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Restoration: Nanotechnology in Tissue Replacement and Prosthetics
Published in Harry F. Tibbals, Medical Nanotechnology and Nanomedicine, 2017
Another example of experimental work demonstrating the potential of nanoengineered bioactive scaffolds used a dorsal skinfold model to evaluate the effectiveness of supramolecular nanofibers formed by self-assembly of a heparin-binding peptide amphiphile and heparan sulfate-like glycosamino-glycans heparin-binding peptides. The heparin compounds were designed to promote angiogenesis, and thus have great potential in regenerative medicine for rapid revascularization of damaged tissue, survival of transplanted cells, and healing of chronic wounds. Dynamic monitoring of the interaction between the nanofiber gel and the microcirculation of the host tissue showed excellent biocompatibility. As the nanofibers biodegraded over 30 days, striking formation of new vascularized connective tissue was observed. Nanofiber-based bioactive gels of this type are being developed as angiogenesis-promoting materials for a number of wound repair and regenerative applications [66].
Nanotechnological Strategies for Engineering Complex Tissues
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Tal Dvir, Brian P. Timko, Daniel S. Kohane, Robert Langer
Despite the simplicity of electrospinning in creating fibrous scaffolds, one substantial disadvantage is that the diameters of the fibres are usually at the upper limits of the 50–500 nm range seen in natural ECM. To emulate natural ECM better, both structurally and functionally, and to promote cell–matrix interaction at the molecular level, 3D scaffolds were created by molecular self-assembly of fibres. This technique involves the spontaneous organization of individual components into an ordered and stable structure with pre-programmed non-covalent bonds (Fig. 12.3b) [32]. The most commonly investigated self-assembled nanofibre matrix for tissue engineering applications is the peptide amphiphile, a chemical compound possessing both hydrophobic and hydrophilic properties [33]. The peptides that assemble to the 3D scaffolds can have a fibre diameter as small as 10 nm and the scaffold pore size can range between 5 and 200 nm, significantly smaller than those produced by electrospinning [22]. An important advantage of this approach is the ability to include functional motif sequences (such as short peptides) that promote adherence, differentiation and maturation [34–36]. This class of scaffolds can provide both mechanical support and instructive cues to the developing tissue. For example, neural progenitor cells were encapsulated within a 3D network of nanofibers [37], designed to present to cells the neurite-promoting laminin epitope IKVAV. Cultivation within this scaffold induced very rapid differentiation of cells into neurons, while discouraging the differentiation to other cell lineages [37], emphasizing the importance and simplicity of controlling cell fate by pre-designing the fibre composition. A challenge in this field is to engineer fibres effectively to provide adhesion and organization motifs that the cells can interact with, and provide multiple cues for intracellular signalling that lead to differentiation and control of gene expression.
A ‘Biomaterial Cookbook’: Biochemically Patterned Substrate to Promote and Control Vascularisation in Vitro and in Vivo
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Katie M. Kilgour, Brendan L. Turner, Augustus Adams, Stefano Menegatti, Michael A. Daniele
A successful engineered tissue construct (ETC) requires a scaffold with instructive functionalisation with biophysical and chemical cues and appropriate resident cell population(s) (Hasan, 2016). The materials employed in tissue scaffolds are typically hydrogels of either natural or synthetic origin. Natural materials comprise polysaccharides (e.g., chitosan, alginate, hyaluronic acid, etc.), proteins (e.g., collagen, gelatin, vitronectin, etc. (J. Zhu & Marchant, 2011)) or self-assembling peptides (e.g., α-helix, β-sheet, collagen-like peptides, elastin-like peptides, or peptide amphiphiles (Hellmund & Koksch, 2019; Rivas, Del Valle, Alemán, & Puiggalí, 2019)). These materials are naturally bioadhesive and exhibit tunable mechanical properties; on the other hand, they are highly variable and often require physicochemical or biochemical modifications that are often challenging to achieve (Cushing & Anseth, 2007; Nguyen & Murphy, 2018; Smithmyer, Sawicki, & Kloxin, 2014). Synthetic materials, instead, are easily tunable both chemically and mechanically and are available in large scale and affordable, but they provide limited biointegration and can trigger adverse foreign-body response in host organisms (Zant & Grijpma, 2016). To date, extensive research has been conducted to fine-tune the mechanical, chemical, and biomolecular properties of synthetic and natural biomaterials and better understand the cell ingredients needed to successfully achieve vascularisation in vitro and in vivo (e.g., at an injury site) (Berthiaume, Maguire, & Yarmush, 2011; Eberli, Filho, Atala, & Yoo, 2009; Vacanti & Vacanti, 2000; Viola, Lal, & Grad, 2003). Current research revolves around developing ‘smart biomaterials’ that can direct cell functions and enhance cell performance (Furth & Atala, 2013). Tissue scaffolds can be applied to various tissues (e.g., heart, kidneys, liver, lungs, etc.) and manipulated based on the native complexity (Eberli et al., 2009).
Octreotide and Octreotide-derived delivery systems
Published in Journal of Drug Targeting, 2023
Mingliang Fan, Yue Huang, Xinlin Zhu, Jiayu Zheng, Mingwei Du
OCT has been utilised to guide theranostic systems with therapeutic and diagnostic functions. Bai et al. developed a core cross-linked hybrid micelle containing OCT-PEG-b-PGu and mPEG-b-PGu for neuroendocrine neoplasms targeted delivery of etoposide, this micelle incorporated borate ester bonds, disulphide bonds and chromophore tetraphenyl ethylene (TPE), making it a multifunctional delivery system with pH and redox dual-responsive drug release and aggregation-induced emission (AIE) active imaging properties [128]. Vijayan and co-authors reported OCT-modified fluorescent nanogels based on photoluminescent PEG-maleic acid-4 aminobenzoic acid and diethylene glycoldimethacrylate, these nanogels had good performance in near-IR imaging and doxorubicin delivery [129]. Kim et al. fabricated a novel kind of one dimensional theranostic nanofibril via self-assembly of peptide amphiphiles. As shown in Figure 9, OCT or Cd3+-chelated DOTA was coupled with these peptide amphiphiles, resulting in a successful formation of MRI nanofibrils which can deliver doxorubicin in a SSTR specific manner [130].
Developments with investigating descriptors for antimicrobial AApeptides and their derivatives
Published in Expert Opinion on Drug Discovery, 2018
Olapeju Bolarinwa, Jianfeng Cai
Antimicrobial peptides (AMPs), also known as host-defense peptides (HDPs), have been studied for their intriguing antimicrobial properties. HDPs are short cationic amphiphilic peptides with antimicrobial and/or immunomodulatory activities and forms an essential component of the innate immune system in multicellular organisms [7]. With broad-spectrum antimicrobial activity against bacteria, fungi, protozoans, and enveloped viruses, HDPs are dispatched at the first line of the defense system for quicker intervention than the adaptive immune system[8]. HDPs show broad-spectrum antimicrobial activity against bacteria, fungi, protozoans, and even enveloped viruses [9]. The amino-acid composition of HDPs typically ranges from 10 to 50 residues and are mostly basic and hydrophobic. These residues are arranged to form peptide amphiphiles that can easily interact with bacterial membranes [10]. The antimicrobial activity of HDPs is largely dependent on electrostatic interactions with the negatively charged bacterial membranes or cell walls [10,11]. However, the outer layers of cell membranes in eukaryotes have zwitterionic components, which make them interact poorly with HDPs [12–14]. As such, HDPs display considerable selectivity toward bacteria instead of mammalian cells. In addition to targeting bacterial membranes, HDPs could have other mechanisms of action including targeting multiple bacterial proteins and nucleic acids, and inhibition of bacterial cellular pathways and gene expression [15–17]. The diverse cellular and membrane targets of HDPs have made a widespread of bacterial resistance less possible [15].
Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Samaneh Mohammadi, Parvin Zakeri-Milani, Nasim Golkar, Samad Mussa Farkhani, Ali Shirani, Javid Shahbazi Mojarrad, Ali Nokhodchi, Hadi Valizadeh
Peptides and proteins are generally worthy in many aspects, such as their possible high potency, good selectivity and acceptable toxicity [24]. Two decades ago, a new kind of peptides, commonly known as cell penetrating peptide (CPP), was discovered. These peptides have been extracted from natural proteins and have the capability to cross cellular membranes and mediate the uptake of a wide range of macromolecular cargoes [1,25–28]. The discovered peptides as non-invasive vectors with very limited toxicity introduced a novel field in drug delivery [29]. In addition, they can be modified or designed de novo. They are typically short; usually 5–30 amino acids long [28,30–35]. These bioactive and biodegradable peptides are able to carry and deliver their cargos such as nucleic acids, proteins, drugs, or imaging agents, to the cytoplasm or nuclei of cells [30,33–35]. In the recent years, numerous natural and synthetic CPPs such as polyarginines, TAT (trans-acting activator of transcription) [27] and peptide amphiphiles (PA) [23] have improved the cellular uptake of various drugs such as taxol [36], methotrexate [16] and doxorubicin [12]. Among these CPPs, peptide amphiphiles appear to be among the efficient systems in drug delivery [37–39]. Universally, peptide amphiphiles consist of hydrophobic segments such as tryptophan and charged segments such as arginine or lysine [37]. These peptides have a helical secondary structure with the hydrophobic and hydrophilic domains. They use the charged region for cell membrane interaction and the hydrophobic region for membrane perturbation and translocation [30,40]. Moreover, several studies have shown that the presence of tryptophan and backbone spacing can affect the uptake efficiency as well as its mechanism [41].