Browsing by Subject "Biomimetics"

Now showing 1 - 4 of 4
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    Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo.
    (Proc Natl Acad Sci U S A, 2014-04-15) Juhas, Mark; Engelmayr, George C; Fontanella, Andrew N; Palmer, Gregory M; Bursac, Nenad
    Tissue-engineered skeletal muscle can serve as a physiological model of natural muscle and a potential therapeutic vehicle for rapid repair of severe muscle loss and injury. Here, we describe a platform for engineering and testing highly functional biomimetic muscle tissues with a resident satellite cell niche and capacity for robust myogenesis and self-regeneration in vitro. Using a mouse dorsal window implantation model and transduction with fluorescent intracellular calcium indicator, GCaMP3, we nondestructively monitored, in real time, vascular integration and the functional state of engineered muscle in vivo. During a 2-wk period, implanted engineered muscle exhibited a steady ingrowth of blood-perfused microvasculature along with an increase in amplitude of calcium transients and force of contraction. We also demonstrated superior structural organization, vascularization, and contractile function of fully differentiated vs. undifferentiated engineered muscle implants. The described in vitro and in vivo models of biomimetic engineered muscle represent enabling technology for novel studies of skeletal muscle function and regeneration.
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    Comprehensive pharmacokinetic studies and oral bioavailability of two Mn porphyrin-based SOD mimics, MnTE-2-PyP5+ and MnTnHex-2-PyP5+.
    (Free radical biology & medicine, 2013-05) Weitner, Tin; Kos, Ivan; Sheng, Huaxin; Tovmasyan, Artak; Reboucas, Julio S; Fan, Ping; Warner, David S; Vujaskovic, Zeljko; Batinic-Haberle, Ines; Spasojevic, Ivan
    The cationic, ortho Mn(III) N-alkylpyridylporphyrins (alkyl=ethyl, E, and n-hexyl, nHex) MnTE-2-PyP(5+) (AEOL10113, FBC-007) and MnTnHex-2-PyP(5+) have proven efficacious in numerous in vivo animal models of diseases having oxidative stress in common. The remarkable therapeutic efficacy observed is due to their: (1) ability to catalytically remove O2(•-) and ONOO(-) and other reactive species; (2) ability to modulate redox-based signaling pathways; (3) accumulation within critical cellular compartments, i.e., mitochondria; and (4) ability to cross the blood-brain barrier. The similar redox activities of both compounds are related to the similar electronic and electrostatic environments around the metal active sites, whereas their different bioavailabilities are presumably influenced by the differences in lipophilicity, bulkiness, and shape. Both porphyrins are water soluble, but MnTnHex-2-PyP(5+) is approximately 4 orders of magnitude more lipophilic than MnTE-2-PyP(5+), which should positively affect its ability to pass through biological membranes, making it more efficacious in vivo at lower doses. To gain insight into the in vivo tissue distribution of Mn porphyrins and its impact upon their therapeutic efficacy and mechanistic aspects of action, as well as to provide data that would ensure proper dosing regimens, we conducted comprehensive pharmacokinetic (PK) studies for 24h after single-dose drug administration. The porphyrins were administered intravenously (iv), intraperitoneally (ip), and via oral gavage at the following doses: 10mg/kg MnTE-2-PyP(5+) and 0.5 or 2mg/kg MnTnHex-2-PyP(5+). Drug levels in plasma and various organs (liver, kidney, spleen, heart, lung, brain) were determined and PK parameters calculated (Cmax, C24h, tmax, and AUC). Regardless of high water solubility and pentacationic charge of these Mn porphyrins, they are orally available. The oral availability (based on plasma AUCoral/AUCiv) is 23% for MnTE-2-PyP(5+) and 21% for MnTnHex-2-PyP(5+). Despite the fivefold lower dose administered, the AUC values for liver, heart, and spleen are higher for MnTnHex-2-PyP(5+) than for MnTE-2-PyP(5+) (and comparable for other organs), clearly demonstrating the better tissue penetration and tissue retention of the more lipophilic MnTnHex-2-PyP(5+).
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    Exosome and Biomimetic Nanoparticle Therapies for Cardiac Regenerative Medicine.
    (Current stem cell research & therapy, 2020-01) Stine, Sydney J; Popowski, Kristen D; Su, Teng; Cheng, Ke
    Exosomes and biomimetic nanoparticles have great potential to develop into a wide-scale therapeutic platform within the regenerative medicine industry. Exosomes, a subgroup of EVs with diameter ranging from 30-100 nm, have recently gained attention as an innovative approach for the treatment of various diseases, including heart disease. Their beneficial factors and regenerative properties can be contrasted with various cell types. Various biomimetic nanoparticles have also emerged as a unique platform in regenerative medicine. Biomimetic nanoparticles are a drug delivery platform, which have the ability to contain both biological and fabricated components to improve therapeutic efficiency and targeting. The novelty of these platforms holds promise for future clinical translation upon further investigation. In order for both exosome therapeutics and biomimetic nanoparticles to translate into large-scale clinical treatment, numerous factors must first be considered and improved. Standardization of different protocols, from exosome isolation to storage conditions, must be optimized to ensure batches are pure. Standardization is also important to ensure no variability in this process across studies, thus making it easier to interpret data across different disease models and treatments. Expansion of clinical trials incorporating both biomimetic nanoparticles and exosomes will require a standardization of fabrication and isolation techniques, as well as stricter regulations to ensure reproducibility across various studies and disease models. This review will summarize current research on exosome therapeutics and the application of biomimetic nanoparticles in cardiac regenerative medicine, as well as applications for exosome expansion and delivery on a large clinical scale.
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    MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management.
    (Redox biology, 2019-01) Bellot, Gregory Lucien; Dong, Xiaoke; Lahiri, Amitabha; Sebastin, Sandeep Jacob; Batinic-Haberle, Ines; Pervaiz, Shazib; Puhaindran, Mark Edward
    Negative Pressure Wound Therapy (NPWT), a widely used modality in the management of surgical and trauma wounds, offers clear benefits over conventional wound healing strategies. Despite the wide-ranging effects ascribed to NPWT, the precise molecular mechanisms underlying the accelerated healing supported by NPWT remains poorly understood. Notably, cellular redox status-a product of the balance between cellular reactive oxygen species (ROS) production and anti-oxidant defense systems-plays an important role in wound healing and dysregulation of redox homeostasis has a profound effect on wound healing. Here we investigated potential links between the use of NPWT and the regulation of antioxidant mechanisms. Using patient samples and a rodent model of acute injury, we observed a significant accumulation of MnSOD protein as well as higher enzymatic activity in tissues upon NPWT. As a proof of concept and to outline the important role of SOD activity in wound healing, we replaced NPWT by the topical application of a MnSOD mimetic, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+, MnE, BMX-010, AEOl10113) in the rodent model. We observed that MnE is a potent wound healing enhancer as it appears to facilitate the formation of new tissue within the wound bed and consequently advances wound closure by two days, compared to the non-treated animals. Taken together, these results show for the first time a link between NPWT and regulation of antioxidant mechanism through the maintenance of MnSOD activity. Additionally this discovery outlined the potential role of MnSOD mimetics as topical agents enhancing wound healing.