Hydrogel Scaffolds Research Articles

A dual-gelling poly(N-isopropylacrylamide)-based ink and thermoreversible poloxamer support bath for high-resolution bioprinting

Extrusion bioprinting is a popular method for fabricating tissue engineering scaffolds because of its potential to rapidly produce complex, bioactive or cell-laden scaffolds. However, due to the relatively high viscosity required to maintain shape fidelity during printing, many extrusion-based inks lack the ability to achieve precise structures at scales lower than hundreds of micrometers. In this work, we present a novel poly(N-isopropylacrylamide) (PNIPAAm)-based ink and poloxamer support bath system that produces precise, multi-layered structures on the tens of micrometers scale. The support bath maintains the structure of the ink in a hydrated, heated environment ideal for cell culture, while the ink undergoes rapid thermogelation followed by a spontaneous covalent crosslinking reaction. Through the combination of the PNIPAAm-based ink and poloxamer bath, this system was able to produce hydrogel scaffolds with uniform fibers possessing diameters tunable from 80 to 200 μm. A framework of relationships between several important printing factors involved in maintaining support and thermogelation was also elucidated. As a whole, this work demonstrates the ability to produce precise, acellular and cell-laden PNIPAAm-based scaffolds at high-resolution and contributes to the growing body of research surrounding the printability of extrusion-based bioinks with support baths.

Sustained Delivery of SARS-CoV-2 RBD Subunit Vaccine Using a High Affinity Injectable Hydrogel Scaffold.

The receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein that mediates viral entry into host cells is a good candidate immunogen for vaccine development against coronavirus disease 2019 (COVID‐19). Because of its small size, most preclinical and early clinical efforts have focused on multimerizing RBD on various formats of nanoparticles to increase its immunogenicity. Using an easily administered injectable hydrogel scaffold that is rationally designed for enhanced retainment of RBD, an alternative and facile approach for boosting RBD immunogenicity in mice is demonstrated. Prolonged delivery of poly (I:C) adjuvanted RBD by the hydrogel scaffold results in sustained exposure to lymphoid tissues, which elicits serum IgG titers comparable to those induced by three bolus injections, but more long‐lasting and polarized toward TH1‐mediated IgG2b. The hydrogel scaffold induces potent germinal center (GC) reactions, correlating with RBD‐specific antibody generation and robust type 1 T cell responses. Besides being an enduring RBD reservoir, the hydrogel scaffold becomes a local inflammatory niche for innate immune cell activation. Collectively, the injectable hydrogel scaffold provides a simple, practical, and inexpensive means to enhance the efficacy of RBD‐based subunit vaccines against COVID‐19 and may be applicable to other circulating and emerging pathogens.

Improved functional recovery of rat transected spinal cord by peptide-grafted PNIPAM based hydrogel

Facilitating angiogenesis, reducing the formation of glial scar tissue, and the occurrence of a strong inflammatory response are of great importance for the repair of central nerve damage. In our previous study, a temperature-sensitive hydrogel grafted with bioactive isoleucine-lysine-valine-alanine-valine (IKVAV) peptide was prepared and it showed regular three-dimensional porous structure, rapid (de)swelling performance and good biological activity. Therefore, in this study, we used this hydrogel scaffold to treat for SCI to study the effect of it to facilitate angiogenesis, inhibit the differentiation and adhesion of keratinocytes, and further reduce the formation of glial scar tissue. The results reveal that the peptide hydrogel scaffold achieved excellent performance and can also promote the expression of angiogenic factors and reduce the secretion of pro-inflammatory factors to a certain extent. Particularly, it can also inhibit the formation of glial scar tissue and repair damaged tissue. The proposed strategy for developing this hydrogel scaffold provides a new insight into designing biomaterials for a broad range of applications in the tissue engineering of the central nervous system (CNS).

Anisotropic Silk-Inspired Nerve Conduit with Peptides Improved the Microenvironment for Long-Distance Peripheral Nerve Regeneration.

A lack of effective bioactivity to create a desirable microenvironment for peripheral nerve regeneration has been challenging in successful treatment of long-distance injuries using nerve guidance conduits (NGCs) clinically. Herein, we developed a silk-inspired phototriggered gelation system combining dual therapeutic cues of anisotropic topography and adhesive ligands for improving peripheral nerve regeneration. Importantly, enhanced cell recruitment and myelination of Schwann cells were successfully achieved by the Arg-Gly-Asp (RGD)-peptide-immobilized hydrogel scaffolds to promote axon growth. Moreover, as the orientated growth of Schwann cells and rapid axon growth were facilitated by aligned grooved micropatterns, this multifunctional bioactive system provides remarkable nerve regeneration with function recovery for long-distance nerve injury. Therefore, this bioengineered silk-inspired nerve guidance conduit delivers a platform for desirable peripheral nerve repair.

Forskolin-Loaded Halloysite Nanotubes as Osteoconductive Additive for the Biopolymer Tissue Engineering Scaffolds.

Here we report the use of forskolin-modified halloysite nanotubes (HNTs) as a dopant for biopolymer porous hydrogel scaffolds to impart osteoinductive properties. Forskolin is a labdane diterpenoid isolated from the Indian Coleus plant. This small molecule is widely used as a supplement in molecular biology for cell differentiation. It has been reported in some earlier publications that forskolin can activate osteodifferentiation process by cyclic adenosine monophosphate (c-AMP) signalling activation in stem cells. In presented study it was demonstrated that forskolin release from halloysite-doped scaffolds induced the osteodifferentiation of equine mesenchymal stem cells (MSCs) in vitro without addition of any specific growth factors. The reinforcement of mechanical properties of cells and intercellular space during the osteodifferentiation was demonstrated using atomic force microscopy (AFM). These clay-doped scaffolds may find applications to accelerate the regeneration of horse bone defects by inducing the processes of osteodifferentiation of endogenous MSCs.

Oxygen generating scaffolds regenerate critical size bone defects

Recent innovations in bone tissue engineering have introduced biomaterials that generate oxygen to substitute vasculature. This strategy provides the immediate oxygen required for tissue viability and graft maturation. Here we demonstrate a novel oxygen-generating tissue scaffold with predictable oxygen release kinetics and modular material properties. These hydrogel scaffolds were reinforced with microparticles comprised of emulsified calcium peroxide (CaO2) within polycaprolactone (PCL). The alterations of the assembled materials produced constructs within 5 ± 0.81 kPa to 34 ± 0.9 kPa in mechanical strength. The mass swelling ratios varied between 11% and 25%. Our in vitro and in vivo results revealed consistent tissue viability, metabolic activity, and osteogenic differentiation over two weeks. The optimized in vitro cell culture system remained stable at pH 8–9. The in vivo rodent models demonstrated that these scaffolds support a 70 mm3 bone volume that was comparable to the native bone and yielded over 90% regeneration in critical size cranial defects. Furthermore, the in vivo bone remodeling and vascularization results were validated by tartrate-resistant acid phosphatase (TRAP) and vascular endothelial growth factor (VEGF) staining. The promising results of this work are translatable to a repertoire of regenerative medicine applications including advancement and expansion of bone substitutes and disease models.

Rapid 3D BioPrinting of a human iPSC-derived cardiac micro-tissue for high-throughput drug testing

With cardiac disease a reigning problem in the world, the need for accurate and high-throughput drug testing is paramount. 3D cardiac tissues are promising models, as they can recapitulate the cell-cell, cell-matrix, and cell-tissue interactions that impact response to a drug. Using an in-house developed micro-continuous optical printing system, we created a cardiac micro-tissue in mere seconds with microscale alignment cues in a hydrogel scaffold that is small enough to fit in a 96-well plate. The 3D printed, asymmetric, cantilever-based tissue scaffold allows one to directly measure the deformation produced by the beating micro-tissue. After 7 days, the micro-tissue exhibited a high level of sarcomere organization and a significant increase in maturity marker expression. The cardiac micro-tissues were validated against two representative drugs, isoproterenol and verapamil at various doses, showing corresponding and measurable changes in beating frequency and displacement. Such rapidly bioprinted cardiac micro-tissues in a multi-well plate offer a promising solution for high-throughput screening in drug discovery.

Calcium-Enriched Nanofibrillated Cellulose/Poloxamer in-situ Forming Hydrogel Scaffolds as a Controlled Delivery System of Raloxifene HCl for Bone Engineering [Retraction

[This retracts the article DOI: 10.2147/IJN.S323974.].

Composite Scaffolds from Gelatin and Bone Meal Powder for Tissue Engineering.

Bone tissue engineering offers versatile solutions to broaden clinical options for treating skeletal injuries. However, the variety of robust bone implants and substitutes remains largely uninvestigated. The advancements in hydrogel scaffolds composed of natural polymeric materials and osteoinductive microparticles have shown to be promising solutions in this field. In this study, gelatin methacrylate (GelMA) hydrogels containing bone meal powder (BP) particles were investigated for their osteoinductive capacity. As natural source of the bone mineral, we expect that BP improves the scaffold’s ability to induce mineralization. We characterized the physical properties of GelMA hydrogels containing various BP concentrations (0, 0.5, 5, and 50 mg/mL). The in vitro cellular studies revealed enhanced mechanical performance and the potential to promote the differentiation of pre-osteoblast cells. The in vivo studies demonstrated both promising biocompatibility and biodegradation properties. Overall, the biological and physical properties of this biomaterial is tunable based on BP concentration in GelMA scaffolds. The findings of this study offer a new composite scaffold for bone tissue engineering.

Living Bacterial Hydrogels for Accelerated Infected Wound Healing.

Damaged skin cannot prevent harmful bacteria from invading tissues, causing infected wounds and even serious tissue damage. Traditional treatments can not only kill pathogenic bacteria, but also suppress the growth of beneficial bacteria, thus destroying the balance of the damaged skin microbial ecosystem. Here, a living bacterial hydrogel scaffold is reported that accelerates infected wound healing through beneficial bacteria secreting antibacterial substances. Lactobacillus reuteri, a common probiotic, is encapsulated in hydrogel microspheres by emulsion polymerization and further immobilized in a hydrogel network by covalent cross‐linking of methacrylate‐modified hyaluronic acid. Owing to light‐initiated crosslinking, the hydrogel dressing can be generated in situ at the wound site. This hydrogel scaffold not only protects bacteria from immune system attack, but also prevents bacteria from escaping into the local environment, thus avoiding potential threats. Both in vitro and in vivo experiments show that it has excellent ability against harmful bacteria and anti‐inflammatory capabilities, promoting infected wound closure and new tissue regeneration. This work may open up new avenues for the application of living bacteria in the clinical management of infected wounds.

Development of bioactive catechol functionalized nanoparticles applicable for 3D bioprinting

Efficient wound treatments to target specific events in the healing process of chronic wounds constitute a significant aim in regenerative medicine. In this sense, nanomedicine can offer new opportunities to improve the effectiveness of existing wound therapies. The aim of this study was to develop catechol bearing polymeric nanoparticles (NPs) and to evaluate their potential in the field of wound healing. Thus, NPs wound healing promoting activities, potential for drug encapsulation and controlled release, and further incorporation in a hydrogel bioink formulation to fabricate cell-laden 3D scaffolds are studied. NPs with 2 and 29 M % catechol contents (named NP2 and NP29) were obtained by nanoprecipitation and presented hydrodynamic diameters of 100 and 75 nm respectively. These nanocarriers encapsulated the hydrophobic compound coumarin-6 with 70% encapsulation efficiency values. In cell culture studies, the NPs had a protective effect in RAW 264.7 macrophages against oxidative stress damage induced by radical oxygen species (ROS). They also presented a regulatory effect on the inflammatory response of stimulated macrophages and promoted upregulation of the vascular endothelial growth factor (VEGF) in fibroblasts and endothelial cells. In particular, NP29 were used in a hydrogel bioink formulation using carboxymethyl chitosan and hyaluronic acid as polymeric matrices. Using a reactive mixing bioprinting approach, NP-loaded hydrogel scaffolds with good structural integrity, shape fidelity and homogeneous NPs dispersion, were obtained. The in vitro catechol NPs release profile of the printed scaffolds revealed a sustained delivery. The bioprinted scaffolds supported viability and proliferation of encapsulated L929 fibroblasts over 14 days. We envision that the catechol functionalized NPs and resulting bioactive bioink presented in this work offer promising advantages for wound healing applications, as they: 1) support controlled release of bioactive catechol NPs to the wound site; 2) can incorporate additional therapeutic functions by co-encapsulating drugs; 3) can be printed into 3D scaffolds with tailored geometries based on patient requirements.

Recent advances in three-dimensional bioprinted nanocellulose-based hydrogel scaffolds for biomedical applications

Recent advances in three-dimensional bioprinted nanocellulose-based hydrogel scaffolds for biomedical applications

Fabrication and evaluation of homogeneous alginate/polyacrylamide–chitosan–gelatin composite hydrogel scaffolds based on the interpenetrating networks for tissue engineering

AbstractInterpenetrating polymer network (IPN) is generally considered to be one of the most effective methods for imparting high‐strength mechanical properties to hydrogel materials. To broaden the application of alginate hydrogel in skeletal muscle or muscle tissue engineering, the interpenetrating network technology and layer‐by‐layer (LBL) electrostatic assembly were proposed to fabricate the homogeneous alginate/polyacrylamide–chitosan–gelatin (Alg/PAAM–CS–GT) composite hydrogel scaffolds, using the hydroxyapatite/d‐glucono‐δ‐lactone (HAP/GDL) complex as the gelling system. The effects of different components of alginate/polyacrylamide (Alg/PAAM) on the morphology, mechanical properties, swelling, degradability, and cytocompatibility of the hydrogel scaffolds were comparatively characterized. Experimental results showed that the as‐prepared Alg/PAAM–CS–GT composite hydrogel scaffolds exhibited sharp edges and regular 3D structures. Their pore structure could be regulated by changing the content of PAAM in Alg/PAAM–CS–GT composite hydrogel scaffolds. And the filling of PAAM reduced the pores and thickened the pore walls, which obviously enhanced the mechanical properties of Alg/PAAM–CS–GT composite hydrogel scaffolds. FT‐IR and thermogravimetric analysis showed that O‧‧‧N hydrogen bonding between COOH of SA and NH2 of PAAM could be helpful to improve the thermal stability of the composite hydrogel scaffolds. The swelling and biodegradation measurements indicated that the swelling and degradation of Alg/PAAM–CS–GT composite hydrogel scaffolds could be effectively regulated by changing the component content of the composite hydrogel. In addition, the in vitro cytocompatibility analysis showed that the Alg/PAAM–CS–GT composite hydrogel scaffolds could support the growth of MC3T3‐E1 cells and promote cell proliferation and differentiation. According to the in vitro cytocompatibility test results, the optimum PAAM content for the Alg/PAAM–CS–GT composite hydrogel scaffolds was 60%. Because of good morphology, well‐developed pores, excellent mechanical properties, and high biological activity of Alg/PAAM–CS–GT composite hydrogel scaffolds, they could be suitable for application in the tissue engineering field.

Osteo-conductive hydrogel scaffolds of poly(vinylalcohol) with silk fibroin particles for bone augmentation: Structural formation and in vitro testing

Bone augmentation is an effective approach to treat patients who have bone loss at the maxillofacial area. In this research, osteo-conductive hydrogel scaffolds of poly(vinylalcohol) (PVA) with silk fibroin particles (SFP) were fabricated. The SFP were formed by dropping a solution of silk fibroin into acetone at different volume ratios (v/v) of silk to acetone: 1:3 (SFP-3), 1:6 (SFP-6), 1:12 (SFP-12), and 1:24 (SFP-24). The various SFP solutions were mixed with a PVA solution before fabrication into hydrogels by freeze-thawing. Afterwards, the hydrogels were freeze-dried to fabricate the scaffolds. The particle size and charge, molecular organization, and morphology of the SFP were characterized and observed with dynamic light scattering, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy (SEM). The morphologies of the hydrogel scaffolds were observed with SEM. Swelling percentage was used to assess the swelling behavior of the hydrogel scaffolds. The mechanical properties were also tested. The scaffolds were cultured with osteoblast cells to test the biological performance, cell viability and performance, alkaline phosphatase activity, calcium deposition, and total protein. The SFP-24 was the smallest in particle size. PVA hydrogel scaffolds with SFP-24 demonstrated low particle aggregation, good particle distribution within the scaffold, and a lower swelling percentage. PVA hydrogel scaffolds with SFP had higher mechanical stability than scaffolds without the SFP. Furthermore, the PVA hydrogel scaffold with SFP-24 had better biological performance. Finally, the results demonstrated that PVA hydrogel scaffolds with SFP-24 showed good osteo-conductive performance which is promising for bone augmentation.

Development of a magnetically aligned regenerative tissue-engineered electronic nerve interface for peripheral nerve applications

Peripheral nerve injuries can be debilitating to motor and sensory function, with severe cases often resulting in complete limb amputation. Over the past two decades, prosthetic limb technology has rapidly advanced to provide users with crude motor control of up to 20° of freedom; however, the nerve-interfacing technology required to provide high movement selectivity has not progressed at the same rate. The work presented here focuses on the development of a magnetically aligned regenerative tissue-engineered electronic nerve interface (MARTEENI) that combines polyimide “threads” encapsulated within a magnetically aligned hydrogel scaffold. The technology exploits tissue-engineered strategies to address concerns over traditional peripheral nerve interfaces including poor axonal sampling through the nerve and rigid substrates. A magnetically templated hydrogel is used to physically support the polyimide threads while also promoting regeneration in close proximity to the electrode sites on the polyimide. This work demonstrates the utility of magnetic templating for use in tuning the mechanical properties of hydrogel scaffolds to match the stiffness of native nerve tissue while providing an aligned substrate for Schwann cell migration in vitro. MARTEENI devices were fabricated and implanted within a 5-mm-long rat sciatic-nerve transection model to assess regeneration at 6 and 12 weeks. MARTEENI devices do not disrupt tissue remodeling and show axon densities equivalent to fresh tissue controls around the polyimide substrates. Devices are observed to have attenuated foreign-body responses around the polyimide threads. It is expected that future studies with functional MARTEENI devices will be able to record and stimulate single axons with high selectivity and low stimulation regimes.

Resveratrol‐Loaded Poly(d,l‐Lactide‐Co‐Glycolide) Microspheres Integrated in a Hyaluronic Acid Injectable Hydrogel for Cartilage Regeneration

Cartilage tissue has a relatively low regenerative capacity which leads to a need for disease‐modifying active pharmaceutical ingredients (APIs) which can stimulate its regeneration and more urgently, effective ways of introducing APIs into the cartilage defects. Herein, an integrated system is proposed in which a hyaluronic acid (HA)‐based injectable hydrogel scaffold is embedded with API‐loaded poly(d,l‐lactide‐co‐glycolide) microspheres (PLGA MPs). This new injectable drug delivery system can successfully deliver APIs locally, increase drug retention time, and promote endogenous cartilage regeneration. In this study, resveratrol (RSV), a small hydrophobic compound is introduced as the selected API. PLGAs with differing copolymer ratios and endgroups are evaluated to study their effects on particle formation, RSV encapsulation, and drug release kinetics. This system is optimized as a 1 month sustained release formulation. In addition, the long‐acting chondrogenic induction of the RSV‐loaded system is evaluated by coculturing with cartilage‐derived progenitor cells in vitro. PLGA–RSV MPs stimulated the expression of cartilage‐related genes and the production of the cartilage‐specific extracellular matrix. This integrated system shows great potential as an injectable formulation for long‐acting chondrogenesis and endogenous cartilage tissue regeneration.

Ethanol fermentation using macroporous monolithic hydrogels as yeast cell scaffolds

Ethanol fermentation with a hybrid system containing free and immobilized yeast cells on a macroporous monolithic hydrogel scaffold was investigated. Cell immobilization was achieved using N-isopropylacrylamide (NIPA) and methoxy triethyleneglycol acrylate (MTGA) hydrogels having macroporous monolithic structures containing interconnected micrometer-sized macropores. The immobilized cells grow within the hydrogel and can exit through the macropores into the fermentation medium, and thus a hybrid bioreactor consisting of free and immobilized yeast cells is constructed. The transformation of d-glucose to ethanol using Saccharomyces cerevisiae in batch and continuous fermentation processes was examined. Ethanol was successfully fermented using the macroporous hydrogels, whereas the conventional nonporous NIPA hydrogel does not effectively act as a cell scaffold. In continuous fermentation, the hybrid system containing both free yeast cells and those immobilized in the macroporous MTGA hydrogel showed higher ethanol productivity than the control system containing only free cells. Crucially, the macroporous hydrogel allowed the stable growth of immobilized yeast cells, resulting in a high cell density in the reactor. The hybrid system under steady-state fermentation had free and immobilized cell densities of 1.72 kg-free-cell/m3 and 29 kg-immobilized-cell/m3-gel, respectively, and the ethanol productivities 0.421 kg-ethanol/(kg-free-cell·h) and 0.128 kg-ethanol/(kg-immobilized-cell·h), respectively.

Tunable 3D Hydrogel Microchannel Networks to Study Confined Mammalian Cell Migration.

Cells adapt and move due to chemical, physical, and mechanical cues from their microenvironment. It is therefore important to create materials that mimic human tissue physiology by surface chemistry, architecture, and dimensionality to control cells in biomedical settings. The impact of the environmental architecture is particularly relevant in the context of cancer cell metastasis, where cells migrate through small constrictions in their microenvironment to invade surrounding tissues. Here, a synthetic hydrogel scaffold with an interconnected, random, 3D microchannel network is presented that is functionalized with collagen to promote cell adhesion. It is shown that cancer cells can invade such scaffolds within days, and both the microarchitecture and stiffness of the hydrogel modulate cell invasion and nuclear dynamics of the cells. Specifically, it is found that cell migration through the microchannels is a function of hydrogel stiffness. In addition to this, it is shown that the hydrogel stiffness and confinement, influence the occurrence of nuclear envelope ruptures of cells. The tunable hydrogel microarchitecture and stiffness thus provide a novel tool to investigate cancer cell invasion as a function of the 3D microenvironment. Furthermore, the material provides a promising strategy to control cell positioning, migration, and cellular function in biological applications, such as tissue engineering.

A novel bioavailable curcumin-galactomannan complex modulates the genes responsible for the development of chronic diseases in mice: A RNA sequence analysis

BackgroundChronic diseases or non-communicable diseases are a major burden worldwide due to the lack of highly efficacious treatment modalities and the serious side effects associated with the available therapies. Purpose/study designA novel self-emulsifying formulation of curcumin with fenugreek galactomannan hydrogel scaffold as a water-dispersible non-covalent curcumin-galactomannan molecular complex (curcumagalactomannosides, CGM) has shown better bioavailability than curcumin and can be used for the prevention and treatment of chronic diseases. However, the exact potential of this formulation has not been studied, which would pave the way for its use for the prevention and treatment of multiple chronic diseases. MethodsThe whole transcriptome analysis (RNAseq) was used to identify differentially expressed genes (DEGs) in the liver tissues of mice treated with LPS to investigate the potential of CGM on the prevention and treatment of chronic diseases. Expression analysis using DESeq2 package, GO, and pathway analysis of the differentially expressed transcripts was performed using UniProtKB and KEGG-KAAS server. ResultsThe results showed that 559 genes differentially expressed between the liver tissue of control mice and CGM treated mice (100 mg/kg b.wt. for 14 days), with adjusted p-value below 0.05, of which 318 genes were significantly upregulated and 241 were downregulated. Further analysis showed that 33 genes which were upregulated (log2FC > 8) in the disease conditions were significantly downregulated, and 32 genes which were downregulated (log2FC < −8) in the disease conditions were significantly upregulated after the treatment with CGM. ConclusionOverall, our study showed CGM has high potential in the prevention and treatment of multiple chronic diseases.

Biopolymer Hydrogel Scaffolds Containing Doxorubicin as A Localized Drug Delivery System for Inhibiting Lung Cancer Cell Proliferation.

A hydrogel scaffold is a localized drug delivery system that can maintain the therapeutic level of drug concentration at the tumor site. In this study, the biopolymer hydrogel scaffold encapsulating doxorubicin was fabricated from gelatin, sodium carboxymethyl cellulose, and gelatin/sodium carboxymethyl cellulose mixture using a lyophilization technique. The effects of a crosslinker on scaffold morphology and pore size were determined using scanning electron microscopy. The encapsulation efficiency and the release profile of doxorubicin from the hydrogel scaffolds were determined using UV-Vis spectrophotometry. The anti-proliferative effect of the scaffolds against the lung cancer cell line was investigated using an MTT assay. The results showed that scaffolds made from different types of natural polymer had different pore configurations and pore sizes. All scaffolds had high encapsulation efficiency and drug-controlled release profiles. The viability and proliferation of A549 cells, treated with gelatin, gelatin/SCMC, and SCMC scaffolds containing doxorubicin significantly decreased compared with control. These hydrogel scaffolds might provide a promising approach for developing a superior localized drug delivery system to kill lung cancer cells.