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Pro-angiogenic and anti-inflammatory regulation by functional peptides loaded in polymeric implants for soft tissue regeneration.
Zachman AL, Crowder SW, Ortiz O, Zienkiewicz KJ, Bronikowski CM, Yu SS, Giorgio TD, Guelcher SA, Kohn J, Sung HJ
(2013) Tissue Eng Part A 19: 437-47
MeSH Terms: Angiogenic Proteins, Animals, Anti-Inflammatory Agents, Drug Implants, Equipment Design, Guided Tissue Regeneration, Laminin, Mice, Peptides, Polyethylenes, Regeneration, Soft Tissue Infections, Thymosin, Tissue Scaffolds, Treatment Outcome
Show Abstract · Added September 24, 2012
Inflammation and angiogenesis are inevitable in vivo responses to biomaterial implants. Continuous progress has been made in biomaterial design to improve tissue interactions with an implant by either reducing inflammation or promoting angiogenesis. However, it has become increasingly clear that the physiological processes of inflammation and angiogenesis are interconnected through various molecular mechanisms. Hence, there is an unmet need for engineering functional tissues by simultaneous activation of pro-angiogenic and anti-inflammatory responses to biomaterial implants. In this work, the modulus and fibrinogen adsorption of porous scaffolds were tuned to meet the requirements (i.e., ~100 kPa and ~10 nm, respectively), for soft tissue regeneration by employing tyrosine-derived combinatorial polymers with polyethylene glycol crosslinkers. Two types of functional peptides (i.e., pro-angiogenic laminin-derived C16 and anti-inflammatory thymosin β4-derived Ac-SDKP) were loaded in porous scaffolds through collagen gel embedding so that peptides were released in a controlled fashion, mimicking degradation of the extracellular matrix. The results from (1) in vitro coculture of human umbilical vein endothelial cells and human blood-derived macrophages and (2) in vivo subcutaneous implantation revealed the directly proportional relationship between angiogenic activities (i.e., tubulogenesis and perfusion capacity) and inflammatory activities (i.e., phagocytosis and F4/80 expression) upon treatment with either type of peptide. Interestingly, cotreatment with both types of peptides upregulated the angiogenic responses, while downregulating the inflammatory responses. Also, anti-inflammatory Ac-SDKP peptides reduced production of pro-inflammatory cytokines (i.e., interleukin [IL]-1β, IL-6, IL-8, and tumor necrosis factor alpha) even when treated in combination with pro-angiogenic C16 peptides. In addition to independent regulation of angiogenesis and inflammation, this study suggests a promising approach to improve soft tissue regeneration (e.g., blood vessel and heart muscle) when inflammatory diseases (e.g., ischemic tissue fibrosis and atherosclerosis) limit the regeneration process.
2 Communities
4 Members
0 Resources
15 MeSH Terms
Controlled release of dopamine from a polymeric brain implant: in vivo characterization.
During MJ, Freese A, Sabel BA, Saltzman WM, Deutch A, Roth RH, Langer R
(1989) Ann Neurol 25: 351-6
MeSH Terms: Animals, Brain, Corpus Striatum, Dopamine, Drug Implants, Male, Polymers, Prostheses and Implants, Rats, Rats, Inbred Strains, Tissue Distribution
Show Abstract · Added May 27, 2014
Intracerebral microdialysis was used to evaluate the long-term in vivo release of dopamine from ethylene-vinyl acetate (EVAc)-dopamine copolymer matrix discs for up to 65 days following striatal implantation. Dopamine release occurred through a single cavity present on one side of the disc, which was otherwise fully coated with an additional, impermeable layer of EVAc. At 20 days following implantation of the device, extracellular concentrations of dopamine within the striatum reached micromolar levels, over 200-fold greater than control values. Release of dopamine was shown to be stable and maintained for the 2-month duration of the experiment. Histological examination confirmed the biocompatible nature of the implant. There are potential applications of this technology to the treatment of Parkinson's disease and other neurological and psychiatric disorders.
0 Communities
1 Members
0 Resources
11 MeSH Terms
Induced ovulation in aged female rats by L-dopa implants into the medial preoptic area.
Cooper RL, Brandt SJ, Linnoila M, Walker RF
(1979) Neuroendocrinology 28: 234-40
MeSH Terms: Age Factors, Animals, Brain Mapping, Drug Implants, Estrus, Female, Hypothalamus, Levodopa, Ovulation, Pregnancy, Preoptic Area, Rats, Septum Pellucidum, Stimulation, Chemical, Temporal Lobe
Show Abstract · Added March 5, 2014
Direct placement of L-dopa into the medial preoptic area (MPOA) of aged pseudopregnant or constant vaginal estrous female rats resulted in a reinitiation of vaginal cycles and ovulation. Similar treatment with L-dopa in the dorsomedial septum or cortex was ineffective. Direct placement of leucine into any of the three brain regions did not have an effect on ovarian function. Intermittent treatment with L-dopa to MPOA was found to reinstate and maintain vaginal cycles in constant estrous females only when administered on the day of vaginal estrus of successive cycles. These findings support the hypothesis that age-dependent disturbances in ovarian function may be initiated by changes in neurotransmitter metabolism within the central nervous system.
0 Communities
1 Members
0 Resources
15 MeSH Terms