Table 1.
Applications of chitosan-based bioactive materials in various fields of tissue engineering.
| Application | Materials | In vivo/In vitro/Ex vivo testing | Key features | Date and References |
|---|---|---|---|---|
| Cartilage tissue engineering | Chitosan-gelatin hydrogel | In vitro | Controlled biodegradability, cytocompatibility, microporous structures, and excellent mechanical properties; Strong, tough, and functional scaffolds having potential applications in cartilage tissue engineering | 2015 [68] |
| Glycol chitosan/poly(ethylene oxide-co-glycidol) hydrogels |
In vivo In vitro |
Chondrocytes were highly viable in the hydrogels, and no dedifferentiation of chondrocytes was observed; Demonstrated potential as an artificial extracellular matrix for cartilage tissue |
2015 [236] | |
| Chitosan/gelatin/chondoitin-6-sulfate-hyaluronan (GCH) scaffold | In vitro | Exhibits larger pores, higher ultimate strain (stress) and elastic modulus, and lower stress relaxation percentage; Incorporation of chitosan diminishes cell proliferation but up-regulates glycosaminoglycans (GAGs) and type II collagen (COL II) secretion |
2015 [67] | |
| Chitosan/poly(l-lactide) scaffolds using different crosslinkers | In vitro | Spongy scaffolds with improved physical properties; Promote chondrogenesis; In vivo condition is needed for better evaluation |
2016 [95] | |
| Poly(hydroxybutyrate)/chitosan blend fibrous scaffolds | In vitro | Better attachment of Chondrocytes to the surfaces of the scaffolds | 2016 [237] | |
| Silk fibroin-chitosan porous scaffold | In vitro | Exhibits cell supportive property of the scaffold in terms of cell attachment, cell viability, and proliferation | 2016 [77] | |
| Chitosan scaffolds cross-linked with hydrothermal treatment | In vitro | Improved physical and mechanical properties of the scaffolds due to cross-linking; Showed considerable proliferation in comparison to uncross-linked; Negligible impact of thermal treatment on porosity, pore size and permeability |
2017 [238] | |
| Chitosan/PVA/graphene oxide composite nanofibers | In vitro | Increased mechanical properties of nanofibers; Chitosan/PVA/GO showed most appropriate environment for the growth of ATDC5 cells compared to chitosan/PVA |
2017 [105] | |
| Chitosan/poly(l-lactide)/pectin composite scaffolds | In vitro | Superior neo-cartilage tissue regeneration; Exhibits suitable swelling property, moderate biodegradation and hemocompatibility in nature and possess suitable mechanical strength for cartilage tissue regeneration |
2018 [96] | |
| Chitosan/poly (3-hydroxybutyrate)- β-tricalcium phosphate scaffold | In vitro | Better mechanical and biological properties | 2019 [97] | |
| Chitosan/collagen/hydroxyapatite scaffold | In vitro | Inexpensive materials; Poor mechanical properties | 2019 [73] | |
| Bone tissue engineering | Chitosan/nano‐hydroxyapatite/polyethylene glycol | In vitro | Good mechanical strength supportive of bone tissue ingrowths | 2014 [127] |
| Chitosan/polycaprolactone -poly(ε-caprolactone) nanofibers | In vitro | Good cell attachment, cell viability, and metabolic activity for potential applications in bone tissue engineering. | 2015 [129] | |
| Chitosan/clay/hydroxyapatite scaffold | In vitro | Potential candidate for non-load bearing bone tissue engineering; Exhibits improved mechanical and in vitro biological properties |
2016 [117] | |
| Strontium hydroxyapatite/chitosan nanohybrid scaffolds | In vitro | Exhibits the excellent osteoinductivity | 2017 [125] | |
| Chitosan/gelatin/bioactive glass nanoparticles composites | In vitro | Promising temporary injectable matrix for bone tissue engineering; Improved elastic modulus |
2018 [153] | |
| Clay/chitosan/hydroxyapatite/zinc oxide | In vitro | Enhanced mechanical and biological properties for the application in bone tissue engineering | 2018 [121] | |
| Collagen/chitosan/polyethylene glycol/HAp | In vitro | Poor mechanical strength; Increased resistance to enzymatic degradation. |
2019 [116] | |
| Chitosan/poly(methyl methacrylate)/HAp | In vitro | Good mechanical strength; Can be utilized as a scaffold for bone cells ingrowth and also be used for drug delivery during the bone repairing |
2019 [239] | |
| Chitosan/PEG/ZnO/CuO/biphasic calcium phosphate (BCP) | In vitro | Better bacteriostatic activity and exhibited no cytotoxic effects towards the Vero cell line; Enhanced mechanical properties |
2019 [126] | |
| Chitosan anchored on porous poly(ε-caprolactone) (PCL)/bioactive glass (BG) composite scaffolds |
In vivo In vitro |
Enhanced protein adsorption, cell adhesion, and osteogenic differentiation; Promoted cranial bone regeneration |
2019 [240] | |
| Chitosan/gelatin/bioactive glass nanocomposite hydrogels |
In vivo In vitro |
In vivo and In vitro evaluation demonstrated good candidate as temporary injectable matrix in order to promote bone regeneration | 2019 [241] | |
| Intervertebral disc tissue engineering | Chitosan/disodium-glycerophosphate | In vitro | Thermosensitive hydrogels; Shows excellent biocompatibilities and bioactivities for Adipose-derived stem cells (ADSCs) induced NP-like cells |
2014 [242] |
| Chitosan–poly(hydroxybutyrate-co-valerate) with chondroitin sulfate nanoparticles | In vitro | Significantly enhanced viability and chondrogenic differentiation of mesenchymal stem cells (MSCs); Offers great potential for NP tissue engineering |
2015 [243] | |
| Chitosan-β glycerophosphate/hyaluronic acid/chondroitin-6-sulfate/type II of Collagen/gelatin/fibroin silk (Ch-β-GP-HA–CS–Col-Ge-FS) hydrogel | In vitro | At 4 °C, hydrogel is an injectable transparent solution; Gelation temperature of hydrogel was 37 °C; Exhibit constant storage modulus over a wide range of strain |
2017 [177] | |
| Chitosan/cellulose nanofibers | In vitro | Combating mechanical disc failure shows promising results as nanofibril-reinforced and non-cellularized bioactive biomaterial to promote intervertebral disc regeneration | 2018 [176] | |
| Chitosan hydrogel with an outer ring of poly(ether ether ketone) (PEEK) and an inner layer of poly(butylene succinate-co-terephthalate) (PBST) |
In vitro In vivo |
Provides an appropriate environment for supporting IVD cells growth; Gross morphology and biological functions of the tissue engineered IVD are similar to those of natural porcine IVD |
2018 [244] | |
| Glycol chitosan-based hydrogel for treatment of degenerative disc disease |
In vitro In vivo |
Thermo-sensitive injectable hydrogels with tunable thermo-sensitivity and enhanced stability; Can be used an alternative material for treatment of disc herniation |
2018 [245] | |
| Chitosan based hydrogels, filled with cellulose nanofibers (CNFs) |
In vitro Ex vivo using spine pig models |
Can be used for the repair and regeneration of the intervertebral disc (IVD) annulus fibrosus (AF) tissue | 2019 [22] | |
| Chitosan with various combinations of three gelling agents: sodium hydrogen carbonate (SHC) and/or beta-glycerophosphate (BGP) and/or phosphate buffer (PB) | In vitro | A novel thermosensitive CH hydrogel; Exhibits enhanced strength and suitable cytocompatibility and rheological properties, similar to human NP tissue |
2019 [179] | |
| Chitosan hydrogel/poly (butylene succinate‐co‐terephthalate) copolyester (PBST) electrospun fibers |
In vitro In vivo |
Mechanical property meets the requirement of the normal IVD; Both in vitro and in vivo experiments suggest the hydrogel as promising candidate for IVD replacement therapies |
2019 [180] | |
| Bloodvesseltissueengineering | Glycosamino-glycans/chitosan complex membranes |
In vitro In vivo |
Removes the shortcomings of existing small diameter vascular grafts by eliminating incomplete endothelialization and smooth muscle cell hyperplasia | 2000 [183] |
| Chitosan derived sandwiched tubular scaffold | In vitro | Regulation of pore diameter, very high burst strength, high suture retention strength. | 2006 [184] | |
| Electrospun collagen-chitosan-thermoplastic polyurethane nanofibrous scaffold | In vitro | Flexible with a high tensile strength; No in-vivo experiments were done; degradation of plastics in-vivo remains a question |
2011 [185] | |
| Chitosan/poly ε-caprolactone nanofibrous scaffold | In vitro | Characterized with properties of anticoagulation and rapid induction of re-endothelialization | 2012 [246] | |
| Chitosan/polycaprolactone (PCL) |
In vitro In vivo |
No calcification or aneurysm observed; Fast degradation and good cell infiltration but longer length grafts indicated lower patency |
2016 [182] | |
| Chitosan/poly(vinyl alcohol) (PVA) -polycaprolactone (PCL) hydrogel containing heparin |
In vitro In vivo |
High porous structure capable of carrying heparin; Increases new blood vessel formation into the hydrogels |
2016 [247] | |
| Chitosan/gelatin bi-layer microporous scaffold | In vitro | Tubular architecture; Similar morphological and mechanical properties of blood vessel |
2017 [187] | |
| Poly-l-lactic acid/chitosan/collagen electrospun tube | In vitro | Shows workable range of tensile strength, burst pressure, cell viability and hemolysis | 2018 [190] | |
| Chitosan/heparin layer by layer patch |
In vitro In vivo |
Showed long term patency and is workable with any substrate | 2019 [186] | |
| 3D printing PCL/chitosan/hydrogel biocomposites | In vitro | Elastic Moduli of range 56–174 MPa was obtained, Showed cell proliferation | 2019 [248] | |
| Cornealregeneration | Collagen/chitosan hydrogel |
In vitro In vivo |
Good permeability to glucose and albumin; Regeneration of corneal epithelium, stroma and nerves |
2008 [249] |
| Hydroxypropyl chitosan/gelatin scaffold | In vitro | Addition of chondroitin sulfate improved cell compatibility; suitable for keratocytes growing on its surface | 2009 [196] | |
| Hydroxyethyl chitosan/gelatin and chondroitin sulfate blend scaffold |
In vitro In vivo |
Scaffold can be used as a carrier for corneal endothelial cell transplantation; Water content, ion permeability and glucose permeability of the scaffold was remarkably close to the native cornea | 2011 [250] | |
| Genipin crosslinked chitosan |
In vitro In vivo |
Improved cell preservation and better anti-inflammatory activities than non-crosslinked counterparts but free-floating implants cause mechanical damage to tissue | 2012 [251] | |
| Chitosan/silk fibroin scaffold |
In vitro In vivo |
Reconstructed comparable lamellar cornea | 2013 [252] | |
| Chitosan/PEG hydrogel | In vitro | Good candidate for the regeneration and transplantation of Corneal Endothelial Cells; High optical transparency with cell adhesion and proliferation; Display desirable mechanical, optical and degradation properties | 2013 [198] | |
| Silicone modified chitosan membrane | In vitro | High tensile strength and inexpensive support for culturing corneal cells compared to currently used amniotic membrane | 2018 [253] | |
| Carboxymethyl chitosan and sodium alginate dialdehyde hydrogel |
In vitro In vivo |
Remarkable healing effect for alkali burn wounds with significant improvement in epithelial reconstruction; Post injection inflammation was observed | 2018 [254] | |
| Chitosan scaffold with PVA and amine coupling | In vitro | Addresses the issues of present amniotic membrane for corneal epithelium; Better mechanical strength |
2018 [255] | |
| Thiolated chitosan nanoparticles |
In vitro In vivo |
Potential anti-fibrotic and anti-angiogenic therapeutics for corneal injuries | 2018 [197] | |
| Carboxymethyl chitosan/gelatin/hyaluronic acid blended membrane |
In vitro In vivo |
Improves corneal epithelial reconstruction and restore cornea transparency and thickness | 2018 [256] | |
| Chitosan/polycaprolactone blend | In vitro | A suitable alternative for cadaveric cornea transplantation; Limited biodegradability and cell support after long term co-culture from artificial substrate | 2019 [199] | |
| Skintissueengineering | Chitosan/polycaprolactone blend fibrous mat | In vitro | Showed improved swelling property, tensile strength, thermal stability and surface roughness; Better attachment and proliferation of keratinocytes |
2015 [257] |
| Collagen/chitosan scaffolds | In vitro | Effectively promotes and accelerate cell proliferation | 2016 [258] | |
| Gelatin/carboxymethyl chitosan-based scaffolds | In vitro | Provide growth and proliferation along with potential support for angiogenesis during wound healing; Show sustained ampicillin and bovine serum albumin release, confirming their suitability as a therapeutic delivery vehicle during wound healing |
2016 [259] | |
| Chitosan/poly(caprolactone) nanofibers |
In vitro In vivo |
Increased the wound healing rate and promoted complete wound closure | 2017 [260] | |
| Chitosan/gelatin/polycaprolactone nanofibrous scaffold | In vitro | Possess promising physico-chemical and biological; In vivo testing should be performed to evaluate possibility in human body application |
2017 [261] | |
| Henna leaves extract-loaded chitosan based nanofibrous mats |
In vitro In vivo |
Incorporation of Henna extract exhibited significant synergistic antibacterial activity against bacterial cells; In vivo experiment supported cell viability and proliferation of human foreskin fibroblast cells on the prepared scaffolds |
2017 [262] | |
| Chitosan/g-pluronic hydrogel (nanocurcumin-formulated) |
In vitro In vivo |
Enhances burn wound repair; Has great potential to apply for wound healing |
2018 [263] | |
| Cellulose/chitosan hybrid sponges | In vitro | Exhibits superior blood coagulation, adsorption performance, and shape recovery properties; Displays good biocompatibility to human foreskin fibroblast cells |
2018 [264] | |
| Gelatin/chitosan electrospun scaffold | In vitro | Possess porosity of 92% maintaining good tensile strength; Exhibiting spindle-like shape |
2018 [209] | |
| Chitosan/maleic terminated polyethylene glycol hydrogels |
In vitro In vivo |
Show a porous structure with swelling ratio in the range of 240–280%; Good candidate for wound healing applications as they enhance the wound contraction process with improved vascularization. |
2019 [265] | |
| Chitosan/vitamin C/lactic acid composite membrane | In vitro | Provides optimum environment for skin cell (fibroblast NIH 3T3 cell–line) attachment, growth, and spreading | 2019 [214] | |
| Tissuefixation | High performance chitosan prepared by in situ coagulation | In vitro | Better bending strength, bending modulus and shear strength; Can be used in Internal bone fracture fixation |
2003 [215] |
| Chitosan/chitin coated polyester fabric |
In vitro In vivo |
Effectively induced bone formation in the spaces between the fibers and enhanced biological fixation of the fibrous materials to the bone; Good mechanical properties | 2008 [223] | |
| Chitosan rods crosslinked at higher temperature | In vitro | Good mechanical properties; Lower water absorption; Can be used in Internal bone fracture fixation |
2008 [217] | |
| Chitosan and hydroxyapatite | In vitro | Improved mechanical properties (bending strength and bending modulus); Can be used in Internal bone fracture fixation |
2010 [220] | |
| Chitin fiber and chitosan composites | In vitro | Better crystallinity and thermal stability; Insufficient bending strength and bending modulus; Possible application as a bone fracture internal fixation element. |
2010 [219] | |
| Chitin with glutaraldehyde as crosslinker |
In vitro In vivo |
Improved mechanical properties; Can be used in internal bone fracture fixation |
2010 [218] | |
| Chitosan with poly(p-amino-phenylacetylene)/multi-walled carbon nanotubes impregnated by superparamagnetic Fe3O4 | In vitro | Good cell proliferation, bending strength and bending modulus make them better candidate for bone fracture fixing | 2011 [222] | |
| Chitosan rod | In vitro | CS rods with excellent mechanical properties are a good candidate for bone fracture internal fixation. | 2011 [218] | |
| Chitosan and nanocrystalline hydroxyapatite composites | In vitro | Higher mechanical strength, positive cellular behavior and cell compatibility | 2012 [221] | |
| Periodate/oxidized chitosan/polyethylene glycol/tyramine hydrogel |
In vitro In vivo |
Highly cytocompatible and exhibited high tensile strength on porcine skin; Demonstrated good performance in wound sealing |
2015 [266] | |
| Oxidized dextran and chitosan based surgical adhesives |
In vitro In vivo |
Can stop bleeding, bond the tissues well as well as possess tissue sealing properties; Act as a hemostat, as vehicle for delivery of drugs and therapeutic peptides and proteins |
2017 [267] | |
| Microfiber nonwoven chitin fabric |
In vitro In vivo |
Promoted bone formation in the bone tunnel and increased the density of collagen fibers | 2018 [268] | |
| Periodontaltissueengineering | Chitosan-gelatin scaffolds with embedded chitosan/plasmid DNA nanoparticles encoding platelet derived growth factor (PDGF) | In vitro | Sustained and steady release of DNA, formed connective tissue like structure; Pore size preservation; promote periodontal ligament cells (PDLCs) proliferation, which would help defects regeneration in periodontal tissue engineering | 2008 [232] |
| Chitosan-tripolyphosphate | In vitro | Prevents bacterial growth in dental cone; Slow release of incorporated drug; good antibacterial agent; Crosslinking decreases sponge thickness and diameter | 2008 [230] | |
| Chitosan- HAp scaffolds loaded with basic fibroblast growth factor (bFGF) | In vitro | Three-dimensional structure provides better cellular structure, proliferation, and mineralization suitable for periodontal tissue engineering | 2009 [231] | |
| Chitosan-bioactive glass nanoparticles composite membranes | In vitro | Increases bioactivity properties; potentially be used as a temporary guided tissue regeneration membrane in periodontal regeneration | 2012 [235] | |
| Chitosan scaffolds with morphogenetic protein-6 (BMP-6) loaded alginate microspheres | In vitro | A controlled release vehicle for BMP-6 delivery; Enhances the osteoblastic differentiation of bone marrow |
2012 [233] | |
| Chitosan and quaternized chitosan (HTCC) | In vitro | Chitosan acts as anti-inflammatory and quartrernized chitosan acts against periodontal inflammation | 2013 [269] | |
| Chitosan microparticles loaded with clindamycin phosphate (CDP) | In vitro | Good drug delivery and sustained antimicrobial efficacy | 2014 [270] | |
| Chitosan/hyaluronic acid hydrogel scaffold | In vitro | Promotes cell migration for periodontal regeneration | 2015 [271] | |
| Chitosan based trilayer scaffold cross-linked with genipin |
In vitro In vivo |
Possess high biocompatibility, tissue ingrowth, and vascularization within the scaffold | 2017 [272] | |
| Chitosan gel |
In vitro In vivo |
Good local delivery system for a statin group drug, atorvastatin which is promising for the treatment of periodontal disease. | 2018 [273] | |
| Pure polylactic acid (PLA) and chitosan/PLA blends nanofibrous scaffolds | In vitro | Promoted cell adhesion, osteogenic differentiation of bone marrow stem cells (BMSCs); Caused higher expression of inflammatory mediators and TLR4 (Toll-like receptor 4) of human periodontal ligament cells |
2018 [274] | |
| Chitosan/dicarboxylic acid scaffold |
In vitro In vivo |
Promoted bone tissue repair in a critical-size mouse calvarial defect; Can serve as a carrier for stem cells or used alone to repair bone defects | 2019 [275] | |
| Transforming growth factor-β3/chitosan sponge |
In vitro In vivo |
Promotes osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs); Can repair periodontal soft and hard tissue defects | 2019 [276] | |
| Poly(lactic-co-glycolic acid)/chitosan/Ag nanoparticles |
In vitro In vivo |
No cytotoxicity and contributed to cell mineralization | 2019 [277] |