RESUMO
The creation of biodegradable and biocompatible shape memory polymers amenable to biofabrication techniques remains a challenge. The ability to create shape-changing biodegradable objects that are triggered at body temperature opens up possibilities in tissue engineering, minimally invasive surgery, and actuating bioimplants. Merging Digital Light Processing (DLP) printing with shape memory polymers brings us closer to new smart biomedical outcomes. Previously, we developed a poly(caprolactone-co-trimethylenecarbonate) urethane acrylate resin for the DLP fabrication of biodegradable 3D objects. In further studies, we observed that some of these resins possessed shape memory properties, triggered by body temperature (37 °C). In this subsequent study, we explored the shape memory properties and tunability of this resin family via changes in copolymer composition, molecular weight, and identity of the acrylate end-capping unit. We found that we could create a library of shape memory resins, amenable to DLP printing, which allowed the creation of shape-actuating structures with some tunability over the speed of shape memory and mechanical properties. We observed that increased mole fraction of caprolactone in the copolymer and increased molecular weight of the polymer led to a decrease in speed of the shape memory switch. Furthermore, we observed a trade-off between the composition and the end-capping moiety on the mechanical properties of the polymers. These polymeric resins were able to be processed into shapes that were able to perform work, including the release of cargo and grabbing/lifting of an object. This platform now provides a way to tune the speed and mechanical properties of a shape memory DLP object created from common and scalable polymerization techniques. This work ultimately provides a new platform to develop customizable and biodegradable devices capable of actuating and delivery devices for numerous biomedical applications.
Assuntos
Materiais Biocompatíveis , Materiais Biocompatíveis/química , Impressão Tridimensional , Engenharia Tecidual/métodos , Materiais Inteligentes/química , Poliésteres/químicaRESUMO
3D printing has emerged as vanguard technique of biofabrication to assemble cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissues. In this work, gelatin methacrylate (GelMA)/alginate hydrogel scaffolds were obtained by 3D printing and 14-3-3ε protein was encapsulated in the hydrogel to induce osteogenic differentiation of human adipose-derived mesenchymal stem cells (hASC). GelMA/alginate-based grid-like structures were printed and remained stable upon photo-crosslinking. The viscosity of alginate allowed to control the pore size and strand width. A higher viscosity of hydrogel ink enhanced the printing accuracy. Protein-loaded GelMA/alginate-based hydrogel showed a clear induction of the osteogenic differentiation of hASC cells. The results are relevant for future developments of GelMA/alginate for bone tissue engineering given the positive effect of 14-3-3ε protein on both cell adhesion and proliferation.
Assuntos
Proteínas 14-3-3/química , Hidrogéis/química , Osteogênese/fisiologia , Impressão Tridimensional , Tecido Adiposo/metabolismo , Alginatos/química , Adesão Celular , Diferenciação Celular , Proliferação de Células , Reagentes de Ligações Cruzadas , Gelatina , Humanos , Tinta , Células-Tronco Mesenquimais/metabolismo , Metacrilatos/química , Osteogênese/efeitos dos fármacos , Proteínas Recombinantes/química , ViscosidadeRESUMO
Tissue engineering and regenerative medicine are confronted with a persistent challenge: the urgent demand for robust, load-bearing, and biocompatible scaffolds that can effectively endure substantial deformation. Given that inadequate mechanical performance is typically rooted in structural deficienciesâspecifically, the absence of energy dissipation mechanisms and network uniformityâa crucial step toward solving this problem is generating synthetic approaches that enable exquisite control over network architecture. This work systematically explores structure-property relationships in poly(ethylene glycol)-based hydrogels constructed utilizing thiol-yne chemistry. We systematically vary polymer concentration, constituent molar mass, and cross-linking protocols to understand the impact of architecture on hydrogel mechanical properties. The network architecture was resolved within the molecular model of Rubinstein-Panyukov to obtain the densities of chemical cross-links and entanglements. We employed both nucleophilic and radical pathways, uncovering notable differences in mechanical response, which highlight a remarkable degree of versatility achievable by tuning readily accessible parameters. Our approach yielded hydrogels with good cell viability and remarkably robust tensile and compression profiles. Finally, the hydrogels are shown to be amenable to advanced processing techniques by demonstrating injection- and extrusion-based 3D printing. Tuning the mechanism and network regularity during the cell-compatible formation of hydrogels is an emerging strategy to control the properties and processability of hydrogel biomaterials by making simple and rational design choices.
RESUMO
Human Adipose-Derived Mesenchymal Stem/Stromal Cells (hAD-MSCs) have great potential for tissue regeneration. Since transplanted hAD-MSCs are likely to be placed in a hypoxic environment, culturing the cells under hypoxic conditions might improve their post-transplantation survival and regenerative performance. The combination of hAD-MSCs and PCL-nHA nanofibers synergically improves the contribution of both components for osteoblast differentiation. In this work, we hypothesized that this biomaterial constitutes a hypoxic environment for hAD-MSCs. We studied the cellular re-arrangement and the subcellular ultrastructure by Transmission Electron Microscopy (TEM) of hAD-MSCs grown into PCL-nHA nanofibers, and we compared them with the same cells grown in two-dimensional cultures, over tissue culture-treated plastic, or glass coverslips. Among the most evident changes, PCL-nHA grown cells showed enlarged mitochondria, and accumulation of glycogen granules, consistent with a hypoxic environment. We observed a 3.5 upregulation (p = 0.0379) of Hypoxia Inducible Factor (HIF)-1A gene expression in PCL-nHA grown cells. This work evidences for the first time intra-cellular changes in three-dimensional compared to two-dimensional cultures, which are adaptive responses of the cells to an environment more closely resembling that of the in vivo niche after transplantation, thus PCL-nHA nanofibers are adequate for hAD-MSCs pre-conditioning.
Assuntos
Células-Tronco Mesenquimais , Nanofibras , Humanos , Alicerces Teciduais/química , Durapatita/química , Durapatita/metabolismo , Poliésteres/química , Materiais Biocompatíveis/química , Diferenciação Celular , Nanofibras/química , Engenharia Tecidual/métodosRESUMO
Traditional synthetic covalent hydrogels lack the native tissue dynamics and hierarchical fibrous structure found in the extracellular matrix (ECM). These dynamics and fibrous nanostructures are imperative in obtaining the correct cell/material interactions. Consequently, the challenge to engineer functional dynamics in a fibrous hydrogel and recapitulate native ECM properties remains a bottle-neck to biomimetic hydrogel environments. Here, the molecular tuning of a supramolecular benzene-1,3,5-tricarboxamide (BTA) hydrogelator via simple modulation of hydrophobic substituents is reported. This tuning results in fibrous hydrogels with accessible viscoelasticity over 5 orders of magnitude, while maintaining a constant equilibrium storage modulus. BTA hydrogelators are created with systematic variations in the number of hydrophobic carbon atoms, and this is observed to control the viscoelasticity and stress-relaxation timescales in a logarithmic fashion. Some of these BTA hydrogels are shear-thinning, self-healing, extrudable, and injectable, and can be 3D printed into multiple layers. These hydrogels show high cell viability for chondrocytes and human mesenchymal stem cells, establishing their use in tissue engineering applications. This simple molecular tuning by changing hydrophobicity (with just a few carbon atoms) provides precise control over the viscoelasticity and 3D printability in fibrillar hydrogels and can be ported onto other 1D self-assembling structures. The molecular control and design of hydrogel network dynamics can push the field of supramolecular chemistry toward the design of new ECM-mimicking hydrogelators for numerous cell-culture and tissue-engineering applications and give access toward highly biomimetic bioinks for bioprinting.
Assuntos
Bioimpressão , Hidrogéis , Humanos , Hidrogéis/química , Biomimética , Matriz Extracelular/química , Engenharia Tecidual/métodos , Bioimpressão/métodos , Impressão TridimensionalRESUMO
Additive manufacturing and injection are essential tools in the rapidly developing field of personalized medicine and are particularly promising for applications in regenerative medicine. One of the biggest challenges in this vibrant research domain remains the processing of complex formulations with robust mechanical properties. Mimicking the native extracellular matrix associated with many tissues requires materials that have high degrees of functionality for performing the complex array of functions within the cellular environment. Furthermore, native tissues often possess outstanding mechanical properties, particularly in connective tissues. These exceptional mechanics are a challenge to emulate in their own right, especially considering the accompanying demands for additional functionality. Double-network hydrogels have emerged as strong candidates for tissue engineering because of the impressive mechanics and versatility in terms of chemical makeup. Combining advances in processing (i.e., additive manufacturing and injection) with dual-network hydrogel formulations has led to an impressive collection of results, making great strides toward systems capable of addressing the demanding environment surrounding tissues while being amenable to personalized fabrication techniques. This review provides a brief summary of the most contemporary trends collected from the literature describing dual-network hydrogels being demonstrated in additive manufacturing and injectable applications.
Assuntos
Hidrogéis , Engenharia Tecidual , Injeções , Medicina RegenerativaRESUMO
The development of biomimetic highly-porous scaffolds is essential for successful tissue engineering. Electrospun nanofibers are highly versatile platforms for a broad range of applications in different research areas. In the biomedical field, micro/nanoscale fibrous structures have gained great interest for wound dressings, drug delivery systems, soft and hard-tissue engineering scaffolds, enzyme immobilization, among other healthcare applications. In this mini-review, electrospun gelatin-based scaffolds for a variety of tissue engineering applications, such as bone, cartilage, skin, nerve, and ocular and vascular tissue engineering, are reviewed and discussed. Gelatin blends with natural or synthetic polymers exhibit physicochemical, biomechanical, and biocompatibility properties very attractive for scaffolding. Current advances and challenges on this research field are presented.
Assuntos
Gelatina/química , Engenharia Tecidual , Alicerces Teciduais , Nanofibras/química , PolímerosRESUMO
The bioadhesive polymeric films as topical drug delivery systems are interesting alternatives to improve the pharmacotherapy and patient compliances. New derivate biomaterials based on weisocyanate- dendronized PVP- crosslinked chitosan and loaded with ciprofloxacin (CIP), as model drug, were used to prepare bioadhesive films. Relevant in vitro/in vivo attributes to define main physicochemical and biopharmaceutical characteristics for topical wound-healing applications were evaluated. A high proportion of CIP, uniformly dispersed along throughout the film, was loaded. An extended release of CIP and different behaviors of release profiles, depending on the presence of dendron, were observed. The films loaded with CIP were effective in inhibiting the growth of both Gram positive and Gram negative bacteria. In addition, biocompatibility and bioadhesion into conjuntival-sacs of the rabbits suggests that these films have good properties to be applied over skin wounds for topical applications, allowing a reduction of the frequency of administration and improving the residence time of the films.