A rapid temperature-responsive sol-gel reversible poly(N-isopropylacrylamide)-g-methylcellulose copolymer hydrogel

Poly(N-isopropylacrylamide) (PNIPAAm) was grafted to methylcellulose (MC) with various feeding ratios using ammonium persulfate and N,N,N',N'-tetramethyl ethylene diamine as an initiator. FTIR results confirm the formation of PNIPAAm-g-MC copolymers. The temperature responsiveness of copolymer gels was investigated by turbidimetry, dynamic contact angle (DCA), differential scanning calorimetry and dynamic mechanical analysis (DMA). The results indicate that PNIPAAm-g-MC hydrogels are strongly temperature responsive. At lower contents of MC, the lower critical solution temperature (LCST) is decreased, whereas further increasing MC contents raises the LCSTs. It is observed that the phase transition of the hydrogels occurs reversibly within 1 min, and near body temperature, a rigid gel can be generated in a certain range of MC content. What is more, the incorporation of MC prevents the syneresis of copolymer hydrogel. DMA measurement reveals that the storage moduli (E') of the gels increase upon increasing MC contents, and moreover the values of E' go up markedly above LCST. The copolymer hydrogels hold a promise as a blood vessel barrier by tuning gelation temperature, gelation time and mechanical strength.     

Material design for an artificial extracellular matrix: Cell entrapment in poly (N-isopropylacrylamide) (PNIPAM)-grafted gelatin hydrogel

As a thermoresponsive extracellular matrix, PNIPAM-derivatized gelatin (PNIPAM-gelatin) was synthesized by an iniferter-based graft polymerization of NIPAM on side chains of gelatin (molecular weight, ca. 9.5 ×10⁴ g/mol). The degree of grafting was 22.6 groups per molecule, and the estimated molecular weight of PNIPAM was ca. 1.2×10⁴ g/mol. The phase transition of dissolution/precipitation of PNIPAM-gelatin occurred at around 35°C. At concentrations above 15 w/v% over about 35°C, the solution was converted to hydrogel. The mechanical strength of the produced hydrogel increased with the concentration of PNIPAM-gelatin. The apparent elastic modulus of the hydrogel at a concentration of 20 w/v% was 1.2×10⁴Pa, which is nearly equal to that of collagen gel prepared at 0.15w/v%. When a culture medium containing the PNIPAM-gelatin (concentration, 20 w/v%) and bovine smooth muscle cells was incubated at 37°C, the cells were entrapped into a hydrogel. The entrapped cells apparently died in hydrogel with a thickness of 1 mm. However, the use of thinner hydrogel (thickness, 0.1 mm) or comixing with a small amount of PNIPAM-derivatized hyaluronic acid (PNIPAM-HA), even at 1 mm thickness, appeared to increase the survival of entrapped cells.     

A thermo-sensitive poly(organophosphazene) hydrogel used as an extracellular matrix for artificial pancreas

A poly(organophosphazene) bearing alpha-amino-omega-methyl-poly(ethylene glycol) (AMPEG) and hydrophobic L-isoleucine ethyl ester (IleOEt) side groups has been synthesized. This material exhibited 4 phase transitions in an aqueous solution on gradually increasing the temperature, i.e., a transparent sol, a transparent gel, an opaque gel and a turbid sol. A 10 wt% buffered solution of the polymer was employed to entrap islets of Langerhans in an artificial pancreas. Rat islets entrapped in the gel showed prolonged insulin secretion in response to basal (5.5 mM) glucose concentration compared to free rat islets and islets entrapped in other types of polymer gels. Over a 28-day culture period, the rat islets in the poly(organophosphazene) hydrogel maintained higher cell viability and insulin production versus rat islets in different hydrogels and free islets. This thermo-sensitive injectable, biodegradable matrix can be used with several cell types, including nerve cells, to promote nerve regeneration.     

A novel two-level microstructured poly(N-isopropylacrylamide) hydrogel for controlled release

The aim of this work was to demonstrate that conventional poly(N-isopropylacrylamide) (PNIPAAm) hydrogels can improve their shrinkage and release properties solely due to the introduction of a heterogeneous density fluctuation-based microstructure. To this end, a novel structurally engineered PNIPAAm hydrogel was designed and compared with a chemically similar, but homogeneous, PNIPAAm hydrogel reference. For the two-step preparation PNIPAAm microgels were firstly synthesized with surface amine groups and further functionalized with polymerizable acrylate groups. In the second step the microgels, themselves acting as crosslinkers, were crosslinked to form a bulk network by inter-connecting the microgels with linear PNIPAAm chains. Although the chemical composition of the newly prepared hydrogel was generally the same as conventional PNIPAAm hydrogels (a relative control), significantly improved shrinkage properties and a more efficient “on–off” switching induced by temperature modulations were observed for the novel gel as compared with the homogeneous reference. These improved shrinkage properties were ascribed to the novel structure, which is believed to enable rapid shrinking of the small microgel crosslinkers and, thereupon, the generation of a sufficient number of diffusion channels for quick water release. Rhodamine B and ibuprofen (IBU) as model compounds were completely released from this novel gel at 20 °C, whereas at temperatures above the lower critical solution temperature release stopped after initial 40% and 70% “bursts” for rhodamine B and IBU, respectively, due to shrinkage of the gel network. This approach may provide an avenue to design temperature-sensitive drug delivery systems with state of the art switching properties and fast release kinetics by combining the here presented innovative strategy with complementary enhancements, such as the introduction of porosity.     

Preparation of fast responsive,temperature-sensitive poly(N-isopropylacrylamide) hydrogel

A new poly(N-isopropylacrylamide) (PNIPA) hydrogel was prepared by decreasing the temperature of polymerization/crosslinking reaction below the freezing point (–18°C). This PNIPA hydrogel shows a large swelling ratio at room temperature and exhibits a fast deswelling and reswelling rate in response to external temperature changes. These properties are attributed to the macroporous and regularly arranged network of this PNIPA hydrogel.     

Poly (N-isopropylacrylamide) (PNIPAM)-grafted gelatin as thermoresponsive three-dimensional artificial extracellular matrix: molecular and formulation parameters vs. cell proliferation potential

A series of poly(N-isopropylacrylamide)-grafted gelatins (PNIPAM gelatins) of three different graft densities (approx. 11, 22 and 34 graft chains per gelatin molecule) and three different molecular weights of their graft chains (molecular weight approximately 1.2 × 10⁴, 5.0 × 10⁴ and 1.3 × 10⁵ g/mol) were prepared by multiple derivatization of dithiocarbamyl (DC) group in a gelatin molecule and subsequent iniferter (acts as an initiator, transfer-agent and terminator)-based photopolymerization of NIPAM. The weight ratio of PNIPAM graft chains to gelatin (P/G) varied from 1.4 to 49. Aqueous solutions of PNIPAM-gelatins showed thermo-responsiveness, depended on the graft density and the molecular weight of PNIPAM graft chain or P/G. Aqueous solutions (10 or 20%, w/v) of PNIPAM-gelatins with P/G of more than 5.8 were converted to gels at 37°C. Focal plane images of PNIPAM-gelatin gels by confocal laser scanning microscopy revealed that the size of hydrophobically clustered aggregates increased with P/G, whereas the space of microvoids decreased with concentration. Compressive strain–stress measurements revealed that compressive strength of PNIPAM-gelatin increased with P/G. Bovine smooth muscle cells (SMCs)-entrapped gels were produced from PNIPAM-gelatin-containing cell-suspended medium solutions at 37°C. The entrapped cells proliferated in the gel with P/G of more than 12. A higher cell proliferativity was obtained at low concentration (5%, w/v) and higher P/G (> 18). Tissue formation composed of proliferative SMCs and cell-secreted extracellular matrices (collagen) was obtained at 14 days incubation. The inter-relationship between the molecular parameters of PNIPAM-gelatin, internal structural features and cell proliferation potential was discussed.     

Poly(N-isopropylacrylamide) (PNIPAM)-grafted gelatin as thermoresponsive three-dimensional artificial extracellular matrix: molecular and formulation parameters vs. cell proliferation potential

A series of poly(N-isopropylacrylamide)-grafted gelatins (PNIPAM gelatins) of three different graft densities (approx. 11, 22 and 34 graft chains per gelatin molecule) and three different molecular weights of their graft chains (molecular weight approximately 1.2 x 10(4), 5.0 x 10(4) and 1.3 x 10(5) g/mol) were prepared by multiple derivatization of dithiocarbamyl (DC) group in a gelatin molecule and subsequent iniferter (acts as an initiator, transfer-agent and terminator)-based photopolymerization of NIPAM. The weight ratio of PNIPAM graft chains to gelatin (P/G) varied from 1.4 to 49. Aqueous solutions of PNIPAM-gelatins showed thermo-responsiveness, depended on the graft density and the molecular weight of PNIPAM graft chain or P/G. Aqueous solutions (10 or 20%, w/v) of PNIPAM-gelatins with P/G of more than 5.8 were converted to gels at 37 degrees C. Focal plane images of PNIPAM-gelatin gels by confocal laser scanning microscopy revealed that the size of hydrophobically clustered aggregates increased with P/G, whereas the space of microvoids decreased with concentration. Compressive strain-stress measurements revealed that compressive strength of PNIPAM-gelatin increased with P/G. Bovine smooth muscle cells (SMCs)-entrapped gels were produced from PNIPAM-gelatin-containing cell-suspended medium solutions at 37 degrees C. The entrapped cells proliferated in the gel with P/G of more than 12. A higher cell proliferativity was obtained at low concentration (5%, w/v) and higher P/G (>18). Tissue formation composed of proliferative SMCs and cell-secreted extracellular matrices (collagen) was obtained at 14 days incubation. The inter-relationship between the molecular parameters of PNIPAM-gelatin, internal structural features and cell proliferation potential was discussed.     

A thermosensitive poly(organophosphazene) hydrogel for injectable tissue-engineering applications

A poly(organophosphazene) hydrogel has been synthesized which exhibits thermoreversible sol-gel transition behavior against temperature. Viscometric measurements indicated that a thermosensitive hydrogel exhibiting excellent strength could be formed at body temperature from the polymer solutions, at concentrations of 10 wt%. In this study, we have conducted an evaluation of this poly(organophosphazene) hydrogel with regard to its efficacy and suitability as an injectable tissue-engineering matrix within an in vivo system. A 10 wt% solution of poly(organophosphazene) containing MC3T3-E1 mouse preosteoblasts and collagen was injected subcutaneously into nude mice, thereby forming an in situ gelation-injected site. In order to determine the optimal conditions for subcutaneous injection, various cell numbers and collagen concentrations were tested in this nude mouse model. Cellular proliferation was found to depend on the collagen concentration employed (0.001-0.1 wt%), as well as the number of cells ((2-10) x 10(5)). Cellular proliferation increased gradually after injection into nude mouse (1, 3, 5 and 7 days) at the given collagen concentration (0.01 wt%). The proliferative characteristics of MC3T3-E1 cells were shown to be enhanced dramatically in the poly(organophosphazene)-based collagen containing construct when injected into the model nude mice, whereas no increases in proliferation were observed in the only poly(organophosphazene) gel lacking collagen.     

Thermoresponsive artificial extracellular matrix: N-isopropylacrylamide-graft-copolymerized gelatin

Poly(N-isopropylacrylamide)-graft-copolymerized gelatin (PNIPAM-gelatin) was prepared by iniferter-based photopolymerization of multiply derivatized dithiocarbamylated gelatin. PNIPAM-gelatins exhibited low critical solution temperature (LCST) immediately below the physiological temperature. PNIPAAm-gelatin-coated dishes induced cell adhesion at 37°C but incomplete detachment at room temperature, whereas dishes coated with PNIPAM or a mixture of PNIPAAm and gelatin showed little cell adhesion. The mixture of PNIPAAm-gelatin and PNIPAAm induced cell adhesion at 37°C and detachment at 20°C: the degrees of cell adhesion and detachment depended on the mixed ratio of PNIPAAm-gelatin and PNIPAAm. Complete thermoresponsive adhesion and detachment were found for the mixture containing a small fraction of PNIPAAm-gelatin (approximately 5 wt% with respect to PNIPAAm; gelatin content in the mixture is 2.7 wt%). Such a mixture may serve as thermoresponsive cell matrix for fabrication of a tissue-engineered device.     

Nonwoven supported temperature-sensitive poly(N-isopropylacrylamide)/polyurethane copolymer hydrogel with antibacterial activity

This article is focused on the study of the antibacterial activity of temperature sensitive poly(N-isopropylacrylamide/polyurethane (PNIPAAm/PU) hydrogel grafted nonwoven fabrics with chitosan modification. A series of temperature sensitive hydrogel grafted nonwoven fabrics with different N-isopropylacrylamide/polyurethane (NIPAAm/PU) feeding ratios have been synthesized by using ammonium persulfate (APS) as initiator and N,N,N',N'-tetramethyl-ethane-1,2-diamine (TEMED) as accelerator. FTIR and XPS were used to examine the surface modification of chitosan. The phase transition temperature of hydrogel grafted nonwoven fabrics was about 32 degrees C by DSC. S. aureus and E. coli were used to evaluate the antibacterial efficiency of the fabric composite. After chitosan modification, the hydrogel grafted nonwoven cellulose fabrics demonstrates an antibacterial activity to S. aureus. and E. coli and the antibacterial efficiency is about 80%.     

Solution properties of poly(N-isopropylacrylamide)

The results obtained by light scattering and viscosity measurements on unfractionated samples of poly(N-isopropylacrylamide) dissolved in methanol and in water seem to show that the chain molecules assume different conformations in the two solvents. In methanol solutions at 25°C, poly(N-isopropylacrylamide) (poly[1-(N-isopropylaminocarbonyl)ethylene]) molecules apparently behave as normal flexible chains, whereas in aqueous solutions at the same temperature the interactions between polymer molecules and the solvent seem to produce chain uncoiling toward more extended structures which become unstable at higher temperatures.     

Thermoresponsive degradable poly(ethylene glycol) analogues

Thermoresponsive polymers have many biomedical applications, but their nondegradability limits their in vivo applications. Herein, we report a new type of degradable thermoresponsive polymers-degradable poly (ethylene glycol) analogues (DPEGs) having lower critical solution temperatures (LCSTs) ranging 10-50 degrees C. DPEGs were synthesized by condensation polymerization of PEG-di(meth)acrylates (PEGDA or PEGDMA) with dithiols. Their LCSTs could be easily tuned by the PEG-chain length and the types of the double bond in the PEG monomers and dithiols. Long PEG chain and the presence of hydrophilic groups in the dithiol monomer increased the LCST of the resulting DPEG. Crosslinking DPEG chains produced thermoresponsive hydrogels. The hydrogels prepared by the end-capping method maintained the thermoresponsive properties of the linear DPEG. The degradable thermoresponsive DPEGs and their hydrogels have great potentials for in vivo biomedical applications.     

Dextran permeation through poly(N-isopropylacrylamide) Hydrogels

The permeation of macromolecules such as fluoroescein-labeled dextran fractions through thermally reversible hydrogels has been investigated. A permeation model has been formulated, which takes into account hydrogel porosity and tortuosity as well as the combined effect of a geometric restraint for a relatively large solute molecule at a pore entrance and the friction between solute molecules moving through the pores and pore walls. Based on this model, we have estimated the tortuosity and average pore size of a swollen hydrogel, poly(N-isopropylacrylamide) [poly(NIPAAm)] and a swollen heterogel, poly(N-isopropylacrylamide-co-vinyl-terminated dimethylsiloxane) [poly(NIPAAm-co-VTPDMS)]. The permeation data for dextran molecules up to the size of 43.5 Å in radius show good agreement with the values predicted from the model.     

Cytotoxicity of thermosensitive polymers poly(N-isopropylacrylamide), poly(N-vinylcaprolactam) and amphiphilically modified poly(N-vinylcaprolactam)

Thermosensitive polymers poly(N-isopropylacrylamide) (PNIPAM), poly(N-vinylcaprolactam) (PVCL) and PVCL grafted with amphiphilic poly(ethylene oxide) (PEO) chains (PVCL-graft-C11EO42) were prepared and characterized and their putative cytotoxicity was evaluated. The cytotoxicity of these thermosensitive polymers and their monomers was investigated as a function of polymer concentration, incubation time and incubation temperature by using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) cytotoxicity tests in Caco-2 and Calu-3 cell cultures. Also, the influence of the chain end functionality on toxicity was examined. Viability (MTT) and cellular damage (LDH) of the cells were shown to be dependent on the surface properties of the polymers, hydrophilicity or hydrophobicity. Hydrophilic PVCL and PVCL-graft-C11EO42 were well tolerated at all polymer concentrations (0.1-10.0 mg/ml) after 3 h of incubation at room temperature and at physiological temperature (37 degrees C). The more hydrophobic PNIPAM induced more clear cellular cytotoxicity at 37 degrees C. The monomers N-isopropylacrylamide and vinylcaprolactam and PEO-macromonomer showed dramatically higher cytotoxicity values with respect to the corresponding polymers. Cell damage was directly dependent on concentration, temperature and incubation time.     

Mining the extracellular matrix for tissue engineering applications

Tissue engineering is a rapidly evolving interdisciplinary field that aims to regenerate new tissue to replace damaged tissues or organs. The extracellular matrix (ECM) of animal tissues is a complex mixture of macromolecules that play an essential instructional role in the development of tissues and organs. Therefore, tissue engineering approaches rely on the need to present the correct cues to cells, to guide them to maintain tissue-specific functions. Recent research efforts have allowed us to mine various sequences and motifs, which play key roles in these guidance functions, from the ECM. Small conserved peptide sequences mined from ECM molecules can mimic some of the biological functions of their large parent molecules. In addition, these peptide sequences can be linked to various biomaterial scaffolds that can provide the cells with mechanical support to ensure appropriate cell growth and aid the formation of the correct tissue structure. The tissue engineering field will continue to benefit from the advent of these mined ECM sequences which have two major advantages over recombinant ECM molecules: material consistency and scalability.     

Thermosensitive/magnetic poly(organophosphazene) hydrogel as a long-term magnetic resonance contrast platform

A thermosensitive/magnetic poly(organophosphazene) hydrogel (a magnetic hydrogel) was designed and synthesized for long-term magnetic resonance (MR) imaging. To turn a thermosensitive poly(organophosphazene) hydrogel (an original hydrogel) into a long-term MR contrast platform, cobalt ferrite (CoFe₂O₄) nanoparticles, which have hydrophobic surfaces, were bound to the original hydrogel via interactions between the hydrophobic surfaces of the nanoparticles and the _L-isoleucine ethyl esters of the polymer. The magnetic hydrogel showed extremely low cytotoxicity and adequate magnetic properties for use in long-term MR imaging, in addition to possessing the same properties of the original hydrogel, such as viscosity, thermosensitivity, biodegradability, biocompatibility, a reversible sol-to-gel phase transition near body temperature, and injectability. The magnetic hydrogel was injected into a rat brain using stereotactic surgery. After the injection, the applicable potentiality as a long-term MR contrast platform was successfully estimated over 4-5 weeks. Consequently, it was shown that a magnetic hydrogel as a long-term MR contrast platform has the potential to be applied in a long-term theranostic hydrogel system. Furthermore, it is expected that this platform can be useful in the clinical field of incurable diseases due to either surgical difficulties or lethality, such as with brain tumors, when the platform is combined with therapeutic drugs for long-term MR theragnosis in further studies.     

Engineering cell de-adhesion dynamics on thermoresponsive poly(N-isopropylacrylamide)

Poly(N-isopropylacrylamide) (PIPAAm) has been demonstrated as an effective thermoresponsive polymer for non-invasive cell regeneration/recovery. However, little is known about the intricate relationship between the biophysical response of cells and physiochemical properties of PIPAAm during cell recovery. In this study, the de-adhesion kinetics of smooth muscle cell (SMC) on PIPAAm surfaces is probed with unique biophysical techniques. Water-immersion atomic force microscope (AFM) first showed that the nanotopology of PIPAAm surfaces is dependent on the polymerization time and collagen coating. It is found that the initial rate of cell de-adhesion increases with the increase in polymerization time. Moreover, the degree of cell deformation (a/R) and average adhesion energy are reduced with the increase of grafted PIPAAm density during 40min of cell de-adhesion. It has been shown that collagen coating regulates cell adhesion on biomaterial surface. Interestingly, lower collagen density on PIPAAm leads to higher adhesion energy per cell during the initial 20min compared with as-prepared PIPAAm, while the initial rate of cell de-adhesion remains unchanged. In contrast, higher collagen density leads to 50% reduction in the initial rate of cell de-adhesion and higher adhesion energy per cell during the entire 90min. Furthermore, immunostaining of actin provides supporting evidence that the de-adhesion kinetics is correlated with the cytoskeleton transformation during cell de-adhesion below the lower solution critical temperature (LCST).     

Antibacterial and cell-adhesive polypeptide and poly(ethylene glycol) hydrogel as a potential scaffold for wound healing

The ideal wound-healing scaffold should provide the appropriate physical and mechanical properties to prevent secondary infection, as well as an excellent physiological environment to facilitate cell adhesion, proliferation and/or differentiation. Therefore, we developed a synthetic cell-adhesive polypeptide hydrogel with inherent antibacterial activity. A series of polypeptides, poly(Lys)_x(Ala)_y (x + y = 100), with varied hydrophobicity via metal-free ring-opening polymerization of NCA-Lys(Boc) and NCA-Ala monomers (NCA = N-carboxylic anhydride) mediated by hexamethyldisilazane (HMDS) were synthesized. These polypeptides were cross-linked with 6-arm polyethylene glycol (PEG)-amide succinimidyl glutarate (ASG) (M_w = 10 K) to form hydrogels with a gelation time of five minutes and a storage modulus (G′) of 1400-3000 Pa as characterized by rheometry. The hydrogel formed by cross-linking of poly(Lys)₆₀(Ala)₄₀ (5 wt.%) and 6-arm PEG-ASG (16 wt.%) (Gel-III) exhibited cell adhesion and cell proliferation activities superior to other polypeptide hydrogels. In addition, Gel-III displays significant antibacterial activity against Escherichia coli JM109 and Staphylococcus aureus ATCC25923. Thus, we have developed a novel, cell-adhesive hydrogel with inherent antibacterial activity as a potential scaffold for cutaneous wound healing.     

Adhesion strength of human tenocytes to extracellular matrix component-modified poly(DL-lactide-co-glycolide) substrates

We report a direct measurement of the adhesion strength of human embryonic tenocytes (HETCs) and transformed human embryonic tenocytes (THETCs) to fibronectin (FN)- and type I collagen (CNI)- modified poly(DL-lactide-co-glycolide) (PLGA) substrates with a micropipette aspiration technique. PLGA substrates were first coated with poly-D-lysine (PDL), and then with various concentrations (1 microg/ml, 2 microg/ml, 5 microg/ml, and 10 microg/ml) of FN and CNI in serum-free F12 media. Anti-FN and Anti-CNI antibodies were used to inhibit attachment of tenocytes to FN- and CNI- modified substrates in a dilution range of 1:5000-1:500 and 1:1500-1:250, respectively. The substrates were employed for incubation of HETCs and THETCs for 30 min at 37 degrees C before the adhesion strength measurements. We found that the adhesion strengths showed a strong dependence on the seeding time and FN or CNI concentrations. Anti-FN and Anti-CNI antibodies significantly compromised adhesion of HETCs and THETCs to the corresponding modified substrates (P < 0.05). These findings show that FN- or CNI-modified polymer substrates offer significant advantages for tissue engineering tendon scaffolds concerning tenocyte adhesion. In addition, HETCs and THETCs bear similar biological behaviors in terms of adhesion, indicating the possibility of using THETCs in place of HETCs in tissue engineering construction of human tendons.     

Poly(N-isopropylacrylamide)-based semi-interpenetrating polymer networks for tissue engineering applications. Effects of linear poly(acrylic acid) chains on rheology

Semi-interpenetrating polymer networks (semi-IPNs), comprised of poly(N-isopropylacrylamide-co-acrylic acid) (p(NIPAAm-co-AAc)) hydrogels and linear p(AAc) chains, were synthesized, and the effects of the p(AAc) chains on semi-IPN rheology were examined. Oscillatory shear rheometry studies were performed and the rheological data were analyzed as a function of temperature, frequency, and p(AAc) chain amount (weight average molecular weight (Mw) 4.5 x 10(5) g/mol). At 22 degrees C, the semi-IPNs, as well as control p(NIPAAm-co-AAc) hydrogels, demonstrated rheological data that were representative of soft, loosely cross-linked solids. Furthermore, only the highest p(AAc) chain amount tested affected the rigidity of the p(NIPAAm-co-AAc)-based semi-IPNs, as compared to the p(NIPAAm-co-AAc) hydrogels. At 37 degrees C, the complex shear moduli (G*) demonstrated by the p(NIPAAm-co-AAc)-based semi-IPNs were significantly greater than G* exhibited by the p(NIPAAm-co-AAc) hydrogels, and the semi-IPN G* values significantly increased with increasing p(AAc) chain amount. These results can be used to develop p(NIPAAm)-based semi-IPNs with tailored mechanical properties that may function as scaffolds in tissue engineering initiatives.