Compression Modulus Of Hydrogel Research Articles

Copper nanoparticles loaded gelatin/ polyvinyl alcohol/ guar gum-based 3D printable multimaterial hydrogel for tissue engineering applications

Hydrogels are becoming increasingly significant in tissue engineering because of their numerous benefits, including biocompatibility, biodegradability, and their ability to provide a supportive structure for cell proliferation. This study presents the synthesis and characterization of a new multimaterial hydrogel with 3D-printing capabilities composed of copper nanoparticle-reinforced gelatin, polyvinyl alcohol (PVA), and guar gum-based biomaterials intended for tissue engineering applications. Combining CuNPs aims to enhance the hydrogel's antibacterial properties, mechanical strength, and bioactivity, which are essential for successful tissue regeneration. Hydrogels are chemically cross-linked with glyoxal and analyzed through different assessments to examine the compressive behavior, surface morphology, sorbing capacity, biocompatibility, thermal stability, and degradation properties. The results demonstrated that including CuNPs significantly improved the hydrogel's compressive modulus (4.18 MPa) for the hydrogel with the CuNPs and provided better antibacterial activity against common pathogens with controlled degradation. All the hydrogels exhibited a lower coefficient of friction, which was below 0.1. In vitro cell culture studies using chondrocytes indicated that the CuNPs-loaded hydrogel supported cell proliferation and growth of chondrogenic genes such as collagen type II (COL2) and aggrecan (ACAN). The biocompatibility and enhanced mechanical properties of the multimaterial hydrogel make it a promising candidate for developing customized, patient-specific tissue engineering scaffolds.

Injectable cell-laden hybrid bioactive scaffold containing bioactive glass microspheres.

The rising incidence of bone disorders has resulted in the need for minimally invasive therapies to meet this demand. Injectable bioactive filler, alone or with cells, could be applied in a minimally invasive manner to fulfill irregular cavities in non-load bearing sites, which do not require high mechanical properties. Thermosensitive chitosan hydrogels that transition from a liquid to a mechanically stable solid at body temperature provide interesting features as in-situ injectable cytocompatible biomaterials, but they are not osteoconductive. Osteoconductivity can be applied in combination with bioactive ceramics e.g., 45S5-Bioglass® (BG). However, BG addition in chitosan hydrogels results in pH elevation, due to rapid ions release, which adversely affects gel formation, mechanical properties, and cytocompatibility. To address this, we created hybrid hydrogels, where BG is concentrated in chitosan-based microbeads, incorporated in in-situ gelling chitosan hydrogels. We then compared the hybrid hydrogels' properties to chitosan hydrogels with homogenously distributed BG. By varying the stirred emulsification process, BG percentage, and CH formulation, we could tune the microbeads' properties. Incorporation of BG microbeads drastically improved the hydrogel's compressive modulus in comparison to homogeneously distributed BG. It also strongly increased the survival and metabolic activities of encapsulated cells. Calcium/phosphate increase on BG microbeads suggests hydroxyapatite formation. The small diameter of microbeads allows minimally invasive injection through small needles. The feasibility of freezing and thawing microbeads provides the possibility of long-term storage for potential clinical applications. These data indicate that this hybrid hydrogel forms a promising injectable cell-laden bioactive biomaterial for the treatment of unloaded bone defects.

Preparation and preliminary research on the characteristics of modified nano-bioglass hydrogel

Preparation and preliminary research on the characteristics of modified nano-bioglass hydrogel

Alter macrophage adhesion and modulate their response on hydrophobically modified hydrogels

• Facile modification of naturally derived polymers to increase hydrophobicity. • Hydrogels were crosslinked via in situ thiol-ene chemistry. • Protein adsorption and macrophage proliferation increased on hydrophobic hydrogels. • Macrophages pro-inflammatory response was suppressed on hydrophobic hydrogels. Adhesion of macrophages to material substrates plays an essential role in many biological behaviors and biomedical procedures, including wound healing, cancer treatment and biomaterial implantation. Therefore, altering the adhesion of macrophages using biomaterial design may help control their biological function. In this work, we developed a straightforward method to render the hydrogel surface more hydrophobic and demonstrated that the adhesion of macrophages on hydrogels was enhanced on these more hydrophobic surfaces. Compared to the unmodified methacrylated gellan gum (MGG) hydrogel, the water contact angle increased and the swelling ratio decreased for modified MGG hydrogels. The degree of hydrophobicity was controlled by attaching hydrophobic branches of different lengths to the MGG, while the modification did not change the hydrogel compressive modulus. This ensured that the observed different cell responses were mainly due to hydrophobicity change and not the mechanical property difference among the hydrogels. Cell (RAW 264.7 macrophages) proliferation and spreading increased with increasing surface hydrophobicity. Protein adsorption on hydrogel surfaces showed the same trend. Quantification of adhesion to hydrogel surfaces using a hydrophobic probe showed that adhesion was enhanced as substrate hydrophobicity increased. This suggests that cell adhesion may be promoted due to the increase in hydrophobic adhesion that could enhance protein adsorption. In addition, tumor necrosis factor-α (TNF-α) secretion by lipopolysaccharide (LPS) activated M1 and interleukin-4 (IL-4) activated M2 macrophages was also altered by substrate hydrophobicity. TNF-α production, a marker of pro-inflammatory macrophages, decreased with substrate hydrophobicity. These results suggest that substrate hydrophobic can be used to modulate macrophage responses.

Macrophage Adhesion and Phenotypic Shifts on Hydrophobically Modified Hydrogels

A balance of macrophage phenotypes is essential in successful implantation. Therefore, biomaterials should be carefully designed to better regulate the response of macrophages. We demonstrate macrophage adhesion and phenotypic shifts can be modulated with hydrophobically modified hydrogels. This study represents a fundamental concept in controlling cell adhesion and differentiation with substrate hydrophobicity. Gel synthesis was carried out using methacrylated gellan gum (MGG), which was polymerized and crosslinked through a photo-initiated thiol-ene reaction in situ. The degree of hydrophobicity was controlled by attaching hydrophobic branches of different lengths to the MGG. The attachment was carefully controlled so that the hydrogel compressive modulus was not affected by the hydrophobic modification. Compared to unmodified MGG, the water contact angle increased and the swelling ratio decreased for modified MGG hydrogels. Naive and activated macrophages were subsequently seeded on the hydrogels with different surface wettability. Cell proliferation and spreading increased with increasing surface hydrophobicity. Hydrogel surface adhesion to a hydrophobic probe was quantified and showed an increasing trend with increasing substrate hydrophobicity. This suggests that the hydrophobic surface may increase protein adsorption, which, in turn, increases cell spreading. Cytokine secretion by M1 and M2 macrophages were also altered by substrate hydrophobicity. Both nitrite production, a marker of M1, and urea production, a marker of M2, increased with substrate hydrophobicity, with nitrate production being more pronounced. RAW 264.7 macrophages seeded on these substrates shifted to a more pro-inflammatory phenotype with increasing substrate hydrophobicity.

Local Heterogeneities Improve Matrix Connectivity in Degradable and Photoclickable Poly(ethylene glycol) Hydrogels for Applications in Tissue Engineering.

Hydrolytically degradable poly(ethylene glycol) (PEG) hydrogels are promising platforms for cell encapsulation and tissue engineering. However, hydrolysis leads to bulk degradation and a decrease in hydrogel mechanical integrity. Despite these challenges, hydrolytically degradable hydrogels have supported macroscopic neotissue growth. The goal of this study was to combine experimental methods with a multiscale mathematical model to analyze hydrogel degradation concomitant with neocartilage growth in PEG hydrogels. Primary bovine chondrocytes were encapsulated at increasing densities (50, 100, and 150 million cells/mL of precursor solution) in a radical-mediated photoclickable hydrogel formed from 8-arm PEG-co-caprolactone end-capped with norbornene and cross-linked with PEG dithiol. Two observations were made in the experimental system: (1) the cell distribution was not uniform and cell clustering was evident, which increased with increasing cell density and (2) a significant decrease in the initial hydrogel compressive modulus was observed with increasing cell concentration. By introducing heterogeneities in the form of cell clusters and spatial variations in the network structure around cells, the mathematical model explained the drop in initial modulus and captured the experimentally observed spatial evolution of ECM and the construct modulus as a function of cell density and culture time. Overall, increasing cell density led to improved ECM formation, ECM connectivity, and overall modulus. This study strongly points to the importance of heterogeneities within a cell-laden hydrogel in retaining mechanical integrity as the construct transitions from hydrogel to neotissue.

An approach to improve the efficiency of polymerization and enhance biological activity of poly(lactide‐co‐ethylene oxide fumarate) hydrogels

ABSTRACTThe synthesis and purification of poly(lactide ethylene oxide fumarate) (PLEOF) involved using organic solvents and triethylamine, an acid scavenger that produces toxic complexes. These issues were addressed by using potassium carbonate as an alternative acid scavenger and CO2 gas expanded solution as a media for reaction. Conducting the reaction at these conditions resulted in reducing the number of stages for purification, enhancing the yield of polymerization by 31%, and increasing the fumarate fraction by 110% compared with conventionally produced polymers. Therefore, the capacity of polymer for crosslinking was significantly promoted that resulted in elevating the compression modulus of hydrogel by 119%. Eliminating the toxic chemical residues and strengthening the mechanical property of PLEOF led to enhancement in primary osteoblast cell proliferation on this hydrogel. The new strategy for the synthesis of PLEOF had paramount impact on the characteristics of this polymer and enhanced its biocompatibility for tissue engineering applications, particularly bone repair. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1291–1299

Comparison of photopolymerizable thiol-ene PEG and acrylate-based PEG hydrogels for cartilage development

When designing hydrogels for tissue regeneration, differences in polymerization mechanism and network structure have the potential to impact cellular behavior. Poly(ethylene glycol) hydrogels were formed by free-radical photopolymerization of acrylates (chain-growth) or thiol-norbornenes (step-growth) to investigate the impact of hydrogel system (polymerization mechanism and network structure) on the development of engineered tissue. Bovine chondrocytes were encapsulated in hydrogels and cultured under free swelling or dynamic compressive loading. In the acrylate system immediately after encapsulation chondrocytes exhibited high levels of intracellular ROS concomitant with a reduction in hydrogel compressive modulus and higher variability in cell deformation upon compressive strain; findings that were not observed in the thiol-norbornene system. Long-term the quantity of sulfated glycosaminoglycans and total collagen was greater in the acrylate system, but the quality resembled that of hypertrophic cartilage with positive staining for aggrecan, collagens I, II, and X and collagen catabolism. The thiol-norbornene system led to hyaline-like cartilage production especially under mechanical loading with positive staining for aggrecan and collagen II and minimal staining for collagens I and X and collagen catabolism. Findings from this study confirm that the polymerization mechanism and network structure have long-term effects on the quality of engineered cartilage, especially under mechanical loading.

Analysis of the in vitro swelling behavior of poly(vinyl alcohol) hydrogels in osmotic pressure solution for soft tissue replacement

An osmotic solution was used to evaluate poly(vinyl alcohol) (PVA) hydrogels as potential non-degradable soft tissue replacements in vitro. Osmotic solutions are necessary in order to mimic the swelling pressure observed in vivo for soft tissues present in load-bearing joints. In vitro studies indicated that PVA hydrogels experience minimal changes in swelling with a polymer concentration of 20 wt.% PVA in phosphate-buffered saline solution (0 atm) and between 30 and 35 wt.% PVA in osmotic solution with a pressure of 0.95 atm. Swelling in osmotic pressure solutions caused decreases in the equilibrium hydrogel hydration. An investigation of hydrogel compressive modulus indicated that PVA hydrogels are within the range of articular cartilage, meniscal tissue, and the temporomandibular joint disk. Furthermore, it is possible to tailor PVA hydrogels through careful modification of the polymer concentration and freeze–thaw cycles during hydrogel preparation to match both a desired swelling ratio and a desired compressive modulus or porosity. The microstructure of the PVA hydrogels was also evaluated as a function of freeze–thaw cycles and polymer concentration to give an insight into the processes occurring during synthesis and swelling in osmotic solutions.

Synthesis of highly porous crosslinked elastin hydrogels and their interaction with fibroblasts in vitro

In this study the feasibility of using high pressure CO2 to produce porous α-elastin hydrogels was investigated. α-Elastin was chemically crosslinked with hexamethylene diisocyanate that can react with various functional groups in elastin such as lysine, cysteine, and histidine. High pressure CO2 substantially affected the characteristics of the fabricated hydrogels. The pore size of the hydrogels was enhanced 20-fold when the pressure was increased from 1bar to 60bar. The swelling ratio of the samples fabricated by high pressure CO2 was also higher than the gels produced under atmospheric pressure. The compression modulus of α-elastin hydrogels was increased as the applied strain magnitude was modified from 40% to 80%. The compression modulus of hydrogels produced under high pressure CO2 was 3-fold lower than the gels formed at atmospheric conditions due to the increased porosity of the gels produced by high pressure CO2. The fabrication of large pores within the 3D structures of these hydrogels substantially promoted cellular penetration and growth throughout the matrices. The highly porous α-elastin hydrogel structures fabricated in this study have potential for applications in tissue engineering.