Field Of Tissue Engineering Research Articles

Current progress of in vitro vascular models on microfluidic chips.

The vascular tissue, as an integral component of the human circulatory system, plays a crucial role in retaining normal physiological functions within the body. Pathologies associated with the vasculature, whether direct or indirect, also constitute significant public health concerns that afflict humanity, leading to the wide studies on vascular physiology and pathophysiology. Given the precious nature of human derived vascular tissue, substantial efforts have been dedicated to the construction of vascular models. Due to the high cost associated with animal experimentation and the inability to directly translate results to human, there is an increasing emphasis on the use of primary human cells for the development of in vitro vascular models. For instance, obtaining an ApoE-/- mouse model for atherosclerosis research typically requires feeding a high-fat diet for over 10 weeks, whereas in vitro vascular models can usually be formed within 2 weeks. With advancements in microfluidic technology, in vitro vascular models capable of precisely emulating the hemodynamic environment within human vessels are becoming increasingly sophisticated. Microfluidic vascular models are primarily constructed through two approaches: 1) directly constructing the vascular models based on the three-layer structure of the vascular wall; 2) co-culture of endothelial cells and supporting cells within hydrogels. The former is effective to replicate vascular tissue structure mimicking vascular wall, while the latter has the capacity to establish microvascular networks. This review predominantly presents and discusses recent advancements in template design, construction methods, and potential applications of microfluidic vascular models based on polydimethylsiloxane (PDMS) soft lithography. Additionally, some refined methodologies addressing the limitations of conventional PDMS-based soft lithography techniques are also elaborated, which might hold profound importance in the field of vascular tissue engineering on microfluidic chips.

The Biological Properties of Co-Doped Monetite Are Influenced by Thermal Treatment.

Calcium phosphates, notably monetite, are valued biomaterials for bone applications owing to their osteogenic properties and rapid uptake by bone cells. This study investigates the enhancement of these properties through Cobalt doping, which is known to induce hypoxia and promote bone cell differentiation. Heat treatments at 700°C, 900°C, and 1050°C are applied to both monetite and Cobalt-doped monetite, facilitating the development of purer, more crystalline phases with varied particle sizes and optimized cellular responses. Comprehensive physicochemical characterization through XRD, FTIR, Raman, SEM/EDS, and ASAP analyses shows significant phase transformations into pyrophosphate, influencing the materials' structural and functional attributes. When utilized to condition a culture medium for MC3T3-E1 cells, these materials demonstrate non-cytotoxic behavior and provoke specific gene responses associated with the osteoblastic phenotype, angiogenesis, adhesion, and extracellular matrix remodeling. Significantly, non-heat-treated Cobalt-doped Monetite retains properties advantageous for clinical applications such as dental and orthopedic implants, where lower processing temperatures are crucial. This attribute, combined with the material's straightforward production, highlights its practicality and potential cost-effectiveness. Further research is essential to assess the long-term safety and efficacy of these materials in clinical settings. Our findings underscore the promising role of Cobalt-doped Monetite in advancing bone repair and regeneration, setting the stage for future innovations in treating bone lesions, enhancing implant integration, and developing advanced prosthetic coatings within the field of tissue engineering.

Liquid Metal-Based Conductive Nerve Guidance Conduit Combined With Electrical Stimulation Boosts Peripheral Nerve Repair.

The combination of nerve guide conduits (NGCs) and electrical stimulation (ES) is an effective treatment for peripheral nerve injury (PNI). Flexible conductive materials with mechanical properties similar to those of biological tissues have been shown to have better long-term biointegration and functionality than rigid conductive materials. In this study, liquid metal (LM)-based conductive polycaprolactone/gelatin/polypyrrole/LM (PCL/Gel/PPy/LM, PGPL) NGC was combined with exogenous ES to repair PNI. PGPL membranes had good hydrophilicity, degradability, and mechanical properties, and its conductivity reached 0.66 ± 0.02 S/m. Invitro studies showed that the combination of PGPL membranes and ES (2 Hz, 100 mV/cm, 30 min/d) could significantly increase the expression of neuromarkers and had a better pro-neural differentiation effect. Invivo studies demonstrated that PGPL NGCs in combination with ES (2 Hz, 200 mV/mm, 30 min/d) could effectively promote morphological reconstruction and functional recovery of the sciatic nerve in rats. At 3 months post-surgery, PGPL NGCs combined with ES restored the nerve conduction velocity to 73.85% ± 5.45% of the normal value. The LM-based NGCs prepared in this study could effectively repair long sciatic nerve defects, which may further expand the application of LM in the field of nerve tissue engineering.

Recent advances of bioaerogels in medicine: Preparation, property and application.

Bioaerogels represent a type of three-dimensional porous materials fabricated from natural biopolymers, and show a significant potential for medical application due to their characteristics of extremely low density, high specific surface area, excellent biocompatibility and biodegradability. The preparation method and parameters of bioaerogels are focused on, and their influence on the structure and properties of bioaerogels are discussed in detail. Then, to match the properties of bioaerogels with the medical applications, this work emphasizes the main properties (including biocompatibility, degradability, and mechanical properties), structural parameters (such as suitable porosity, pore size and high specific surface area), and further summarizes the influence of single-component and composite bioaerogels on their properties. Moreover, according to the different applications (wound healing, drug delivery, and tissue engineering and other fields), the function method, mechanism and practical effect of bioaerogels are comprehensively analyzed. Finally, the challenges, future research directions, and solutions for the practical application of bioaerogels in medicine are discussed.

Effects of Chemical Pretreatments of Wood Cellulose Nanofibrils on Protein Adsorption and Biological Outcomes.

Wood-based nanocellulose is emerging as a promising nanomaterial in the field of tissue engineering due to its unique properties and versatile applications. Previously, we used TEMPO-mediated oxidation (TO) and carboxymethylation (CM) as chemical pretreatments prior to mechanical fibrillation of wood-based cellulose nanofibrils (CNFs) to produce scaffolds with different surface chemistries. The aim of the current study was to evaluate the effects of these chemical pretreatments on serum protein adsorption on 2D and 3D configurations of TO-CNF and CM-CNF and then to investigate their effects on cell adhesion, spreading, inflammatory mediator production in vitro, and the development of foreign body reaction (FBR) in vivo. Mass spectrometry analysis revealed that the surface chemistry played a key role in determining the proteomic profile and significantly influenced the behavior of periodontal ligament fibroblasts and osteoblast-like cells (Saos-2). The surface of TO-CNF 2D samples showed the highest protein adsorption followed by TO-CNF 3D samples. CM-CNF 2D samples adsorbed a higher number of proteins than their 3D counterparts. None of the CNF scaffolds showed toxicity in vitro or in vivo. However, carboxymethylation pretreatment negatively affected the adhesion, morphology, and spreading of both cell types. Although the CNF materials displayed clear differences in surface chemistry and proteomic profiles, both triggered the same foreign body response after being subcutaneously implanted in rats for 90 days. This observation highlights that the degradation rate of CNF scaffolds plays a central role in maintaining the foreign body response in vivo. It is imperative to comprehend the impact of chemical pretreatments of CNFs on protein adsorption and their interaction with diverse host cell types prior to the investigation of potential modifications. This knowledge is indispensable for the advancement of CNFs in regenerative applications within tissue engineering.

3D-Printed PCL/SrHA@DFO Bone Tissue Engineering Scaffold with Bone Regeneration and Vascularization Function.

The application of a three-dimensional (3D)-printed biological functional scaffold in the repair of bone defects is a promising strategy. In this study, strontium-containing hydroxyapatite (SrHA) powder was synthesized by the hydrothermal method, and then poly(ε-caprolactone) (PCL)/HA and PCL/SrHA composite scaffolds were prepared by the high-temperature melt extrusion 3D printing technology. The basic physical and chemical properties, in vitro biological properties, osteogenesis, and angiogenesis abilities of the scaffold were studied. The results showed that HA and SrHA were uniformly embedded in the composite scaffold, and the scaffold exhibited a 3D interconnected porous structure and rough microsurface. The in vitro release curve showed that Sr2+ and Ca2+ were continuously released from the PCL/SrHA scaffold. In order to verify the performance of the composite scaffold in bone regeneration, the proliferation and osteogenic differentiation of mouse embryonic osteoblasts (MC3T3E1) grown on the scaffold were evaluated. The experimental results showed that the incorporation of SrHA significantly promoted cell proliferation. Compared with the PCL/HA scaffold, the PCL/SrHA scaffold could better promote cell osteogenic differentiation. Deferoxamine (DFO) was loaded on the surface of the PCL/SrHA scaffold. By studying the proliferation, angiogenesis, and expression of osteogenesis and angiogenesis-related genes of human umbilical vein endothelial cells (HUVECs) on PCL/SrHA@DFO scaffold, it was verified that DFO had the ability to promote angiogenesis. It could induce angiogenesis in vitro in combination with Sr2+. Therefore, we believe that the composite scaffold has potential application prospects in the field of bone tissue engineering.

Bioinspired Composite Hydrogels with Osteogenic, Angiogenic, and Antioxidant Properties for Enhanced Bone Repair

The increasing demand of advanced biomedical materials for bone repair and regeneration has spurred significant research in recent years. While traditional hydrogels offer promising biocompatibility and easy fabrication, their application in bone reconstruction is often impeded by inadequate structural integrity and biological functions. Graphene oxide (GO) has emerged as a transformative additive, renowned for its exceptional mechanical and chemical properties, as well as its ability to enhance the structural integrity of hydrogels. In this study, the incorporation of GO into chitosan (CS) hydrogels is investigated, achieving bioinspired hydrogels with enhanced mechanical strength and stability, which are crucial for supporting bone regeneration. Additionally, self‐assembled synthetic peptide nanofibers (PNFs) are employed to enhance biocompatibility and facilitate biomimetic mineralization of the bioinspired hydrogels, a critical process for effective bone remodeling. This innovative composite hydrogel not only achieves biomimetic mineralization but also exhibits osteogenic, pro‐angiogenic, and antioxidant properties essential for bone repair. This novel method takes advantage of the distinctive properties of GO, PNFs, and biomass hydrogels, providing a robust and effective material solution with the potential to significantly advance the field of bone tissue engineering.

Quality and Regulatory Requirements for the Manufacture of Master Cell Banks of Clinical Grade iPSCs: The EU and USA Perspectives.

The discovery of induced pluripotent stem cells (iPSCs) and protocols for their differentiation into various cell types have revolutionized the field of tissue engineering and regenerative medicine. Developing manufacturing guidelines for safe and GMP-compliant final products has become essential. Allogeneic iPSCs-derived cell therapies are now the preferred manufacturing alternative. This option requires the establishment of clinical-grade master cell banks of iPSCs. This study aimed at reviewing the Quality and Regulatory requirements from the two main authorities in the world-Europe (EMA) and the United States (FDA)-regarding the manufacture of clinical grade master cell banks (iPSCs). The minimum requirements for iPSCs to be used in first-in-human clinical trials were also reviewed, as well as current best practices currently followed by iPSC bank manufacturers for final product characterisation. The methodology used for this work was a review of various sources of information ranging from scientific literature, published guidance documents available on the EMA and FDA websites, GMP and ICH guidelines, and applicable compendial monographs. Manufacturers of iPSCs cell banks looking to qualify them for clinical use are turning to the ICH guidelines and trying to adapt their requirements. Specifically with the impact of the field of iPSC cell banks, the following areas should be subject to guidance and harmonisation: i) expression vectors authorized for iPSC generation; ii) minimum identity testing; iii) minimum purity testing (including adventitious agent testing); and iv) stability testing. Current ICH guidelines for biotechnological/biological products should be extended to cover cell banks used for cell therapies.

Current Concepts and Clinical Applications in Cartilage Tissue Engineering.

Cartilage injuries are extremely common in the general population, and conventional interventions have failed to produce optimal results. Tissue engineering (TE) technology has been developed to produce neocartilage for use in a variety of cartilage-related conditions. However, progress in the field of cartilage TE has historically been difficult due to the high functional demand and avascular nature of the tissue. Recent advancements in cell sourcing, biostimulation, and scaffold technology have revolutionized the field and made the clinical application of this technology a reality. Cartilage engineering technology will continue to expand its horizons to fully integrate three-dimensional printing, gene editing, and optimal cell sourcing in the future. This review focuses on the recent advancements in the field of cartilage TE and the landscape of clinical treatments for a variety of cartilage-related conditions.

Applications and prospects of graphene and its derivatives in bone repair

To summarize the latest research progress of graphene and its derivatives (GDs) in bone repair. The relevant research literature at home and abroad in recent years was extensively accessed. The properties of GDs in bone repair materials, including mechanical properties, electrical conductivity, and antibacterial properties, were systematically summarized, and the unique advantages of GDs in material preparation, functionalization, and application, as well as the contributions and challenges to bone tissue engineering, were discussed. The application of GDs in bone repair materials has broad prospects, and the functionalization and modification technology effectively improve the osteogenic activity and material properties of GDs. GDs can induce osteogenic differentiation of stem cells through specific signaling pathways and promote osteogenic activity through immunomodulatory mechanisms. In addition, the parameters of GDs have significant effects on the cytotoxicity and degradation behavior. GDs has great potential in the field of bone repair because of its excellent physical and chemical properties and biological properties. However, the cytotoxicity, biodegradability, and functionalization strategies of GDs still need to be further studied in order to achieve a wider application in the field of bone tissue engineering.

Aerogels Based on Chitosan and Collagen Modified with Fe2O3 and Fe3O4 Nanoparticles: Fabrication and Characterization.

The necessity to mitigate the intrinsic issues associated with tissue or organ transplants, in order to address the rising prevalence of diseases attributable to increased life expectancy, provides a rationale for the pursuit of innovation in the field of biomaterials. Specifically, biopolymeric aerogels represent a significant advancement in the field of tissue engineering, offering a promising solution for the formation of temporary porous matrices that can replace damaged tissues. However, the functional characteristics of these materials are inadequate, necessitating the implementation of matrix reinforcement methods to enhance their performance. In this study, chemical and green iron oxide nanoparticles, previously synthesized and documented in existing research, were incorporated into hybrid aerogels combining collagen (C) and chitosan (CH). The characterization of these aerogels was conducted through rheological, microstructural, and functional analyses. The results demonstrate that the incorporation of iron oxide nanoparticles has a significant influence on the properties of the aerogels fabricated with them. In particular, the incorporation of these nanoparticles has been observed to modify the mechanical properties, with an increase in strength and porosity that may support cell proliferation.

3D bioprinting approaches for enhancing stem cell-based neural tissue regeneration.

Three-dimensional (3D) bioprinting holds immense promise for advancing stem cell research and developing novel therapeutic strategies in the field of neural tissue engineering and disease modeling. This paper critically analyzes recent breakthroughs in 3D bioprinting, specifically focusing on its application in these areas. We comprehensively explore the advantages and limitations of various 3D printing methods, the selection and formulation of bioink materials tailored for neural stem cells, and the incorporation of nanomaterials with dual functionality, enhancing the bioprinting process and promoting neurogenesis pathways. Furthermore, the paper reviews the diverse range of stem cells employed in neural bioprinting research, discussing their potential applications and associated challenges. We also introduce the emerging field of 4D bioprinting, highlighting current efforts to develop time-responsive constructs that improve the integration and functionality of bioprinted neural tissues. In short, this manuscript aims to provide a comprehensive understanding of this rapidly evolving field. It underscores the transformative potential of 3D and 4D bioprinting technologies in revolutionizing stem cell research and paving the way for novel therapeutic solutions for neurological disorders and injuries, ultimately contributing significantly to the advancement of regenerative medicine. STATEMENT OF SIGNIFICANCE: This comprehensive review critically examines the current bioprinting research landscape, highlighting efforts to overcome key limitations in printing technologies-improving cell viability post-printing, enhancing resolution, and optimizing cross-linking efficiencies. The continuous refinement of material compositions aims to control the spatiotemporal delivery of therapeutic agents, ensuring better integration of transplanted cells with host tissues. Specifically, the review focuses on groundbreaking advancements in neural tissue engineering. The development of next-generation bioinks, hydrogels, and scaffolds specifically designed for neural regeneration complexities holds the potential to revolutionize treatments for debilitating neural conditions, especially when nanotechnologies are being incorporated. This review offers the readers both a comprehensive analysis of current breakthroughs and an insightful perspective on the future trajectory of neural tissue engineering.

Characterization and Machine Learning-Driven Property Prediction of a Novel Hybrid Hydrogel Bioink Considering Extrusion-Based 3D Bioprinting.

The field of tissue engineering has made significant advancements with extrusion-based bioprinting, which uses shear forces to create intricate tissue structures. However, the success of this method heavily relies on the rheological properties of bioinks. Most bioinks use shear-thinning. While a few component-based efforts have been reported to predict the viscosity of bioinks, the impact of shear rate has been vastly ignored. To address this gap, our research presents predictive models using machine learning (ML) algorithms, including polynomial fit (PF), decision tree (DT), and random forest (RF), to estimate bioink viscosity based on component weights and shear rate. We utilized novel bioinks composed of varying percentages of alginate (2-5.25%), gelatin (2-5.25%), and TEMPO-Nano fibrillated cellulose (0.5-1%) at shear rates from 0.1 to 100 s-1. Our study analyzed 169 rheological measurements using 80% training and 20% validation data. The results, based on the coefficient of determination (R2) and mean absolute error (MAE), showed that the RF algorithm-based model performed best: [(R2, MAE) RF = (0.99, 0.09), (R2, MAE) PF = (0.95, 0.28), (R2, MAE) DT = (0.98, 0.13)]. These predictive models serve as valuable tools for bioink formulation optimization, allowing researchers to determine effective viscosities without extensive experimental trials to accelerate tissue engineering.

Design Principles and Frontiers of Applications for Thermo-Responsive and Self-Healing Hydrogels

Hydrogels are a class of hydrophilic polymer networks formed through chemical or physical cross-linking, which have been widely used in the biomedical field due to their high water absorption and biocompatibility. This article deeply analyzes the principles, classification, synthesis methods, physicochemical properties, and applications of temperature-sensitive hydrogels and self-healing hydrogels in drug release, tissue engineering, and other fields. By revealing their characteristics and mechanisms of action, it provides theoretical support for further research on hydrogels, looks forward to future research directions, and promotes innovation and development in practical applications.

Decellularized cartilage tissue bioink formulation for osteochondral graft development.

Articular cartilage and osteochondral defect repair and regeneration presents significant challenges to the field of tissue engineering (TE). TE and regenerative medicine strategies utilizing natural and synthetic-based engineered scaffolds have shown potential for repair, however, they face limitations in replicating the intricate native microenvironment and structure to achieve optimal regenerative capacity and functional recovery. Herein, we report the development of a cartilage extracellular matrix (ECM) as a printable biomaterial for tissue regeneration. The biomaterial was prepared through decellularization and solubilization of articular cartilage. The effects of two different viscosity modifiers, xanthan gum and Laponite®, and the introduction of a secondary photo-crosslinkable component on the rheological behavior and stability were studied. dcECM-Laponite® bioink formulations demonstrated storage modulus (G') ranging from 750 to 4000 Pa, which is three orders of magnitude higher than that of the dcECM-XG bioink formulations. The rheological evaluation of the bioinks demonstrated the tunability of the bioinks in terms of their viscosity and degree of shear thinning, allowing the formulations to be readily extruded during 3D printing. Also, a spreadable ink composition was identified to form a uniform cartilage layer post-printing. The choice of viscosity modifier along with UV cross-linking warrants shape fidelity of the structure post-printing, as well as improvements in the storage and loss moduli. The modified ECM-based bioink also significantly improved the stability and allowed for prolonged and sustained release of loaded growth factors through the addition of Laponite®. The ECM-based bioink supported human bone-marrow derived stromal cell and chondrocyte viability and increased chondrogenic differentiationin vitro. By forming decellularized cartilage ECM biomaterials in a printable and stable bioink form, we develop a 'Cartilage Ink' that can support cartilaginous tissue formation by closely resembling the native cartilage ECM in structure and function.

Dentin tubules as a long-term sustained release carrier to accelerate bone repair by loading FTY720

The controlled release of drugs remains a huge challenge in the field of tissue engineering. Current research focuses on the construction of drug carriers by using various advanced technologies. However, the pore-like structure that exists within our human body is ignored. Herein, a dental particle loaded with FTY720 by using dentin tubules (Dent-FTY720) was successfully prepared, which could achieve long-term sustained release of drugs. Meanwhile, Dent-FTY720 significantly promoted bone defect repair because of the similarity in composition to bone including hydroxyapatite and collagen. Furthermore, the loaded drugs exhibited both anti-immune and anti-inflammatory properties. This research introduces a novel concept in drug loading, highlighting the potential of dentin tubules as a drug delivery system.

The maturation state and density of human cartilage microtissues influence their fusion and development into scaled-up grafts.

Functional cartilaginous tissues can potentially be engineered by bringing together numerous microtissues (µTs) and allowing them to fuse and re-organize into larger, structurally organized grafts. The maturation level of individual microtissues is known to influence their capacity to fuse, however its impact on the long-term development of the resulting tissue remains unclear. The first objective of this study was to investigate the influence of the maturation state of human bone-marrow mesenchymal stem/stromal cells (hBM-MSCSs) derived microtissues on their fusion capacity and the phenotype of the final engineered tissue. Less mature (day 2) cartilage microtissues were found to fuse faster, supporting the development of a matrix that was richer in sulphated glycosaminoglycans (sGAG) and collagen, while low in calcium deposits. This enhanced fusion in less mature microtissues correlated with enhanced expression of N-cadherin, followed by a progressive increase in markers associated with cell-extracellular matrix (ECM) interactions. We then engineered larger constructs with varying initial numbers (50, 150 or 300 µTs per well) of less mature microtissues, observing enhanced sGAG synthesis with increased microtissue density. We finally sought to engineer a scaled-up cartilage graft by fusing 4,000 microtissues and maintaining the resulting constructs under either dynamic or static culture conditions. Robust and reliable fusion was observed between microtissues at this scale, with no clear benefit of dynamic culture on the levels of matrix accumulation or the tensile modulus of the resulting construct. These results support the use of BM-MSCs derived microtissues for the development of large-scale, engineered functional cartilaginous grafts. STATEMENT OF SIGNIFICANCE: Microtissues are gaining attention for their use as biological building blocks in the field of tissue engineering. The fusion of multiple microtissues is crucial for achieving a cohesive engineered tissue of scale, however the impact of their maturation level on the long-term properties of the engineered graft is poorly understood. This paper emphasizes the importance of using less mature cartilage microtissues for supporting appropriate cell-cell interactions and robust chondrogenesis in vitro. We demonstrate that tissue development is not negatively impacted by increasing the initial numbers of microtissues within the graft. This biofabrication strategy has significant translation potential, as it enables the engineering of scaled-up cartilage grafts of clinically relevant sizes using bone marrow derived MSCs.

Silk fibroin as a potential candidate for bone tissue engineering applications.

Silk fibroin (SF), a pivotal biomaterial, holds immense promise for diverse applications within the realm of bone tissue engineering. SF is an ideal scaffold material with exceptional biocompatibility, mechanical robustness, biodegradability, and bioactivity. A plethora of investigations have corroborated SF's efficacy in supporting bone tissue repair and regeneration. This comprehensive review delves into the structural attributes, physicochemical characteristics, and extraction methodologies of SF. Moreover, it elucidates the strides taken in harnessing SF across a spectrum of forms, including films, hydrogels, scaffolds, electrospun fibers, and composites for bone tissue engineering applications. Moreover, the application bottleneck of SF as a bone repair material is highlighted, and its development prospects and potential biomedical applications are also presented in this review. We expect that this review can inspire the broad interest of a wide range of readers working in the fields of materials science, tissue engineering, biomaterials, bioengineering, and biomedicine.

Next-generation biopolymer gels: innovations in drug delivery and theranostics.

Biopolymers or natural polymers like chitosan, cellulose, alginate, collagen, etc. have gained significant interest recently due to their remarkable tunable properties that make them appropriate for a variety of applications & play a crucial role in everyday life. The features of biopolymers which include biodegradability, biocompatibility, sustainability, affordability, & availability are vital for creating products for use in biomedical fields. Apart from these characteristics, smart or stimuli-responsive biopolymers also show a distinctive property of being susceptible to various factors like pH, temperature, light intensity, & electrical or magnetic fields. The current review would present a brief idea about smart biopolymer gels along with their biomedical applications. The use of smart biopolymers gels as theranostic agents are also discussed in the present review. This review also focuses on the application of biopolymers in the fields of drug delivery, cancer treatment, tissue engineering & wound healing. These areas demonstrate the development and utilization of different types of biopolymers in current biomedical applications.

Synthesis and Characterization of Novel pH-Responsive Aminated Alginate Derivatives Hydrogels for Tissue Engineering and Drug Delivery.

The aims of this study are to synthesize new derivatives of sodium alginate that improve the inherent properties, such as hydrogel strengthening, and create environmental sensitivity, such as pH sensitivity, for use in drug delivery. Today, hydrogels, due to outstanding properties such as biodegradability, biocompatibility, mechanical properties, and response to stimuli properties, are widely used as harmless biomaterials in various fields in drug delivery, wound dressing, and tissue engineering. Stimulus-sensitive polymers significantly respond to slight changes in their environment. Different types of stimuli are used to influence the properties of polymers, the most important of which are temperature and pH because these are two vital factors in the human body; hence, temperature-sensitive and pHsensitive hydrogels have been extensively studied. The ability to absorb water and swell the hydrogel is due to hydrophilic chains in the hydrogel network, and water absorption by hydrogel can be controlled by response to the stimuli. Since hydrogels mimic human tissue, the ability to retain water in them is essential. As a result, it is considered in many biomedical drug delivery systems. Stimulusresponsive swelling can control diffusion out of and into the hydrogel network, which allows temporal and spatial control of drug release. When a drug is loaded onto a biodegradable and stimulisensitive hydrogel, the drug delivery system has the added advantage of sustained release of the drug, which reduces side effects. In this study, two different hydrocarbons, [1,3-diaminopropane (DAP)] as a short-chain hydrocarbon, and [1,7-diaminoheptane (DAH)] as a long-chain hydrocarbon were grafted onto three types ofsodium alginate (SA), through amide bond linkages. The hydrogel copolymer matrices were compared with sodium alginate (SA) beads. The graft copolymers were characterized using FTIR, 1HNMR, XRD spectroscopy, elemental analysis (CHNS) and thermal analysis (TGA, DTA and DSC). An environmental scanning electron microscope (ESEM) was used to investigate the surface morphology of hydrogels. Effects of variables such as the length of hydrocarbon chains cross-linked to alginate, temperature, pH, and cross-linkers on the properties of hydrogels investigated in the temperature range of 2-70 ˚C and two different pH values (4.4 and 7.4). The results showed that when the hydrocarbon chain length of diamines decreases, the extent of cross-linking and strength of the hydrogels are increased. Other results suggest that the hydrogels obtained from high-viscosity alginate derivatives had positive pH sensitivity. Hydrogels prepared in this study demonstrated good mechanical and swelling ratios that are necessary for wound dressing. DAP-g-SA and DAH-g-SA pH-sensitive hydrogels were successfully synthesized through amide bond linkages. The new synthesis derivatives showed lower swelling levels at low pH (4.4). In contrast, their swelling levels at higher pH (7.4) were significantly enhanced. Higher swelling degree could be obtained at high pH. pH-responsive hydrogels are especially useful for various biological applications due to their unique feature of controlled swelling, biodegradability, biocompatibility, and fluid retention in their network structures. pH-responsive hydrogels, as intelligent systems, can be used in controlled-release drug delivery systems such as insulin delivery.