs and a more tightly crosslinked network in one-third the time of UV polymerization with I2959.


Lujan T.J.,Legacy Research and Technology Center | Wirtz K.M.,Legacy Research and Technology Center | Bahney C.S.,Oregon Health And Science University | Madey S.M.,Legacy Research and Technology Center | And 2 more authors.
Tissue Engineering - Part C: Methods | Year: 2011

Systematic advancements in the field of musculoskeletal tissue engineering require clear communication about the mechanical environments that promote functional tissue growth. To support the rapid discovery of effective mechanostimulation protocols, this study developed and validated a mechanoactive transduction and evaluation bioreactor (MATE). The MATE provides independent and consistent mechanical loading of six specimens with minimal hardware. The six individual chambers accurately applied static and dynamic loads (1 and 10Hz) in unconfined compression from 0.1 to 10N. The material properties of poly(ethylene glycol) diacrylate hydrogels and bovine cartilage were measured by the bioreactor, and these values were within 10% of the values obtained from a standard single-chamber material testing system. The bioreactor was able to detect a 1-day 12% reduction (2kPa) in equilibrium modulus after collagenase was added to six collagenase sensitive poly(ethylene glycol) diacrylate hydrogels (p=0.03). By integrating dynamic stimulation and mechanical evaluation into a single batch-testing research platform, the MATE can efficiently map the biomechanical development of tissue-engineered constructs during long-term culture. © Mary Ann Liebert, Inc. 2011.


Lujan T.J.,Legacy Research and Technology Center | Henderson C.E.,University of Iowa | Madey S.M.,Legacy Research and Technology Center | Fitzpatrick D.C.,Slocum Center for Orthopedics | And 2 more authors.
Journal of Orthopaedic Trauma | Year: 2010

Objectives: Locked plating constructs may be too stiff to reliably promote secondary bone healing. This study used a novel imaging technique to quantify periosteal callus formation of distal femur fractures stabilized with locking plates. It investigated the effects of cortex-to-plate distance, bridging span, and implant material on periosteal callus formation. Design: Retrospective cohort study. Setting: One Level I and one Level II trauma center. Patients: Sixty-four consecutive patients with distal femur fractures (AO types 32A, 33A-C) stabilized with periarticular locking plates. Intervention: Osteosynthesis using indirect reduction and bridge plating with periarticular locking plates. Main Outcome Measurement: Periosteal callus size on lateral and anteroposterior radiographs. Results: Callus size varied from 0 to 650 mm. Deficient callus (20 mm or less) formed in 52%, 47%, and 37% of fractures at 6, 12, and 24 weeks postsurgery, respectively. Callus formation was asymmetric, whereby the medial cortex had on average 64% more callus (P = 0.001) than the anterior or posterior cortices. A longer bridge span correlated minimally with an increased callus size at Week 6 (P = 0.02), but no correlation was found at Weeks 12 and 24 postsurgery. Compared with stainless steel plates, titanium plates had 76%, 71%, and 56% more callus at Week 6 (P = 0.04), Week 12 (P = 0.03), and Week 24 (P = 0.09), respectively. Conclusions: Stabilization of distal femur fractures with periarticular locking plates can cause inconsistent and asymmetric formation of periosteal callus. A larger bridge span only minimally improves callus formation. The more flexible titanium plates enhanced callus formation compared with stainless steel plates. Copyright © 2010 by Lippincott Williams & Wilkins.


Tsai S.,Legacy Research and Technology Center | Fitzpatrick D.C.,Slocum Center for Orthopedics and Sports Medicine | Madey S.M.,Legacy Research and Technology Center | Bottlang M.,Legacy Research and Technology Center
Journal of Orthopaedic Research | Year: 2015

Axial dynamization of an osteosynthesis construct can promote fracture healing. This biomechanical study evaluated a novel dynamic locking plate that derives symmetric axial dynamization by elastic suspension of locking holes within the plate. Standard locked and dynamic plating constructs were tested in a diaphyseal bridge-plating model of the femoral diaphysis to determine the amount and symmetry of interfragmentary motion under axial loading, and to assess construct stiffness under axial loading, torsion, and bending. Subsequently, constructs were loaded until failure to determine construct strength and failure modes. Finally, strength tests were repeated in osteoporotic bone surrogates. One body-weight axial loading of standard locked constructs produced asymmetric interfragmentary motion that was over three times smaller at the near cortex (0.1±0.01) than at the far cortex (0.32±0.02). Compared to standard locked constructs, dynamic plating constructs enhanced motion by 0.32 at the near cortex and by 0.33 at the far cortex and yielded a 77% lower axial stiffness (p<0.001). Dynamic plating constructs were at least as strong as standard locked constructs under all test conditions. In conclusion, dynamic locking plates symmetrically enhance interfragmentary motion, deliver controlled axial dynamization, and are at least comparable in strength to standard locked constructs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1218-1225, 2015.


Doornink J.,Legacy Research and Technology Center | Fitzpatrick D.C.,Slocum Center for Orthopedics and Sports Medicine | Madey S.M.,Legacy Research and Technology Center | Bottlang M.,Legacy Research and Technology Center
Journal of Orthopaedic Trauma | Year: 2011

The high stiffness of periarticular locked plating constructs can suppress callus formation and fracture healing. Replacing standard locking screws with far cortical locking (FCL) screws can decrease construct stiffness and can improve fracture healing in diaphyseal plating constructs. However, FCL function has not been tested in conjunction with periarticular plating constructs in which FCL screws are confined to the diaphyseal segment. This biomechanical study evaluated if diaphyseal fixation of a periarticular locking plate with FCL screws reduces construct stiffness and induces parallel interfragmentary motion without decreasing construct strength. Periarticular locking plates were applied to stabilize distal femur fractures in 22 paired femurs using either a standard locked plating approach (LP group) or FCL for diaphyseal fixation (FCL group) using MotionLoc screws (Zimmer, Warsaw, IN). Each specimen was evaluated under quasiphysiological loading to assess construct stiffness, construct durability under dynamic loading, and residual strength after dynamic loading. FCL constructs had an 81% lower initial stiffness than LP constructs. They induced nearly five times more interfragmentary motion than LP constructs under one body weight loading (P < 0.001). FCL constructs generated parallel interfragmentary motion, whereas LP constructs exhibited 48% less motion at the near cortex than at the far cortex (P = 0.002). Seven LP constructs and eight FCL constructs survived 100,000 loading cycles. The residual strength of surviving constructs was 4.9 ± 1.6 kN (LP group) and 5.3 ± 1.1 kN (FCL group, P = 0.73). In summary, FCL screws reduce stiffness, generate parallel interfragmentary motion, and retain the strength of a periarticular locked plating construct. Therefore, FCL fixation may be advisable for stiffness reduction of periarticular plating constructs to promote fracture healing by callus formation. Copyright © 2011 by Lippincott Williams & Wilkins.


Girard M.J.A.,Devers Eye Institute | Girard M.J.A.,Tulane University | Girard M.J.A.,Imperial College London | Francis Suh J.-K.,Tulane University | And 6 more authors.
Investigative Ophthalmology and Visual Science | Year: 2011

Purpose. To characterize scleral biomechanics in both eyes of eight monkeys in which chronic intraocular pressure (IOP) elevation was induced in one eye. Methods. Each posterior sclera was mounted on a pressurization apparatus, IOP was elevated from 5 to 45 mm Hg while the 3D displacements of the scleral surface were measured by speckle interferometry. Finite element (FE) models of each scleral shell were constructed that incorporated stretch-induced stiffening and multidirectionality of the collagen fibers. FE model predictions were then iteratively matched to experimental displacements to extract unique sets of scleral biomechanical properties. Results. For all eyes, the posterior sclera exhibited inhomogeneous, anisotropic, nonlinear biomechanical behavior. Biomechanical changes caused by chronic IOP elevation were complex and specific to each subject. Specifically: (1) Glaucomatous eyes in which the contralateral normal eyes displayed large modulus or thickness were less prone to biomechanical changes; (2) glaucomatous scleral modulus associated with an IOP of 10 mm Hg decreased (when compared with that of the contralateral normal) after minimal chronic IOP elevation; (3) glaucomatous scleral modulus associated with IOPs of 30 and 45 mm Hg increased (when compared with that of the contralateral normal) after moderate IOP elevation; and (4) FE-based estimates of collagen fiber orientation demonstrated no change in the glaucomatous eyes. Conclusions. Significant stiffening of the sclera follows exposure to moderate IOP elevations in most eyes. Scleral hypercompliance may precede stiffening or be a unique response to minimal chronic IOP elevation in some eyes. These biomechanical changes are likely to be the result of scleral extracellular matrix remodeling. © 2011 The Association for Research in Vision and Ophthalmology, Inc.


Bottlang M.,Legacy Research and Technology Center | Feist F.,Legacy Research and Technology Center
Journal of Orthopaedic Trauma | Year: 2011

The development of far cortical locking (FCL) was motivated by a conundrum: locked plating constructs provide inherently rigid stabilization, yet they should facilitate biologic fixation and secondary bone healing that relies on flexible fixation to stimulate callus formation. Recent studies have confirmed that the high stiffness of standard locked plating constructs can suppress interfragmentary motion to a level that is insufficient to reliably promote secondary fracture healing by callus formation. Furthermore, rigid locking screws cause an uneven stress distribution that may lead to stress fracture at the end screw and stress shielding under the plate. This review summarizes four key features of FCL constructs that have been shown to enhance fixation and healing of fractures: flexible fixation, load distribution, progressive stiffening, and parallel interfragmentary motion. Specifically, flexible fixation provided by FCL reduces the stiffness of a locked plating construct by 80% to 88% to actively promote callus proliferation similar to an external fixator. Load is evenly distributed between FCL screws to mitigate stress risers at the end screw. Progressive stiffening occurs by near cortex support of FCL screws and provides additional support under elevated loading. Finally, parallel interfragmentary motion by the S-shaped flexion of FCL screws promotes symmetric callus formation. In combination, these features of FCL constructs have been shown to induce more callus and to yield significantly stronger and more consistent healing compared with standard locked plating constructs. As such, FCL constructs function as true internal fixators by replicating the biomechanical behavior and biologic healing response of external fixators. Copyright © 2011 by Lippincott Williams & Wilkins.


Henderson C.E.,University of Iowa | Kuhl L.L.,University of Iowa | Fitzpatrick D.C.,Legacy Research and Technology Center | Marsh J.L.,University of Iowa
Journal of Orthopaedic Trauma | Year: 2011

Objectives: Fractures of the distal femur are severe injuries that present many clinical challenges. Nonunion, delayed union, implant failure, and the need for secondary procedures can reflect complications of healing. This article reviews the literature on distal femur fractures treated with locking plates to determine the reported rate of healing difficulties. Data Sources: The PubMed database and the Orthopaedic Trauma Association and American Academy of Orthopedic Surgeons abstract archives were searched for studies including the key words distal femur fracture, supracondylar femur fracture, or locking plate from the year 2000 to the present. Study Selection: Reports were included when distal femur fractures were treated with locking plates and when the number of healed fractures was identified in the study. The reported healing rates and the rate of healing complications were determined from the studies. The time to implant failure was recorded. Those articles that included periprosthetic fractures were separated from those only including acute distal femur fractures. Data Synthesis: Fifteen full-length publications and three abstracts were included. The rate of complications related to healing ranged from 0% to 32% in these studies. Implant failures occurred late with 75% of the failures occurring after 3 months and 50% occurring after 6 months. Conclusions: Complications of healing including nonunion, delayed union, and implant failure are not infrequent and represent ongoing problems with distal femur fracture treatment. Further clinical research combined with innovation in surgical techniques and implant design will be necessary to improve the results of the last decade. Copyright © 2011 by Lippincott Williams & Wilkins.


Lujan T.J.,Legacy Research and Technology Center | Madey S.M.,Legacy Research and Technology Center | Fitzpatrick D.C.,Slocum Center for Orthopedics and Sports Medicine | Byrd G.D.,Legacy Research and Technology Center | And 2 more authors.
Journal of Biomechanics | Year: 2010

Callus formation occurs in the presence of secondary bone healing and has relevance to the fracture's mechanical environment. An objective image processing algorithm was developed to standardize the quantitative measurement of periosteal callus area in plain radiographs of long bone fractures. Algorithm accuracy and sensitivity were evaluated using surrogate models. For algorithm validation, callus formation on clinical radiographs was measured manually by orthopaedic surgeons and compared to non-clinicians using the algorithm. The algorithm measured the projected area of surrogate calluses with less than 5% error. However, error will increase when analyzing very small areas of callus and when using radiographs with low image resolution (i.e. 100 pixels per inch). The callus size extracted by the algorithm correlated well to the callus size outlined by the surgeons (R 2=0.94, p<0.001). Furthermore, compared to clinician results, the algorithm yielded results with five times less inter-observer variance. This computational technique provides a reliable and efficient method to quantify secondary bone healing response. © 2009 Elsevier Ltd.


Henderson C.E.,University of Iowa | Lujan T.J.,Legacy Research and Technology Center | Kuhl L.L.,University of Iowa | Bottlang M.,Legacy Research and Technology Center | And 2 more authors.
Clinical Orthopaedics and Related Research | Year: 2011

Background: Several mechanical studies suggest locking plate constructs may inhibit callus necessary for healing of distal femur fractures. However, the rate of nonunion and factors associated with nonunion are not well established. Questions/purposes: We (1) determined the healing rate of distal femur fractures treated with locking plates, (2) assessed the effect of patient injury and treatment variables on fracture healing, and (3) compared callus formation in fractures that healed with those that did not heal. Patients and Methods: We retrospectively reviewed 82 patients treated with 86 distal femur fractures using lateral locking plates. We reviewed all charts and radiographs to determine patient and treatment variables and then determined the effects of these variables on healing. We quantitatively measured callus at 6, 12, and 24 weeks. The minimum time for telephone interviews and SF-36v2™ scores was 1 year (mean, 4.2 years; range, 1-7.2 years). Results: Fourteen fractures (20%) failed to unite. Demographics and comorbidities were similar in patients who achieved healing compared with those who had nonunions. There were more empty holes in the plate adjacent to fractures that healed; comminuted fractures failed to heal more frequently than less comminuted fractures. Less callus formed in fractures with nonunions and in patients treated with stainless steel plates compared with titanium plates. Complications occurred in 28 of 70 fractures (40%), 19 of which had additional surgery. Conclusions: We found a high rate of nonunion in distal femur fractures treated with locking plates. Nonunion presented late without hardware failure and with limited callus formation suggesting callus inhibition rather than hardware failure is the primary problem. Mechanical factors may play a role in the high rate of nonunion. Level of Evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. © 2011 The Association of Bone and Joint Surgeons®.

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