Showing papers on "Self-healing hydrogels published in 2006"
TL;DR: This work highlights recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for biomedical and biological applications and shows how such systems' intelligent behavior can be used in sensors, microarrays, and imaging.
Abstract: Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range of biomedical and biological applications. Here we highlight recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for these applications. Natural, biohybrid, and synthetic hydrophilic polymers and hydrogels are analyzed and their thermodynamic responses are discussed. In addition, examples of the use of hydrogels for various therapeutic applications are given. We show how such systems’ intelligent behavior can be used in sensors, microarrays, and imaging. Finally, we outline challenges for the future in integrating hydrogels into biomedical applications.
3,524 citations
TL;DR: Alginate, being an anionic polymer with carboxyl end groups, is a good mucoadhesive agent and cross-linked alginate has more capacity to retain the entrapped drugs and mixing of alginates with other polymers such as neutral gums, chitosan, and eudragit have been found to solve the problem of drug leaching.
1,724 citations
TL;DR: The objective of this article is to review the fundamentals and recent advances in hydrogel network design as well as mathematical modeling approaches related to controlled molecule release from hydrogels.
1,515 citations
TL;DR: The composition and synthesis of hydrogels, the character of their absorbed water, and permeation of solutes within their swollen matrices are reviewed to identify the most important properties relevant to their biomedical applications.
Abstract: This paper 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, in particular for use of hydrogels as drug and cell carriers, and as tissue engineering matrices
1,229 citations
TL;DR: A number of short peptide amphiphiles consisting of dipeptides linked to fluorenylmethoxycarbonyl spontaneously form fibrous hydrogels under physiological conditions, and the gels support the three-dimensional cell culture of chondrocytes.
Abstract: A number of short peptide amphiphiles consisting of dipeptides linked to fluorenylmethoxycarbonyl spontaneously form fibrous hydrogels under physiological conditions (see figure). The structural and physical properties of these gels are dictated by the amino acid sequence of the peptide building blocks, and the gels support the three-dimensional cell culture of chondrocytes.
910 citations
706 citations
TL;DR: The construction of a hydrogel entirely from branched DNA that are three-dimensional and can be crosslinked in nature is reported, allowing the hydrogels to be tailored for specific applications such as controlled drug delivery, tissue engineering, 3D cell culture, cell transplant therapy and other biomedical applications.
Abstract: DNA is a remarkable polymer that can be manipulated by a large number of molecular tools including enzymes. A variety of geometric objects, periodic arrays and nanoscale devices have been constructed. Previously we synthesized dendrimer-like DNA and DNA nanobarcodes from branched DNA via ligases. Here we report the construction of a hydrogel entirely from branched DNA that are three-dimensional and can be crosslinked in nature. These DNA hydrogels were biocompatible, biodegradable, inexpensive to fabricate and easily moulded into desired shapes and sizes. The distinct difference of the DNA hydrogel to other bio-inspired hydrogels (including peptide-based, alginate-based and DNA (linear)-polyacrylamide hydrogels) is that the crosslinking is realized via efficient, ligase-mediated reactions. The advantage is that the gelling processes are achieved under physiological conditions and the encapsulations are accomplished in situ-drugs including proteins and even live mammalian cells can be encapsulated in the liquid phase eliminating the drug-loading step and also avoiding denaturing conditions. Fine tuning of these hydrogels is easily accomplished by adjusting the initial concentrations and types of branched DNA monomers, thus allowing the hydrogels to be tailored for specific applications such as controlled drug delivery, tissue engineering, 3D cell culture, cell transplant therapy and other biomedical applications.
681 citations
TL;DR: It is found that phenylalanine-mediated inter-repeat interactions indeed cross-link FG-repeat domains into elastic and reversible hydrogels and obtained evidence that such hydrogel formation is required for viability in yeast.
Abstract: Nuclear pore complexes permit rapid passage of cargoes bound to nuclear transport receptors, but otherwise suppress nucleocytoplasmic fluxes of inert macromolecules ≥30 kilodaltons. To explain this selectivity, a sieve structure of the permeability barrier has been proposed that is created through reversible cross-linking between Phe and Gly (FG)–rich nucleoporin repeats. According to this model, nuclear transport receptors overcome the size limit of the sieve and catalyze their own nuclear pore-passage by a competitive disruption of adjacent inter-repeat contacts, which transiently opens adjoining meshes. Here, we found that phenylalanine-mediated inter-repeat interactions indeed cross-link FG-repeat domains into elastic and reversible hydrogels. Furthermore, we obtained evidence that such hydrogel formation is required for viability in yeast.
576 citations
TL;DR: New PEG-based hydrogel materials have been synthesized by Click chemistry and shown to result in well-defined networks having significantly improved mechanical properties.
546 citations
TL;DR: It is demonstrated that proteases can be used to selectively trigger the self-assembly of peptide hydrogels via reversed hydrolysis.
Abstract: We demonstrate that proteases can be used to selectively trigger the self-assembly of peptide hydrogels via reversed hydrolysis.
473 citations
TL;DR: A new paradigm for generating 3D microcontrolled materials using two-photon absorption (TPA) photolithography to pattern bioactivity into existing photoactive materials is developed and the ability to spatially tailor material biomechanical and biochemical properties at the microscale and to create freeform 3D patterns and gradients is demonstrated.
Abstract: The ability to tailor the biochemical and biomechanical properties of 3D materials at the microscale is important for a range of biotechnology applications, including the engineering of complex tissues, the development of biosensors, the elucidation of cell–cell and cell–material interactions, and the guidance of cellular differentiation. To this end, techniques have emerged for the fabrication of 3D microcontrolled materials, including conventional photolithographic patterning, electrochemical deposition, 3D printing, and soft-lithographic approaches. To create internally complex 3D materials, these methods are repeated in a layer-by-layer fashion until a scaffold of the desired dimensionality is achieved. However, an alternate approach to the fabrication of internally complex 3D scaffolds, that is, the patterning of bioactivity into preformed materials of the desired final dimensions, has not been similarly examined. Here, we develop a new paradigm for generating 3D microcontrolled materials using two-photon absorption (TPA) photolithography to pattern bioactivity into existing photoactive materials. We demonstrate the ability to spatially tailor material biomechanical and biochemical properties at the microscale and to create freeform 3D patterns and gradients. Furthermore, to illustrate the power of this approach for guiding cell behavior, proteolytically degradable hydrogels were patterned in 3D with the cell adhesive peptide arginine–glycine–aspartic acid–serine (RGDS), and cells were shown to invade and migrate into only the RGDS-containing regions. In the present study, we first establish the feasibility of patterning bioactive features into optically transparent, photoactive materials using an adaptation of conventional photolithography, that is, single-photon absorption (SPA) photolithography. Although, as previously mentioned, SPA photolithography has been used to create topographical microstructures on surfaces, it has not, to the best of our knowledge, been developed for the internal modification of preformed materials. We show that SPA photolithography allows for rapid and inexpensive biochemical and biomechanical patterning of existing photoactive materials in three dimensions. However, pattern complexity is limited to features of axially uniform cross section, since light passes vertically through the entire sample. Thus, we went on to develop TPA photolithography for creating axially complex, freeform 3D biochemical and biomechanical patterns and gradients in existing photoactive materials. TPA has enabled the development of 3D fluorescence imaging, 3D lithographic microfabrication, and new approaches to 3D optical data storage. Each of these applications takes advantage of the fact that, by tightly focusing an excitation beam, the region of TPA can be confined to a focal volume roughly half the excitation wavelength in dimension. Any subsequent process, such as a photoinitiated or radical-based polymerization, is also localized to this small volume, assuming the timescale of radical diffusion to be large compared to the radical half life. Thus, by specifying the location of the laser-beam focal point, regions of photoinduced conjugation can be precisely dictated. In the present work, poly(ethylene glycol) (PEG)-diacrylate (PEGDA) hydrogels are used as model materials for the generation of internal 3D patterns. PEG-based materials have been studied extensively as tissue-engineering scaffolds and are biocompatible and intrinsically resistant to protein adsorption and cell adhesion. In addition, acrylate-terminated PEG macromers undergo rapid polymerization in the presence of photoinitiators that generate radicals when exposed to light. Thus, PEGDA hydrogels are in themselves biological “blank slates” into which desired bioactivity can be tailored via light-based patterning. To create 3D patterns using SPA photolithography, masks were first prepared by printing the lateral cross section of the desired pattern onto transparencies. A precursor solution containing appropriate photoinitiator and fluorescently labeled acryloyl (ACRL)-PEG-peptide or low-molecular-weight (MW) PEGDA was allowed to diffuse into a preswelled PEGDA hydrogel. The transparency mask was applied with the printed side in contact with the hydrogel surface, and the acrylate-derivatized moieties in the precursor solution were conjugated to specific regions within the hydrogel by applying UV light through the transparency mask. Since the 600 MW PEGDA is diacrylate derivatized rather than monoacrylate derivatized (as is ACRL-PEG-peptide), immobilization of 600 MW PEGDA into the existing 6000 MW PEGDA hydrogel alters the local crosslinking density of the hydrogel (Fig. 1A). Thus, the transport and mechanical C O M M U N IC A IO N S
TL;DR: A kinase/phosphatase switch is used to control the phosphorylation and dephosphorylation of the hydrogelator and to regulate the formation of supramolecular hydrogels, which promises a new way to design and construct biomaterials.
Abstract: We have designed and synthesized a new hydrogelator Nap−FFGEY (1), which forms a supramolecular hydrogel. A kinase/phosphatase switch is used to control the phosphorylation and dephosphorylation of the hydrogelator and to regulate the formation of supramolecular hydrogels. Adding a kinase to the hydrogel induces a gel−sol phase transition in the presence of adenosine triphosphates (ATP) because the tyrosine residue is converted into tyrosine phosphate by the kinase to give a more hydrophilic molecule of Nap−FFGEY−P(O)(OH)2 (2); treating the resulting solution with a phosphatase transforms 2 back to 1 and restores the hydrogel. Electron micrographs of the hydrogels indicate that 1 self-assembles into nanofibers. Subcutaneous injection of 2 in mice shows that 80.5 ± 1.2% of 2 turns into 1 and results in the formation of the supramolecular hydrogel of 1 in vivo. This simple biomimetic approach for regulating the states of supramolecular hydrogels promises a new way to design and construct biomaterials.
TL;DR: P(AA-g-EG) hydrogels can be successfully used as drug delivery systems because their versatility to be designed with specifically tuned release properties renders these biomaterials promising pharmaceutical carriers for therapeutic agents.
TL;DR: This patterning method may find use in tissue engineering, the elucidation of fundamental structure-function relationships, and the formation of immobilized cell and protein arrays for biotechnology.
TL;DR: In this article, the authors used confocal microscopy to non-invasively monitor these key cell functions over time, and showed that neural cells cultured within three-dimensional polymer networks create their own cellular microenvironment to survive, proliferate and differentiate and form neurons and glia that are electrophysiologically responsive to neurotransmitter.
TL;DR: Combined, these data suggest that the mechanical and chemical properties of PEG hydrogels can be tuned to influence SMC phenotype in both 2-D and 3-D.
TL;DR: Novel poly(vinyl alcohols) (PVA) functionalized with pendant acetylene and azide groups were prepared by carbonyldiimidazole (CDI)-mediated couplings of the amines terminated with functional groups, 1-azido-2-aminoethane, propargylamine, or N-methylpropargyamine, to PVA.
Abstract: Novel poly(vinyl alcohols) (PVA) functionalized with pendant acetylene and azide groups were prepared by carbonyldiimidazole (CDI)-mediated couplings of the amines terminated with functional groups, 1-azido-2-aminoethane, propargylamine, or N-methylpropargylamine, to PVA. Low degrees (1−5%) of PVA modification were required in order to retain solubility in water. Azide-modified PVA and alkyne-modified PVA components were cross-linked by mixing of their solutions together with Cu(I) catalyst, a type of Huisgen's 1,3-dipolar azide−alkyne cycloaddition, recently defined as a powerful “click” chemistry. Reaction of the two different polymers results in a chemoselective coupling between alkynyl and azido functional groups with the multiple formation of triazole cross-links to give hydrogel formation. In another version the PVA-based hydrogels were obtained by cross-linking of alkyne-modified PVA with the telechelic bifunctional poly(ethylene glycol)−diazide cross-linker. The hydrogels prepared by these two met...
TL;DR: By combining the strengths of injection molding tissue engineering with those of solid freeform fabrication (SFF), three-dimensional pre-seeded implants were fabricated without custom-tooling, enabling efficient production of patient-specific implants.
Abstract: A major challenge in tissue engineering is the generation of cell-seeded implants with structures that mimic native tissue, both in anatomic geometries and intratissue cell distributions. ...
TL;DR: The results presented here indicate that the use of SL and photocross linkable biomaterials, such as photocrosslinkable PEG, appears feasible for fabricating complex bioactive scaffolds with living cells for a variety of important tissue engineering applications.
Abstract: Stereolithography (SL) was used to fabricate complex 3-D poly(ethylene glycol) (PEG) hydrogels. Photopolymerization experiments were performed to characterize the solutions for use in SL, where the crosslinked depth (or hydrogel thickness) was measured at different laser energies and photoinitiator (PI) concentrations for two concentrations of PEG-dimethacrylate in solution (20% and 30% (w/v)). Hydrogel thickness was a strong function of PEG concentration, PI type and concentration, and energy dosage, and these results were utilized to successfully fabricate complex hydrogel structures using SL, including structures with internal channels of various orientations and multi-material structures. Additionally, human dermal fibroblasts were encapsulated in bioactive PEG photocrosslinked in SL. Cell viability was at least 87% at 2 and 24 h following fabrication. The results presented here indicate that the use of SL and photocrosslinkable biomaterials, such as photocrosslinkable PEG, appears feasible for fabricating complex bioactive scaffolds with living cells for a variety of important tissue engineering applications.
TL;DR: A technique to encapsulate live cells in three-dimensional (3D) microscale hydrogels (microgels) of controlled shapes and sizes in the form of harvestable free standing units to lead to applications in 3D co-cultures for tissue/organ regeneration and cell-based assays in which it is important to mimic the architectural intricacies of physiological cell-cell interactions.
TL;DR: It is considered that the role of the solvated polymer network existing in the extracellular matrix as a gel state is critically important in the specific frictional behavior of cartilages.
Abstract: Biological connective tissues, such as cartilage and corneal stroma, are essentially hydrogels consisting of fibrous collagen and proteoglycans. Little is known of the surface properties of the hydrogel, although we observe fascinating tribological behavior in biological soft tissues, such as extremely low friction between animal cartilages. We consider that the role of the solvated polymer network existing in the extracellular matrix as a gel state is critically important in the specific frictional behavior of cartilages. In order to elucidate the general tribological features of a solvated polymer matrix, the friction of various kinds of hydrogels has been investigated, and very rich and complex frictional behaviors are observed. The friction force and its dependence on the load differ with the chemical structure of the gels, surface properties of the opposing substrates, and the measurement conditions, which are totally different from those of solids. Most importantly, the coefficient of friction of gels, μ, varies over a wide range and exhibits very low values (μ
≈ 10−3–10−4), which cannot be obtained from the friction between two solid materials. A repulsion–adsorption model has been proposed to explain the gel friction, which says that the friction is due to lubrication of a hydrated layer of polymer chains when the polymer chain of the gel is non-adhesive (repulsive) to the substrate, and the friction is due to elastic deformation of the adsorbed polymer chain when it is adhesive to the substrate.
TL;DR: The results indicate that release profiles can be tailored through controlling nanofiber-diffusant molecular level interactions.
TL;DR: A novel method for preparing a spheroid microarray on microfabricated hydrogels, alone or in co-cultures is described, which could be a useful platform for studying heterotypic cell-cell interactions, for drug screening, and for developing implantable bioartificial organs.
TL;DR: The electron-conducting redox hydrogels serve to electrically connect the redox centers of enzymes to electrodes, enabling their use whenever leaching of electron-shuttling diffusional redox mediators must be avoided, which is the case in subcutaneously implanted biosensors for diabetes management and in miniature, potentially implantable, glucose-O2 biofuel cells.
TL;DR: This review focuses on the recent developments and future trends dealing with stimuli-responsive hydrogels based on grafting/blending of polysaccharides such as chitosan, alginate, cellulose, dextran and their derivatives with thermo-sensitive polymers.
Abstract: In recent years, intelligent hydrogels which can change their swelling behavior and other properties in response to environmental stimuli such as temperature, pH, solvent composition and electric fields, have attracted great interest. The hydrogels based on polysaccharides incorporated with thermo-responsive polymers have shown unique properties such as biocompatibility, biodegradability, and biological functions in addition to the stimuli-responsive characters. These "smart" hydrogels exhibit single or multiple stimuli-responsive characters which could be used in biomedical applications, including controlled drug delivery, bioengineering or tissue engineering. This review focuses on the recent developments and future trends dealing with stimuli-responsive hydrogels based on grafting/blending of polysaccharides such as chitosan, alginate, cellulose, dextran and their derivatives with thermo-sensitive polymers. This review also screens the current applications of these hydrogels in the fields of drug delivery, tissue engineering and wound healing.
TL;DR: In this paper, Fourier transform infrared spectroscopy (FTIR) spectra of PVA hydrogel samples showed the absorption regions of the specific chemical groups associated with poly(vinyl alcohol) (-OH, -CO, -CH2) and PVA/GA confirming the formation of crosslinked hydrogels (duplet -CH).
Abstract: Polyvinyl alcohol (PVA), PVA crosslinked with glutaraldehyde hydrogels (PVA/GA), PVA with tetraethylorthosilicate (PVA/TEOS) and PVA/GA/TEOS hybrids with recombinant MPB70 protein (rMPB70) incorporated were chemically characterized by Fourier transform infrared spectroscopy (FTIR). FTIR spectra of PVA hydrogel samples showed the absorption regions of the specific chemical groups associated with poly(vinyl alcohol) (-OH, -CO, -CH2) and PVA/GA confirming the formation of crosslinked hydrogel (duplet -CH). It was observed C-H broad alkyl stretching band (n = 2850-3000 cm-1) and typical strong hydroxyl bands for free alcohol (nonbonded -OH stretching band at n = 3600-3650 cm-1), and hydrogen bonded band (n = 3200-3570 cm-1). The most important vibration bands related to silane alcoxides have been verified on FTIR spectra of PVA/TEOS and PVA/GA/TEOS hybrids (Si-O-Si, n = 1080 and n = 450 cm-1; Si-OH, n = 950 cm-1). FTIR spectra of f PVA hydrogel with rMPB70 incorporated have indicated the specific groups usually found in protein structures, such as amides I, II and III, at 1680-1620 cm-1, 1580-1480 cm-1 and 1246 cm-1, respectively. These results have given strong evidence that recombinant protein rMPB70 was successfully adsorbed in the hydrogels and hybrids networks. These PVA based hydrogels and hybrids were further used in immunological assays (Enzyme-Linked Immunosorbent Assay - ELISA). Tests were performed to detect antibodies against rMPB70 protein in serum samples from bovines that were positive in the tuberculin test. Corresponding tests were carried out without PVA samples in microtiter plates as control. Similar results were found for commercially available microplates and PVA based hydrogels and hybrids developed in the present work regarding to immunoassay sensitivity and specificity response.
TL;DR: It is shown that alpha-d-glucose is the glucose anomer binding to the boronic acid derivative, and unusual temperature-dependent kinetics, which derive from glucose mutarotation in solution are found.
Abstract: We developed new photonic crystal polymerized crystalline colloidal array (PCCA) glucose sensing materials, which operate on the basis of formation of cross-links in the hydrogel. These materials are composed of hydrogels that embed an array of approximately 100-nm-diameter monodisperse polystyrene colloids that Bragg diffract light in the visible spectral region. The hydrogels change volume as the glucose concentration varies. This changes the lattice spacing, which changes the wavelength of the diffracted light. In contrast to our previous glucose sensing photonic crystal materials, we no longer require Na+ chelating agents. These photonic crystal materials are being designed for use in glucose sensing contact lens for people with diabetes mellitus. We describe methods to speed up the response kinetics of these PCCA sensing materials. Rapid-response kinetics is achieved by controlling the elasticity and the hydrophilic-hydrophobic balance of the hydrogel system. A more hydrophobic hydrogel composition is obtained by copolymerizing n-hexylacrylate into an acrylamide-bisacrylamide hydrogel. The response rate significantly increases to where it fully responds within 90 s to the average glucose concentrations found in blood (5 mM) and within 300 s to the average glucose concentrations found in tear fluid (0.15 mM). We find unusual temperature-dependent kinetics, which derive from glucose mutarotation in solution. It is shown that alpha-d-glucose is the glucose anomer binding to the boronic acid derivative. Care must be taken in any glucose determination to ensure that the glucose mutarotation equilibrium has been established. We have demonstrated that the sensor is responsive to approximately 0.15 mM glucose concentrations in artificial tear fluid solution.
TL;DR: The results indicate that precursor cells characteristic of a MSC population can be cultured from differentiating hESCs through embryoid bodies, thus holding great promise for a potentially unlimited source of cells for cartilage tissue engineering.
Abstract: Human embryonic stem cells (hESCs) have the potential to self-renew and generate multiple cell types, producing critical building blocks for tissue engineering and regenerative medicine applications. Here, we describe the efficient derivation and chondrogenic differentiation of mesenchymal-like cells from hESCs. These cells exhibit mesenchymal stem cell (MSC) surface markers, including CD29, CD44, CD105, and platelet-derived growth factor receptor-alpha. Under appropriate growth conditions, the hESC-derived cells proliferated without phenotypic changes and maintained MSC surface markers. The chondrogenic capacity of the cells was studied in pellet culture and after encapsulation in poly(ethylene glycol)-diacrylate (PEGDA) hydrogels with exogenous extracellular proteins or arginineglycine- aspartate (RGD)-modified PEGDA hydrogels. The hESC-derived cells exhibited growth factor- dependent matrix production in pellet culture but did not produce tissue characteristic of cartilage morphology. In PEGDA hydrogels containing exogenous hyaluronic acid or type I collagen, no significant cell growth or matrix production was observed. In contrast, when these cells were encapsulated in RGDmodified poly(ethylene glycol)hydrogels, neocartilage with basophilic extracellular matrix deposition was observed within 3 weeks of culture, producing cartilage-specific gene up-regulation and extracellular matrix production. Our results indicate that precursor cells characteristic of a MSC population can be cultured from differentiating hESCs through embryoid bodies, thus holding great promise for a potentially unlimited source of cells for cartilage tissue engineering.
TL;DR: The clinical study revealed that the implantation of BMCs into patients is safe, as there were no complications following cell administration and treatment with different bone marrow cell populations had a positive effect on behavioral outcome and histopathological assessment after SCI in rats.
Abstract: 1. Emerging clinical studies of treating brain and spinal cord injury (SCI) led us to examine the effect of autologous adult stem cell transplantation as well as the use of polymer scaffolds in spinal cord regeneration. We compared an intravenous injection of mesenchymal stem cells (MSCs) or the injection of a freshly prepared mononuclear fraction of bone marrow cells (BMCs) on the treatment of an acute or chronic balloon-induced spinal cord compression lesion in rats. Based on our experimental studies, autologous BMC implantation has been used in a Phase I/II clinical trial in patients (n=20) with a transversal spinal cord lesion. 2. MSCs were isolated from rat bone marrow by their adherence to plastic, labeled with iron-oxide nanoparticles and expanded in vitro. Macroporous hydrogels based on derivatives of 2-hydroxyethyl methacrylate (HEMA) or 2-hydroxypropyl methacrylamide (HPMA) were prepared, then modified by their copolymerization with a hydrolytically degradable crosslinker, N,O-dimethacryloylhydroxylamine, or by different surface electric charges. Hydrogels or hydrogels seeded with MSCs were implanted into rats with hemisected spinal cords. 3. Lesioned animals grafted with MSCs or BMCs had smaller lesions 35 days postgrafting and higher scores in BBB testing than did control animals and also showed a faster recovery of sensitivity in their hind limbs using the plantar test. The functional improvement was more pronounced in MSC-treated rats. In MR images, the lesion populated by grafted cells appeared as a dark hypointense area and was considerably smaller than in control animals. Morphometric measurements showed an increase in the volume of spared white matter in cell-treated animals. In the clinical trial, we compared intraarterial (via a. vertebralis, n=6) versus intravenous administration of BMCs (n=14) in a group of subacute (10-33 days post-SCI, n=8) and chronic patients (2-18 months, n=12). For patient follow-up we used MEP, SEP, MRI, and the ASIA score. Our clinical study revealed that the implantation of BMCs into patients is safe, as there were no complications following cell administration. Partial improvement in the ASIA score and partial recovery of MEP or SEP have been observed in all subacute patients who received cells via a. vertebralis (n=4) and in one out of four subacute patients who received cells intravenously. Improvement was also found in one chronic patient who received cells via a. vertebralis. A much larger population of patients is needed before any conclusions can be drawn. The implantation of hydrogels into hemisected rat spinal cords showed that cellular ingrowth was most pronounced in copolymers of HEMA with a positive surface electric charge. Although most of the cells had the morphological properties of connective tissue elements, we found NF-160-positive axons invading all the implanted hydrogels from both the proximal and distal stumps. The biodegradable hydrogels degraded from the border that was in direct contact with the spinal cord tissue. They were resorbed by macrophages and replaced by newly formed tissue containing connective tissue elements, blood vessels, GFAP-positive astrocytic processes, and NF-160-positive neurofilaments. Additionally, we implanted hydrogels seeded with nanoparticle-labeled MSCs into hemisected rat spinal cords. Hydrogels seeded with MSCs were visible on MR images as hypointense areas, and subsequent Prussian blue histological staining confirmed positively stained cells within the hydrogels. 4. We conclude that treatment with different bone marrow cell populations had a positive effect on behavioral outcome and histopathological assessment after SCI in rats; this positive effect was most pronounced following MSC treatment. Our clinical study suggests a possible positive effect in patients with SCI. Bridging the lesion cavity can be an approach for further improving regeneration. Our preclinical studies showed that macroporous polymer hydrogels based on derivatives of HEMA or HPMA are suitable materials for bridging cavities after SCI; their chemical and physical properties can be modified to a specific use, and 3D implants seeded with different cell types may facilitate the ingrowth of axons.
TL;DR: The erosion rate of genetically engineered protein hydrogels can be tuned by harnessing selective molecular recognition, discrete aggregation number and orientational discrimination of coiled-coil protein domains.
Abstract: Erosion behaviour governs the use of physical hydrogels in biomedical applications ranging from controlled release to cell encapsulation. Genetically engineered protein hydrogels offer unique means of controlling the erosion rate by engineering their amino acid sequences and network topology. Here, we show that the erosion rate of such materials can be tuned by harnessing selective molecular recognition, discrete aggregation number and orientational discrimination of coiled-coil protein domains. Hydrogels formed from a triblock artificial protein bearing dissimilar helical coiled-coil end domains (P and A) erode more than one hundredfold slower than hydrogels formed from those bearing the same end domains (either P or A). The reduced erosion rate is a consequence of the fact that looped chains are suppressed because P and A tend not to associate with each other. Thus, the erosion rate can be tuned over several orders of magnitude in artificial protein hydrogels, opening the door to diverse biomedical applications.