In-Vivo Degradation of a Poly(Propylene-Fumarate) Biodegradable, Particulate Composite Bone Cement

1995 ◽  
Vol 394 ◽  
Author(s):  
Daveed D. Frazier ◽  
Vijay K. Lathi ◽  
Tobin N. Gerhart ◽  
David E. Altobelli ◽  
Wilson C. Hayes

AbstractWe have developed a biodegradable particulate composite bone cement consisting of a poly(propylene glycol-fumarate)-(methylmethacrylate) matrix mixed with calcium carbonate and tricalcium phosphate particulates. Previous ex-vivo studies suggest that this system provides sufficient strength for a number of potential clinical applications including structural reinforcement of osseous defects, supplementation of internal fixation of age-related fractures, and delivery of antibiotics to treat osteomyelitis. Ex-vivo degradation assays have also shown that the cement approximates physiologic conditions of bone remodeling as it degrades. In order to evaluate the in-vivo responses to this material, we implanted cement specimens subcutaneously in rats for up to 84 days. Compressive strength of the subcutaneous implants increased linearly through day 21 to 4.91 MPa, then decreased linearly by day 84 to less than 1 MPa. We conclude that this PPFMMA system is biocompatible and biodegradable, and has the potential for use as an orthopedic bone cement. Future studies will be directed toward characterizing the intraosseous histological response and at coordinating the rate of cement degradation with bony ingrowth.

1989 ◽  
Vol 23 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Tobin N. Gerhart ◽  
Andrew A. Renshaw ◽  
Richard L. Miller ◽  
Robert J. Noecker ◽  
Wilson C. Hayes

1987 ◽  
Vol 110 ◽  
Author(s):  
Tobin N. Gerhart ◽  
A. A. Renshaw ◽  
W. C. Hayes

We have developed a particulate composite bone cement consisting of a particulate phase of tricalcium phosphate (TCP) particles bound together by a polymeric matric phase (PPF). This matrix hardens through a free radical polymerization reaction in vivo within several minutes after mixing. The initial mechanical strength of our particulate composite bone cement results from the matrix, but over time this degrades and the strength is augmented by bone ingrowth and incorporation of the tricalcium phosphate particles. Possible orthopaedic applications include fixation of fractures, augmenting fixation of implants in osteoporetic bone, and temporary stabilization of bone ingrowth prostheses.


2014 ◽  
Vol 103 (4) ◽  
pp. 1157-1169 ◽  
Author(s):  
Oluwatoyin A. Adeleke ◽  
Yahya E. Choonara ◽  
Lisa C. Du Toit ◽  
Viness Pillay

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Pedram Honarpisheh ◽  
Juneyoung Lee ◽  
Anik Banerjee ◽  
Maria P. Blasco-Conesa ◽  
Parisa Honarpisheh ◽  
...  

Abstract Background The ability to distinguish resident microglia from infiltrating myeloid cells by flow cytometry-based surface phenotyping is an important technique for examining age-related neuroinflammation. The most commonly used surface markers for the identification of microglia include CD45 (low-intermediate expression), CD11b, Tmem119, and P2RY12. Methods In this study, we examined changes in expression levels of these putative microglia markers in in vivo animal models of stroke, cerebral amyloid angiopathy (CAA), and aging as well as in an ex vivo LPS-induced inflammation model. Results We demonstrate that Tmem119 and P2RY12 expression is evident within both CD45int and CD45high myeloid populations in models of stroke, CAA, and aging. Interestingly, LPS stimulation of FACS-sorted adult microglia suggested that these brain-resident myeloid cells can upregulate CD45 and downregulate Tmem119 and P2RY12, making them indistinguishable from peripherally derived myeloid populations. Importantly, our findings show that these changes in the molecular signatures of microglia can occur without a contribution from the other brain-resident or peripherally sourced immune cells. Conclusion We recommend future studies approach microglia identification by flow cytometry with caution, particularly in the absence of the use of a combination of markers validated for the specific neuroinflammation model of interest. The subpopulation of resident microglia residing within the “infiltrating myeloid” population, albeit small, may be functionally important in maintaining immune vigilance in the brain thus should not be overlooked in neuroimmunological studies.


2017 ◽  
Vol 32 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Bing Ma ◽  
Zhiguang Huan ◽  
Chen Xu ◽  
Nan Ma ◽  
Haibo Zhu ◽  
...  

2015 ◽  
Vol 1 (1) ◽  
pp. 236-239 ◽  
Author(s):  
Sandra Stein ◽  
Christian Simroth-Loch ◽  
Sönke Langner ◽  
Stefan Hadlich ◽  
Oliver Stachs ◽  
...  

AbstractThe in vitro and in vivo characterization of intravitreal injections plays an important role in developing innovative therapy approaches. Using the established vitreous model (VM) and eye movement system (EyeMoS) the distribution of contrast agents with different molecular weight was studied in vitro. The impact of the simulated age-related vitreal liquefaction (VL) on drug distribution in VM was examined either with injection through the gel phase or through the liquid phase. For comparison the distribution was studied ex vivo in the porcine vitreous. The studies were performed in a magnetic resonance (MR) scanner. As expected, with increasing molecular weight the diffusion velocity and the visual distribution of the injected substances decreased. Similar drug distribution was observed in VM and in porcine eye. VL causes enhanced convective flow and faster distribution in VM. Confirming the importance of the injection technique in progress of VL, injection through gelatinous phase caused faster distribution into peripheral regions of the VM than following injection through liquefied phase. VM and MR scanner in combination present a new approach for the in vitro characterization of drug release and distribution of intravitreal dosage forms.


2012 ◽  
Vol 302 (8) ◽  
pp. H1625-H1635 ◽  
Author(s):  
Leroy L. Cooper ◽  
Katja E. Odening ◽  
Min-Sig Hwang ◽  
Leonard Chaves ◽  
Lorraine Schofield ◽  
...  

Aging increases the risk for arrhythmias and sudden cardiac death (SCD). We aimed at elucidating aging-related electrical, functional, and structural changes in the heart and vasculature that account for this heightened arrhythmogenic risk. Young (5–9 mo) and old (3.5–6 yr) female New Zealand White (NZW) rabbits were subjected to in vivo hemodynamic, electrophysiological, and echocardiographic studies as well as ex vivo optical mapping, high-field magnetic resonance imaging (MRI), and histochemical experiments. Aging increased aortic stiffness (baseline pulse wave velocity: young, 3.54 ± 0.36 vs. old, 4.35 ± 0.28 m/s, P < 0.002) and diastolic (end diastolic pressure-volume relations: 3.28 ± 0.5 vs. 4.95 ± 1.5 mmHg/ml, P < 0.05) and systolic (end systolic pressure-volume relations: 20.56 ± 4.2 vs. 33.14 ± 8.4 mmHg/ml, P < 0.01) myocardial elastances in old rabbits. Electrophysiological and optical mapping studies revealed age-related slowing of ventricular and His-Purkinje conduction (His-to-ventricle interval: 23 ± 2.5 vs. 31.9 ± 2.9 ms, P < 0.0001), altered conduction anisotropy, and a greater inducibility of ventricular fibrillation (VF, 3/12 vs. 7/9, P < 0.05) in old rabbits. Histochemical studies confirmed an aging-related increased fibrosis in the ventricles. MRI showed a deterioration of the free-running Purkinje fiber network in ventricular and septal walls in old hearts as well as aging-related alterations of the myofibrillar orientation and myocardial sheet structure that may account for this slowed conduction velocity. Aging leads to parallel stiffening of the aorta and the heart, including an increase in systolic stiffness and contractility and diastolic stiffness. Increasingly, anisotropic conduction velocity due to fibrosis and altered myofibrillar orientation and myocardial sheet structure may contribute to the pathogenesis of VF in old hearts. The aging rabbit model represents a useful tool for elucidating age-related changes that predispose the aging heart to arrhythmias and SCD.


2019 ◽  
Author(s):  
Tapash Jay Sarkar ◽  
Marco Quarta ◽  
Shravani Mukherjee ◽  
Alex Colville ◽  
Patrick Paine ◽  
...  

SummaryAging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels1-3. At the chromatin level, aging is associated with the progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis3. The technology of nuclear reprogramming to pluripotency, through over-expression of a small number of transcription factors, can revert both the age and the identity of any cell to that of an embryonic cell by driving epigenetic reprogramming2,4,5. Recent evidence has shown that transient transgenic reprogramming can ameliorate age-associated hallmarks and extend lifespan in progeroid mice6. However, it is unknown how this form of ‘epigenetic rejuvenation’ would apply to physiologically aged cells and, importantly, how it might translate to human cells. Here we show that transient reprogramming, mediated by transient expression of mRNAs, promotes a rapid reversal of both cellular aging and of epigenetic clock in human fibroblasts and endothelial cells, reduces the inflammatory profile in human chondrocytes, and restores youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity. Our method, that we named Epigenetic Reprogramming of Aging (ERA), paves the way to a novel, potentially translatable strategy for ex vivo cell rejuvenation treatment. In addition, ERA holds promise for in vivo tissue rejuvenation therapies to reverse the physiological manifestations of aging and the risk for the development of age-related diseases.


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