Chitosan and Pectin Hydrogels for Tissue Engineering and In Vitro Modeling

Hydrogels are fascinating biomaterials that can act as a support for cells, i.e., a scaffold, in which they can organize themselves spatially in a similar way to what occurs in vivo. Hydrogel use is therefore essential for the development of 3D systems and allows to recreate the cellular microenvironment in physiological and pathological conditions. This makes them ideal candidates for biological tissue analogues for application in the field of both tissue engineering and 3D in vitro models, as they have the ability to closely mimic the extracellular matrix (ECM) of a specific organ or tissue. Polysaccharide-based hydrogels, because of their remarkable biocompatibility related to their polymeric constituents, have the ability to interact beneficially with the cellular components. Although the growing interest in the use of polysaccharide-based hydrogels in the biomedical field is evidenced by a conspicuous number of reviews on the topic, none of them have focused on the combined use of two important polysaccharides, chitosan and pectin. Therefore, the present review will discuss the biomedical applications of polysaccharide-based hydrogels containing the two aforementioned natural polymers, chitosan and pectin, in the fields of tissue engineering and 3D in vitro modeling.

[1]  A. Polini,et al.  Chitosan-hydroxyapatite composites made from sustainable sources: a morphology and antibacterial study , 2023, Materials Today Sustainability.

[2]  M. Raimondi,et al.  Pectin-based bioinks for 3D models of neural tissue produced by a pH-controlled kinetics , 2022, Frontiers in Bioengineering and Biotechnology.

[3]  April M. Kloxin,et al.  Engineered hydrogels for mechanobiology , 2022, Nature reviews. Methods primers.

[4]  Yuan Luo,et al.  Marine‐Derived Hydrogels for Biomedical Applications , 2022, Advanced Functional Materials.

[5]  Ning Gu,et al.  Stress Relaxation‐Induced Colon Tumor Multicellular Spheroid Culture Based on Biomimetic Hydrogel for Nanoenzyme Ferroptosis Sensitization Evaluation , 2022, Advanced Healthcare Materials.

[6]  Nicholas J. Fiore,et al.  3D biocomposite culture enhances differentiation of dopamine-like neurons from SH-SY5Y cells: A model for studying Parkinson's disease phenotypes. , 2022, Biomaterials.

[7]  A. Khademhosseini,et al.  Thermoresponsive and Injectable Hydrogel for Tissue Agnostic Regeneration , 2022, Advanced healthcare materials.

[8]  Adam T. Melvin,et al.  Generation of 3D Spheroids Using a Thiol–Acrylate Hydrogel Scaffold to Study Endocrine Response in ER+ Breast Cancer , 2022, ACS biomaterials science & engineering.

[9]  A. Maleki,et al.  Recent advances on biomedical applications of pectin-containing biomaterials. , 2022, International journal of biological macromolecules.

[10]  N. Hasırcı,et al.  Potential of pectin for biomedical applications: a comprehensive review , 2022, Journal of biomaterials science. Polymer edition.

[11]  A. Zykwinska,et al.  Mechanical relaxations of hydrogels governed by their physical or chemical crosslinks. , 2022, Journal of the mechanical behavior of biomedical materials.

[12]  P. Le,et al.  Recent developments in chitosan hydrogels carrying natural bioactive compounds. , 2022, Carbohydrate polymers.

[13]  H. S. Rho,et al.  A guide to the organ-on-a-chip , 2022, Nature Reviews Methods Primers.

[14]  V. Gargiulo,et al.  Sulfated lactose-modified chitosan. A novel synthetic glycosaminoglycan-like polysaccharide inducing chondrocyte aggregation. , 2022, Carbohydrate polymers.

[15]  A. Polini,et al.  A thermo-sensitive chitosan/pectin hydrogel for long-term tumor spheroid culture. , 2021, Carbohydrate polymers.

[16]  A. Polini,et al.  Thermosensitive chitosan-based hydrogels supporting motor neuron-like NSC-34 cell differentiation. , 2021, Biomaterials science.

[17]  Shu-ya Wang,et al.  Fabrication of self-healing pectin/chitosan hybrid hydrogel via Diels-Alder reactions for drug delivery with high swelling property, pH-responsiveness, and cytocompatibility. , 2021, Carbohydrate polymers.

[18]  A. Polini,et al.  Preparation and Characterization of Salt-Mediated Injectable Thermosensitive Chitosan/Pectin Hydrogels for Cell Embedding and Culturing , 2021, Polymers.

[19]  S. Ramaswamy,et al.  Pectin in biomedical and drug delivery applications: A review. , 2021, International journal of biological macromolecules.

[20]  D. Barrow,et al.  Droplet Microfluidics for Tumor Drug‐Related Studies and Programmable Artificial Cells , 2021, Global challenges.

[21]  A. Polini,et al.  The convergence of high-tech emerging technologies into the next stage of organ-on-a-chips , 2021, Biomaterials and biosystems.

[22]  C. Malitesta,et al.  Sustainable chitosan-based electrical responsive scaffolds for tissue engineering applications , 2021, Sustainable Materials and Technologies.

[23]  J. Mano,et al.  Stratified 3D Microtumors as Organotypic Testing Platforms for Screening Pancreatic Cancer Therapies. , 2021, Small methods.

[24]  D. Bikiaris,et al.  Preliminary Evaluation of 3D Printed Chitosan/Pectin Constructs for Biomedical Applications , 2021, Marine drugs.

[25]  A. Polini,et al.  Effect of l-Arginine treatment on the in vitro stability of electrospun aligned chitosan nanofiber mats , 2020 .

[26]  Handan Acar,et al.  Natural and Synthetic Biomaterials for Engineering Multicellular Tumor Spheroids , 2020, Polymers.

[27]  Jason A. Burdick,et al.  Enhancing Biopolymer Hydrogel Functionality through Interpenetrating Networks. , 2020, Trends in biotechnology.

[28]  Shu-ya Wang,et al.  An injectable, self-healing hydrogel system from oxidized pectin/chitosan/γ-Fe2O3. , 2020, International journal of biological macromolecules.

[29]  A. Polini,et al.  Development of Injectable Thermosensitive Chitosan-Based Hydrogels for Cell Encapsulation , 2020, Applied Sciences.

[30]  Yapeng Fang,et al.  Egg-box model-based gelation of alginate and pectin: A review. , 2020, Carbohydrate polymers.

[31]  Zihang Yang,et al.  Thermosensitive Injectable Chitosan/Collagen/β-Glycerophosphate Composite Hydrogels for Enhancing Wound Healing by Encapsulating Mesenchymal Stem Cell Spheroids , 2020, ACS omega.

[32]  P. Janmey,et al.  Effects of extracellular matrix viscoelasticity on cellular behaviour , 2020, Nature.

[33]  Zi Kuang Moay,et al.  Composite Hydrogels in Three-Dimensional in vitro Models , 2020, Frontiers in Bioengineering and Biotechnology.

[34]  A. A. Burkov,et al.  Pectin-glycerol gel beads: Preparation, characterization and swelling behaviour. , 2020, Carbohydrate polymers.

[35]  W. Murphy,et al.  Synthetic alternatives to Matrigel , 2020, Nature Reviews Materials.

[36]  Leila Roshangar,et al.  Development of reinforced chitosan/pectin scaffold by using the cellulose nanocrystals as nanofillers: An injectable hydrogel for tissue engineering , 2020 .

[37]  C. Vasile,et al.  New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers , 2020, Molecules.

[38]  Shu-ya Wang,et al.  Design and preparation of quaternized pectin-Montmorillonite hybrid film for sustained drug release. , 2020, International journal of biological macromolecules.

[39]  J. Chen,et al.  Direct 3D Printed Biomimetic Scaffolds Based on Hydrogel Microparticles for Cell Spheroid Growth , 2020, Advanced Functional Materials.

[40]  P. Brun,et al.  The Viability and Anti-Inflammatory Effects of Hyaluronic Acid-Chitlac-Tracimolone Acetonide- β-Cyclodextrin Complex on Human Chondrocytes , 2020, Cartilage.

[41]  Luca Gasperini,et al.  The stiffness of living tissues and its implications for tissue engineering , 2020, Nature Reviews Materials.

[42]  R. Puga,et al.  Comparison of 2D and 3D cell culture models for cell growth, gene expression and drug resistance. , 2020, Materials science & engineering. C, Materials for biological applications.

[43]  Hongfang Li,et al.  Research progress in the application of in situ hydrogel system in tumor treatment , 2020, Drug delivery.

[44]  R. Dahiya,et al.  Engineered chitosan for improved 3D tissue growth through Paxillin-FAK-ERK activation , 2019, Regenerative biomaterials.

[45]  G. Vozzi,et al.  Pectin-GPTMS based biomaterial: toward a sustainable Bioprinting of 3D scaffolds for Tissue Engineering application. , 2019, Biomacromolecules.

[46]  M. Mihai,et al.  The Use of Chitosan, Alginate, and Pectin in the Biomedical and Food Sector—Biocompatibility, Bioadhesiveness, and Biodegradability , 2019, Polymers.

[47]  P. di Nardo,et al.  Extracellular matrix-based hydrogels obtained from human tissues: a work still in progress. , 2019, Current opinion in organ transplantation.

[48]  H. Bianco-Peled,et al.  Shear thinning pectin hydrogels physically cross-linked with chitosan nanogels. , 2019, Carbohydrate polymers.

[49]  Y. Lai,et al.  Recent Progress of Polysaccharide‐Based Hydrogel Interfaces for Wound Healing and Tissue Engineering , 2019, Advanced Materials Interfaces.

[50]  Jianhua Qin,et al.  Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip , 2019, Advances in Materials.

[51]  L. Ambrosio,et al.  Hydrogel-based delivery of Tat-fused protein Hsp70 protects dopaminergic cells in vitro and in a mouse model of Parkinson’s disease , 2019, NPG Asia Materials.

[52]  S. Ray,et al.  A 3D printed chitosan-pectin hydrogel wound dressing for lidocaine hydrochloride delivery. , 2019, Materials science & engineering. C, Materials for biological applications.

[53]  W. Prinyawiwatkul,et al.  Optimising chitosan–pectin hydrogel beads containing combined garlic and holy basil essential oils and their application as antimicrobial inhibitor , 2019, International Journal of Food Science & Technology.

[54]  L. Ambrosio,et al.  Bioactive chitosan-based scaffolds with improved properties induced by dextran-grafted nano-maghemite and l-arginine amino acid. , 2019, Journal of biomedical materials research. Part A.

[55]  C. Viseras,et al.  Complex of chitosan pectin and clay as diclofenac carrier , 2019, Applied Clay Science.

[56]  Xiaoli Shi,et al.  Hierarchical Hydrogel Composite Interfaces with Robust Mechanical Properties for Biomedical Applications , 2019, Advanced materials.

[57]  M. Lutolf,et al.  Bioinspired Hydrogels for 3D Organoid Culture. , 2019, Chimia.

[58]  R. Asmatulu,et al.  Sustained Releasing of Methotrexate from Injectable and Thermosensitive Chitosan–Carbon Nanotube Hybrid Hydrogels Effectively Controls Tumor Cell Growth , 2019, ACS omega.

[59]  Lan Li,et al.  Natural hydrogels for cartilage regeneration: Modification, preparation and application , 2018, Journal of orthopaedic translation.

[60]  Yu Shrike Zhang,et al.  Towards the development of human immune-system-on-a-chip platforms , 2018, Drug discovery today.

[61]  Xiao-Feng Sun,et al.  Preparation and swelling behavior of pH/temperature responsive semi-IPN hydrogel based on carboxymethyl xylan and poly(N-isopropyl acrylamide) , 2018, Cellulose.

[62]  A. Sannino,et al.  Chitosan scaffolds for cartilage regeneration: influence of different ionic crosslinkers on biomaterial properties , 2018, International Journal of Polymeric Materials and Polymeric Biomaterials.

[63]  Alessandro Polini,et al.  Fiber-reinforced colloidal gels as injectable and moldable biomaterials for regenerative medicine. , 2018, Materials science & engineering. C, Materials for biological applications.

[64]  R. Tester,et al.  Dietary Fiber, Gastric Emptying, and Carbohydrate Digestion: A Mini‐Review , 2018 .

[65]  A. F. Rubira,et al.  Chitosan-based hydrogels: From preparation to biomedical applications. , 2018, Carbohydrate polymers.

[66]  Miqin Zhang,et al.  Crosslinked Chitosan‐PEG Hydrogel for Culture of Human Glioblastoma Cell Spheroids and Drug Screening , 2018, Advanced therapeutics.

[67]  I. Donati,et al.  Concepts for Developing Physical Gels of Chitosan and of Chitosan Derivatives , 2018, Gels.

[68]  X. Su,et al.  Multifunctional smart hydrogels: potential in tissue engineering and cancer therapy. , 2018, Journal of materials chemistry. B.

[69]  Kathryn E Luker,et al.  Hybrid collagen alginate hydrogel as a platform for 3D tumor spheroid invasion. , 2018, Acta biomaterialia.

[70]  Kuikui Li,et al.  Pectin Oligosaccharides Ameliorate Colon Cancer by Regulating Oxidative Stress- and Inflammation-Activated Signaling Pathways , 2018, Front. Immunol..

[71]  L. Ballerini,et al.  Exploiting natural polysaccharides to enhance in vitro bio-constructs of primary neurons and progenitor cells. , 2018, Acta biomaterialia.

[72]  K. Popat,et al.  Pectin-chitosan membrane scaffold imparts controlled stem cell adhesion and proliferation. , 2018, Carbohydrate polymers.

[73]  Silvestro Micera,et al.  Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies , 2018, Advanced healthcare materials.

[74]  Pradip S. Thakuri,et al.  Biomaterials‐Based Approaches to Tumor Spheroid and Organoid Modeling , 2018, Advanced healthcare materials.

[75]  M. Guvendiren,et al.  Human Tissue Models: Engineering 3D Hydrogels for Personalized In Vitro Human Tissue Models (Adv. Healthcare Mater. 4/2018) , 2018 .

[76]  Jiandu Lei,et al.  Self-Assembled Nanoparticles Platform Based on Pectin-Dihydroartemisinin Conjugates for Codelivery of Anticancer Drugs. , 2017, ACS Biomaterials Science & Engineering.

[77]  Saad M Ahsan,et al.  Chitosan as biomaterial in drug delivery and tissue engineering. , 2017, International journal of biological macromolecules.

[78]  Fanglian Yao,et al.  Hybrid pectin-Fe3+/polyacrylamide double network hydrogels with excellent strength, high stiffness, superior toughness and notch-insensitivity. , 2017, Soft matter.

[79]  Xin Zhao,et al.  Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment. , 2017, Chemical reviews.

[80]  D. Grainger,et al.  Polysaccharide matrices used in 3D in vitro cell culture systems. , 2017, Biomaterials.

[81]  D. Scariot,et al.  Scaffolds based on chitosan/pectin thermosensitive hydrogels containing gold nanoparticles. , 2017, International journal of biological macromolecules.

[82]  H. Bianco-Peled,et al.  Pectin-chitosan physical hydrogels as potential drug delivery vehicles. , 2017, International journal of biological macromolecules.

[83]  Ali Khademhosseini,et al.  Cell-laden hydrogels for osteochondral and cartilage tissue engineering. , 2017, Acta biomaterialia.

[84]  S. Popov,et al.  Preparation and biocompatibility evaluation of pectin and chitosan cryogels for biomedical application. , 2017, Journal of biomedical materials research. Part A.

[85]  A. Subramanian,et al.  Injectable and 3D Bioprinted Polysaccharide Hydrogels: From Cartilage to Osteochondral Tissue Engineering. , 2017, Biomacromolecules.

[86]  N. Polović,et al.  Tyramine-modified pectins via periodate oxidation for soybean hull peroxidase induced hydrogel formation and immobilization , 2017, Applied Microbiology and Biotechnology.

[87]  Hans Clevers,et al.  Designer matrices for intestinal stem cell and organoid culture , 2016, Nature.

[88]  Mingqiang Li,et al.  Cell-laden microfluidic microgels for tissue regeneration. , 2016, Lab on a chip.

[89]  K. Anseth,et al.  The design of reversible hydrogels to capture extracellular matrix dynamics , 2016, Nature Reviews Materials.

[90]  Fa-Ming Chen,et al.  Advancing biomaterials of human origin for tissue engineering. , 2016, Progress in polymer science.

[91]  Marcia Parente Melo da Costa,et al.  New polyelectrolyte complex from pectin/chitosan and montmorillonite clay. , 2016, Carbohydrate polymers.

[92]  Yongjun Zhang,et al.  Chitosan as inter-cellular linker to accelerate multicellular spheroid generation in hydrogel scaffold , 2015 .

[93]  M. Maire,et al.  Injectable thermosensitive chitosan hydrogels with controlled gelation kinetics and enhanced mechanical resistance. , 2015, Carbohydrate polymers.

[94]  Shelly R. Peyton,et al.  Thermal-Responsive Behavior of a Cell Compatible Chitosan/Pectin Hydrogel. , 2015, Biomacromolecules.

[95]  H. Bianco-Peled,et al.  Small-angle X-ray scattering study on pectin-chitosan mixed solutions and thermoreversible gels. , 2015, Carbohydrate polymers.

[96]  V. Khutoryanskiy,et al.  Biomedical applications of hydrogels: A review of patents and commercial products , 2015 .

[97]  Elizabeth G Loboa,et al.  Naturally derived and synthetic scaffolds for skeletal muscle reconstruction. , 2015, Advanced drug delivery reviews.

[98]  Pei Cao,et al.  Glycerophosphate-based chitosan thermosensitive hydrogels and their biomedical applications. , 2015, Carbohydrate polymers.

[99]  Lorenzo Moroni,et al.  Biofunctionalized pectin hydrogels as 3D cellular microenvironments. , 2015, Journal of materials chemistry. B.

[100]  C. Dispenza,et al.  Maltose-conjugated chitosans induce macroscopic gelation of pectin solutions at neutral pH. , 2014, Carbohydrate polymers.

[101]  A. Polini,et al.  Gellan gum and polyethylene glycol dimethacrylate double network hydrogels with improved mechanical properties , 2014, Journal of Polymer Research.

[102]  L. Visai,et al.  Injectable pectin hydrogels produced by internal gelation: pH dependence of gelling and rheological properties. , 2014, Carbohydrate polymers.

[103]  Chaenyung Cha,et al.  25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine , 2014, Advanced materials.

[104]  Yujie Ma,et al.  25th Anniversary Article: Designer Hydrogels for Cell Cultures: A Materials Selection Guide , 2014, Advanced materials.

[105]  A. Ranga,et al.  Artificial three-dimensional niches deconstruct pancreas development in vitro , 2013, Development.

[106]  P. Cayot,et al.  Silica-coated calcium pectinate beads for colonic drug delivery. , 2013, Acta biomaterialia.

[107]  Yu-Chun Lin,et al.  Spheroid Formation and Enhanced Cardiomyogenic Potential of Adipose-Derived Stem Cells Grown on Chitosan , 2013, BioResearch open access.

[108]  A. Majeed,et al.  PECTIN BASED FORMULATIONS FOR BIOMEDICAL APPLICATIONS: A REVIEW , 2012 .

[109]  A. Hansson,et al.  In vitro evaluation of an RGD-functionalized chitosan derivative for enhanced cell adhesion. , 2012, Carbohydrate polymers.

[110]  P. Petrini,et al.  Advances in biomedical applications of pectin gels. , 2012, International journal of biological macromolecules.

[111]  Z. Werb,et al.  Extracellular matrix degradation and remodeling in development and disease. , 2011, Cold Spring Harbor perspectives in biology.

[112]  P. Ferreira,et al.  Preparation and chemical and biological characterization of a pectin/chitosan polyelectrolyte complex scaffold for possible bone tissue engineering applications. , 2011, International journal of biological macromolecules.

[113]  Barbara Luppi,et al.  Freeze-dried chitosan/pectin nasal inserts for antipsychotic drug delivery. , 2010, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[114]  David J. Mooney,et al.  Inspiration and application in the evolution of biomaterials , 2009, Nature.

[115]  A. Khademhosseini,et al.  Hydrogels in Regenerative Medicine , 2009, Advanced materials.

[116]  E. Place,et al.  Complexity in biomaterials for tissue engineering. , 2009, Nature materials.

[117]  Michael D Buschmann,et al.  Heat-induced transfer of protons from chitosan to glycerol phosphate produces chitosan precipitation and gelation. , 2008, Biomacromolecules.

[118]  F. Godinez,et al.  An alternative hemostatic dressing: comparison of CELOX, HemCon, and QuikClot. , 2008, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[119]  Kevin B. Hicks,et al.  Pectin in controlled drug delivery – a review , 2006 .

[120]  Ali Khademhosseini,et al.  Micromolding of photocrosslinkable chitosan hydrogel for spheroid microarray and co-cultures. , 2006, Biomaterials.

[121]  M. Rinaudo,et al.  Chitin and chitosan: Properties and applications , 2006 .

[122]  K. Knudsen,et al.  Structural and dynamical properties of aqueous mixtures of pectin and chitosan , 2005 .

[123]  S. Hollister Porous scaffold design for tissue engineering , 2005, Nature materials.

[124]  A. Kjøniksen,et al.  Thermoreversible gelation of aqueous mixtures of pectin and chitosan. Rheology. , 2003, Biomacromolecules.

[125]  M. Ralet,et al.  Physico-Chemical Properties of Pectins in the Cell Walls and After Extraction , 2003 .

[126]  T. Fujinaga,et al.  Topical formulations and wound healing applications of chitosan. , 2001, Advanced drug delivery reviews.

[127]  Dong Wang,et al.  Rheological characterisation of thermogelling chitosan/glycerol-phosphate solutions , 2001 .

[128]  D. Mooney,et al.  Hydrogels for tissue engineering. , 2001, Chemical reviews.

[129]  M. N. R. Kumar A review of chitin and chitosan applications , 2000 .

[130]  Nikolaos A. Peppas,et al.  Hydrogels and drug delivery , 1997 .

[131]  M. McCann,et al.  Plant cell wall architecture: the role of pectins , 1996 .

[132]  C. May,et al.  Industrial pectins: Sources, production and applications , 1990 .

[133]  E. Morris,et al.  Biological interactions between polysaccharides and divalent cations: The egg‐box model , 1973 .