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1.  Non-invasive monitoring of BMP-2 retention and bone formation in composites for bone tissue engineering using SPECT/CT and scintillation probes 
Non-invasive imaging can provide essential information for the optimization of new drug delivery-based bone regeneration strategies to repair damaged or impaired bone tissue. This study investigates the applicability of nuclear medicine and radiological techniques to monitor growth factor retention profiles and subsequent effects on bone formation. Recombinant human bone morphogenetic protein-2 (BMP-2, 6.5 μg/scaffold) was incorporated into a sustained release vehicle consisting of poly(lactic-co-glycolic acid) microspheres embedded in a poly(propylene fumarate) scaffold surrounded by a gelatin hydrogel and implanted subcutaneously and in 5-mm segmental femoral defects in 9 rats for a period of 56 days. To determine the pharmacokinetic profile, BMP-2 was radiolabeled with 125I and the local retention of 125I-BMP-2 was measured by single photon emission computed tomography (SPECT), scintillation probes and ex vivo scintillation analysis. Bone formation was monitored by micro-computed tomography (μCT). The scaffolds released BMP-2 in a sustained fashion over the 56-day implantation period. A good correlation between the SPECT and scintillation probe measurements was found and there were no significant differences between the non-invasive and ex-vivo counting method after 8 weeks of follow up. SPECT analysis of the total body and thyroid counts showed a limited accumulation of 125I within the body. Ectopic bone formation was induced in the scaffolds and the femur defects healed completely. In vivo μCT imaging detected the first signs of bone formation at days 14 and 28 for the orthotopic and ectopic implants, respectively, and provided a detailed profile of the bone formation rate. Overall, this study clearly demonstrates the benefit of applying non-invasive techniques in drug delivery-based bone regeneration strategies by providing detailed and reliable profiles of the growth factor retention and bone formation at different implantation sites in a limited number of animals.
doi:10.1016/j.jconrel.2008.11.023
PMCID: PMC3974410  PMID: 19105972
Drug delivery; Controlled release; Bone morphogenetic protein-2; Single photon emission computed; tomography; Scintillation probes; Micro-computed tomography
2.  Are Anidulafungin or Voriconazole Released from Polymethylmethacrylate In Vitro? 
Background
Depot delivery of antimicrobial agents is used for treatment and prevention of bacterial orthopaedic infections; there is little information regarding newer antifungal agents and their potential use in polymethylmethacrylate (PMMA) depot delivery.
Questions/purposes
We determined the percent of anidulafungin or voriconazole present after polymerization in PMMA beads loaded with anidulafungin or voriconazole, and we assessed elution of anidulafungin or voriconazole from beads loaded with anidulafungin or voriconazole.
Materials and Methods
Beads containing 7.5% anidulafungin or voriconazole were pulverized and incubated in Kreb’s ringer buffer for 48 hours; the buffer was assayed for anidulafungin or voriconazole concentration. The in vitro release of anidulafungin and voriconazole from PMMA beads loaded with 7.5% anidulafungin or voriconazole was determined in triplicate in a continuous flow chamber.
Results
0.7% of anidulafungin and 5.6% of voriconazole loaded in the beads were detected after polymerization. No anidulafungin was detected in the elution studies. The mean peak voriconazole concentration in the elution studies was 0.9 μg/mL.
Conclusions
Anidulafungin may not be suitable for depot delivery in PMMA.
doi:10.1007/s11999-010-1643-7
PMCID: PMC3069256  PMID: 20963525
3.  Biomechanical considerations in the pathogenesis of osteoarthritis of the knee 
Osteoarthritis is the most common joint disease and a major cause of disability. The knee is the large joint most affected. While chronological age is the single most important risk factor of osteoarthritis, the pathogenesis of knee osteoarthritis in the young patient is predominantly related to an unfavorable biomechanical environment at the joint. This results in mechanical demand that exceeds the ability of a joint to repair and maintain itself, predisposing the articular cartilage to premature degeneration. This review examines the available basic science, preclinical and clinical evidence regarding several such unfavorable biomechanical conditions about the knee: malalignment, loss of meniscal tissue, cartilage defects and joint instability or laxity.
Level of evidence IV.
doi:10.1007/s00167-011-1818-0
PMCID: PMC3282009  PMID: 22173730
Cartilage; Malalignment; Meniscus; Osteochondral defects; Joint instability; Pathology; Etiology
4.  Enhanced Bone Morphogenetic Protein-2-Induced Ectopic and Orthotopic Bone Formation by Intermittent Parathyroid Hormone (1–34) Administration 
Tissue Engineering. Part A  2010;16(12):3769-3777.
Bone morphogenetic proteins (BMPs) play a central role in local bone regeneration strategies, whereas the anabolic features of parathyroid hormone (PTH) are particularly appealing for the systemic treatment of generalized bone loss. The aim of the current study was to investigate whether local BMP-2-induced bone regeneration could be enhanced by systemic administration of PTH (1–34). Empty or BMP-2-loaded poly(lactic-co glycolic acid)/poly(propylene fumarate)/gelatin composites were implanted subcutaneously and in femoral defects in rats (n = 9). For the orthotopic site, empty defects were also tested. Each of the conditions was investigated in combination with daily administered subcutaneous PTH (1–34) injections in the neck. After 8 weeks of implantation, bone mineral density (BMD) and bone volume were analyzed using microcomputed tomography and histology. Ectopic bone formation and almost complete healing of the femoral defect were only seen in rats that received BMP-2-loaded composites. Additional treatment of the rats with PTH (1–34) resulted in significantly (p < 0.05) enhanced BMD and bone volume in the BMP-2 composites at both implantation sites. Despite its effect on BMD in the humerus and vertebra, PTH (1–34) treatment had no significant effect on BMD and bone volume in the empty femoral defects and the ectopically or orthotopically implanted empty composites. Histological analysis showed that the newly formed bone had a normal woven and trabecular appearance. Overall, this study suggests that intermittent administration of a low PTH dose alone has limited potential to enhance local bone regeneration in a critical-sized defect in rats. However, when combined with local BMP-2-releasing scaffolds, PTH administration significantly enhanced osteogenesis in both ectopic and orthotopic sites.
doi:10.1089/ten.tea.2010.0173
PMCID: PMC2991197  PMID: 20666615
5.  Self-assembled Monolayer Films of Phosphonates for Bonding RGD to Titanium 
Modification of the implant surface with the Arg-Gly-Asp tripeptide (RGD) putatively facilitates osteoblast attachment for improved implant fixation in the laboratory. We compared the histomorphometric and mechanical performance of titanium implants coated with RGD using a novel interface of self-assembled monolayers of phosphonates (RGD/SAMP) and implants coated with RGD using the more conventional thiolate-gold interface (RGD/thiolate-gold). We hypothesized RGD/SAMP-coated implants would show greater bone ongrowth and implant fixation than RGD/thiolate-gold-coated ones. We implanted an RGD/SAMP-coated implant in one femur and an RGD/thiolate-gold-coated in the contralateral femur of 60 rats. At 2, 4, and 8 weeks after implantation, 10 rats were sacrificed for histologic evaluation and another 10 for biomechanical testing. Bone-implant ongrowth and implant force-to-failure of the two implants were similar at all times. Although RGD/SAMP-coated implants did not show superior bone ongrowth and implant fixation, RGD/SAMP-coated implants have at least equally good histomorphometric and mechanical in vivo performance as RGD/thiolate-gold-coated ones. Additional in vivo characterization of self-assembled monolayer films of phosphonates as interface to bond RGD to titanium is needed to explore its full potential and seems justified based on the results of this study.
doi:10.1007/s11999-008-0117-7
PMCID: PMC2504684  PMID: 18224380

Results 1-5 (5)