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Decorin-containing collagen hydrogels as dimensionally stable scaffolds to study the effects of compressive mechanical loading on angiogenesis.

9 min 55 sec ago
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Decorin-containing collagen hydrogels as dimensionally stable scaffolds to study the effects of compressive mechanical loading on angiogenesis.

MRS Commun. 2017 Sep;7(3):466-471

Authors: Ruehle MA, Krishnan L, LaBelle SA, Willett NJ, Weiss JA, Guldberg RE

Abstract
Angiogenesis is a critical component during wound healing, and the process is sensitive to mechanical stimuli. Current in vitro culture environments used to investigate three-dimensional microvascular growth often lack dimensional stability and the ability to withstand compression. We investigated the ability of decorin, a proteoglycan known to modulate collagen fibrillogenesis, incorporated into a collagen hydrogel to increase construct dimensional stability while maintaining vascular growth. Decorin did not affect microvascular growth parameters, while increasing the compressive modulus of collagen gels and significantly reducing the contraction of 3% collagen gels after 16 days in culture.

PMID: 29450108 [PubMed]

Effect of porous orthopaedic implant material and structure on load sharing with simulated bone ingrowth: A finite element analysis comparing titanium and PEEK.

Sat, 2018-02-17 06:15

Effect of porous orthopaedic implant material and structure on load sharing with simulated bone ingrowth: A finite element analysis comparing titanium and PEEK.

J Mech Behav Biomed Mater. 2018 Jan 30;80:68-76

Authors: Carpenter RD, Klosterhoff BS, Torstrick FB, Foley KT, Burkus JK, Lee CSD, Gall K, Guldberg RE, Safranski DL

Abstract
Osseointegration of load-bearing orthopaedic implants, including interbody fusion devices, is critical to long-term biomechanical functionality. Mechanical loads are a key regulator of bone tissue remodeling and maintenance, and stress-shielding due to metal orthopaedic implants being much stiffer than bone has been implicated in clinical observations of long-term bone loss in tissue adjacent to implants. Porous features that accommodate bone ingrowth have improved implant fixation in the short term, but long-term retrieval studies have sometimes demonstrated limited, superficial ingrowth into the pore layer of metal implants and aseptic loosening remains a problem for a subset of patients. Polyether-ether-ketone (PEEK) is a widely used orthopaedic material with an elastic modulus more similar to bone than metals, and a manufacturing process to form porous PEEK was recently developed to allow bone ingrowth while preserving strength for load-bearing applications. To investigate the biomechanical implications of porous PEEK compared to porous metals, we analyzed finite element (FE) models of the pore structure-bone interface using two clinically available implants with high (> 60%) porosity, one being constructed from PEEK and the other from electron beam 3D-printed titanium (Ti). The objective of this study was to investigate how porous PEEK and porous Ti mechanical properties affect load sharing with bone within the porous architectures over time. Porous PEEK substantially increased the load share transferred to ingrown bone compared to porous Ti under compression (i.e. at 4 weeks: PEEK = 66%; Ti = 13%), tension (PEEK = 71%; Ti = 12%), and shear (PEEK = 68%; Ti = 9%) at all time points of simulated bone ingrowth. Applying PEEK mechanical properties to the Ti implant geometry and vice versa demonstrated that the observed increases in load sharing with PEEK were primarily due to differences in intrinsic elastic modulus and not pore architecture (i.e. 4 weeks, compression: PEEK material/Ti geometry = 53%; Ti material/PEEK geometry = 12%). Additionally, local tissue energy effective strains on bone tissue adjacent to the implant under spinal load magnitudes were over two-fold higher with porous PEEK than porous Ti (i.e. 4 weeks, compression: PEEK = 784 ± 351 microstrain; Ti = 180 ± 300 microstrain; and 12 weeks, compression: PEEK = 298 ± 88 microstrain; Ti = 121 ± 49 microstrain). The higher local strains on bone tissue in the PEEK pore structure were below previously established thresholds for bone damage but in the range necessary for physiological bone maintenance and adaptation. Placing these strain magnitudes in the context of literature on bone adaptation to mechanical loads, this study suggests that porous PEEK structures may provide a more favorable mechanical environment for bone formation and maintenance under spinal load magnitudes than currently available porous 3D-printed Ti, regardless of the level of bone ingrowth.

PMID: 29414477 [PubMed - as supplied by publisher]

Design and Structure-Function Characterization of 3D Printed Synthetic Porous Biomaterials for Tissue Engineering.

Thu, 2018-02-08 05:30
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Design and Structure-Function Characterization of 3D Printed Synthetic Porous Biomaterials for Tissue Engineering.

Adv Healthc Mater. 2017 Dec 27;:

Authors: Kelly CN, Miller AT, Hollister SJ, Guldberg RE, Gall K

Abstract
3D printing is now adopted for use in a variety of industries and functions. In biomedical engineering, 3D printing has prevailed over more traditional manufacturing methods in tissue engineering due to its high degree of control over both macro- and microarchitecture of porous tissue scaffolds. However, with the improved flexibility in design come new challenges in characterizing the structure-function relationships between various architectures and both mechanical and biological properties in an assortment of clinical applications. Presently, the field of tissue engineering lacks a comprehensive body of literature that is capable of drawing meaningful relationships between the designed structure and resulting function of 3D printed porous biomaterial scaffolds. This work first discusses the role of design on 3D printed porous scaffold function and then reviews characterization of these structure-function relationships for 3D printed synthetic metallic, polymeric, and ceramic biomaterials.

PMID: 29280325 [PubMed - as supplied by publisher]

Getting PEEK to Stick to Bone: The Development of Porous PEEK for Interbody Fusion Devices.

Thu, 2017-12-28 05:30
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Getting PEEK to Stick to Bone: The Development of Porous PEEK for Interbody Fusion Devices.

Tech Orthop. 2017 Sep;32(3):158-166

Authors: Torstrick FB, Safranski DL, Burkus JK, Chappuis JL, Lee CSD, Guldberg RE, Gall K, Smith KE

Abstract
Interbody fusion cages are routinely implanted during spinal fusion procedures to facilitate arthrodesis of a degenerated or unstable vertebral segment. Current cages are most commonly made from polyether-ether-ketone (PEEK) due to its favorable mechanical properties and imaging characteristics. However, the smooth surface of current PEEK cages may limit implant osseointegration and may inhibit successful fusion. We present the development and clinical application of the first commercially available porous PEEK fusion cage (COHERE®, Vertera, Inc., Atlanta, GA) that aims to enhance PEEK osseointegration and spinal fusion outcomes. The porous PEEK structure is extruded directly from the underlying solid and mimics the structural and mechanical properties of trabecular bone to support bone ingrowth and implant fixation. Biomechanical testing of the COHERE® device has demonstrated greater expulsion resistance versus smooth PEEK cages with ridges and greater adhesion strength of porous PEEK versus plasma-sprayed titanium coated PEEK surfaces. In vitro experiments have shown favorable cell attachment to porous PEEK and greater proliferation and mineralization of cell cultures grown on porous PEEK versus smooth PEEK and smooth titanium surfaces, suggesting that the porous structure enhances bone formation at the cellular level. At the implant level, preclinical animal studies have found comparable bone ingrowth into porous PEEK as those previously reported for porous titanium, leading to twice the fixation strength of smooth PEEK implants. Finally, two clinical case studies are presented demonstrating the effectiveness of the COHERE® device in cervical spinal fusion.

PMID: 29225416 [PubMed - in process]

Contrast Enhanced μCT Imaging of Early Articular Changes in a Pre-Clinical Model of Osteoarthritis.

Tue, 2017-12-12 05:45

Contrast Enhanced μCT Imaging of Early Articular Changes in a Pre-Clinical Model of Osteoarthritis.

Osteoarthritis Cartilage. 2017 Oct 28;:

Authors: Reece DS, Thote T, Lin ASP, Willett NJ, Guldberg RE

Abstract
OBJECTIVE: The objective of this study was to characterize early osteoarthritis (OA) development in cartilage and bone tissues in the rat medial meniscus transection (MMT) model using non-destructive equilibrium partitioning of an ionic contrast agent micro-computed tomography (EPIC-μCT) imaging. Cartilage fibrillation, one of the first physiological developments in OA, was quantified in the rat tibial plateau as three-dimensional (3D) cartilage surface roughness using a custom surface-rendering algorithm.
METHODS: Male Lewis rats underwent MMT or sham-operation in the left leg. At one- and three-weeks post-surgery, the animals (n=7-8 per group) were euthanized and the left legs were scanned using EPIC-μCT imaging to quantify cartilage and bone parameters. In addition, a custom algorithm was developed to measure the roughness of 3D surfaces. This algorithm was validated and used to quantify cartilage surface roughness changes as a function of time post-surgery.
RESULTS: MMT surgery resulted in significantly greater cartilage damage and subchondral bone sclerosis with the damage increasing in both severity and area from one-to three-weeks post-surgery. Analysis of rendered 3D surfaces could accurately distinguish early changes in joints developing OA, detecting significant increases of 45% and 124% in surface roughness at one- and three-weeks post-surgery respectively.
CONCLUSION: Disease progression in the MMT model progresses sequentially through changes in the cartilage articular surface, extracellular matrix composition, and then osteophyte mineralization and subchondral bone sclerosis. Cartilage surface roughness is a quantitative, early indicator of degenerative joint disease in small animal OA models and can potentially be used to evaluate therapeutic strategies.

PMID: 29107695 [PubMed - as supplied by publisher]

Wireless Implantable Sensor for Noninvasive, Longitudinal Quantification of Axial Strain Across Rodent Long Bone Defects.

Tue, 2017-11-07 05:30

Wireless Implantable Sensor for Noninvasive, Longitudinal Quantification of Axial Strain Across Rodent Long Bone Defects.

J Biomech Eng. 2017 Nov 01;139(11):

Authors: Klosterhoff BS, Ghee Ong K, Krishnan L, Hetzendorfer KM, Chang YH, Allen MG, Guldberg RE, Willett NJ

Abstract
Bone development, maintenance, and regeneration are remarkably sensitive to mechanical cues. Consequently, mechanical stimulation has long been sought as a putative target to promote endogenous healing after fracture. Given the transient nature of bone repair, tissue-level mechanical cues evolve rapidly over time after injury and are challenging to measure noninvasively. The objective of this work was to develop and characterize an implantable strain sensor for noninvasive monitoring of axial strain across a rodent femoral defect during functional activity. Herein, we present the design, characterization, and in vivo demonstration of the device's capabilities for quantitatively interrogating physiological dynamic strains during bone regeneration. Ex vivo experimental characterization of the device showed that it possessed promising sensitivity, signal resolution, and electromechanical stability for in vivo applications. The digital telemetry minimized power consumption, enabling extended intermittent data collection. Devices were implanted in a rat 6 mm femoral segmental defect model, and after three days, data were acquired wirelessly during ambulation and synchronized to corresponding radiographic videos, validating the ability of the sensor to noninvasively measure strain in real-time. Together, these data indicate the sensor is a promising technology to quantify tissue mechanics in a specimen specific manner, facilitating more detailed investigations into the role of the mechanical environment in dynamic bone healing and remodeling processes.

PMID: 28975256 [PubMed - in process]

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