Scaffolds For Tissue Engineering Research Articles

Tissue engineering of Cornea via Type 1 Collagen Biomaterials – A perspective

Engineering corneal tissue has advanced significantly in recent years. Engineering a biocompatible, mechanically stable, and optically clear tissue presents significant engineering hurdles. Two fundamental strategies have been explored by scholars to address these issues: cell-based methods for controlling cells their own extracellular matrix and scaffold-based methods for supplying dense, transparent matrices for cell growth. Both approaches have had some level of success. Additionally, new developments in innervating a tissue-engineered construct have been developed. Future research must concentrate on enhancing the mechanical stability of engineered constructions and the host reaction to implantation. Type 1 Collagen Biomaterial has been used for the construction of scaffolds or implantation for the cornea repair. Various methods for fabrication of the scaffolds have been described and mentioned tissue engineering application for cornea repair and regeneration. Given this correspondence, the type 1 collagen was a potential biomaterial for tissue engineering scaffold fabrication for effective regeneration of cornea.

Fabrication of ZnO-loaded, polycaprolactone -based, antibacterial 3D scaffolds for bone tissue engineering using melt-electrowriting

The potential of melt-electrowriting (MEW) to fabricate highly porous 3D composite scaffolds for bone tissue engineering (BTE) with antibacterial attachment properties was explored. Zinc oxide (ZnO) nanoparticles (NPs) were loaded into biodegradable medical grade Polycaprolactone (PCL) loaded with 10 wt% hydroxyapatite (HA) NPs to create antibacterial constructs by the MEW technique. The constructs’ morphology, chemical, thermal and mechanical properties, osteoblasts cell viability and bacterial attachment were investigated. Our results demonstrate a unique homogeneous dispersion of ZnO-HA NPs in the outer shell of the fabricated composite fibres by MEW, leading to significant inhibition of bacterial attachment against microorganisms. This novel composite MEW 3D scaffolds yielded promising multifunctional constructs with high potential in BTE.

Characterization and physiochemical of PCL/extracted collagen blend coated nanostructure Sodium-Alginate substrate for skin tissue engineering application

Abstract This study involves fabrication a nano-membrane of collagen and polycarbolactone by electrospinning and depositing into alginate films prepared by casting method to serve as a scaffold for tissue engineering. Collagen extracted from bovine skin showed poor ability to electrospun, so polycaprolactone (PCL), a synthetic polymer commonly used in tissue engineering scaffolds was chosen to improve the electrospinning process and obtain continuous fibers without beads suitable for application in tissue engineering. The scaffolds were analyzed using Field emission scanning electron microscopy, Fourier transformtion infrared spectroscopy, swelling degree testing, and wettability measurements. FESEM results showed that blending PCL with collagen led to improving the electrospinning process and obtaining uniform, continuous fibers (with average fiber diameter 44.97 ± 1.61 nm) without beads and more crosslinking compared to the polycarbolactone scaffold. The results of the wettability and degree of swelling also showed the effect of collagen on increasing the hydrophilicity of the scaffold, and reducedthe water contact angle to (66.66°) with degree of swelling (1256%), that making it suitable for tissue engineering applications.

A biodegradable piezoelectric scaffold promotes spinal cord injury nerve regeneration

Neural repair and regeneration remain one of the greatest challenges in regenerative medicine. The incorporation of intelligent scaffolds with noninvasive in vivo electrical stimulation illustrates considerable potential for tissue repair and regeneration. Nevertheless, the development of biomaterials that possess both biodegradable tissue scaffolds and electrical stimulation capabilities at a high level remains a significant obstacle. In this study, we effectively integrated the organic piezoelectric material poly-L-lactic acid (PLLA) with inorganic piezoelectric nanowires (potassium sodium niobate coated with polydopamine, KNN@PDA) to fabricate PLLA/KNN@PDA piezoelectric composite fibers. These fibers exhibit in-situ electrical stimulation capabilities, rendering them suitable for direct application in living tissues. The PLLA/KNN@PDA piezoelectric composite fibers not only function as biodegradable scaffolds for regenerative tissue engineering and platforms for in-situ electrical stimulation to enhance dorsal root ganglion axon growth, proliferation, and neuronal differentiation but also serve as versatile scaffolds for broader tissue engineering applications. In the complete spinal cord transection rat model, the piezoelectric scaffold enabled the recovery of rat motor function, indicating its significant ability to promote tissue formation and regeneration. Therefore, combining biodegradable piezoelectric tissue scaffolds with in situ electrical stimulation has significant therapeutic advantages for spinal cord injury repair and may be extended to other damaged tissues regeneration.

Electrically Conductive Lignin Reinforced Polyacrylic Acid/Hyaluronic Acid Scaffolds With PEDOT:HA Nanoparticles

ABSTRACTHydrogel materials are continually developing in biomedical engineering and recently a lot of effort has gone into their engineered performance in physiological applications. Porosity is an important characteristic for tissue engineering scaffolds to allow enhanced biocompatibility and the pore size needed is dependent on the application and type of tissue for which the hydrogel is being used to regenerate. Regarding biomedical applications, the use of conducting polymers is gaining in popularity due to their promising biocompatibility and potential to stimulate cell growth and proliferation through electrical stimulation. Building on previous hydrogel development by the authors, this study focuses on developing a biocompatible hydrogel scaffold with adjustable porosity and swelling capabilities, robust mechanical properties, electrical conductivity, and high thermal stability. The objective of this work is to examine the effect of freezing temperature, cross‐linker and porosity on the final characteristics of the scaffold and to then determine possible applications. The porosity, swelling degree, compression strength, biocompatibility, electrical conductivity, and thermal characteristics of the final material were analyzed and were found to be affected by the varied synthesis methods used. Overall, the synthesized scaffolds exhibit good biocompatibility with increased fluorescence over 3 days and over 70% cell viability, thermal stability up to 200°C and a range of swelling of 1725% to 8472%. They also portray robust mechanical properties with a Young's Moduli range of 11 kPa to 4.54 MPa and a porosity range of 0.78–71.98 μm depending on the synthesis methods used. Through variations in synthesis methods, highly porous, absorbent, and stable scaffolds have been synthesized. Notably, this single recipe is highly tailorable for use in a range of biomedical applications from tissue engineering to drug delivery and wound repair.

Preparation and Properties of Crosslinked Quaternized Chitosan-Based Hydrogel Films Ionically Bonded with Acetylsalicylic Acid for Biomedical Materials.

The aim of the current study is to develop chitosan-based biomaterials which can sustainably release acetylsalicylic acid while presenting significant biological activity. Herein, an innovative ionic bonding strategy between hydroxypropyl trimethyl ammonium chloride chitosan (HACC) and acetylsalicylic acid (AA) was proposed, skillfully utilizing the electrostatic attraction of the ionic bond to achieve the controlled release of drugs. Based on this point, six crosslinked N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan acetylsalicylic acid salt (CHACAA) hydrogel films with varying acetylsalicylic acid contents were prepared by a crosslinking reaction. The results of 1H nuclear magnetic resonance spectroscopy (1H NMR) and scanning electron morphology (SEM) confirmed the crosslinked structure, while the obtained hydrogel films possessed favorable thermal stability, mechanical properties, and swelling ability. In addition, the drug release behavior of the hydrogel films was also investigated. As expected, the prepared hydrogel films demonstrated the capability for the sustainable release of acetylsalicylic acid due to ion pair attraction dynamics. Furthermore, the bioactivities of CHACAA-3 and CHACAA-4 hydrogel films with acetylsalicylic acid molar equivalents of 1.25 and 1.5 times those of HACC were particularly pronounced, which not only exhibited an excellent drug sustained-release ability and antibacterial effect, but also had a higher potential for binding and scavenging inflammatory factors, including NO and TNF-α. These findings suggest that CHACAA-3 and CHACAA-4 hydrogel films hold great potential for applications in wound dressing, tissue engineering scaffolds, and drug carriers.

Evaluation of Additives on the Cell Metabolic Activity of New PHB/PLA-Based Formulations by Means of Material Extrusion 3D Printing for Scaffold Applications

In this study, specific additives were incorporated in polyhydroxyalcanoate (PHB) and polylactic acid (PLA) blend to improve its compatibility, and so enhance the cell metabolic activity of scaffolds for tissue engineering. The formulations were manufactured through material extrusion (MEX) additive manufacturing (AM) technology. As additives, petroleum-based poly(ethylene) with glicidyl metacrylate (EGM) and methyl acrylate-co-glycidyl methacrylate (EMAG); poly(styrene-co-maleic anhydride) copolymer (Xibond); and bio-based epoxidized linseed oil (ELO) were used. On one hand, standard geometries manufactured were assessed to evaluate the compatibilizing effect. The additives improved the compatibility of PHB/PLA blend, highlighting the effect of EMAG and ELO in ductile properties. The processability was also enhanced for the decrease in melt temperature as well as the improvement of thermal stability. On the other hand, manufactured scaffolds were evaluated for the purpose of bone regeneration. The mean pore size and porosity exhibited values between 675 and 718 μm and 50 and 53%, respectively. According to the results, the compression stress was higher (11–13 MPa) than the required for trabecular bones (5–10 MPa). The best results in cell metabolic activity were obtained by incorporating ELO and Xibond due to the decrease in water contact angle, showing a stable cell attachment after 7 days of culture as observed in SEM.

Chemofunctionalization of knitted silk to improve interface connection in a nano/micro scaffold based on polycaprolactone-chitosan-multi-walled carbon nanotube/silk.

Nano/micro hybrid scaffolds in long-term healing tissue engineering can simultaneously offer both mechanical and biological properties. In this study, a hybrid scaffold was fabricated through electrospinning of polycaprolactone (PCL)-chitosan (Cs)/ multi-walled carbon nanotubes (MWCNTs) based nanofibers onto a chemically functionalized knitted silk substrate (F-Silk) and the scaffold were evaluated with regard to morphology, chemical and crystalline structure, hydrophilicity, mechanical properties, bioactivity, biodegradability, and cellular behavior. Chemical functionalization of silk using N-hydroxysuccinimide (NHS) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) resulted in greater integrity in the formation of nanofibers onto the microfibers. The presence of MWCNTs significantly reduced the contact angle of the scaffolds from 79.72°±2.72 to 68.92°±5.63. Chemical functionalization of silk, the presence of nanofiber coating, and the presence of MWCNTs increased the ultimate tensile strength of the hybrid scaffolds by 18%, 20%, and 30% compared to raw silk fabric, respectively. The presence of MWCNTs and chemical functionalization of knitted silk increased the bioactivity and reduced the degradation rate of hybrid scaffolds. The increase in the amount of carboxyl groups as a result of adding 0.5wt% of MWCNTs significantly improved the adhesion, growth and proliferation of chondrocyte cells on the hybrid scaffolds as observed through cell morphology. According to the obtained results, hybrid scaffold based on PCL-Cs-MWCNTs/F-silk can be a suitable option for further research in cartilage tissue engineering.

Polyglycerol Sebacate/polycaprolactone/reduced graphene oxide composite scaffold for myocardial tissue engineering

The aim of this research was to fabricate and evaluate polyglycerol sebacate/polycaprolactone/reduced graphene oxide (PGS-PCL-RGO) composite scaffolds for myocardial tissue engineering. Polyglycerol sebacate polymer was synthesized using glycerol and sebacic acid prepolymers, confirmed by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Six PGS-PCL-RGO composite scaffolds (S1-S6) with various weight ratios were prepared in chloroform (CF) and acetone (Ace) solvents at 8 CF:2Ace and 9 CF:1Ace volume ratios, using the electrospinning method at a rate of 1 ml/h and a voltage of 18 kV. The scaffolds' chemical composition and microstructure were characterized by FTIR, XRD, and scanning electron microscopy (SEM). Further investigations included tensile testing, contact angle testing, four-point probe testing for electrical conductivity, degradation testing, and cytotoxicity testing (MTT). The results showed that adding 2%wt RGO to the composite scaffold decreased fiber diameter and degradation rate, while increasing electrical conductivity and ductility. The 33%PGS-65%PCL-2%RGO (S3) composite scaffold exhibited the lowest degradation rate (23.87 % over 60 days) and the highest electrical conductivity (51E-3 S/m). Mechanical evaluations revealed an elastic modulus of 2.46 MPa and elongation of 62.43 %, aligning closely with the heart muscle's elastomeric properties. The contact angle test indicated that the scaffold was hydrophilic, with a water contact angle of 61 ± 2°. Additionally, the cell toxicity test confirmed that scaffolds containing RGO were non-toxic and supported good cell viability. In conclusion, the 33%PGS-65%PCL-2%RGO composite scaffold exhibits mechanical and structural properties similar to heart tissue, making it an ideal candidate for myocardial tissue engineering.

Leveraging Machine Learning for Optimized Mechanical Properties and 3D Printing of PLA/cHAP for Bone Implant.

This study explores the fabrication and characterisation of 3D-printed polylactic acid (PLA) scaffolds reinforced with calcium hydroxyapatite (cHAP) for bone tissue engineering applications. By varying the cHAP content, we aimed to enhance PLA scaffolds' mechanical and thermal properties, making them suitable for load-bearing biomedical applications. The results indicate that increasing cHAP content improves the tensile and compressive strength of the scaffolds, although it also increases brittleness. Notably, incorporating cHAP at 7.5% and 10% significantly enhances thermal stability and mechanical performance, with properties comparable to or exceeding those of human cancellous bone. Furthermore, this study integrates machine learning techniques to predict the mechanical properties of these composites, employing algorithms such as XGBoost and AdaBoost. The models demonstrated high predictive accuracy, with R2 scores of 0.9173 and 0.8772 for compressive and tensile strength, respectively. These findings highlight the potential of using data-driven approaches to optimise material properties autonomously, offering significant implications for developing custom-tailored scaffolds in bone tissue engineering and regenerative medicine. The study underscores the promise of PLA/cHAP composites as viable candidates for advanced biomedical applications, particularly in creating patient-specific implants with improved mechanical and thermal characteristics.

Synthesis of N, N,O and O-carboxymethyl chitosan derivatives of controllable substitution degrees and their utilization as electrospun scaffolds for bone tissue engineering

Most chitosan (CS) carboxymethylation approaches are weighed down by insufficient description protocols regarding the reaction specificity and the degree of substitution (DS). Here, we provide three carboxymethylation protocols of enhanced specificity towards the amine (N-), amine/hydroxy (N,O-) and hydroxy (O-) groups of CS. The DS for all samples was found to be ∼70 %, as confirmed by NMR analysis. To illustrate the modified materials' potential in bone tissue regeneration, each derivative was blended with poly(vinyl alcohol) to prepare scaffolds via electrospinning. Both materials and electrospun membranes were characterized in terms of their physicochemical properties by Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry and water contact angle measurements. The electrospun membranes' swelling ratio, degradation, tensile strength, as well as morphology were also examined through scanning electron microscopy before and after heat treatment at 120 °C, which was used as a method of physical stabilization, leading to significantly enhanced degradation rate and mechanical strength. The three electrospun scaffold types were loaded with MC3T3-E1 pre-osteoblastic cells and their cell adhesion, viability and growth rate were assessed. Finally, osteogenic differentiation was examined by means of alkaline phosphatase activity measurement, calcium mineralization and formation of extracellular matrix markers, with all materials showing promising prospects.

Bioactive stem cell-laden 3D nanofibrous scaffolds for tissue engineering

This study presents biomimetic nanoscaffolds composed of electrospun polycaprolactone-collagen (PCL-Coll) nanofibers, loaded with bioactive Arnebia euchroma (AE) extract and stem cells, to develop cell-based tissue engineering constructs. The incorporation of AE extract, known for its antioxidant and anti-inflammatory properties, into the PCL-Coll nanofibers resulted in nanoscaffolds denoted as PCL-Coll/AE0, PCL-Coll/AE5, PCL-Coll/AE10, and PCL-Coll/AE15, corresponding to AE extract concentrations of 0.0, 5.0, 10.0, and 15.0 wt%, respectively. The PCL-Coll/AE nanoscaffolds exhibited high porosity values of 62.81 ± 4.78 %, 59.9 ± 2.10 %, 52.44 ± 2.66 %, and 46.32 ± 1.35 %, respectively, thereby providing an optimal 3D environment for cell attachment and proliferation. Analysis of the AE extract revealed the presence of abundant shikonin, a key bioactive compound, as indicated by its characteristic absorption bands at 490, 520, and 560 nm. FE-SEM data confirmed the homogeneous immobilization of AE compounds within the 3D nanofiber scaffolds, with fibers averaging 316 ± 137 nm in diameter, falling within the range of natural collagen fibers. To evaluate the structural integrity of the fully stem cell-laden scaffolds, we assessed cell growth, cell attachment within the PCL-Coll/AE nanoscaffolds, the cytoprotective effects of AE extract, and the expression levels of stemness-related genes, including Nanog, Rex1, Sox2, Oct4, Klf4, and C-Myc. Real-time PCR assays indicated that key indicators of stemness were upregulated, with average increases from 120 ± 15 % in PCL-Coll/AE0 to 250 ± 30 % in PCL-Coll/AE15 over a two-week period. These upregulations promote cell proliferation and facilitate cell cycle progression. Data indicate that increasing the concentration of bioactive AE extract within the scaffolds enhanced cell adhesion on the scaffold surface and improved cell viability after 7 days of culture, with viability rising from 109 ± 6.15 % in PCL-Coll/AE0 to 145.5 ± 10.11 % in PCL-Coll/AE15. Cytoprotective assays against oxidative stress induced by H₂O₂ revealed relative cell viability for PCL-Coll/AE0, PCL-Coll/AE5, PCL-Coll/AE10, and PCL-Coll/AE15 as 42.78 ± 5.85 %, 49.29 ± 6.79 %, 64.98 ± 3.32 %, and 78.68 ± 3.09 %, respectively. These results correlate with the antioxidant potency of AE extract compounds, particularly shikonin and its derivatives. Therefore, the cell-laden biomimetic PCL-Coll/AE15 scaffolds, which demonstrate sustained stemness features and a continuous local release of bioactive AE compounds, represent a promising candidate for tissue engineering applications.

Bone Tissue Engineering Scaffold Film with Controlled Release of Tea Polyphenol-Magnesium Nanoformulations to Prevent Bacterial Infection

Bone Tissue Engineering Scaffold Film with Controlled Release of Tea Polyphenol-Magnesium Nanoformulations to Prevent Bacterial Infection

Fabrication of 3D microfibrous composite polycaprolactone/hydroxyapatite scaffolds loaded with piezoelectric poly (lactic acid) nanofibers by sequential near-field and conventional electrospinning for bone tissue engineering

Near-field electrospinning (NFES) has recently gained considerable interest in fabricating tissue engineering scaffolds. This technique combines the advantages of both 3D printing and electrospinning. It allows for the production of fibers with smaller resolution and the ability to make regular structures with suitable pores. In this study, a microfibrous composite scaffold of polycaprolactone (PCL)/hydroxyapatite (HA) was prepared by NFES in the first step. The microfibrous scaffold had a fiber spacing of 414.674 ± 24.9 μm with an average fiber diameter of 94.695 ± 16.149 μm. However, due to the large fiber spacing, the surface area was insufficient for cell adhesion. Therefore, the hybrid scaffold was prepared by adding aligned and random electrospun poly (L-lactic acid) (PLLA) nanofibers to the microfibrous scaffold. Cellular studies showed that cell adhesion to the hybrid scaffold increased by 334 % compared to the microfibrous scaffold. These nanofibers also exhibited piezoelectric properties, which helped stimulate bone regeneration. Aligned nanofibers in the hybrid scaffold enhanced alkaline phosphatase activity and the intensity of alizarin red staining 1.5 and 1.6 times, respectively, compared to the microfibrous scaffold. Furthermore, the elastic modulus and ultimate tensile strength increased by 268 % and 130 %, respectively, by adding aligned nanofibers to the microfibrous scaffold. Therefore, the hybrid microfibrous composite scaffold of PCL/HA containing aligned electrospun PLLA nanofibers with improved properties showed the potential for bone regeneration.

A 3D hydrogel scaffold with adjustable interlayer spacing for the formation of compact myocardial tissue

AbstractThe design and optimization of three‐dimensional tissue scaffolds have presented a persistent challenge for myocardial tissue engineering. While current scaffolds have made strides in mimicking in vivo three‐dimensional environments, the presence of interlayer spacing has limited the formation of densely packed tissue, impeding cell‐to‐cell connections. We proposed a novel dynamic three‐dimensional myocardial tissue engineering scaffold with adjustable interlayer spacing, aiming to improve the uniformity of cell distribution and facilitate effective cell communication. The device was composed of hydrogel scaffolds that were fabricated with poly (ethylene glycol) diacrylate (PEGDA) and flexible elastomer actuators that composed of polyurethane acrylate (PUA). Human induced pluripotent stem cell‐derived cardiomyocytes mixed with gelatin methacryloyl (GelMA) were seeded onto the multi‐layered scaffold with initial spacing of 100–500 μm. Experimental results indicated the seeding efficiency was maximized at an initial spacing of 400 μm. By decreasing the interlayer spacing, cell growth morphology and gap junction protein expression was improved. This work demonstrated the effect of interlayer spacing modulation to the tissue density and provided a potential approach for cultivation of compact and multi‐layered myocardial tissue.

Molecular Chain Rearrangement-Induced In Situ Formation of Nanofibers for Improving the Strength and Toughness of Hydrogels.

Although poly(vinyl alcohol) (PVA) hydrogel has high elasticity and is suitable for cartilage tissue engineering, it is difficult to have both high strength and toughness. In this study, a simple and universal strategy is proposed to prepare strong and tough PVA hydrogels by in situ forming nanofibers on the original network structure induced by a molecular chain rearrangement. Quenching-tempering alteratively in ethanol and water several times is carried out to strengthen PVA hydrogels (PVA-Etn hydrogels) due to the advantages of noncovalent bonds in adjustability and reversibility. The results show that, after three quenching-tempering cycles, PVA-Et3 hydrogel with water content up to 79 wt % shows comprehensive improved mechanical properties. The compression modulus, tensile modulus, fracture strength, tensile strain, and tear energy of the PVA-Et3 hydrogel are 270, 250, 260, 130, and 180% of the initial PVA hydrogel, respectively. The improved mechanical properties of the PVA-Et3 hydrogel are attributed to the strong cross-linked PVA chains and hydrogen bond-reinforced nanofibers. This study not only provides a simple and efficient solution for the preparation of strong and tough polymer scaffolds in tissue engineering but also provides new insights for understanding the mechanism of improving the mechanical properties of polymer hydrogels by adjusting the molecular structure.

Precision 3D printing of chitosan-bioactive glass inks: Rheological optimization for enhanced shape fidelity in tissue engineering scaffolds

3D printing technology in tissue engineering applications provides several advantages for scaffold development, especially with natural materials, such as chitosan, which provides a biomimetic environment for cellular growth. However, chitosan hydrogel-based inks still show poor printing fidelity. In this article, we overcame this challenge by incorporating bioactive glasses (BG) nanoparticles (up to 5 wt%) into the chitosan hydrogel. The resulting inks were characterized by rheological tests, while their processability was evaluated through measurements of shape fidelity. An indirect cytotoxicity assay was also conducted to evaluate the cell viability of the printed scaffolds. The results indicated that adding BG nanoparticles to the chitosan-based ink modified its rheological properties and improved its shape-fidelity during 3D printing, which we suggest are consequences of hydrogen bonds established between the glass and the chitosan chains. Also, cytotoxicity assessment demonstrated that the resulting scaffold exhibits high cell viability. In conclusion, the proposed composite ink has optimized rheological properties for 3D printing and is promising for applications in tissue engineering.

Hydrogels as a Potential Biomaterial for Multimodal Therapeutic Applications.

Hydrogels, composed of hydrophilic polymer networks, have emerged as versatile materials in biomedical applications due to their high water content, biocompatibility, and tunable properties. They mimic natural tissue environments, enhancing cell viability and function. Hydrogels' tunable physical properties allow for tailored antibacterial biomaterial, wound dressings, cancer treatment, and tissue engineering scaffolds. Their ability to respond to physiological stimuli enables the controlled release of therapeutics, while their porous structure supports nutrient diffusion and waste removal, fostering tissue regeneration and repair. In wound healing, hydrogels provide a moist environment, promote cell migration, and deliver bioactive agents and antibiotics, enhancing the healing process. For cancer therapy, they offer localized drug delivery systems that target tumors, minimizing systemic toxicity and improving therapeutic efficacy. Ocular therapy benefits from hydrogels' capacity to form contact lenses and drug delivery systems that maintain prolonged contact with the eye surface, improving treatment outcomes for various eye diseases. In mucosal delivery, hydrogels facilitate the administration of therapeutics across mucosal barriers, ensuring sustained release and the improved bioavailability of drugs. Tissue regeneration sees hydrogels as scaffolds that mimic the extracellular matrix, supporting cell growth and differentiation for repairing damaged tissues. Similarly, in bone regeneration, hydrogels loaded with growth factors and stem cells promote osteogenesis and accelerate bone healing. This article highlights some of the recent advances in the use of hydrogels for various biomedical applications, driven by their ability to be engineered for specific therapeutic needs and their interactive properties with biological tissues.

Conductive, injectable, and self-healing collagen-hyaluronic acid hydrogels loaded with bacterial cellulose and gold nanoparticles for heart tissue engineering

The increasing demand for advanced biomaterials in nerve tissue engineering presents numerous challenges due to the complexity of nerve tissues and the need for materials that can accurately replicate their intricate structure and function. In response, this study introduces a novel injectable hydrogel that is thermosensitive, self-healing, and conductive, offering promising potential for heart and nerve tissue engineering applications. The hydrogel is based on collagen and hyaluronic acid functionalized with 3-aminopropyl-triethoxysilane (APTES)-grafted oxidized bacterial cellulose and gold nanoparticles (~50 nm). Rheological analysis reveals a substantial enhancement in the elastic modulus of the collagen-hyaluronic acid matrix with the incorporation of bacterial cellulose/gold nanoparticles, improving by an order of magnitude at 1 % strain. This improvement comes with a slight decrease in gelation temperature, from 36 °C to 32 °C. Besides thermo-sensitivity, the nanocomposite hydrogel exhibits a remarkable self-sealing response (about 80 % effectiveness) due to reversible physical crosslinking. Electrical spatial resistance measurements on human embryonic stem cell-derived cardiomyocytes-loaded hydrogels yield a value of ~0.1 S/m, which is suitable for electrical stimulation. In vitro extracellular field potential measurements also affirm the hydrogel's potential as an injectable scaffold for heart tissue engineering, i.e., the electrically stimulated human stem cells exhibit 47 beats per minute with a cell discharge (depletion) of 5.47 μv. A rapid gel formation in the physiological temperature (about 2 min) and high H9C2 cytotoxicity (viability of >90 % after 72 h incubation) is attainable. The developed collagen-based nanocomposite hydrogel offers an injectable, thermosensitive, and self-healing biomaterial platform for nerve or myocardium regeneration.

Multi-parametric Photoacoustic Imaging Combined with Acoustic Radiation Force Impulse Imaging for Applications in Tissue Engineering.

Tissue engineering is a dynamic field focusing on the creation of advanced scaffolds for tissue and organ regeneration. These scaffolds are customized to their specific applications and are often designed to be complex, large structures to mimic tissues and organs. This study addresses the critical challenge of effectively characterizing these thick, optically opaque scaffolds that traditional imaging methods fail to fully image due to their optical limitations. We introduce a novel multi-modal imaging approach combining ultrasound, photoacoustic, and acoustic radiation force impulse imaging. This combination leverages its acoustic-based detection to overcome the limitations posed by optical imaging techniques. Ultrasound imaging is employed to monitor the scaffold structure, photoacoustic imaging is employed to monitor cell proliferation, and acoustic radiation force impulse imaging is employed to evaluate the homogeneity of scaffold stiffness. We applied this integrated imaging system to analyze melanoma cell growth within silk fibroin protein scaffolds with varying pore sizes and therefore stiffness over different cell incubation periods. Among various materials, silk fibroin was chosen for its unique combination of features including biocompatibility, tunable mechanical properties, and structural porosity which supports extensive cell proliferation. The results provide a detailed mesoscale view of the scaffolds' internal structure, including cell penetration depth and biomechanical properties. Our findings demonstrate that the developed multimodal imaging technique offers comprehensive insights into the physical and biological dynamics of tissue-engineered scaffolds. As the field of tissue engineering continues to advance, the importance of non-ionizing and non-invasive imaging systems becomes increasingly evident, and by facilitating a deeper understanding and better characterization of scaffold architectures, such imaging systems are pivotal in driving the success of future tissue-engineering solutions.