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Updated: 17 min 29 sec ago

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

17 min 29 sec ago

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]

Deformation and fatigue of tough 3D printed elastomer scaffolds processed by fused deposition modeling and continuous liquid interface production.

Thu, 2017-10-05 05:45

Deformation and fatigue of tough 3D printed elastomer scaffolds processed by fused deposition modeling and continuous liquid interface production.

J Mech Behav Biomed Mater. 2017 Jul 01;75:1-13

Authors: Miller AT, Safranski DL, Wood C, Guldberg RE, Gall K

Abstract
Polyurethane (PU) based elastomers continue to gain popularity in a variety of biomedical applications as compliant implant materials. In parallel, advancements in additive manufacturing continue to provide new opportunities for biomedical applications by enabling the creation of more complex architectures for tissue scaffolding and patient specific implants. The purpose of this study was to examine the effects of printed architecture on the monotonic and cyclic mechanical behavior of elastomeric PUs and to compare the structure-property relationship across two different printing approaches. We examined the tensile fatigue of notched specimens, 3D crosshatch scaffolds, and two 3D spherical pore architectures in a physically crosslinked polycarbonate urethane (PCU) printed via fused deposition modeling (FDM) as well as a photo-cured, chemically-crosslinked, elastomeric PU printed via continuous liquid interface production (CLIP). Both elastomers were relatively tolerant of 3D geometrical features as compared to stiffer synthetic implant materials such as PEEK and titanium. PCU and crosslinked PU samples with 3D porous structures demonstrated a reduced tensile failure stress as expected without a significant effect on tensile failure strain. PCU crosshatch samples demonstrated similar performance in strain-based tensile fatigue as solid controls; however, when plotted against stress amplitude and adjusted by porosity, it was clear that the architecture had an impact on performance. Square shaped notches or pores in crosslinked PU appeared to have a modest effect on strain-based tensile fatigue while circular shaped notches and pores had little impact relative to smooth samples. When plotted against stress amplitude, any differences in fatigue performance were small or not statistically significant for crosslinked PU samples. Despite the slight difference in local architecture and tolerances, crosslinked PU solid samples were found to perform on par with PCU solid samples in tensile fatigue, when appropriately adjusted for material hardness. Finally, tests of samples with printed architecture localized to the gage section revealed an effect in which fatigue performance appeared to drastically improve despite the localization of strain.

PMID: 28689135 [PubMed - as supplied by publisher]

Enhanced In Vivo Retention of Low Dose BMP-2 Via Heparin Microparticle Delivery Does Not Accelerate Bone Healing in a Critically Sized Femoral Defect.

Mon, 2017-07-10 05:30
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Enhanced In Vivo Retention of Low Dose BMP-2 Via Heparin Microparticle Delivery Does Not Accelerate Bone Healing in a Critically Sized Femoral Defect.

Acta Biomater. 2017 Jun 20;:

Authors: Hettiaratchi MH, Rouse T, Chou C, Krishnan L, Stevens HY, Li MA, McDevitt TC, Guldberg RE

Abstract
Bone morphogenetic protein-2 (BMP-2) is an osteoinductive growth factor used clinically to induce bone regeneration and fusion. Some complications associated with BMP-2 treatment have been attributed to rapid release of BMP-2 from conventional collagen scaffolds, motivating the development of tunable sustained-release strategies. We incorporated BMP-2-binding heparin microparticles (HMPs) into a hydrogel scaffold to improve spatiotemporal control of BMP-2 delivery to large bone defects. HMPs pre-loaded with BMP-2 were mixed into alginate hydrogels and compared to hydrogels containing BMP-2 alone. BMP-2 release from scaffolds in vitro, BMP-2 retention within injury sites in vivo, and bone regeneration in a critically sized femoral defect were evaluated. Compared to hydrogel delivery alone, BMP-2-loaded HMPs reduced BMP-2 release in vitro and increased early BMP-2 retention in the bone defect. BMP-2-loaded HMPs induced bone formation at both ectopic and orthotopic sites; however, the volume of induced bone was lower for defects treated with BMP-2-loaded HMPs compared to hydrogel delivery. To better understand the effect of HMPs on BMP-2 release kinetics, a computational model was developed to predict BMP-2 release from constructs in vivo. The model suggested that HMPs limited BMP-2 release into surrounding tissues, and that changing the HMP density could modulate BMP-2 release. Taken together, these experimental and computational results suggest the importance of achieving a balance of BMP-2 retention within the bone defect and BMP-2 release into surrounding soft tissues. HMP delivery of BMP-2 may provide a method of tuning BMP-2 release in vivo that can be further investigated to improve current methods of bone regeneration.
STATEMENT OF SIGNIFICANCE: The development of effective biomaterials for sustained protein delivery is a crucial component of tissue engineering strategies. However, in most applications, including bone repair, the optimal balance between protein presentation in the injury site and protein release into the surrounding tissues is unknown. Herein, we introduced heparin microparticles (HMPs) into a tissue engineered construct to increase in vivo retention of bone morphogenetic protein-2 (BMP-2) and enhance healing in femoral defects. Although HMPs induced bone regeneration, no increase in bone volume was observed, leading to further experimental and computational analysis of the effect of HMP-BMP-2 interactions on protein retention and release. Ultimately, this work provides insight into designing tunable protein-material interactions and their implications for controlling BMP-2 delivery.

PMID: 28645809 [PubMed - as supplied by publisher]

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