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1.
ACS Appl Mater Interfaces ; 16(34): 45422-45432, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39102678

ABSTRACT

Implantable polymeric biodegradable devices, such as biodegradable vascular scaffolds, cannot be fully visualized using standard X-ray-based techniques, compromising their performance due to malposition after deployment. To address this challenge, we describe a new radiopaque and photocurable liquid polymer-ceramic composite (mPDC-MoS2) consisting of methacrylated poly(1,12 dodecamethylene citrate) (mPDC) and molybdenum disulfide (MoS2) nanosheets. The composite was used as an ink with microcontinuous liquid interface production (µCLIP) to fabricate bioresorbable vascular scaffolds (BVS). Prints exhibited excellent crimping and expansion mechanics without strut failures and, importantly, with X-ray visibility in air and muscle tissue. Notably, MoS2 nanosheets displayed physical degradation over time in phosphate-buffered saline solution, suggesting the potential for producing radiopaque, fully bioresorbable devices. mPDC-MoS2 is a promising bioresorbable X-ray-visible composite material suitable for 3D printing medical devices, such as vascular scaffolds, that require noninvasive X-ray-based monitoring techniques for implantation and evaluation. This innovative biomaterial composite system holds significant promise for the development of biocompatible, fluoroscopically visible medical implants, potentially enhancing patient outcomes and reducing medical complications.


Subject(s)
Citrates , Disulfides , Endovascular Procedures , Molybdenum , Nanostructures , Tissue Scaffolds , Molybdenum/chemistry , Molybdenum/metabolism , Disulfides/chemistry , Disulfides/metabolism , Printing, Three-Dimensional , Citrates/chemistry , Nanostructures/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Polymers/chemistry
2.
J Control Release ; 374: 349-368, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39111600

ABSTRACT

Extracellular vesicles (EVs), or exosomes, play important roles in physiological and pathological cellular communication and have gained substantial traction as biological drug carriers. EVs contain both short and long non-coding RNAs that regulate gene expression and epigenetic processes. To fully capitalize on the potential of EVs as drug carriers, it is important to study and understand the intricacies of EV function and EV RNA-based communication. Here we developed a genetically encodable RNA-based biomaterial, termed EXO-Probe, for tracking EV RNAs. The EXO-Probe comprises an EV-loading RNA sequence (EXO-Code), fused to a fluorogenic RNA Mango aptamer for RNA imaging. This fusion construct allowed the visualization and tracking of EV RNA and colocalization with markers of multivesicular bodies; imaging RNA within EVs, and non-destructive quantification of EVs. Overall, the new RNA-based biomaterial provides a useful and versatile means to interrogate the role of EVs in cellular communication via RNA trafficking to EVs and to study cellular sorting decisions. The system will also help lay the foundation to further improve the therapeutic efficacy of EVs as drug carriers.


Subject(s)
Biocompatible Materials , Extracellular Vesicles , Fluorescent Dyes , RNA , Humans , RNA/genetics , Extracellular Vesicles/metabolism , Fluorescent Dyes/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Aptamers, Nucleotide , Animals
3.
J Biomater Appl ; 39(4): 288-297, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39073096

ABSTRACT

OBJECTIVE: to evaluate a membrane based on type B gelatin (G) and porcine urinary bladder extracellular matrix (PUB-EM), highlighting the potential effect of the combination evaluated by biocompatibility and regulation of the expression of transcription factors involved in tissue regeneration. G-PUB-EM membranes were prepared at 12.5, 25, and 50% w/v, and evaluated for biocompatibility with Fibroblast. Chemical characterization by FTIR-ATR showed complex spectra during crosslinking process with glutaraldehyde. Physical tests were performed in deionized water and PBS for 48 h. A significant increase in swelling was observed during the first 2 h. Biocompatibility testing (MTS) and evaluation of the expression profile of genes involved in the cell cycle (Cyclin-D1 VEGF, TNF and NF-κ-B) by PCR showed an increase in viability in a PUB-EM content-dependent way, except for 50% PUB-EM membrane which showed cytotoxic effects with a decrease in cell viability below 70%. The membranes showed an increase in the expression of some factors of cell cycle, as well as inflammatory processes that could promote tissue repair. 12.5 and 25% gelatin type B/porcine urinary bladder extracellular matrix (G/PUB-EM) based membranes have potential for tissue regeneration applications. IMPACT STATEMENT: The use of membranes based on type B gelatin and porcine urinary bladder for tissue engineering represents a novel strategy. Biocompatibility and signaling pathways play a primary role in tissue repair and wound recovery. Transcription factors that mediate signaling, cell division and vascularization are part of molecules that intervene in the regenerative potential of cells. These techniques will have a significant impact on tissue repair and regeneration and thus stop depending on tissue donors or other surgical sites from the same patient, as is the case with burn patients.


Subject(s)
Biocompatible Materials , Extracellular Matrix , Gelatin , Materials Testing , Tissue Scaffolds , Transcription Factors , Urinary Bladder , Animals , Gelatin/chemistry , Extracellular Matrix/metabolism , Tissue Scaffolds/chemistry , Swine , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Urinary Bladder/metabolism , Urinary Bladder/cytology , Cell Survival/drug effects , Tissue Engineering , Fibroblasts/metabolism , Fibroblasts/cytology , Mice
4.
ACS Biomater Sci Eng ; 10(8): 4916-4926, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-38968389

ABSTRACT

Peptides are widely used within biomaterials to improve cell adhesion, incorporate bioactive ligands, and enable cell-mediated degradation of the matrix. While many of the peptides incorporated into biomaterials are intended to be present throughout the life of the material, their stability is not typically quantified during culture. In this work, we designed a series of peptide libraries containing four different N-terminal peptide functionalizations and three C-terminal functionalizations to better understand how simple modifications can be used to reduce the nonspecific degradation of peptides. We tested these libraries with three cell types commonly used in biomaterials research, including mesenchymal stem/stromal cells (hMSCs), endothelial cells, and macrophages, and quantified how these cell types nonspecifically degraded peptides as a function of terminal amino acid and chemistry. We found that peptides in solution which contained N-terminal amines were almost entirely degraded by 48 h, irrespective of the terminal amino acid, and that degradation occurred even at high peptide concentrations. Peptides with C-terminal carboxylic acids also had significant degradation when cultured with the cells. We found that simple modifications to the termini could significantly reduce or completely abolish nonspecific degradation when soluble peptides were added to cells cultured on tissue culture plastic or within hydrogel matrices, and that functionalizations which mimicked peptide conjugations to hydrogel matrices significantly slowed nonspecific degradation. We also found that there were minimal differences in peptide degradation across cell donors and that sequences mimicking different peptides commonly used to functionalize biomaterials all had significant nonspecific degradation. Finally, we saw that there was a positive trend between RGD stability and hMSC spreading within hydrogels, indicating that improving the stability of peptides within biomaterial matrices may improve the performance of engineered matrices.


Subject(s)
Cell Adhesion , Mesenchymal Stem Cells , Peptides , Proteolysis , Cell Adhesion/drug effects , Peptides/chemistry , Peptides/metabolism , Peptides/pharmacology , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/metabolism , Peptide Library , Mice , Animals , Macrophages/metabolism , Hydrogels/chemistry
5.
Adv Sci (Weinh) ; 11(30): e2400242, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38874525

ABSTRACT

Maxillofacial bone defects exhibit intricate anatomy and irregular morphology, presenting challenges for effective treatment. This study aimed to address these challenges by developing an injectable bioactive composite microsphere, termed D-P-Ak (polydopamine-PLGA-akermanite), designed to fit within the defect site while minimizing injury. The D-P-Ak microspheres biodegraded gradually, releasing calcium, magnesium, and silicon ions, which, notably, not only directly stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) but also activated sensory nerve cells to secrete calcitonin gene-related peptide (CGRP), a key factor in bone repair. Moreover, the released CGRP enhanced the osteogenic differentiation of BMSCs through epigenetic methylation modification. Specifically, inhibition of EZH2 and enhancement of KDM6A reduced the trimethylation level of histone 3 at lysine 27 (H3K27), thereby activating the transcription of osteogenic genes such as Runx2 and Osx. The efficacy of the bioactive microspheres in bone repair is validated in a rat mandibular defect model, demonstrating that peripheral nerve response facilitates bone regeneration through epigenetic modification. These findings illuminated a novel strategy for constructing neuroactive osteo-inductive biomaterials with potential for further clinical applications.


Subject(s)
Bone Regeneration , Mesenchymal Stem Cells , Microspheres , Osteogenesis , Animals , Rats , Mesenchymal Stem Cells/metabolism , Bone Regeneration/genetics , Bone Regeneration/drug effects , Bone Regeneration/physiology , Osteogenesis/physiology , Osteogenesis/genetics , Cell Differentiation , Demethylation , Rats, Sprague-Dawley , Disease Models, Animal , Ceramics , Histones/metabolism , Histones/genetics , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide/genetics , Male , Biocompatible Materials/metabolism
6.
ACS Appl Bio Mater ; 7(7): 4406-4416, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38866715

ABSTRACT

In this research, we utilized an efficient approach to synthesize superparamagnetic graphene oxide (SPGO) rapidly in a one-pot method using microwave irradiation of graphene oxide (GO), urea, and Fe(III) ion. Tannic acid (TA) was introduced to the surface of SPGO through a straightforward and eco-friendly process. Methods were devised to furnish GO nanosheets and modify their surfaces with TA in an environmentally friendly manner. Two series of nanosheets, namely, SPGO/TA-COOH and SPGO/TA-IM, were engineered on the surface and used for immobilizing lipase enzyme. Through various analytical tools, the unique biocatalysts SPGO/TA-COOH/L and SPGO/TA-IM/L were confirmed. These biocatalysts exhibited enhanced stability at high temperatures and pH levels compared with free lipase. They also demonstrated prolonged storage stability and reusability over four months and seven cycles, respectively. Furthermore, the catalytic activity of immobilized lipase showed minimal impairment based on kinetic behavior analysis. The kinetic constants of SPGO/TA-IM/L were determined as Vmax = 0.24 mM min-1, Km = 0.224 mM, and kcat = 0.8 s-1. Additionally, the efficiency of biocatalysts for biodiesel production from palmitic acid was studied, focusing on various reaction parameters, such as temperature, alcohol to palmitic acid molar ratio, water content, and lipase quantity. The esterification reaction of palmitic acid with methanol, ethanol, and isopropanol was tested in the presence of SPGO/TA-COOH/L and SPGO/TA-IM/L, and the corresponding esters were obtained with a yield of 30.6-91.6%.


Subject(s)
Biofuels , Enzymes, Immobilized , Graphite , Lipase , Surface Properties , Graphite/chemistry , Lipase/metabolism , Lipase/chemistry , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Materials Testing , Tannins/chemistry , Particle Size , Biocompatible Materials/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/metabolism , Nanostructures/chemistry
7.
ACS Appl Bio Mater ; 7(7): 4760-4771, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38916249

ABSTRACT

Laccase is an oxidase of great industrial interest due to its ability to catalyze oxidation processes of phenols and persistent organic pollutants. However, it is susceptible to denaturation at high temperatures, sensitive to pH, and unstable in the presence of high concentrations of solvents, which is a issue for industrial use. To solve this problem, this work develops the synthesis in an aqueous medium of a new Mn metalloenzyme with laccase oxidase mimetic catalytic activity. Geobacillus thermocatenulatus lipase (GTL) was used as a scaffold enzyme, mixed with a manganese salt at 50 °C in an aqueous medium. This leads to the in situ formation of manganese(IV) oxide nanowires that interact with the enzyme, yielding a GTL-Mn bionanohybrid. On the other hand, its oxidative activity was evaluated using the ABTS assay, obtaining a catalytic efficiency 300 times higher than that of Trametes versicolor laccase. This new Mn metalloenzyme was 2 times more stable at 40 °C, 3 times more stable in the presence of 10% acetonitrile, and 10 times more stable in 20% acetonitrile than Novozym 51003 laccase. Furthermore, the site-selective immobilized GTL-Mn showed a much higher stability than the soluble form. The oxidase-like activity of this Mn metalloenzyme was successfully demonstrated against other substrates, such as l-DOPA or phloridzin, in oligomerization reactions.


Subject(s)
Laccase , Manganese , Laccase/metabolism , Laccase/chemistry , Manganese/chemistry , Materials Testing , Geobacillus/enzymology , Particle Size , Biocompatible Materials/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/metabolism , Lipase/metabolism , Lipase/chemistry
8.
ACS Appl Bio Mater ; 7(5): 3358-3374, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38717870

ABSTRACT

Exosomes are promising nanocarriers for drug delivery. Yet, it is challenging to apply exosomes in clinical use due to the limited understanding of their physiological functions. While cellular uptake of exosomes is generally known through endocytosis and/or membrane fusion, the mechanisms of origin-dependent cellular uptake and subsequent cargo release of exosomes into recipient cells are still unclear. Herein, we investigated the intricate mechanisms of exosome entry into recipient cells and intracellular cargo release. In this study, we utilized chiral graphene quantum dots (GQDs) as representatives of exosomal cargo, taking advantage of the superior permeability of chiral GQDs into lipid membranes as well as their excellent optical properties for tracking analysis. We observed that the preferential cellular uptake of exosomes derived from the same cell-of-origin (intraspecies exosomes) is higher than that of exosomes derived from different cell-of-origin (cross-species exosomes). This uptake enhancement was attributed to receptor-ligand interaction-mediated endocytosis, as we identified the expression of specific ligands on exosomes that favorably interact with their parental cells and confirmed the higher lysosomal entrapment of intraspecies exosomes (intraspecies endocytic uptake). On the other hand, we found that the uptake of cross-species exosomes primarily occurred through membrane fusion, followed by direct cargo release into the cytosol (cross-species direct fusion uptake). We revealed the underlying mechanisms involved in the cellular uptake and subsequent cargo release of exosomes depending on their cell-of-origin and recipient cell types. Overall, this study envisions valuable insights into further advancements in effective drug delivery using exosomes, as well as a comprehensive understanding of cellular communication, including disease pathogenesis.


Subject(s)
Exosomes , Quantum Dots , Quantum Dots/chemistry , Exosomes/metabolism , Exosomes/chemistry , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Biocompatible Materials/pharmacology , Fluorescent Dyes/chemistry , Particle Size , Materials Testing , Endocytosis , Graphite/chemistry
9.
ACS Appl Bio Mater ; 7(6): 4102-4115, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38758756

ABSTRACT

The diatom's frustule, characterized by its rugged and porous exterior, exhibits a remarkable biomimetic morphology attributable to its highly ordered pores, extensive surface area, and unique architecture. Despite these advantages, the toxicity and nonbiodegradable nature of silica-based organisms pose a significant challenge when attempting to utilize these organisms as nanotopographically functionalized microparticles in the realm of biomedicine. In this study, we addressed this limitation by modulating the chemical composition of diatom microparticles by modulating the active silica metabolic uptake mechanism while maintaining their intricate three-dimensional architecture through calcium incorporation into living diatoms. Here, the diatom Thalassiosira weissflogii was chemically modified to replace its silica composition with a biodegradable calcium template, while simultaneously preserving the unique three-dimensional (3D) frustule structure with hierarchical patterns of pores and nanoscale architectural features, which was evident by the deposition of calcium as calcium carbonate. Calcium hydroxide is incorporated into the exoskeleton through the active mechanism of calcium uptake via a carbon-concentrating mechanism, without altering the microstructure. Our findings suggest that calcium-modified diatoms hold potential as a nature-inspired delivery system for immunotherapy through antibody-specific binding.


Subject(s)
Biocompatible Materials , Calcium , Diatoms , Materials Testing , Particle Size , Diatoms/metabolism , Diatoms/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/metabolism , Calcium/metabolism , Calcium/chemistry , Drug Delivery Systems , Surface Properties , Silicon Dioxide/chemistry , Porosity
10.
J Colloid Interface Sci ; 668: 646-657, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38696992

ABSTRACT

Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo, SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments.


Subject(s)
Fibroins , Hydrogels , Ionic Liquids , Spinal Cord Injuries , Synaptic Transmission , Hydrogels/administration & dosage , Hydrogels/metabolism , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/therapy , Injections , Female , Animals , Rats, Sprague-Dawley , Rats , Fibroins/administration & dosage , Fibroins/metabolism , Ionic Liquids/administration & dosage , Ionic Liquids/metabolism , Disease Models, Animal , Materials Testing , Biocompatible Materials/administration & dosage , Biocompatible Materials/metabolism , PC12 Cells
11.
Bioelectrochemistry ; 158: 108723, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38733720

ABSTRACT

Bidirectional electron transfer is about that exoelectrogens produce bioelectricity via extracellular electron transfer at anode and drive cytoplasmic biochemical reactions via extracellular electron uptake at cathode. The key factor to determine above bioelectrochemical performances is the electron transfer efficiency under biocompatible abiotic/biotic interface. Here, a graphene/polyaniline (GO/PANI) nanocomposite electrode specially interfacing exoelectrogens (Shewanella loihica) and augmenting bidirectional electron transfer was conducted by in-situ electrochemical modification on carbon paper (CP). Impressively, the GO/PANI@CP electrode tremendously improved the performance of exoelectrogens at anode for wastewater treatment and bioelectricity generation (about 54 folds increase of power density compared to blank CP electrode). The bacteria on electrode surface not only showed fast electron release but also exhibited high electricity density of extracellular electron uptake through the proposed direct electron transfer pathway. Thus, the cathode applications of microbial electrosynthesis and bio-denitrification were developed via GO/PANI@CP electrode, which assisted the close contact between microbial outer-membrane cytochromes and nanocomposite electrode for efficient nitrate removal (0.333 mM/h). Overall, nanocomposite modified electrode with biocompatible interfaces has great potential to enhance bioelectrochemical reactions with exoelectrogens.


Subject(s)
Bioelectric Energy Sources , Electrodes , Graphite , Graphite/chemistry , Electron Transport , Bioelectric Energy Sources/microbiology , Aniline Compounds/chemistry , Aniline Compounds/metabolism , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Shewanella/metabolism , Nanocomposites/chemistry , Electrochemical Techniques/methods
12.
Chempluschem ; 89(8): e202400204, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38682248

ABSTRACT

Biocatalysis has emerged in the last decade as a valuable and eco-friendly tool in chemical synthesis, allowing in several instances to reduce or eliminate the use of hazardous reagents, environmentally dangerous solvents and harsh reaction conditions. Enzymes are indeed able to catalyse chemical transformations on non-natural substrates under mild reaction conditions, still maintaining their high chemo-, regio-, and stereoselectivity. Enzyme immobilization, i. e. the grafting of enzymes on solid supports, can be viewed as an enabling technology, as it allows a better control of the reaction and the recycling of the biocatalyst, thus rendering economically viable the use of expensive enzymes also on a large scale. To pursue a sustainable approach, the supports for enzyme immobilization should be eco-friendly and possibly renewable. This review highlights the use of hydroxyapatite (HAP), an inorganic biomaterial able to confer strength and stiffness to the bone tissue in animals, as carrier for enzyme immobilization. HAP is a cheap, non-toxic and biocompatible material, with high surface area and protein affinity. Different enzyme classes, immobilization strategies, and the use of diverse HAP-based supports will be discussed, underlining the immobilization conditions and the properties of the obtained biocatalysts.


Subject(s)
Durapatite , Enzymes, Immobilized , Durapatite/chemistry , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Biocatalysis , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Animals , Green Chemistry Technology
13.
Microb Biotechnol ; 17(4): e14449, 2024 04.
Article in English | MEDLINE | ID: mdl-38593329

ABSTRACT

Bacillus coagulans, recently renamed Weizmannia coagulans, is a spore-forming bacterium that has garnered significant interest across various research fields, ranging from health to industrial applications. The probiotic properties of W. coagulans enhance intestinal digestion, by releasing prebiotic molecules including enzymes that facilitate the breakdown of not-digestible carbohydrates. Notably, some enzymes from W. coagulans extend beyond digestive functions, serving as valuable biotechnological tools and contributing to more sustainable and efficient manufacturing processes. Furthermore, the homofermentative thermophilic nature of W. coagulans renders it an exceptional candidate for fermenting foods and lignocellulosic residues into L-(+)-lactic acid. In this review, we provide an overview of the dual nature of W. coagulans, in functional foods and for the development of bio-based materials.


Subject(s)
Bacillus coagulans , Functional Food , Biocompatible Materials/metabolism , Bacillus coagulans/metabolism , Fermentation , Biotechnology
14.
J Biomater Sci Polym Ed ; 35(10): 1523-1536, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38574261

ABSTRACT

The interaction between the integrin and collagen is important in cell adhesion and signaling. Collagen, as the main component of extracellular matrix, is a base material for tissue engineering constructs. In tissue engineering, the collagen structure and molecule state may be altered to varying degrees in the process of processing and utilizing, thereby affecting its biological properties. In this work, the impact of changes in collagen structure and molecular state on the binding properties of collagen to integrin α2ß1 and integrin specific cell adhesion were explored. The results showed that the molecular structure of collagen is destroyed under the influence of heating, freeze-grinding and irradiation, the triple helix integrity is reduced and molecular breaking degree is increased. The binding ability of collagen to integrin α2ß1 is increased with the increase of triple helix integrity and decays exponentially with the increase of molecular breaking degree. The collagen molecular state can also influences the binding ability of collagen to cellular receptor. The collagen fibrils binding to integrin α2ß1 and HT1080 cells is stronger than to collagen monomolecule. Meanwhile, the hybrid fibril exhibits a different cellular receptor binding performance from corresponding single species collagen fibril. These findings provide ideas for the design and development of new collagen-based biomaterials and tissue engineering research.


Subject(s)
Cell Adhesion , Collagen , Integrin alpha2beta1 , Protein Binding , Integrin alpha2beta1/metabolism , Integrin alpha2beta1/chemistry , Humans , Collagen/chemistry , Collagen/metabolism , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Animals , Tissue Engineering/methods , Cell Line, Tumor
15.
J Mater Chem B ; 12(19): 4736-4747, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38660955

ABSTRACT

Rapid removal of toxic substances is crucial to restore the normal functions of our body and ensure survival. Due to their high substrate specificity and catalytic efficiency, enzymes are unique candidates to deplete toxic compounds. While enzymes display several limitations including low stability and high immunogenicity, these can be overcome by entrapping them in a diverse range of carriers. The resulting micro/nanoreactors shield the enzymes from their surroundings, preventing their misfolding or denaturation thus allowing them to conduct their function. The micro/nanoreactors must circulate in the blood stream for extended periods of time to ensure complete depletion of the toxic agents. Surprisingly, while it is widely acknowledged that non-spherical carriers exhibit longer residence time in the bloodstream than their spherical counterparts, so far, all the reported micro/nanoreactors have been assembled with a spherical architecture. Herein, we address this important issue by pioneering the first shape-specific microreactors. We use UV-assisted punching to create rod-like microgel shapes with dimensions of 8 µm × 1 µm × 2 µm and demonstrate their biocompatibility by conducting hemolysis and cell viability assays with a macrophage and an endothelial cell line. Upon encapsulation of the model enzyme ß-lactamase, the successful fabrication of rod-shaped microreactors is demonstrated by their ability to convert the yellow nitrocefin substrate into its hydrolyzed product.


Subject(s)
Microgels , Humans , Microgels/chemistry , Cell Survival/drug effects , Animals , Mice , Hemolysis , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Biocompatible Materials/pharmacology , Particle Size , Surface Properties
16.
J Biomater Appl ; 39(1): 24-39, 2024 07.
Article in English | MEDLINE | ID: mdl-38616137

ABSTRACT

The reparative properties of amniotic membrane allografts are well-suited for a broad spectrum of specialties. Further enhancement of their utility can be achieved by designing to the needs of each application through the development of novel processing techniques and tissue configurations. As such, this study evaluated the material characteristics and biological properties of two PURION® processed amniotic membrane products, a lyophilized human amnion, intermediate layer, and chorion membrane (LHACM) and a dehydrated human amnion, chorion membrane (DHACM). LHACM is thicker; therefore, its handling properties are ideal for deep, soft tissue deficits; whereas DHACM is more similar to a film-like overlay and may be used for shallow defects or surgical on-lays. Characterization of the similarities and differences between LHACM and DHACM was conducted through a series of in vitro and in vivo studies relevant to the healing cascade. Compositional analysis was performed through histological staining along with assessment of barrier membrane properties through equilibrium dialysis. In vitro cellular response was assessed in fibroblasts and endothelial cells using cell proliferation, migration, and metabolic assays. The in vivo cellular response was assessed in an athymic nude mouse subcutaneous implantation model. The results indicated the PURION® process preserved the native membrane structure, nonviable cells and collagen distributed in the individual layers of both products. Although, LHACM is thicker than DHACM, a similar composition of growth factors, cytokines, chemokines and proteases is retained and consequently elicit comparable in vitro and in vivo cellular responses. In culture, both treatments behaved as potent mitogens, chemoattractants and stimulants, which translated to the promotion of cellular infiltration, neocollagen deposition and angiogenesis in a murine model. PURION® processed LHACM and DHACM differ in physical properties but possess similar in vitro and in vivo activities highlighting the impact of processing method on the versatility of clinical use of amniotic membrane allografts.


Subject(s)
Allografts , Amnion , Chorion , Mice, Nude , Chorion/cytology , Amnion/chemistry , Animals , Humans , Mice , Wound Healing , Cell Proliferation , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Female , Fibroblasts/cytology , Fibroblasts/metabolism , Materials Testing , Cell Movement
17.
ACS Appl Mater Interfaces ; 16(13): 15761-15772, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38513048

ABSTRACT

Utilizing tissue-specific extracellular matrices (ECMs) is vital for replicating the composition of native tissues and developing biologically relevant biomaterials. Human- or animal-derived donor tissues and organs are the current gold standard for the source of these ECMs. To overcome the several limitations related to these ECM sources, including the highly limited availability of donor tissues, cell-derived ECM offers an alternative approach for engineering tissue-specific biomaterials, such as bioinks for three-dimensional (3D) bioprinting. 3D bioprinting is a state-of-the-art biofabrication technology that addresses the global need for donor tissues and organs. In fact, there is a vast global demand for human donor corneas that are used for treating corneal blindness, often resulting from damage in the corneal stromal microstructure. Human adipose tissue is one of the most abundant tissues and easy to access, and adipose tissue-derived stem cells (hASCs) are a highly advantageous cell type for tissue engineering. Furthermore, hASCs have already been studied in clinical trials for treating corneal stromal pathologies. In this study, a corneal stroma-specific ECM was engineered without the need for donor corneas by differentiating hASCs toward corneal stromal keratocytes (hASC-CSKs). Furthermore, this ECM was utilized as a component for corneal stroma-specific bioink where hASC-CSKs were printed to produce corneal stroma structures. This cost-effective approach combined with a clinically relevant cell type provides valuable information on developing more sustainable tissue-specific solutions and advances the field of corneal tissue engineering.


Subject(s)
Bioprinting , Tissue Engineering , Animals , Humans , Tissue Engineering/methods , Corneal Stroma/metabolism , Cornea , Extracellular Matrix/chemistry , Biocompatible Materials/metabolism , Adipose Tissue , Stem Cells , Tissue Scaffolds , Bioprinting/methods
18.
Biomacromolecules ; 25(4): 2286-2301, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38502906

ABSTRACT

Bone defects show a slow rate of osteoconduction and imperfect reconstruction, and the current treatment strategies to treat bone defects suffer from limitations like immunogenicity, lack of cell adhesion, and the absence of osteogenic activity. In this context, bioactive supramolecular peptides and peptide gels offer unique opportunities to develop biomaterials that can play a dominant role in the biomineralization of bone tissues and promote bone formation. In this article, we have demonstrated the potential of six tetrapeptides for specific binding to hydroxyapatite (HAp), a major inorganic component of the bone, and their effect on the growth and osteogenic differentiation of mesenchymal stem cells (MSCs). We adopted a simplistic approach of rationally designing amphiphilic peptides by incorporating amino acids, Ser, pSer, Pro, Hyp, Asp, and Glu, which are present in either collagenous or noncollagenous proteins and render properties like antioxidant, calcification, and mineralization. A total of six tetrapeptides, Trp-Trp-His-Ser (WWHS), Trp-Trp-His-pSer (WWHJ), Trp-Trp-His-Pro (WWHP), Trp-Trp-His-Hyp (WWHO), Trp-Trp-His-Asp (WWHD), and Trp-Trp-His-Glu (WWHE), were synthesized. Four peptides were found to self-assemble into nanofibrillar gels resembling the extracellular matrix (ECM), and the remaining two peptides (WWHJ, WWHP) self-assembled into nanorods. The peptides showed excellent cell adhesion, encapsulation, proliferation, and migration and induced the differentiation of mesenchymal stem cells (MSCs), as evident from the enhanced mineralization, resulting from the upregulation of osteogenic markers, RUNX 2, COL I, OPN, and OCN, alkaline phosphatase (ALP) production, and calcium deposition. The peptides also induced the downregulation of inflammatory markers, TNF-α and iNOS, and the upregulation of the anti-inflammatory marker, IL-10, resulting in M2 macrophage polarization. RANKL and TRAP genes were downregulated in a coculture system of MC3T3-E1 and RAW 264.7 cells, implying that peptides promote osteogenesis and inhibit osteoclastogenesis. The peptide-based biomaterials developed in this work can enhance bone regeneration capacity and show strong potential as scaffolds for bone tissue engineering.


Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Amino Acids/metabolism , Bone Regeneration , Biocompatible Materials/pharmacology , Biocompatible Materials/metabolism , Cell Differentiation , Durapatite/chemistry , Peptides/pharmacology , Peptides/metabolism , Gels/pharmacology , Cells, Cultured
19.
Science ; 383(6690): 1492-1498, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38547269

ABSTRACT

Transient implantable piezoelectric materials are desirable for biosensing, drug delivery, tissue regeneration, and antimicrobial and tumor therapy. For use in the human body, they must show flexibility, biocompatibility, and biodegradability. These requirements are challenging for conventional inorganic piezoelectric oxides and piezoelectric polymers. We discovered high piezoelectricity in a molecular crystal HOCH2(CF2)3CH2OH [2,2,3,3,4,4-hexafluoropentane-1,5-diol (HFPD)] with a large piezoelectric coefficient d33 of ~138 picocoulombs per newton and piezoelectric voltage constant g33 of ~2450 × 10-3 volt-meters per newton under no poling conditions, which also exhibits good biocompatibility toward biological cells and desirable biodegradation and biosafety in physiological environments. HFPD can be composite with polyvinyl alcohol to form flexible piezoelectric films with a d33 of 34.3 picocoulombs per newton. Our material demonstrates the ability for molecular crystals to have attractive piezoelectric properties and should be of interest for applications in transient implantable electromechanical devices.


Subject(s)
Biocompatible Materials , Ferric Compounds , Polymers , Biodegradation, Environmental , Polymers/chemistry , Polymers/metabolism , Polyvinyl Alcohol/chemistry , Polyvinyl Alcohol/metabolism , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Electricity , Animals , Rats , Rats, Sprague-Dawley , Ferric Compounds/chemistry , Ferric Compounds/metabolism
20.
Int J Mol Sci ; 25(6)2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38542453

ABSTRACT

Promoting the efficiency of bone regeneration in bone loss diseases is a significant clinical challenge. Traditional therapies often fail to achieve better therapeutic outcomes and shorter treatment times. However, in recent years, extracellular vesicles (EVs) have gained significant attention due to their exceptional osteogenic function in bone regeneration and superior therapeutic effects compared to traditional cell therapy. EVs have emerged as a promising therapy for tissue defect regeneration due to their various physiological functions, such as regulating the immune response and promoting tissue repair and regeneration. Moreover, EVs have good biocompatibility, low immunogenicity, and long-term stability, and can be improved through pretreatment and other methods. Studies investigating the mechanisms by which extracellular vesicles promote bone regeneration and applying EVs from different sources using various methods to animal models of bone defects have increased. Therefore, this paper reviews the types of EVs used for bone regeneration, their sources, roles, delivery pathways, scaffold biomaterials, and applications.


Subject(s)
Bone Diseases , Extracellular Vesicles , Animals , Bone Regeneration/physiology , Osteogenesis , Extracellular Vesicles/metabolism , Biocompatible Materials/metabolism , Cell- and Tissue-Based Therapy , Bone Diseases/therapy , Bone Diseases/metabolism
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