Dually responsive biodegradable drug releasing 3D printed structures

Abstract

The aim of this study was to develop temperature and pH‐responsive biodegradable 3D printed drug‐releasing constructs using the Digital Light Processing (DLP) printing technique. The printable molecules, named “inks” throughout this study, comprised polyethylene oxide–polypropylene oxide–polyethylene oxide (PEO–PPO–PEO) triblocks and acrylic acid (AAc) that rendered them reverse thermo‐responsive (RTR) and pH‐sensitive, respectively. Additionally, the inks' biodegradability was imparted to them by incorporating lactide (LA) and ε‐caprolactone (CL) units into their composition, while their printability was achieved by end‐capping them with 2‐Isocyanatoethyl methacrylate (IEMA). By fine tuning the LA/CL composition, a broad range of inks displaying different water absorption behavior, biodegradation as well as bovine serum albumin (BSA) release profiles at different conditions. All the hydrogels showed a fast and reversible swelling–deswelling response, as they fluctuated between pH 2.0 and pH 7.4 or between 10 and 37°C. The resultant hydrogels showed good water uptake capacity (6340%) at pH 7.4 and 10°C temperature. BSA release from the loaded 3D printed hydrogel showed a maximum (80.5%) at pH 7.4 and 10°C in comparison to pH 7.4 and 37°C (65%). The proposed dual responsive 3D printed biodegradable hydrogels objects will shed light as a drug carrier.

4D Printing: The Development of Responsive Materials Using 3D-Printing Technology

“…In this case, the secondary crosslinking of the material with Ca 2+ gave the tablets an active response at different pH values. A pH-sensitive 3D-printed formulation was developed for colon-specific protein release [ 174 ]. For this, they used the digital light processing (DLP) printing technique to co-print constructs based on the reverse thermo-responsive poly (ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) (PEO–PPO–PEO) triblocks and the pH-responsive acrylic acid to provide them pH sensitivity.…”

“…GelMA-filled silicate nanoplatelets containing hMSCs Promotion of the formation, stability, and maturation of vascular vessels in vitro [174] PEG tetrabicyclononyne (Mn ~20,000 Da), diazide-functionalized synthetic peptide Generation of endothelialized 3D vascular networks [206] Hyaluronic acid functionalized with photoisomerized tetra-ortho-methoxy-substituted Azo crosslinked to cyclodextrins Regeneration of functional multi-tissue complex under an external control [208] PCL, lauric acid, and melanin Controlled release of insulin [211] Dihydrazide-modified HA hydrogel Effective, localized delivery of anti-cancer agents [212] PCL impregnated with gold nanoparticles-decorated carbon nanofibers Controlled drug release [215] Chitosan microswimmers Controlled drug release [218] Wool keratin modified with TTFAP and AzA Wound healing and tissue-engineering applications.Antimicrobial activity [221] Alginate-gelatin hydrogels coated with PCL and PDA Controlled release of doxorubicin for cancer therapy [223] CNTs-doped N-isopropylacrylamide (NIPAM) composite hydrogel Biomimetic aortic valve microstructure [224] Gelatin methacryloyl with iron oxide nanoparticles Generation of bioinspired soft robotic systems [213] Nanoclay-incorporated double-network hydrogel with magnetite nanoparticles Magnetic guided movement [214] Humidity PEG bilayers 3D biological studies and tissue engineering [248] Multisomes Domain of synthetic biology and medicine [249] Zein gel in a supporting bath of Carbopol Development of controlled self-assembly biomedical materials [250] Enzymes PEGDA hydrogel with alkaline phosphatase and thrombin Formation of calcified structures and fiber patterns [252] 2-carboxyethyl acrylate added to photocurable resins and derivatized with urease and glucose oxidase On-site determination of urea and glucose [193]…”

Block Copolymers in 3D/4D Printing: Advances and Applications as Biomaterials

“…In the literature, the last year’s other architectures based on the same polymers as AB/ABA architectures or other polymers are currently under investigation. Moreover, using natural polymers, polypeptides, hydroxyapatite, or clay has contributed much to 3D printing in the last few years [ 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ].…”

“…It has been shown that the PLA/PCL ratio plays an important role. It has been suggested that these materials can be good candidates for colon protein release formulations [ 111 ].…”