Tissue Engineering Purposes Research Articles

Porous photo-crosslinked hybrid networks based on poly(trimethylene carbonate-co-ε-caprolactone) and recombinant human-like collagen

Hybrid hydrogel networks were prepared from recombinant human-like collagen (rh-collagen) and poly(trimethylene carbonate-co-ε-caprolactone) (P (TMC-co-ε-CL)) to overcome the mechanical and bioactivity limitations associated with the respective individual networks. Both polymers were functionalised with methacrylic anhydride to yield photo-crosslinkable materials. Porous hybrid networks of different compositions were prepared by photo-crosslinking frozen mixtures of solutions of the functionalized polymers in acidified DMSO. After extraction with water, the obtained networks had the intended compositions, high porosities and gel content. Upon equilibration in water, the total water content was found to increase with increasing collagen content. The tensile properties and suture retention strength (SRS) of the hybrids were improved compared to a rh-collagen network. In particular, the 17:83 wt% rh-collagen:P(TMC-co-ε-CL) network had considerably higher toughness and SRS, showing promise as a hybrid hydrogel network to be further investigated for tissue engineering purposes.

Role of Pyrrolidine dithiocarbamate in inducing odontoblastic differentiation of dental pulp stem cells

Abstract Background: Pyrrolidine dithiocarbamate (PDTC) is an efficient, reproducible, and biological antioxidant of clinical utility, which may also be preferred for obtaining human dental pulp stem cells (hDPSCs) for the purpose of tissue engineering and regenerative medicine. Aim and Objectives: The study was conducted to evaluate the effects of PDTC on the propagation and differentiation of hDPSCs. Materials and Methods: hDPSCs were isolated by explant culture method and characterized for stem cell properties using flow cytometry method. The effects of PDTC-induced odontoblastic differentiation of hDPSC at different concentrations (0.5, 1.0, and 5.0 mM) were determined by staining for mineralization. Results: Mineralization was more prominent and significantly higher in the induced hDPSCs treated with 1.0 mM concentration of PDTC. Conclusion: PDTC at 1.0 mM concentration could have a significant pharmacological role in activating and enhancing odontogenic differentiation of dental stem cells and make it an important step in regenerative dentistry.

257 - Epithelial organoids for urethral tissue engineering purposes

257 - Epithelial organoids for urethral tissue engineering purposes

Effect of viscosity of gelatin methacryloyl-based bioinks on bone cells

The viscosity of gelatin methacryloyl (GelMA)-based bioinks generates shear stresses throughout the printing process that can affect cell integrity, reduce cell viability, cause morphological changes, and alter cell functionality. This study systematically investigated the impact of the viscosity of GelMA-gelatin bioinks on osteoblast-like cells in 2D and 3D culture conditions. Three bioinks with low, medium, and high viscosity prepared by supplementing a 5% GelMA solution with different concentrations of gelatin were evaluated. Cell responses were studied in a 2D environment after printing and incubation in non-cross-linked bioinks that caused the gelatin and GelMA to dissolve and release cells for attachment to tissue culture plates. The increased viscosity of the bioinks significantly affected cell area and aspect ratio. Cells printed using the bioink with medium viscosity exhibited greater metabolic activity and proliferation rate than those printed using the high viscosity bioink and even the unprinted control cells. Additionally, cells printed using the bioink with high viscosity demonstrated notably elevated expression levels of alkaline phosphatase and bone morphogenetic protein-2 genes. In the 3D condition, the printed cell-laden hydrogels were photo-cross-linked prior to incubation. The medium viscosity bioink supported greater cell proliferation compared to the high viscosity bioink. However, there were no significant differences in the expression of osteogenic markers between the medium and high viscosity bioinks. Therefore, the choice between medium and high viscosity bioinks should be based on the desired outcomes and objectives of the bone tissue engineering application. Furthermore, the bioprinting procedure with the medium viscosity bioink was used as an automated technique for efficiently seeding cells onto 3D printed porous titanium scaffolds for bone tissue engineering purposes.

3D bioprinting for tissue engineering: Stem cells in hydrogels

Surgical limitations require alternative methods of repairing and replacing diseased and damaged tissue. Regenerative medicine is a growing area of research with engineered tissues already being used successfully in patients. However, the demand for such tissues greatly outweighs the supply and a fast and accurate method of production is still required. 3D bioprinting offers precision control as well as the ability to incorporate biological cues and cells directly into the material as it is being fabricated. Having precise control over scaffold morphology and chemistry is a significant step towards controlling cellular behaviour, particularly where undifferentiated cells, i.e., stem cells, are used. This level of control in the early stages of tissue development is crucial in building more complex systems that morphologically and functionally mimic in vivo tissue. Here we review 3D printing hydrogel materials for tissue engineering purposes and the incorporation of cells within them. Hydrogels are ideal materials for cell culture. They are structurally similar to native extracellular matrix, have a high nutrient retention capacity, allow cells to migrate and can be formed under mild conditions. The techniques used to produce these materials, as well as their benefits and limitations, are outlined.

Synthesis and rheological analyzes of temperature and light sensitive gels comprising amphiphilic azobenzene polymers, chitosan and pluronic F127

AbstractThis study investigates the reinforcement of pluronic (PF127) based temperature responsive hydrogels with photosensitive functionalities to create smart and injectable materials. For this purpose, 4‐[4‐[(4‐phenyl)azo]phenoxy] methacrylate (PAzPMA) was synthesized and further polymerized via reversible addition‐fragmentation chain transfer (RAFT) polymerization. The structures of the copolymers were characterized by several techniques such as Fourier‐transform infrared (FT‐IR), nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). The azobenzene‐functionalized copolymer was combined with P127 solid polymer in micelle form and with P127 micelles in solid form to obtain PF127‐AzoMx and PF127‐AzoPx gels, respectively. When the temperature profiles of the PF127‐AzoMx and PF127‐AzoPx systems were compared with PF127, sol–gel phase transition were shifted to lower temperatures due to stronger hydrophobic interactions. Additionally, different concentrations of N,N,N‐trimethyl chitosan (f‐chitosan) were added to the gel systems and their rheological properties were investigated by exposing them to UV light. It has been observed that the presence and concentration of f‐chitosan are important for the variation of the interactions' strength between the micelles. The study highlights the potential of multifunctional hydrogels for specific biomedical applications that combine sensitivity to both thermal and optical stimuli for controlled drug delivery and tissue engineering purposes.

Strategies for the Codelivery of Osteoclasts and Mesenchymal Stem Cells in 3D-Printable Osteochondral Scaffolds.

Osteochondral defects, characterized by structural compromises to articular cartilage and subchondral bone, can cause pain and lead to progressive cartilage damage and eventual osteoarthritis. Unfortunately, repairing these defects remains difficult because of the poor regenerative properties of cartilage and complex mechanical demands of the joint. As such, the field of tissue engineering aims to develop multiphasic implants that replace pathological cartilage and bone tissue and restore mechanical functionality to the joint. Recent bone physiology investigations have demonstrated that osteoclast (OC) lineage cells are inextricably involved in osteoblastic bone formation through an extensive network of anabolic signaling pathways, and so the codelivery OC and osteoblast (OB) lineage cells within scaffolds is being actively explored for bone tissue engineering purposes. However, it remains unclear how these cells can be incorporated into the design of multiphasic osteochondral scaffolds to potentially enhance subchondral bone formation and subsequent implant osseointegration. To explore this question, we examined direct surface seeding and hydrogel encapsulation as potential scaffold cellularization strategies. First, we examined how OC precursor cells and peripheral blood monocytes (PBMCs) influence early-stage bone matrix development and osteogenesis in 2D coculture. Then, we evaluated the osteogenic potential of mesenchymal stem cells (MSCs) and PBMCs cocultures encapsulated within a gelatin methacrylate (GelMA) hydrogel system. Our findings demonstrate that coculturing PBMCs with MSCs in 2D cultures significantly enhanced cell proliferation, early bone matrix deposition, and the formation of cell clusters by Day 28. However, we observed no significant difference in type I collagen deposition between GelMA hydrogel scaffolds cultured in basal and OC conditions during the same period. In addition, we found that the GelMA hydrogel system with MSC/PBMC cocultures in OC conditions exhibited decreased osteogenic activity by Day 28. Collectively, our findings support the osteogenic potential of OC-lineage cells in 2D culture conditions, and the potential benefits of surface-seeding for the codelivery of OC-lineage cells and MSCs in osteo-scaffolds for enhanced osteochondral regeneration and broader bone tissue engineering purposes.

An instructional design strategy for optimization of GelMA hydrogels material properties

Gelatin methacryloyl (GelMA) hydrogels have become a key biomaterial in various biomedical fields, such as tissue regeneration engineering and drug delivery, due to their exceptional biocompatibility and customizable physical and chemical characteristics. The resemblance of GelMA to the extracellular matrix and its ability to be cured with light make it a popular choice for researchers. This research delves into how the material properties of GelMA hydrogels, specifically the density of the molecular network (DMN), impact their performance in different applications. By preparing GelMA hydrogels with different degrees of substitution (DS) and concentrations, and utilizing these attributes as key measurable parameters for determining DMN, we conducted a comprehensive evaluation of properties relevant to biological applications. We also suggest strategies for optimizing these properties. Through the application of the DMN theory, we show that precise control over material properties allows for tailored customization of GelMA hydrogels for specific tissue engineering and drug delivery purposes. This study offers valuable insights into the optimization of GelMA hydrogel properties to advance the field of tissue engineering and improve customization of cellular microenvironments.

Photo-Clickable Triazine-Trione Thermosets as Promising 3D Scaffolds for Tissue Engineering Applications.

There is an overwhelming demand for new scaffolding materials for tissue engineering (TE) purposes. Polymeric scaffolds have been explored as TE materials; however, their high glass transition state (Tg) limits their applicability. In this study, a novel materials platform for fabricating TE scaffolds is proposed based on solvent-free two-component heterocyclic triazine-trione (TATO) formulations, which cure at room temperature via thiol-ene/yne photochemistry. Three ester-containing thermosets, TATO-1, TATO-2, and TATO-3, are used for the fabrication of TE scaffolds including rigid discs, elastic films, microporous sponges, and 3D printed objects. After 14 days' incubation the materials covered a wide range of properties, from the soft TATO-2 having a compression modulus of 19.3MPa and a Tg of 30.4°C to the hard TATO-3 having a compression modulus of 411MPa and a Tg of 62.5°C. All materials exhibit micro- and nano-surface morphologies suited for bone tissue engineering, and in vitro studies found them all to be cytocompatible, supporting fast cell proliferation while minimizing cell apoptosis and necrosis. Moreover, bone marrow-derived mesenchymal stem cells on the surface of the materials are successfully differentiated into osteoblasts, adipocytes, and neuronal cells, underlining the broad potential for the biofabrication of TATO materials for TE clinical applications.

Forward programming of human induced pluripotent stem cells via the ETS variant transcription factor 2: rapid, reproducible, and cost-effective generation of highly enriched, functional endothelial cells.

Endothelial cell (EC) dysfunction plays a key role in the initiation and progression of cardiovascular disease. However, studying these disorders in ECs from patients is challenging; hence, the use of human induced pluripotent stem cells (hiPSCs) and their in vitro differentiation into ECs represents a very promising approach. Still, the generation of hiPSC-derived ECs (hECs) remains demanding as a cocktail of growth factors and an intermediate purification step are required for hEC enrichment. Therefore, we probed the utility of a forward programming approach using transgenic hiPSC lines. We have used the transgenic hiPSC line PGP1 ETV2 isoform 2 to explore the in vitro differentiation of hECs via doxycycline-dependent induction of the ETS variant transcription factor 2 (ETV2) and compared these with a standard differentiation protocol for hECs using non-transgenic control hiPSCs. The transgenic hECs were highly enriched without an intermediate purification step and expressed-as non-transgenic hECs and human umbilical vein endothelial cells-characteristic EC markers. The viability and yield of transgenic hECs were strongly improved by applying EC growth medium during differentiation. This protocol was successfully applied in two more transgenic hiPSC lines yielding reproducible results with low line-to-line variability. Transgenic hECs displayed typical functional properties, such as tube formation and LDL uptake, and a more mature phenotype than non-transgenic hECs. Transgenic hiPSCs preferentially differentiated into the arterial lineage; this was further enhanced by adding a high concentration of vascular endothelial growth factor to the medium. We also demonstrate that complexing lentivirus with magnetic nanoparticles and application of a magnetic field enables efficient transduction of transgenic hECs. We have established a highly efficient, cost-effective, and reproducible differentiation protocol for the generation of functional hECs via forward programming. The transgenic hECs can be genetically modified and are a powerful tool for disease modelling, tissue engineering, and translational purposes.

The Development of a 3D PET Fibrous Scaffold Modified with an Umbilical Cord dECM for Liver Tissue Engineering.

Organ and tissue dysfunction represents a clinically significant condition. By integrating cell biology with materials science, tissue engineering enables the reconstruction and restoration of damaged tissues or organs, offering a noninvasive repair approach. In our study, we replicated the cellular growth environment by utilizing a human umbilical cord-derived decellularized extracellular matrix (dECM) as a modifying agent for the polyethylene terephthalate (PET) polymeric fiber scaffold. This allowed us to create a dECM-coated polyester fiber-based scaffold, PET-dECM, tailored for liver tissue engineering purposes. We effectively produced a decellularized human umbilical cord-derived ECM through a combined decellularization process involving trypsin/EDTA, TritonX-100, and sodium deoxycholate. The application of the dECM coating onto the PET material was accomplished through several steps, such as ester hydrolysis, EDC/NHS-activated crosslinking, and dECM conjugation. The biological performance of the PET-dECM was validated using RG cell culture assays. Notably, the dECM coating significantly improved PET's hydrophilicity and biocompatibility, thereby aiding cell adhesion, proliferation, and functional differentiation (p < 0.05). It was further found that the hepatocyte function of HepaRG was significantly enhanced on the PET-dECM, which may be attributed to the dECM's ability to facilitate the restoration of cell polarity. The PET-dECM holds promise as an effective hepatocyte culture carrier and could potentially find application in liver tissue engineering.

A Multidisciplinary Evaluation of Three-Dimensional Polycaprolactone Bioactive Glass Scaffolds for Bone Tissue Engineering Purposes.

In the development of bone graft substitutes, a fundamental step is the use of scaffolds with adequate composition and architecture capable of providing support in regenerative processes both on the tissue scale, where adequate resistance to mechanical stress is required, as well as at the cellular level where compliant chemical-physical and mechanical properties can promote cellular activity. In this study, based on a previous optimization study of this group, the potential of a three-dimensional construct based on polycaprolactone (PCL) and a novel biocompatible Mg- and Sr-containing glass named BGMS10 was explored. Fourier-transform infrared spectroscopy and scanning electron microscopy showed the inclusion of BGMS10 in the scaffold structure. Mesenchymal stem cells cultured on both PCL and PCL-BGMS10 showed similar tendencies in terms of osteogenic differentiation; however, no significant differences were found between the two scaffold types. This circumstance can be explained via X-ray microtomography and atomic force microscopy analyses, which correlated the spatial distribution of the BGMS10 within the bulk with the elastic properties and topography at the cell scale. In conclusion, our study highlights the importance of multidisciplinary approaches to understand the relationship between design parameters, material properties, and cellular response in polymer composites, which is crucial for the development and design of scaffolds for bone regeneration.

Core/shell nanofibrous conduit containing natural surfactant enhanced axonal regrowth guiding for peripheral nerve regeneration

This study illustrated the impact of Saponins in electrospun nanofibers on nerve regeneration and compared them with Tween 80, which is commonly used as a synthetic surfactant. The study explores the effect of Saponins, natural emulsifiers known for their effectiveness in forming and stabilizing emulsions. Surfactant choice is crucial due to its effects on fluid stability, influenced by parameters like polymer concentration, homogenization rate, and surfactant type/amount. This study explored PCL as the core and PVA as the shell.Core/shell scaffolds displayed favorable wettability (contact angle: 67.0° ± 1.3) and improved mechanical properties (wet state tensile strength: PVA 1.1 ± 0.2 MPa, PVA/PCL-Saponin 2.0 ± 0.5 MPa). The MTT viability assay demonstrated higher viability of PC12 cells on Saponin-containing nanofibers (85.0 % ± 0.1) compared to Tween 80 (69.0 % ± 0.1) after 24 h. Subcutaneous implantation in rats showed no significant inflammation after one week. Eventually, in the animal model, the conduit containing Saponin was more effective than Tween 80 in repairing the rat's sciatic nerve within six weeks, as evidenced by NF-200 counts and histological studies. Overall, the study indicates that PVA/PCL-Saponin nanofibers, without requiring Saponin surfactant removal, show high quality and effectiveness for tissue engineering and medical purposes.

Nanocomposite Methacrylated Silk Fibroin-Based Scaffolds for Bone Tissue Engineering.

The treatment of bone defects is a clinical challenge. Bone tissue engineering is gaining interest as an alternative to current treatments, with the development of 3D porous structures (scaffolds) helpful in promoting bone regeneration by ensuring temporary functional support. In this work, methacrylated silk fibroin (SilMA) sponges were investigated as scaffolds for bone tissue engineering by exploiting the combination of physical (induced by NaCl salt during particulate leaching) and chemical crosslinking (induced by UV-light exposure) techniques. A biomimetic approach was adopted to better simulate the extracellular matrix of the bone by introducing either natural (mussel shell-derived) or synthetic-origin hydroxyapatite nanoparticles into the SilMA sponges. The obtained materials were characterized in terms of pore size, water absorption capability and mechanical properties to understand both the effect of the inclusion of the two different types of nanoparticles and the effect of the photocrosslinking. Moreover, the SilMA sponges were tested for their bioactivity and suitability for bone tissue engineering purposes by using osteosarcoma cells, studying their metabolism by an AlamarBlue assay and their morphology by scanning electron microscopy. Results indicate that photocrosslinking helps in obtaining more regular structures with bimodal pore size distributions and in enhancing the stability of the constructs in water. Moreover, the addition of naturally derived hydroxyapatite was observed to be more effective at activating osteosarcoma cell metabolism than synthetic hydroxyapatite, showing a statistically significant difference in the AlamarBlue measurement on day 7 after seeding. The methacrylated silk fibroin/hydroxyapatite nanocomposite sponges developed in this work were found to be promising tools for targeting bone regeneration with a sustainable approach.

Unraveling and Harnessing the Immune Response at the Cell-Biomaterial Interface for Tissue Engineering Purposes.

Biomaterials are defined as "engineered materials" and include a range of natural and synthetic products, designed for their introduction into and interaction with living tissues. Biomaterials are considered prominent tools in regenerative medicine that support the restoration of tissue defects and retain physiologic functionality. Although commonly used in the medical field, these constructs are inherently foreign toward the host and induce an immune response at the material-tissue interface, defined as the foreign body response (FBR). A strong connection between the foreign body response and tissue regeneration is suggested, in which an appropriate amount of immune response and macrophage polarization is necessary to trigger autologous tissue formation. Recent developments in this field have led to the characterization of immunomodulatory traits that optimizes bioactivity, the integration of biomaterials and determines the fate of tissue regeneration. This review addresses a variety of aspects that are involved in steering the inflammatory response, including immune cell interactions, physical characteristics, biochemical cues, and metabolomics. Harnessing the advancing knowledge of the FBR allows for the optimization of biomaterial-based implants, aiming to prevent damage of the implant, improve natural regeneration, and provide the tools for an efficient and successful in vivo implantation.

Development of a microfluidic-assisted open-source 3D bioprinting system (MOS3S) for the engineering of hierarchical tissues

The engineering of new 3D bioprinting approaches has shown great promise in the field of tissue engineering and disease modelling. However, the high cost of commercial 3D bioprinters has limited their accessibility, especially to those laboratories in resource-limited settings. Moreover, the need for a 3D bioprinting system capable of dispensing multiple materials is growing apace. Therefore, the development of a Microfluidic-assisted Open Source 3D bioprinting System (MOS3S) for the engineering of hierarchical tissues is needed to progress in fabricating functional tissues, but with a technology accessible to a wider range of researchers. The MOS3S platform is designed to allow the deposition of biomaterial inks using microfluidic printheads or coaxial nozzles for the in-situ crosslinking and scaffolds fabrication. The coupling of 3D printed syringe pumps with the motion control system is used for driving the tunable extrusion of inks for the fabrication of centimeter scale hierarchical lattice constructs for tissue engineering purposes. MOS3S performance have been validated to fabricate high-resolution structures with coaxial microfluidic technology, opening to new frontiers for seminal studies in pre-clinical disease modelling and tissue regeneration.

Enhancing the Regenerative Potential of Adipose-Derived Mesenchymal Stem Cells Through TLR4-Mediated Signaling.

Toll-like receptor 4 (TLR4) is a receptor that traditionally plays an important role in immunomodulation (regulation of the immune system) and the initiation of proinflammatory responses. TLR4 is used in the body to recognize molecular patterns of pathogens or damaged cells from outside. However, in recent years, it has also become clear that TLR4 can affect the immune system and the function of stem cells, especially mesenchymal stem cells. Therefore, understanding how TLR4 signaling works at the cellular and molecular level and using this knowledge in regenerative medicine could be potentially useful, especially in the treatment of adipose- derived mesenchymal stem cells (ADMSCs). How these cells can use TLR4 signaling when used to increase their regenerative potential and repair tissues is an area of research. This study aims to elucidate the multifaceted role of TLR4-mediated signaling in ADMSCs. Employing a comprehensive set of assays, including MTT for cell viability, flow cytometry for surface marker expression, and gene expression analysis, we demonstrate that TLR4 activation significantly modulates key aspects of ADMSC biology. Specifically, TLR4 signaling was found to regulate ADMSCs proliferation, surface marker expression, and regenerative capacity in a dose- and time-dependent manner. Furthermore, TLR4 activation conferred cytoprotective effects against Doxorubicin (DOX)-induced cellular apoptosis. These findings suggest that TLR4 signaling could be used to enhance the regenerative abilities of ADMSCs and enable ADMSC-based therapies to be used more effectively for tissue engineering and therapeutic purposes. However, it is important to note that research in this area needs more details and clinical studies.

Microfluidic fiber spinning for 3D bioprinting: Harnessing microchannels to build macrotissues

Microfluidics is rapidly revolutionizing the scientific panorama, providing unmatched high-throughput platforms that find application in numerous areas of physics, chemistry, biology, and materials science. Recently, microfluidic chips have been proposed, in combination with bioactive materials, as promising tools for spinning cell-laden fibers with on-demand characteristics. However, cells encapsulated in filaments produced via microfluidic spinning technology are confined in a quasi-three-dimensional (3D) environment that fails to replicate the intricate 3D architecture of biological tissues. Thanks to the recent synergistic combination of microfluidic devices with 3D bioprinting technologies that enable the production of sophisticated microfibers serving as the backbone of 3D structures, a new age of tissue engineering is emerging. This review looks at how combining microfluidics with 3D printing is contributing to the biofabrication of relevant human substitutes and implants. This paper also describes the whole manufacturing process from the production of the microfluidic tool to the printing of tissue models, focusing on cutting-edge fabrication technologies and emphasizing the most noticeable achievements for microfluidic spinning technology. A theoretical insight for thixotropic hydrogels is also proposed to predict the fiber size and shear stress developing within microfluidic channels. The potential of using microfluidic chips as bio-printheads for multi-material and multi-cellular bioprinting is discussed, highlighting the challenges that microfluidic bioprinting still faces in advancing the field of biofabrication for tissue engineering and regenerative medicine purposes.

3D-Bioprinted GelMA Scaffold with ASCs and HUVECs for Engineering Vascularized Adipose Tissue.

The purpose of tissue engineering is to reconstruct parts of injured tissues and to resolve the shortage of organ donations. However, the main concern is the limited size of engineered tissue due to insufficient oxygen and nutrition distribution in large three-dimensional (3D) tissue constructs. To provide better support for cells inside the scaffolds, the vascularization of blood vessels within the scaffold could be a solution. This study compared the effects of different culturing systems using human adipose tissue-derived stem/stromal cells (ASCs), human umbilical vein endothelial cells (HUVECs), and coculture of ASCs and HUVECs in 3D-bioprinted gelatin methacrylate (GelMA) hydrogel constructs. The in vitro results showed that the number of live cells was highest in the coculture of ASCs and HUVECs in the GelMA hydrogel after culturing for 21 days. Additionally, the tubular structure was the most abundant in the GelMA hydrogel, containing both ASCs and HUVECs. In the in vivo test, blood vessels were present in both the HUVECs and the coculture of ASCs and HUVECs hydrogels implanted in mice. However, the blood vessel density was the highest in the HUVEC and ASC coculture groups. These findings indicate that the 3D-bioprinted GelMA hydrogel coculture system could be a promising biomaterial for large tissue engineering applications.

Fabrication of alginate/sericin/cellulose nanocrystals interpenetrating network composite hydrogels with enhanced physicochemical properties and biological activity

AbstractSodium alginate (SA) possesses good biocompatibility and can form hydrogel materials under certain conditions, which has been widely used in tissue engineering. However, the absence of cellular recognition sites and low mechanical strength for single‐component alginate (ALG) hydrogels limit their practical applications. Therefore, enhancing the shortcomings of ALG hydrogels and augmenting their characteristics hold immense importance for their medical uses. In this study, comprehensively considering the excellent properties of cellulose nanocrystals (CNCs) and sericin (SS), the alginate/sericin/cellulose nanocrystalline (ALG/SS/CNCS) composite hydrogels were constructed by interpenetrating network (IPN) technique using hydroxyapatite/D‐glucono‐δ‐lactone (HAP/GDL) as the endogenous ionic cross‐linking agent of SA, 1‐ethyl‐(3‐dimethylaminopropyl) carbodiimide hydrochloride/N‐hydroxysuccinimide (EDC/NHS) as the chemical covalent cross‐linking agent of SS and CNCS as the reinforcing agent. The effects of SS and CNCs additions on the comprehensive properties of ALG/SS/CNCs composite hydrogels, such as their morphologies, structure, mechanical properties, swelling, degradability, and cytocompatibility were investigated. The findings indicated that the ALG/SS/CNCS IPN composite hydrogels which were created through the physical blending of SA and SS, displayed a consistent three‐dimensional form and a porous configuration. The weak mechanical strength of pure ALG hydrogels can be effectively improved and the swelling stability and mechanical properties of the composite hydrogels can be enhanced through the construction of IPN network and the incorporation of CNCs, thanks to the presence of intermolecular hydrogen bonding. The biodegradability of ALG/SS/CNCS composite hydrogels increased as the SS content increased, indicating that SS facilitated their biomineralization due to its inherent susceptibility to degradation. The results of the cell compatibility test conducted in a laboratory setting showed that SS and CNCS had the ability to enhance the attachment, proliferation, and differentiation of MC3T3‐E1 cells on the ALG/SS/CNCS composite hydrogels. Hence, incorporating SS and CNCS into the alginate matrix to create IPN composite hydrogels could significantly enhance the physicochemical and biological characteristics of ALG hydrogels, thus rendering them appropriate for tissue engineering purposes.