Robert E Guldberg

Georgia Institute of Technology, Atlanta, Georgia, United States

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Publications (151)665.99 Total impact

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    ABSTRACT: Pioglitazone, the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist is an effective therapy for type 2 diabetes, but has been associated with increased risk for bone fracture. Preclinical studies suggest that PPAR-α agonists (e.g., fenofibrate) increase bone mineral density/content, although clinical data on bone effects of fibrates are lacking. We investigated the effects of pioglitazone (10 mg/kg/day) and fenofibrate (25 mg/kg/day) on bone strength and bone histomorphometric parameters in osteopenic ovariectomized (OVX) rats. An additional group of rats received a combination of pioglitazone + fenofibrate to mimic the effects of a dual PPAR-α/γ agonist. The study consisted of a 13-week treatment phase followed by a 6-week treatment-free recovery period. Pioglitazone significantly reduced biomechanical strength at the lumbar spine and femoral neck compared with rats administered fenofibrate. Co-treatment with pioglitazone + fenofibrate had no significant effect on bone strength in comparison with OVX vehicle controls. Histomorphometric analysis of the proximal tibia revealed that pioglitazone suppressed bone formation and increased bone resorption at both cancellous and cortical bone sites relative to OVX vehicle controls. In contrast, fenofibrate did not affect bone resorption and only slightly suppressed bone formation. Discontinuation of pioglitazone treatment, both in the monotherapy and in the combination therapy arms, resulted in restoration of bone formation and resorption rates, demonstrating reversibility of effects. The above data support the concept that dual activation of PPAR-γ and PPAR-α attenuates the negative effects of PPAR-γ agonism on bone strength.
    Journal of Bone and Mineral Metabolism 12/2014; DOI:10.1007/s00774-014-0632-4 · 2.11 Impact Factor
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    ABSTRACT: Despite its widespread clinical use in load-bearing orthopaedic implants, polyether-ether-ketone (PEEK) is often associated with poor osseointegration. In this study, a surface porous PEEK material (PEEK-SP) was created using a melt extrusion technique. The porous layer thickness was 399.6±63.3 μm and possessed a mean pore size of 279.9±31.6 μm, strut spacing of 186.8±55.5 μm, porosity of 67.3±3.1%, and interconnectivity of 99.9±0.1%. Monotonic tensile tests showed that PEEK-SP preserved 73.9% of the strength (71.06±2.17 MPa) and 73.4% of the elastic modulus (2.45±0.31 GPa) of as-received, injection molded PEEK. PEEK-SP further demonstrated a fatigue strength of 60.0 MPa at one million cycles, preserving 73.4% of the fatigue resistance of injection molded PEEK. Interfacial shear testing showed the pore layer shear strength to be 23.96±2.26 MPa. An osseointegration model in the rat revealed substantial bone formation within the pore layer at 6 and 12 weeks via μCT and histological evaluation. Ingrown bone was more closely apposed to the pore wall and fibrous tissue growth was reduced in PEEK-SP when compared to non-porous PEEK controls. These results indicate that PEEK-SP could provide improved osseointegration while maintaining the structural integrity necessary for load-bearing orthopaedic applications. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
    Acta Biomaterialia 11/2014; 13. DOI:10.1016/j.actbio.2014.11.030 · 5.68 Impact Factor
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    ABSTRACT: Tissue engineering strategies have utilized a wide spectrum of synthetic and naturally-derived scaffold materials. Synthetic scaffolds are better defined and offer the ability to precisely and reproducibly control their properties, while naturally-derived scaffolds typically have inherent biological and structural properties that may facilitate tissue growth and remodeling. More recently, efforts to design optimized biomaterial scaffolds have blurred the line between these two approaches. Naturally-derived scaffolds can be engineered through the manipulation of intrinsic properties of the pre-existing backbone (e.g. structural properties), as well as the addition of controllable functional components (e.g. biological properties). Chemical and physical processing techniques used to modify structural properties of synthetic scaffolds have been tailored and applied to naturally-derived materials. Such strategies include manipulation of mechanical properties, degradation, and porosity. Furthermore, biofunctional augmentation of natural scaffolds via incorporation of exogenous cells, proteins, peptides, or genes has been shown to enhance functional regeneration over endogenous response to the material itself. Moving forward, the regenerative mode of action of naturally-derived materials requires additional investigation. Elucidating such mechanisms will allow for the determination of critical design parameters to further enhance efficacy and capitalize on the full potential of naturally-derived scaffolds.
    Annals of Biomedical Engineering 11/2014; 43(3). DOI:10.1007/s10439-014-1192-4 · 3.23 Impact Factor
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    ABSTRACT: Localized intra-articular delivery of anti-inflammatory proteins can reduce inflammation in osteoarthritis but poses a challenge because of rapid clearance within few hours of injection. On page 1562, A. J. García and co-workers report a new class of polymer that forms self-assembled nanoparticles with therapeutic proteins for prolonged retention in intra-articular joint spaces compared to bolus protein doses.
    Advanced Healthcare Materials 10/2014; 3(10). DOI:10.1002/adhm.201470051 · 4.88 Impact Factor
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    ABSTRACT: Localized intra-articular delivery of anti-inflammatory proteins can reduce inflammation in osteoarthritis but poses a challenge because of raid clearance within few hours of injection. A new class of polymer is developed that forms self-assembled nanoparticles ranging from 300 to 900 nm and demonstrates particle size dependent prolonged retention in intra-articular joint spaces compared to bolus protein over a period of 14 d.
    Advanced Healthcare Materials 10/2014; 3(10). DOI:10.1002/adhm.201400051 · 4.88 Impact Factor
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    ABSTRACT: Autograft treatment of large bone defects and fracture non-unions is complicated by limited tissue availability and donor site morbidity. Polymeric biomaterials such as alginate hydrogels provide an attractive tissue engineering alternative due to their biocompatibility, injectability, and tunable degradation rates. Irradiated RGD-alginate hydrogels have been used to deliver proteins such as bone morphogenetic protein-2 (BMP-2), to promote bone regeneration and restoration of function in a critically sized rat femoral defect model. However, slow degradation of irradiated alginate hydrogels may impede integration and remodeling of the regenerated bone to its native architecture. Oxidation of alginate has been used to promote degradation of alginate matrices. The objective of this study was to evaluate the effects of alginate oxidation on BMP-2 release and bone regeneration. We hypothesized that oxidized-irradiated alginate hydrogels would elicit an accelerated release of BMP-2, but degrade faster in vivo, facilitating the formation of higher quality, more mature bone compared to irradiated alginate. Indeed, oxidation of irradiated alginate did accelerate in vitro BMP-2 release. Notably, the BMP-2 retained within both constructs was bioactive at 26 days, as observed by induction of alkaline phosphatase activity and positive Alizarin Red S staining of MC3T3-E1 cells. From the in vivo study, robust bone regeneration was observed in both groups through 12 weeks by radiography, micro-computed tomography analyses, and biomechanical testing. Bone mineral density was significantly greater for the oxidized-irradiated alginate group at 8 weeks. Histological analyses of bone defects revealed enhanced degradation of oxidized-irradiated alginate and suggested the presence of more mature bone after 12 weeks of healing.
    Acta Biomaterialia 10/2014; 10(10):4390-9. DOI:10.1016/j.actbio.2014.06.015 · 5.68 Impact Factor
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    ABSTRACT: Bone loss due to age and disuse contributes to osteoporosis and increases fracture risk. It has been hypothesized that such bone loss can be attenuated by modulation of the C-C chemokine receptor 2 (CCR2) and/or its ligands. The objectives of this study were to examine the effects of genetic elimination of CCR2 on cortical and trabecular bones in the mouse tibia and how bone loss was impacted following disuse and estrogen loss. Female CCR2 knockout (CCR2(-/-)) and wildtype mice underwent ovariectomy (OVX) or denervation of musculature adjacent to the tibia (DEN) to induce bone loss. Cortical and trabecular structural properties as well as mechanical properties (i.e., strength) of tibial bones were measured. Compared to wildtype mice, CCR2(-/-) mice had tibiae that were up to 9 % larger and stronger; these differences could be explained mainly by the 17 % greater body mass (P < 0.001) of CCR2(-/-) mice. The majority of the tibia's structural and functional responses to OVX and DEN were similar regardless of the lack or presence of CCR2, indicating that CCR2 is not protective against bone loss per se. These findings indicate that while CCR2(-/-) mice do have larger and stronger bones than do wildtype mice, there is minimal evidence that CCR2 elimination provides protection against bone loss during disuse and estrogen loss.
    Calcified Tissue International 09/2014; 95(5). DOI:10.1007/s00223-014-9914-z · 2.75 Impact Factor
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  • L. Tran, L. Krishnan, L.B. Priddy, R.E. Guldberg
    Journal of Oral and Maxillofacial Surgery; 09/2014
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    ABSTRACT: Craniosynostosis is the premature fusion of cranial sutures, which can result in progressive cranial deformations, increased intracranial pressure, and restricted brain growth. Most cases of craniosynostosis require surgical reconstruction of the cranial vault with the goal of increasing the intracranial volume and correcting the craniofacial deformities. However, patients often experience rapid post-operative bone regrowth, known as re-synostosis, which necessitates additional surgical intervention. Bone morphogenetic protein (BMP) inhibitors have tremendous potential to treat re-synostosis, but the realization of a clinically viable inhibitor-based therapeutic requires the development of a delivery vehicle that can localize the release to the site of administration. Here, we present an in situ rapidly crosslinking injectable hydrogel that has the properties necessary to encapsulate co-administered proteins and demonstrate that the delivery of rmGremlin1 via our hydrogel system delays bone regrowth in a weanling mouse model of re-synostosis. Our hydrogel is composed of two mutually reactive poly(ethylene glycol) macromolecules, which when mixed crosslink via a bio-orthogonal Cu free click reaction. Hydrogels containing Gremlin caused a dose dependent inhibition of bone regrowth. In addition to craniofacial applications, our injectable click hydrogel has the potential to provide customizable protein, small molecule, and cell delivery to any site accessible via needle or catheter.
    Biomaterials 08/2014; 35(36). DOI:10.1016/j.biomaterials.2014.07.065 · 8.31 Impact Factor
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    ABSTRACT: Skeletal development and growth are complex processes regulated by multiple microenvironmental cues, including integrin-ECM interactions. The β1 sub-family of integrins is the largest integrin sub-family and constitutes the main integrin binding partners of collagen I, the major ECM component of bone. As complete β1 integrin knockout results in embryonic lethality, studies of β1 integrin function in vivo rely on tissue-specific gene deletions. While multiple in vitro studies indicate that β1 integrins are crucial regulators of osteogenesis and mineralization, in vivo osteoblast-specific perturbations of β1 integrins have resulted in mild and sometimes contradictory skeletal phenotypes. To further investigate the role of β1 integrins on skeletal phenotype, we used the Twist2-Cre, Osterix-Cre and osteocalcin-Cre lines to generate conditional β1 integrin deletions, where Cre is expressed primarily in mesenchymal condensation, pre-osteoblast, and mature osteoblast lineage cells respectively within these lines. Mice with Twist2-specific β1 integrin disruption were smaller, had impaired skeletal development, especially in the craniofacial and vertebral tissues at E19.5, and did not survive beyond birth. Osterix-specific β1 integrin deficiency resulted in viable mice which were normal at birth but displayed early defects in calvarial ossification, incisor eruption and growth as well as femoral bone mineral density, structure, and mechanical properties. Although these defects persisted into adulthood, they became milder with age. Finally, a lack of β1 integrins in mature osteoblasts and osteocytes resulted in minor alterations to femur structure but had no effect on mineral density, biomechanics or fracture healing. Taken together, our data indicate that β1 integrin expression in early mesenchymal condensations play an important role in skeletal ossification, while β1 integrin-ECM interactions in pre-osteoblast, odontoblast- and hypertrophic chondryocyte-lineage cells regulate incisor eruption and perinatal bone formation in both intramembranously and endochondrally formed bones in young, rapidly growing mice. In contrast, the osteocalcin-specific β1 integrin deletion had only minor effects on skeletal phenotype.
    Bone 08/2014; 68. DOI:10.1016/j.bone.2014.08.008 · 4.46 Impact Factor
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    ABSTRACT: The objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups. In vivo and ex vivo contractile function of the anterior crural and extensor digitorum longus muscles, respectively, were assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for histological and triglyceride analyses and subcutaneous and visceral fat pads were excised and weighed. Tibial bones were dissected and analyzed by micro-computed tomography for trabecular morphometry at the metaphysis, and cortical geometry and density at the mid-diaphysis. Three-point bending tests were used to assess cortical bone mechanical properties and a subset of tibiae was processed for dynamic histomorphometry. Vibration training for 8 wks did not alter trabecular morphometry, dynamic histomorphometry, cortical geometry, or mechanical properties (P≥0.34). Vibration did not alter any measure of muscle contractile function (P≥0.12); however the preservation of muscle function and morphology in mdx mice indicates vibration is not deleterious to muscle lacking dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher intramuscular triglyceride concentrations (P = 0.03). These data suggest that vibration training at 45 Hz and 0.6 g did not significantly impact the tibial bone and the surrounding musculature, but may influence fat distribution in mice.
    PLoS ONE 08/2014; 9(8):e104339. DOI:10.1371/journal.pone.0104339 · 3.53 Impact Factor
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    ABSTRACT: Despite progress in bone tissue engineering, the healing of critically sized diaphyseal defects remains a clinical challenge. A stem cell based approach is an attractive alternative to current treatment techniques. The objective of this study was to examine the ability of adult stem cells to enhance bone formation when co-delivered with the osteoinductive factor bone morphogenetic protein-2 (BMP-2) in a biologically functionalized hydrogel. First, adipose and bone marrow derived stem cells (ADSCs and BMMSCs) were screened for their potential to form bone when delivered in an RGD functionalized alginate hydrogel using a subcutaneous implant model. BMMSCs co-delivered with BMP-2 produced significantly more mineralized tissue compared to either ADSCs co-delivered with BMP-2 or acellular hydrogels containing BMP-2. Next, the ability of BMMSCs to heal a critically sized diaphyseal defect with a non-healing dose of BMP-2 was tested using the alginate hydrogel as an injectable cell carrier. The effect of timing of therapeutic delivery on bone regeneration was also tested in the diaphyseal model. A 7 day delayed injection of the hydrogel into the defect site resulted in less mineralized tissue formation than immediate delivery of the hydrogel. By 12 weeks, BMMSC loaded hydrogels produced significantly more bone than acellular constructs regardless of immediate or delayed treatment. For immediate delivery, bridging of defects treated with BMMSC loaded hydrogels occurred at a rate of 75% compared to a 33% bridging rate for acellular treated defects. No bridging was observed in any of the delayed delivery samples for any of the groups. Therefore, for this cell based bone tissue engineering approach, immediate delivery of constructs leads to an overall enhanced healing response compared to delayed delivery techniques. Further, these studies demonstrate that co-delivery of adult stem cells, specifically BMMSCs, with BMP-2 enhances bone regeneration in a critically sized femoral segmental defect compared to acellular hydrogels containing BMP-2.
    Tissue Engineering Part A 07/2014; 21(1-2). DOI:10.1089/ten.TEA.2014.0057 · 4.70 Impact Factor
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    ABSTRACT: Severe extremity trauma often results in large zones of injury comprising multiple types of tissue and presents many clinical challenges for reconstruction. Considerable investigation is ongoing in tissue engineering and regenerative medicine therapeutics to improve reconstruction outcomes; however, the vast majority of musculoskeletal trauma models employed for testing the therapeutics consist of single-tissue defects, offering limited utility for investigating strategies for multi-tissue repair. Here we present the first model of composite lower limb bone and nerve injury, characterized by comparison to well-established, single-tissue injury models, using biomaterials-based technologies previously demonstrated to show promise in those models. Quantitative functional outcome measures were incorporated to facilitate assessment of new technologies to promote structural and functional limb salvage following severe extremity trauma. Nerve injury induced significant changes in the morphology and mechanical properties of intact bones. However, BMP-mediated segmental bone regeneration was not significantly impaired by concomitant nerve injury, as evaluated via radiographs, microcomputed tomography (μCT) and biomechanical testing. Neither was nerve regeneration significantly impaired by bone injury when evaluated via histology and electrophysiology. Despite the similar tissue regeneration observed, the composite injury group experienced a marked functional deficit in the operated limb compared to either of the single-tissue injury groups, as determined by quantitative, automated CatWalk gait analysis. As a whole, this study presents a challenging, clinically relevant model of severe extremity trauma to bone and nerve tissue, and emphasizes the need to incorporate quantitative functional outcome measures to benchmark tissue engineering therapies. Copyright © 2012 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 06/2014; 8(6). DOI:10.1002/term.1537 · 4.43 Impact Factor
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    ABSTRACT: Biomaterials capable of providing localized and sustained presentation of bioactive proteins are critical for effective therapeutic growth factor delivery. However, current biomaterial delivery vehicles commonly suffer from limitations that can result in low retention of growth factors at the site of interest or adversely affect growth factor bioactivity. Heparin, a highly sulfated glycosaminoglycan, is an attractive growth factor delivery vehicle due to its ability to reversibly bind positively charged proteins, provide sustained delivery, and maintain protein bioactivity. This study describes the fabrication and characterization of heparin methacrylamide (HMAm) microparticles for recombinant growth factor delivery. HMAm microparticles were shown to efficiently bind several heparin-binding growth factors (e.g. bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2)), including a wide range of BMP-2 concentrations that exceeds the maximum binding capacity of other common growth factor delivery vehicles, such as gelatin. BMP-2 bioactivity was assessed on the basis of alkaline phosphatase (ALP) activity induced in skeletal myoblasts (C2C12). Microparticles loaded with BMP-2 stimulated comparable C2C12 ALP activity to soluble BMP-2 treatment, indicating that BMP-2-loaded microparticles retain bioactivity and potently elicit a functional cell response. In summary, our results suggest that heparin microparticles stably retain large amounts of bioactive BMP-2 for prolonged periods of time, and that presentation of BMP-2 via heparin microparticles can elicit cell responses comparable to soluble BMP-2 treatment. Consequently, heparin microparticles present an effective method of delivering and spatially retaining growth factors that could be used in a variety of systems to enable directed induction of cell fates and tissue regeneration.
    Biomaterials 05/2014; 35(25). DOI:10.1016/j.biomaterials.2014.05.011 · 8.31 Impact Factor
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    ABSTRACT: Non-healing bone defects present tremendous socioeconomic costs. Although successful in some clinical settings, bone morphogenetic protein (BMP) therapies require supraphysiological dose delivery for bone repair, raising treatment costs and risks of complications. We engineered a protease-degradable poly(ethylene glycol) (PEG) synthetic hydrogel functionalized with a triple helical, α2β1 integrin-specific peptide (GFOGER) as a BMP-2 delivery vehicle. GFOGER-functionalized hydrogels lacking BMP-2 directed human stem cell differentiation and produced significant enhancements in bone repair within a critical-sized bone defect compared to RGD hydrogels or empty defects. GFOGER functionalization was crucial to the BMP-2-dependent healing response. Importantly, these engineered hydrogels outperformed the current clinical carrier in repairing non-healing bone defects at low BMP-2 doses. GFOGER hydrogels provided sustained in vivo release of encapsulated BMP-2, increased osteoprogenitor localization in the defect site, enhanced bone formation and induced defect bridging and mechanically robust healing at low BMP-2 doses which stimulated almost no bone regeneration when delivered from collagen sponges. These findings demonstrate that GFOGER hydrogels promote bone regeneration in challenging defects with low delivered BMP-2 doses and represent an effective delivery vehicle for protein therapeutics with translational potential.
    Biomaterials 04/2014; DOI:10.1016/j.biomaterials.2014.03.055 · 8.31 Impact Factor
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    ABSTRACT: The use of multicomponent scaffolds for cell implantation has necessitated sophisticated techniques for tracking of cell survival in vivo. Bioluminescent imaging (BLI) has emerged as a non-invasive tool for evaluating the therapeutic potential of cell-based tissue engineering strategies. However, the ability to use BLI measurements to longitudinally assess large 3D cellular constructs in vivo and the effects of potential confounding factors are poorly understood. In this study, luciferase-expressing human mesenchymal stem cells (hMSCs) were delivered subcutaneously within agarose and RGD-functionalized alginate hydrogel vehicles to investigate the impact of construct composition and tissue formation on BLI signal. Results showed that alginate constructs exhibited 2-fold greater BLI counts than agarose constructs at comparable hMSC doses. However, each hydrogel type produced a linear correlation between BLI counts and live cell number, indicating that within a given material, relative differences in cell number could be accurately assessed at early time points. The survival efficiency of delivered hMSCs was highest for the lower cell doses embedded within alginate matrix. BLI signal remained predictive of live cell number through one week in vivo, although the strength of correlation decreased over time. Irrespective of hydrogel type or initial hMSC seeding dose, all constructs demonstrated a degree of vascularization and development of a fibrotic capsule after one week. Formation of tissue within and adjacent to the constructs was accompanied by an attenuation of BLI signal during the initial period of the image acquisition time-frame. In alginate constructs only, greater vessel volume led to a delayed rise in BLI signal following luciferin delivery. This study identified vascular and fibrotic tissue ingrowth as potential confounding variables for longitudinal BLI studies. Further investigation into the complexities of non-invasive BLI data acquisition from multicomponent constructs, following implantation and subsequent tissue formation, is warranted.
    Tissue Engineering Part C Methods 02/2014; DOI:10.1089/ten.TEC.2013.0587 · 4.64 Impact Factor
  • F Brennan Torstrick, Robert E Guldberg
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    ABSTRACT: Despite advances in systemic osteoporosis therapeutic outcomes, management of fragility fractures and implant fixation in osteoporotic bone remain difficult clinical challenges. Low initial bone density and a prolonged healing response can lead to fracture nonunion and aseptic implant loosening. Local treatment strategies could be used to prevent fracture, accelerate healing, and increase implant fixation by locally stimulating anabolic pathways or inhibiting catabolic pathways. Local strategies under investigation include direct drug release from injectable materials or implant surface coatings. Common locally delivered drugs include bisphosphonates, parathyroid hormone, and bone morphogenetic proteins, yet additional compounds targeting novel pathways in bone biology are also being actively explored. Mechanical stimulation via low intensity pulsed ultrasound, alone or in combination with drug therapy, may also prove effective to promote local bone healing and implant fixation within osteoporotic bone.
    Current Osteoporosis Reports 02/2014; 12(1). DOI:10.1007/s11914-014-0191-6
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    ABSTRACT: Micronized dehydrated human amnion/chorion membrane (mu-dHACM) is derived from donated human placentae and has anti-inflammatory, low immunogenic and anti-fibrotic properties. The objective of this study was to quantitatively assess the efficacy of mu-dHACM as a disease modifying intervention in a rat model of osteoarthritis (OA). It was hypothesized that intra-articular injection of mu-dHACM would attenuate OA progression. Lewis rats underwent medial meniscal transection (MMT) surgery to induce OA. 24 hours post-surgery, mu-dHACM or saline was injected intra-articularly into the rat joint. Naive rats also received mu-dHACM injections. Microstructural changes in the tibial articular cartilage were assessed using equilibrium partitioning of an ionic contrast agent (EPIC-muCT) at 21 days post-surgery. The joint was also evaluated histologically and synovial fluid was analyzed for inflammatory markers at 3 and 21 days post-surgery. There was no measured baseline effect of mu-dHACM on cartilage in naive animals. Histological staining of treated joints showed presence of mu-dHACM in the synovium along with local hypercellularity at 3 and 21 days post-surgery. In MMT animals, development of cartilage lesions at 21 days was prevented and number of partial erosions was significantly reduced by treatment with mu-dHACM. EPIC-muCT analysis quantitatively showed that mu-dHACM reduced proteoglycan loss in MMT animals. mu-dHACM is rapidly sequestered in the synovial membrane following intra-articular injection and attenuates cartilage degradation in a rat OA model. These data suggest that intra-articular delivery of mu-dHACM may have a therapeutic effect on OA development.
    Arthritis research & therapy 02/2014; 16(1):R47. DOI:10.1186/ar4476 · 4.12 Impact Factor
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    ABSTRACT: The functional regeneration of thick vascularized tissues such as bone and muscle is complicated by the large volume of lost tissue, challenging biomechanical environment, and the need to reproduce the highly organized structure of both the native tissue extracellular matrix and its vascular support system. Stem cell or progenitor cell delivery approaches, for example, continue to be plagued by low viability and engraftment in part due to the initial absence of a vascular supply. Recognition of diffusion limitations in thick tissues has prompted regenerative strategies that seek to accelerate establishment of a functional vasculature. The successful design of robust regeneration strategies for these challenging clinical scenarios will rely on a thorough understanding of interactions between construct design parameters and host biological and biomechanical factors. Here, we discuss the critical role of vascularization in normal bone tissue homeostasis and repair, vascular network adaptation to the local biomechanical environment, and the future directions of revascularization approaches being developed and integrated with bone regeneration strategies.
    Annals of Biomedical Engineering 01/2014; 42(2). DOI:10.1007/s10439-014-0969-9 · 3.23 Impact Factor

Publication Stats

5k Citations
665.99 Total Impact Points

Institutions

  • 1999–2014
    • Georgia Institute of Technology
      • • Department of Biomedical Engineering
      • • Institute for Bioengineering and Bioscience
      • • School of Mechanical Engineering
      Atlanta, Georgia, United States
  • 2013
    • VU University Amsterdam
      • Oral Cell Biology and Functional Anatomy
      Amsterdamo, North Holland, Netherlands
  • 2011–2012
    • Queensland University of Technology
      • Institute of Health and Biomedical Innovation
      Brisbane, Queensland, Australia
  • 2010
    • Emory University
      • Division of Plastic and Reconstructive Surgery
      Atlanta, GA, United States
  • 2008–2009
    • Morehouse College
      Atlanta, Georgia, United States
  • 2007
    • University of Rochester
      • Center for Musculoskeletal Research
      Rochester, NY, United States
    • University of Michigan
      • Department of Biomedical Engineering
      Ann Arbor, MI, United States
  • 2006
    • University Center Rochester
      • Center for Musculoskeletal Research
      Rochester, Minnesota, United States
    • Baylor College of Medicine
      • Center for Cell and Gene Therapy
      Houston, Texas, United States