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Journal ArticleDOI: 10.1039/D0TB02604B

Designed protein- and peptide-based hydrogels for biomedical sciences

04 Mar 2021-Journal of Materials Chemistry B (The Royal Society of Chemistry)-Vol. 9, Iss: 8, pp 1919-1940
Abstract: Proteins are fundamentally the most important macromolecules for biochemical, mechanical, and structural functions in living organisms. Therefore, they provide us with diverse structural building blocks for constructing various types of biomaterials, including an important class of such materials, hydrogels. Since natural peptides and proteins are biocompatible and biodegradable, they have features advantageous for their use as the building blocks of hydrogels for biomedical applications. They display constitutional and mechanical similarities with the native extracellular matrix (ECM), and can be easily bio-functionalized via genetic and chemical engineering with features such as bio-recognition, specific stimulus-reactivity, and controlled degradation. This review aims to give an overview of hydrogels made up of recombinant proteins or synthetic peptides as the structural elements building the polymer network. A wide variety of hydrogels composed of protein or peptide building blocks with different origins and compositions – including β-hairpin peptides, α-helical coiled coil peptides, elastin-like peptides, silk fibroin, and resilin – have been designed to date. In this review, the structures and characteristics of these natural proteins and peptides, with each of their gelation mechanisms, and the physical, chemical, and mechanical properties as well as biocompatibility of the resulting hydrogels are described. In addition, this review discusses the potential of using protein- or peptide-based hydrogels in the field of biomedical sciences, especially tissue engineering.

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Topics: Self-healing hydrogels (60%)

8 results found

Open accessJournal ArticleDOI: 10.3390/BIOMEDICINES9050570
18 May 2021-Biomedicines
Abstract: Carbon nanomaterials include diverse structures and morphologies, such as fullerenes, nano-onions, nanodots, nanodiamonds, nanohorns, nanotubes, and graphene-based materials. They have attracted great interest in medicine for their high innovative potential, owing to their unique electronic and mechanical properties. In this review, we describe the most recent advancements in their inclusion in hydrogels to yield smart systems that can respond to a variety of stimuli. In particular, we focus on graphene and carbon nanotubes, for applications that span from sensing and wearable electronics to drug delivery and tissue engineering.

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Topics: Carbon nanotube (50%)

4 Citations

Open accessJournal ArticleDOI: 10.1016/J.MTBIO.2021.100115
O. Burgos-Morales1, O. Burgos-Morales2, M. Gueye2, L. Lacombe2  +10 moreInstitutions (3)
01 Jun 2021-
Abstract: Materials in nature have fascinating properties that serve as a continuous source of inspiration for materials scientists. Accordingly, bio-mimetic and bio-inspired approaches have yielded remarkable structural and functional materials for a plethora of applications. Despite these advances, many properties of natural materials remain challenging or yet impossible to incorporate into synthetic materials. Natural materials are produced by living cells, which sense and process environmental cues and conditions by means of signaling and genetic programs, thereby controlling the biosynthesis, remodeling, functionalization, or degradation of the natural material. In this context, synthetic biology offers unique opportunities in materials sciences by providing direct access to the rational engineering of how a cell senses and processes environmental information and translates them into the properties and functions of materials. Here, we identify and review two main directions by which synthetic biology can be harnessed to provide new impulses for the biologization of the materials sciences: first, the engineering of cells to produce precursors for the subsequent synthesis of materials. This includes materials that are otherwise produced from petrochemical resources, but also materials where the bio-produced substances contribute unique properties and functions not existing in traditional materials. Second, engineered living materials that are formed or assembled by cells or in which cells contribute specific functions while remaining an integral part of the living composite material. We finally provide a perspective of future scientific directions of this promising area of research and discuss science policy that would be required to support research and development in this field.

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Topics: Synthetic biology (50%)

3 Citations

Journal ArticleDOI: 10.1039/D1TB00598G
Abstract: The development of suitable biomaterials is one of the key factors responsible for the success of the tissue-engineering field. Recently, significant effort has been devoted to the design of biomimetic materials that can elicit specific cellular responses and direct new tissue formation mediated by bioactive peptides. The success of the design principle of such biomimetic scaffolds is mainly related to the cell–extracellular matrix (ECM) interactions, whereas cell–cell interactions also play a vital role in cell survival, neurite outgrowth, attachment, migration, differentiation, and proliferation. Hence, an ideal strategy to improve cell–cell interactions would rely on the judicious incorporation of a bioactive motif in the designer scaffold. In this way, we explored for the first time the primary functional pentapeptide sequence of the N-cadherin protein, HAVDI, which is known to be involved in cell–cell interactions. We have formulated the shortest N-cadherin mimetic peptide sequence utilizing a minimalistic approach. Furthermore, we employed a classical molecular self-assembly strategy through rational modification of the basic pentapeptide motif of N-cadherin, i.e. HAVDI, using Fmoc and Nap aromatic moieties to modify the N-terminal end. The designed N-cadherin mimetic peptides, Fmoc-HAVDI and Nap-HAVDI, self-assembled to form a nanofibrous network resulting in a bioactive peptide hydrogel at physiological pH. The nanofibrous network of the pentapeptide hydrogels resembles the topology of the natural ECM. Furthermore, the mechanical strength of the gels also matches that of the native ECM of neural cells. Interestingly, both the N-cadherin mimetic peptide hydrogels supported cell adhesion and proliferation of the neural and non-neural cell lines, highlighting the diversity of these peptidic scaffolds. Further, the cultured neural and non-neural cells on the bioactive scaffolds showed normal expression of β-III tubulin and actin, respectively. The cellular response was compromised in control peptides, which further establishes the significance of the bioactive motifs towards controlling the cellular behaviour. Our study indicated that our designer N-cadherin-based peptidic hydrogels mimic the structural as well as the physical properties of the native ECM, which has been further reflected in the functional attributes offered by these scaffolds, and thus offer a suitable bioactive domain for further use as a next-generation material in tissue-engineering applications.

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Topics: Self-healing hydrogels (51%)

2 Citations

Open accessJournal ArticleDOI: 10.1016/J.EURPOLYMJ.2021.110881
Yuanhan Tang1, Xin Zhang1, Xinyue Li1, Chiyue Ma1  +3 moreInstitutions (1)
Abstract: Over the past few decades, polymeric hydrogels have gained significant progress in various fields. As the most biochemically and structurally functional macromolecules in biological organisms, proteins have structural and mechanical properties similar to that of natural extracellular matrices (ECM). By combination of polymers with protein, protein-polymer hydrogel can be constructed as biomaterials with diverse properties and possess a wide range of applications. In this review, we summarized the progress of research on protein-polymer hydrogels and introduced the common fabrication methods. The properties of the protein-polymer hydrogels were briefly described, including biocompatibility, adhesion properties, responsiveness, mechanical properties, swelling properties, and degradability. In addition, we also reviewed the applications of protein-polymer hydrogels in tissue engineering, drug delivery and encapsulation, wearable sensors, adsorption, and other applications. Finally, we summarize the research on protein-polymer hydrogels and highlight the current challenges and future prospects of the field, which may provide a meaningful reference for the field of protein-polymer hydrogels.

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Topics: Self-healing hydrogels (65%)

Journal ArticleDOI: 10.1016/J.POLYMER.2021.123841
Hongyu Zhu1, Yu Liu1, Dongxu Gu1, Zikun Rao1  +2 moreInstitutions (1)
04 Jun 2021-Polymer
Abstract: It is a challenging work to design novel responsive materials by controlling the secondary structure of polypeptide, especially β-sheet. We designed and synthesized a novel dual responsive diblock copolymer of methyl poly (ethylene glycol)-b-poly (O-benzyl- l -threonine) (mPEG-b-PBnLT). The copolymer solutions exhibited unusual and reversible gel-to-sol-to-gel transition behavior with temperature, and the transition temperature window could be easily adjusted by changing copolymer concentration or PBnLT block length. It was confirmed that low temperature gel-to-sol transition was due to the disassembly of the preliminary β-sheet layered nano-assemblies that induced the transformation of self-organized morphology from nanosized fibrils to spherical aggregates, while the high temperature sol-to-gel transition was ascribed to the dehydration of PEG segments. The disassembly of β-sheet structures was caused by the change in the polarity of the pendant benzyl ether bond of PBnLT block in water with temperature. This stimuli-responsiveness of secondary self-assembled nanostructures and the corresponding change in macroscopic phase transition inspires a brand-new strategy for structural design and functional control of polypeptide materials.

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Topics: Copolymer (52%), Ethylene glycol (51%)


284 results found

Journal ArticleDOI: 10.1002/JCC.20035
Abstract: We describe here a general Amber force field (GAFF) for organic molecules. GAFF is designed to be compatible with existing Amber force fields for proteins and nucleic acids, and has parameters for most organic and pharmaceutical molecules that are composed of H, C, N, O, S, P, and halogens. It uses a simple functional form and a limited number of atom types, but incorporates both empirical and heuristic models to estimate force constants and partial atomic charges. The performance of GAFF in test cases is encouraging. In test I, 74 crystallographic structures were compared to GAFF minimized structures, with a root-mean-square displacement of 0.26 A, which is comparable to that of the Tripos 5.2 force field (0.25 A) and better than those of MMFF 94 and CHARMm (0.47 and 0.44 A, respectively). In test II, gas phase minimizations were performed on 22 nucleic acid base pairs, and the minimized structures and intermolecular energies were compared to MP2/6-31G* results. The RMS of displacements and relative energies were 0.25 A and 1.2 kcal/mol, respectively. These data are comparable to results from Parm99/RESP (0.16 A and 1.18 kcal/mol, respectively), which were parameterized to these base pairs. Test III looked at the relative energies of 71 conformational pairs that were used in development of the Parm99 force field. The RMS error in relative energies (compared to experiment) is about 0.5 kcal/mol. GAFF can be applied to wide range of molecules in an automatic fashion, making it suitable for rational drug design and database searching.

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Topics: Intermolecular force (51%)

10,937 Citations

Journal ArticleDOI: 10.1016/S0169-409X(01)00239-3
Allan S. Hoffman1Institutions (1)
Abstract: This article reviews the composition and synthesis of hydrogels, the character of their absorbed water, and permeation of solutes within their swollen matrices. The most important properties of hydrogels relevant to their biomedical applications are also identified, especially for use of hydrogels as drug and cell carriers, and as tissue engineering matrices.

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Topics: Self-healing hydrogels (64%)

4,906 Citations

Journal ArticleDOI: 10.1016/S0142-9612(03)00340-5
Jeanie L. Drury1, David J. Mooney1Institutions (1)
01 Nov 2003-Biomaterials
Abstract: Polymer scaffolds have many different functions in the field of tissue engineering. They are applied as space filling agents, as delivery vehicles for bioactive molecules, and as three-dimensional structures that organize cells and present stimuli to direct the formation of a desired tissue. Much of the success of scaffolds in these roles hinges on finding an appropriate material to address the critical physical, mass transport, and biological design variables inherent to each application. Hydrogels are an appealing scaffold material because they are structurally similar to the extracellular matrix of many tissues, can often be processed under relatively mild conditions, and may be delivered in a minimally invasive manner. Consequently, hydrogels have been utilized as scaffold materials for drug and growth factor delivery, engineering tissue replacements, and a variety of other applications.

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Topics: Self-healing hydrogels (57%), Scaffold (53%), Tissue engineering (53%)

4,191 Citations

Journal ArticleDOI: 10.1021/CR000108X
Kuen Yong Lee1, David J. Mooney1Institutions (1)
31 May 2001-Chemical Reviews
Topics: Self-healing hydrogels (56%)

4,117 Citations

Open accessJournal ArticleDOI: 10.1038/NATURE11409
06 Sep 2012-Nature
Abstract: Hydrogels with improved mechanical properties, made by combining polymer networks with ionic and covalent crosslinks, should expand the scope of applications, and may serve as model systems to explore mechanisms of deformation and energy dissipation. Hydrogels are used in flexible contact lenses, as scaffolds for tissue engineering and in drug delivery. Their poor mechanical properties have so far limited the scope of their applications, but new strong and stretchy materials reported here could take hydrogels into uncharted territories. The new system involves a double-network gel, with one network forming ionic crosslinks and the other forming covalent crosslinks. The fracture energy of these materials is very high: they can stretch to beyond 17 times their own length even when containing defects that usually initiate crack formation in hydrogels. The materials' toughness is attributed to crack bridging by the covalent network accompanied by energy dissipation through unzipping of the ionic crosslinks in the second network. Hydrogels are used as scaffolds for tissue engineering1, vehicles for drug delivery2, actuators for optics and fluidics3, and model extracellular matrices for biological studies4. The scope of hydrogel applications, however, is often severely limited by their mechanical behaviour5. Most hydrogels do not exhibit high stretchability; for example, an alginate hydrogel ruptures when stretched to about 1.2 times its original length. Some synthetic elastic hydrogels6,7 have achieved stretches in the range 10–20, but these values are markedly reduced in samples containing notches. Most hydrogels are brittle, with fracture energies of about 10 J m−2 (ref. 8), as compared with ∼1,000 J m−2 for cartilage9 and ∼10,000 J m−2 for natural rubbers10. Intense efforts are devoted to synthesizing hydrogels with improved mechanical properties11,12,13,14,15,16,17,18; certain synthetic gels have reached fracture energies of 100–1,000 J m−2 (refs 11, 14, 17). Here we report the synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks. Although such gels contain ∼90% water, they can be stretched beyond 20 times their initial length, and have fracture energies of ∼9,000 J m−2. Even for samples containing notches, a stretch of 17 is demonstrated. We attribute the gels’ toughness to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping the network of ionic crosslinks. Furthermore, the network of covalent crosslinks preserves the memory of the initial state, so that much of the large deformation is removed on unloading. The unzipped ionic crosslinks cause internal damage, which heals by re-zipping. These gels may serve as model systems to explore mechanisms of deformation and energy dissipation, and expand the scope of hydrogel applications.

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2,952 Citations

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