Table 4.
Smart/stimuli-responsive hydrogels employed for the engineering of different tissues.
| Tissue engineering applications | Smart hydrogel polymers | Employed smart hydrogel systems | Stimuli responsiveness | Study model | Purpose of use | Year | Refs. |
|---|---|---|---|---|---|---|---|
| Cardiac tissue engineering | Poly (N-isopropylacrylamide) (PNIPAAm) | PNIPAAm/SWCNTs | Temperature-responsive | -In vivo Study (Rat model of MI) | Delivery of BASCs to the targeted site of MI for myocardial repair | 2014 | [345] |
| Mixed Supramolecular hydrogel of Cur-FFE-SH gelator | Curcumin and NO laden-supramolecular Cur-FFE-ss-ERGD (Cur-FFE-ss-ERGD/Nap-FFGGG-NO) | β -gal enzyme-responsive | -In vivo Study (Mice model of MI) | Dual delivery of curcumin and NO to the targeted site of MI for myocardial repair | 2017 | [346] | |
| Poly(vinyl alcohol) (PVA) | PVA-TSPBA | ROS-responsive | -In vivo (rat and pig model of I/R) | Delivery of bFGF to the targeted site of ischemia for myocardial repair | 2021 | [347] | |
| Neural tissue engineering | Carboxymethyl Chitosan (CMCH) | Conductive PEDOT/CMCH hydrogel composites | Electro-responsive | -In vitro (neuron-like rat PC12 cells) | Study the cytocompatibility of PEDOT/CMCH for nerve tissue engineering | 2018 | [335] |
| Polyacrylamide (PAM) | Conducting polymer hydrogel (CPH) based on copolymerized PANI and PAM (PAM/PANI CPH) | Light/Photo-responsive | -In vitro (white corded sciatic nerves of a hoptoad) -In Vivo (rat peripheral nerve injury model) |
Conductive bridge for replacement of lost peripheral (sciatic) nerve | 2020 | [334] | |
| Dermal tissue engineering | Methacrylate gelatin (GelMA) | GelMA-PDA-ASP nanofibrous hydrogels | Temperature-responsive | -In vitro Study (L929 and HaCaT cells) -In vivo Study (mice skin wound) |
Wound dressing for delivery of Aspirin (ASP) | 2021 | [333] |
| Chitosan (CH) | Silver sulfadiazine loaded CH/PVP | PH-responsive | -In vitro Study | Wound dressing for delivery of silver sulfadiazine to the injury site | 2019 | [349] | |
| Carboxy Methylcellulose (CMC) | FU-loaded PCNCHFs composites (PCNCHFs@FU) | PH-responsive | -In vitro Study | Wound dressing for delivery of FU to the injury site | 2021 | [350] | |
| Corneal tissue engineering | Chitosan (CH) | CH combined with DGP (CH/DGP) | Temperature-responsive | -In vitro -In vivo (allergic conjunctivitis in New Zealand Albino rabbits and Guinea Pigs) | Ocular drug (levocetirizine dihydrochloride) delivery system | 2012 | [352] |
| Hyaluronic acid (HA) | HA and Pluronic F-127 (HA-F) | Temperature-responsive | -In vitro (BCECs with and without P-PRP) | Regeneration of the injured corneal endothelium | 2017 | [351] | |
| Gellan maleate (MA-G) | Gellan maleate (MA-G) with NIPAm (MA-G/NIPAm) |
Temperature-responsive | -In vitro -In vivo (rat model) |
Ocular drug (Adrenaline and Chloramphenicol) delivery system | 2019 | [143] | |
| Osseous tissue engineering | Chitosan (CH) | Hemicellulose xylan/CH composite | Temperature-responsive | -In vivo (Rat non-union femoral fracture and Mouse tibial fracture) | Enhancement of bone defects repair and regeneration | 2016 | [356] |
| Chitosan (CH) | CH/β-glycerophosphate (CH/β-GP) | Temperature-responsive | -In vivo (Class III bone defects in beagle dogs) | Cargo for delivery of BMP-7 and ORN for periodontal regeneration | 2019 | [355] | |
| Alginate (Alg.) | P(Alg-g-NIPAAm) hydrogels mixed with Hydroxyapatite (HAp) | Temperature and Ultrasound-responsive | -In vitro | Cargo for delivery of different therapeutics (NaF, BSA, and BMP-2) | 2021 | [354] | |
| Cartilaginous tissue engineering | Chitosan-g-poly(N-isopropylacrylamide) (CH-g-PNIPAAm) | 3D Mesenchymal stem cells (MSCs) encapsulated in CH-g-PNIPAAm (CH-g-PNIPAAm@MSCs) | Temperature-responsive | -In vitro study (Murine MSCs) | Support the proliferation and chondrogenic differentiation of MSCs | 2017 | [357] |
| poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCEC) | TGF-β1-loaded PCEC | Temperature-responsive | -In vivo (Rat full-thickness knees cartilage defects) | Delivery of TGF-β1 for proper chondrogenesis | 2017 | [358] | |
| Chitosan (CH) | CH/CG composites | pH and Ionic strength-responsive | -In vitro Study (ATDC5 Cells) | Support the chondrogenic differentiation of ATDC5 cells | 2018 | [338] | |
| Tendinous tissue engineering | poly(N-isopropylacrylamide) (PNIPAAm) | Hydrophilic biopolymers Chitosan (CH) and Hyaluronic acid (HA) to PNIPAM HA–CH–PNIPAM (HACPN) |
Temperature-responsive | -In vitro (NIH 3T3 cells) -In vivo (Rabbit deep flexor tendon) |
Enhancement of tendon regeneration with prevention of post-operative peritendinous adhesion | 2017 | [360] |
| Methacrylated chondroitin sulfate (MA-CS) | Platelet lysate (PL) enriched MA-CS entrapping iron-based superparamagnetic nanoparticles (MA-CS MNPs-PL) | Magnetic- responsive | -In vitro (hTDCs and hASCs cells) | Delivery of PL for release of PL-derived growth factors | 2018 | [359] | |
| Meniscal tissue engineering | Glycol Chitosan GC/4-Arm PEG-CHO Hydrogel | BMSC-, and TGF- β1laden crosslinked glycol chitosan (GC) and multialdehyde functionalized 4-arm (4-arm PEG-CHO) (GC/4-Arm PEG-CHO @ BMSC-TGF- β1) hydrogel composites | Temperature-responsive | -In vitro (BMSCs cells) -In vivo (Rabbit meniscal defect) |
Release of TGF-β1 to support the fibrochondrogenic differentiation of BMSCs and improve meniscal defects in rabbit model | 2020 | [361] |
| Intervertebral disc tissue engineering | Polyethylene Glycol (PEG) | miRNA/PGPC Polyplex encapsulated in PEG Hydrogels (miRNA/PGPC@PEG HG) | Enzyme (MMPs)-responsive | -In vivo (Rabbit model) | Two stage miR-29a delivery to the nucleus pulposus cells to promote engineering of degenerated IVD | 2018 | [362] |
| Collagen (Col) | Col-JK1 | Dual pH and enzyme-responsive | -In vivo (Rat model of IVDD) | Delivery of hydrogen sulfide (H2S) to the site of IVDD | 2019 | [337] |
SWCNTs, Single Wall Carbon Nanotubes; MI, Myocardial Infarction; BASCs, Brown Adipose Tissue Derived Sem Cells, β -gal, β-galactosidase; NO, Nitric Oxide; TSPBA, N1 -(4-boronobenzyl)-N3 - (4-boronophenyl)-N1, N1, N3, N3 -tetramethylpropane-1,3-diaminium; ROS, Reactive Oxygen Species; I/R, Ischemia-Reperfusion; bFGF, Basic fibroblast growth factor; PEDOT, poly(3,4ethylenedioxythiophene); PC12, phaeochromocytoma; CPH, Conducting polymer hydrogel; PANI, polyaniline; β-CD, β-cyclodextrin; NIPAM, N-isopropyl acrylamide; CNT, Carbon nanotubes; PPY, polypyrrole; DAMC, Dialdehyde methylcellulose; PP, polypropylene non-woven fabric; -g-, γ-rays; AA, acrylic acid; PVP, N-vinyl-2-pyrrolidone; CMC, caboxymethyl cellulose; PCNCHFs, Polymer–clay nanocomposite hydrogel films; FU, 5-fluorouracil; BCECs, Bovine corneal endothelial cells; P-PRP, Porcine platelet rich plasma; DGP, disodium α-d-Glucose 1-phosphate; NPC, N-palmitoyl chitosan; NaF, Sodium fluorescein; BSA, Bovine serum albumin; BMP-2, Bone morphogenetic protein 2, BMP-7, Bone morphogenetic protein-7; ORN, ornidazole; CG, Carrageenan; TGF-β1, Transforming growth factor β1; KGN, kartogenin; hTDCs, Human tendon-derived cells; hASCs, Human adipose-derived stem cells; BMSCs, Bone mesenchymal stromal cells; PGPC, PEG-GPLGVRG-PAsp(DET)-Chole).