TY - JOUR
T1 - Injectable pH- and Temperature-Responsive Hydrogels for Scaffold Applications in Tissue Engineering
AU - Madech, Pawitchaya
AU - Khammata, Nuttawut
AU - Saba, Ain Us
AU - Kamdenlek, Patipat
AU - Punyodom, Winita
AU - Manaspon, Chawan
AU - Daranarong, Donraporn
AU - Punyamoonwongsa, Patchara
AU - Mahomed, Anisa
AU - Derry, Matthew
AU - Topham, Paul
AU - Tighe, Brian
AU - Manokruang, Kiattikhun
N1 - This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, copyright © 2026 American Chemical Society. To access the final edited and published work see: https://doi.org/10.1021/acs.biomac.5c01591
PY - 2026/1/3
Y1 - 2026/1/3
N2 - Injectable hydrogels offer promising alternatives for scaffold-based tissue engineering due to their minimally invasive delivery and in situ forming capability. In this study, we reported the first development of an injectable hydrogel scaffold combining carboxymethyl cellulose (CMC), poly(ethylene glycol) (PEG), and poly(ε-caprolactone) (PCL) into a single system. This novel approach integrated the biocompatibility of CMC, tunable responsiveness of PEG, and mechanical robustness/degradability of PCL, which had not been previously reported. A pH- and temperature-responsive carboxymethyl cellulose (CMC) grafted with a methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) [CMC-g-(mPEG-b-PCL)] system was synthesized. The diblock copolymers were first prepared by ring-opening polymerization of ε-caprolactone using a poly(ethylene glycol) methyl ether (mPEG) in combination with a stannous octoate initiator, followed by grafting onto the pH-responsive CMC backbone using simple 1-ethyl-3-(3-(dimethylamino)propyl carbodiimide)/N-hydroxysuccinimide (EDC/NHS) coupling chemistry in N,N-dimethylformamide (DMF). Structural characterization by 1H NMR and FTIR spectroscopy confirmed the presence of characteristic functional groups from both CMC and mPEG-b-PCL. Aqueous CMC-g-(mPEG-b-PCL) hydrogels were subsequently formulated, with 32 wt % CMC-g-(mPEG17-b-PCL12) showing the most favorable sol–gel phase-transition behavior based on the test tube inversion. Rheological analysis demonstrated that the hydrogel remained injectable in the sol state and formed a stable gel under physiological conditions, with the range of storage moduli comparable to that of early stage cartilage tissue. In addition, the hydrogel exhibited an interconnected porous structure, as observed by scanning electron microscopy. Cytocompatibility was validated through MTT and live/dead staining assays using L929 fibroblasts and MG63 osteoblast-like cells. The results showed that the cell morphology was preserved, and the cell viability was stable throughout 5 days of incubation. These findings support the cytocompatibility of the synthesized CMC-g-(mPEG-b-PCL) graft copolymer and suggest its potential for further investigation as an injectable hydrogel scaffold for bone and cartilage tissue engineering applications.
AB - Injectable hydrogels offer promising alternatives for scaffold-based tissue engineering due to their minimally invasive delivery and in situ forming capability. In this study, we reported the first development of an injectable hydrogel scaffold combining carboxymethyl cellulose (CMC), poly(ethylene glycol) (PEG), and poly(ε-caprolactone) (PCL) into a single system. This novel approach integrated the biocompatibility of CMC, tunable responsiveness of PEG, and mechanical robustness/degradability of PCL, which had not been previously reported. A pH- and temperature-responsive carboxymethyl cellulose (CMC) grafted with a methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) [CMC-g-(mPEG-b-PCL)] system was synthesized. The diblock copolymers were first prepared by ring-opening polymerization of ε-caprolactone using a poly(ethylene glycol) methyl ether (mPEG) in combination with a stannous octoate initiator, followed by grafting onto the pH-responsive CMC backbone using simple 1-ethyl-3-(3-(dimethylamino)propyl carbodiimide)/N-hydroxysuccinimide (EDC/NHS) coupling chemistry in N,N-dimethylformamide (DMF). Structural characterization by 1H NMR and FTIR spectroscopy confirmed the presence of characteristic functional groups from both CMC and mPEG-b-PCL. Aqueous CMC-g-(mPEG-b-PCL) hydrogels were subsequently formulated, with 32 wt % CMC-g-(mPEG17-b-PCL12) showing the most favorable sol–gel phase-transition behavior based on the test tube inversion. Rheological analysis demonstrated that the hydrogel remained injectable in the sol state and formed a stable gel under physiological conditions, with the range of storage moduli comparable to that of early stage cartilage tissue. In addition, the hydrogel exhibited an interconnected porous structure, as observed by scanning electron microscopy. Cytocompatibility was validated through MTT and live/dead staining assays using L929 fibroblasts and MG63 osteoblast-like cells. The results showed that the cell morphology was preserved, and the cell viability was stable throughout 5 days of incubation. These findings support the cytocompatibility of the synthesized CMC-g-(mPEG-b-PCL) graft copolymer and suggest its potential for further investigation as an injectable hydrogel scaffold for bone and cartilage tissue engineering applications.
UR - https://pubs.acs.org/doi/full/10.1021/acs.biomac.5c01591
U2 - 10.1021/acs.biomac.5c01591
DO - 10.1021/acs.biomac.5c01591
M3 - Article
SN - 1525-7797
JO - Biomacromolecules
JF - Biomacromolecules
ER -