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Comparative analysis of 3D-printed and freeze-dried biodegradable gelatin methacrylate/ poly‐ε‐caprolactone- polyethylene glycol-poly‐ε‐caprolactone (GelMA/PCL-PEG-PCL) hydrogels for bone applications

  • Roghayeh Khoeini , Leila Roshangar , Marziyeh Aghazadeh , Saeideh Soltani , Somaieh Soltani , Hossein Danafar , Rasoul Hosseinpour and Soodabeh Davaran EMAIL logo
Published/Copyright: November 4, 2024
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Journal of Polymer Engineering
From the journal Journal of Polymer Engineering Volume 44 Issue 10

Abstract

Gelatin methacrylate (GelMA) is a photo-cross-linkable biopolymer. A combination of GelMA with biodegradable polyesters such as PCL (poly‐ε‐caprolactone) and their triblock derivatives improve the mechanical properties of GelMA. PCL-PEG-PCL (PCEC) was synthesized using ring-opening polymerization of ε-caprolactone in the presence of polyethylene glycol (PEG). The GelMA- PCEC was fabricated using freeze-drying and 3D printing and their porosity, mechanical properties, and swelling behavior were investigated. Human dental pulp stem cells were cultured on the scaffolds for a period of 14 days and cell adhesion was evaluated by scanning electron microscopy. Cell viability was analyzed by MTT and osteogenic differentiation was evaluated by Alizarin red S. Results showed that the 3D-printed scaffold had higher water absorption rate, retaining its structure up to a strain of 0.2 %, and a higher Young’s modulus compared to the freeze-dried scaffold. In terms of cell viability, the 3D-printed scaffold outperformed the freeze-dried scaffold with a percentage of 86 % and 63 % viability respectively. Moreover, the 3D-printed scaffold exhibited better osteodifferentiation with calcium deposition. Overall, these findings suggest that the 3D-printed scaffold may have advantages over the freeze-dried scaffold in tissue engineering applications that require high water absorption, elasticity, and cell viability. The fabricated scaffolds provided suitable cell proliferation.

Keywords: tissue engineering; biomaterials; scaffold

1 Introduction

Cells, bioactive molecules, and scaffolds are used to regenerate and repair damaged tissue by stimulating the process of host tissue regeneration. 1 , 2 , 3 Hydrogels are biodegradable three-dimensional networks with hydrophilic chains and high water absorption capability that are extensively used in regenerative medicine and tissue engineering as scaffolds. 4 , 5 , 6 Their application in bone regeneration is frequently investigated for their bone biomimetic properties. 7 , 8 , 9 The GelMA-PCEC, to be fabricated as outlined in Scheme 1, is expected to demonstrate promising properties for bone applications.

Scheme 1: PCL-PEG-PCL (PCEC), which was synthesized in the presence of polyethylene glycol (PEG). The GelMA- PCEC was fabricated using freeze-drying and 3D printing.
Scheme 1:

PCL-PEG-PCL (PCEC), which was synthesized in the presence of polyethylene glycol (PEG). The GelMA- PCEC was fabricated using freeze-drying and 3D printing.

GelMA is a biomaterial that resembles the natural components in the extracellular matrix (ECM), which shows high biodegradability, biocompatibility, and cell adhesion. It also possesses lower RGD (Arg-Gly-Asp) motif-based antigenicity. 10 , 11 GelMA displays rapid enzymatic degradation properties and insufficient mechanical properties that limit its biomedical application. 12 , 13

Poly‐ε‐caprolactone (PCL) is a hydrophobic synthetic polymer polyester that is extensively used due to its mechanical strength, biocompatibility, and biodegradability. 14 , 15 PCL’s lengthy degradation time, hydrophobicity, and cell adhesion properties are usually modified by its combination with various bioactive materials such as polyethylene glycol (PEG). 16 , 17 , 18 , 19 , 20

The frequent reporting of the application of synthesis scaffolds in bone tissue engineering is evident in the academic literature. 21 , 22

GelMA/PCL-PEG-PCL is a novel polymer that has not been studied before. The fabrication of 3D-printed and freeze-dried scaffolds has usually been achieved by extrusion-based and air freeze-dried methods, respectively, while researchers have recently used 3D-printing methods to improve bone regeneration. 23 3D-printing methods, as a type of additive manufacturing technology, offer a mechanism for producing three-dimensional objects.

Various GelMA-based scaffolds have been fabricated for different applications, while the fabrication of GelMA-PCEC has not been reported until now. Also, the synthesizing of the PCEC using the ring opening method has not been reported elsewhere. In addition, the application of GelMA-PCEC in bone tissue engineering has not been reported yet. Further, the suitability of 3D printing for the GelMA-PCEC scaffolds has not been investigated.

In the current study, we reported the fabrication and characterization of GelMA-PCL (poly‐ε‐caprolactone) and GelMA-PCL-PEG-PCL (PCEC). GelMA-PCEC hydrogels scaffolds were prepared with two distinctive procedures. The triblock copolymer of PCEC has been utilized to improve the mechanical properties of GelMA. The structures of the scaffolds were determined by Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR spectroscopy. Dental pulp stem cells were utilized to assess their cell compatibility. The study, conducted at Tabriz University of Medical Sciences, adhered to the Code of Ethics and received ethical approval from the university’s ethics committee (Approval ID: IR.TBZMED.VCR.REC.1397.307).

2 Materials and methods

Gelatin (porcine skin, type A), toluidine blue and stannous 2-ethyl hexanoate (stannous octoate, Sn (Oct)2), methacrylic anhydride (MA), N-vinyl caprolactam (VC), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide), and EosinY were purchased from Sigma Aldrich (USA). ε-Caprolactone (ε-CL), PEG (Mw = 6,000), triethanolamine (TEA), Alizarin Red S, and solvents were purchased from Merck Inc. (USA). Dulbecco’s modified Eagle’s medium (DMEM), trypsin, EDTA, and fetal bovine serum (FBS) were purchased from Gibco (USA).

2.1 Synthesis of the scaffolds

2.1.1 PCL−PEG−PCL (PCEC) copolymer

The triblock copolymer of PCEC was synthesized through the process of ε-caprolactone ring-opening polymerization facilitated by PEG6000 and employing stannous octoate (Sn (Oct)2) as a catalyst. 24 , 25 In a round bottom flask containing three necks, 1 g of PEG6000 was heated to 90 °C for 20 min. Subsequently, 2 mL of ε-CL and 2 mL of Sn (Oct)2 (1 % w/w) were added to the flask. When the reaction temperature was increased to 130 °C, the reaction mixture was stirred for 10 h under a nitrogen atmosphere. The reaction product was dissolved in dichloromethane. Cold diethyl ether was added to the obtained dichloromethane up to the amount that precipitation occurred.

2.1.2 Methacrylate gelatin (GelMA)

Ten gram of gelatin was dissolved in 100 mL of phosphate-buffered saline (PBS) at 50 °C and heated at 50 °C under intensive stirring. Then 8 mL of methacrylic anhydride (MA) was added to the mixture, and the solution was stirred for 3 h at 50 °C. The solution was then diluted with pre-warmed PBS and dialyzed using a dialysis membrane (MWCO = 12–14 kDa) against distilled water at 40 °C for 7 days, and then lyophilized by freeze-drying. 23 , 26

2.2 Fabrication of GelMA-PCEC scaffolds

To prepare GelMA hydrogel, 12.5 % (w/v) of GelMA solution was dissolved in PBS including 1.25 % (w/v) VC and 1.875 % (w/v) TEA at 40 °C. 0.5 mM EosinY was dissolved in fresh PBS and 2 μL of the solution was added to 8 μL of GelMA solution. Then 10 % (w/w) of PCEC was dissolved in 70 % ethanol and added to the GelMA solution. After mixing, the solution was placed in a petri dish, followed by exposure under blue-green light in the 450–550 nm range for 15 min to carry out the hydrogel crosslinking process. Ultimately, the synthesized scaffolds are lyophilized by freeze-drying. Another technique used to prepare the scaffolds was the extrusion-based 3D-printing system. The scaffold was printed using an extrusion-based 3D printing system equipped with two nozzles with a diameter of 3.8 mm and 0.4 mm. In this process, the GelMA hydrogel is first placed in a printer syringe and illuminated with turquoise light during 3D printing until crosslinking is complete. GelMA scaffolds were printed with a nozzle diameter of 3.8 mm, a temperature of 18 °C, a pressure of 150 kPa and a deposition rate of 300 %. After GelMA printing, the PCEC copolymer was printed onto a 3D-printed GelMA scaffold. The PCEC scaffold was printed with a 0.4 mm nozzle diameter, 80 °C temperature, 180 kPa pressure and 200 % deposition rate. The GelMA layer was then reprinted onto the PCEC layer according to the above procedure. Finally, 10 mm × 10 mm × 5 mm printed frames were prepared for in vitro studies. The GelMA-PCEC scaffold was fabricated in three layers to ensure overlapping layers. The top and bottom layers are GelMA hydrogels, and the middle layers are PCEC triple block copolymers. 27

2.3 Characterization

2.3.1 FTIR

FTIR spectra were recorded on a FTIR spectrometer (BRUKER, Tensor27, Germany). The samples were mixed with potassium bromide (KBr) and FTIR spectra utilizing the KBr Pellet Method were recorded in the wavenumber range of 400 and 4,000 cm−1.

2.3.2 1H-NMR analysis

Before 1H-NMR measurement, GelMA-PCEC samples were dissolved in deuterium oxide at 40 mg/mL. After that, 1H-NMR was performed with a Bruker Avance 400 spectrometer with a single-axis gradient inverse probe at 37 °C.

2.3.3 Water absorption capacity

The investigation of swelling behavior is an important factor and this property influences the absorption of body fluids, nutrients, metabolites diffusion, and cell penetration right into scaffolds, which supports better cell adhesion. To study the swelling behavior the weights of the scaffolds were measured in a completely dry state (Wd). The scaffolds were placed in PBS at pH 7.4 at 37 °C for various lengths of time (0, 3, 24, 48, 72, 96, 120, and 144 h). At certain time points mentioned above, the scaffolds were taken out of the PBS, the filter paper removed the absorbed surface water, and the weight of the scaffolds was measured (Ww) and then the swelling ratio was then calculated by Equation (1). 28 , 29

(1) Swelling ratio = ( W w − W d ) / W d

2.3.4 Scanning electron microscope (SEM) analysis

SEM (MIRA3 FEG-SEM, Czech) was used for the study of freeze-dried and 3D-printed GelMA-PCEC scaffolds before and after cell seeding. The fabricated scaffolds were seeded with hDPSCs to investigate cell adhesion. After 14 days of cell culture, scaffolds containing cells were washed two times with PBS, then fixed in 2.5 % glutaraldehyde for 30 min, dehydrated in 70 % ethanol for 2 s, and then qualitative assessment using SEM was carried out after coating by gold sputtering.

2.3.5 Mechanical characterization

A tensile test was done to assess the mechanical properties of scaffolds using a universal testing machine (AI-7000-L5, Gotech Testing Machine Inc., Taiwan). At room temperature, samples with 10 mm × 10 mm × 5 mm dimensions were placed inside the plate with a tensile test speed of 5 mm/min. The modulus was calculated from the initial linear slope of the stress-strain curve. 30 , 31 , 32

2.4 Cell culture studies

The scaffolds without cells were immersed in a 70 % ethanol solution for 2 s and washed three times with PBS and then the fabricated scaffolds were sterilized under UV light for 24 h. Before cell seeding, the scaffolds were immersed in DMEM for 4 days at 37 °C. 3D-printed and freeze-dried scaffolds were positioned individually into 2 plates of 12-well dishes and human dental pulp stem cells (hDPSCs) were seeded in well plates containing DMEM and 10 % fetal bovine serum (FBS). After 72 h, the scaffold media was replaced with an osteogenic differentiation medium for cell differentiation studies. The osteogenic media containing 100 units of penicillin/streptomycin and DMEM/F12 supplemented with 10 % FBS and 50 μg/mL ascorbic acid, 10 mM β-glycerophosphate, 10–7 M dexamethasone and were afterward placed in a humidified incubator at 37 °C with 5 % CO2. 33 The osteogenic differentiation medium was changed every 3 days.

2.4.1 Cell proliferation analysis by MTT assay

Human dental pulp stem cells with 86 % confluency were detached from the cell culture flask using trypsin (0.05 % trypsin with 1 mM EDTA). Cells were seeded at a density of 3 × 104 cells per scaffold. Culturing studies were carried out in triplicate for each scaffold. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to examine cell proliferation. In this test, the mitochondrial dehydrogenase activity of viable cells was revealed by spectrophotometry. At predetermined times, the primary medium was removed and 450 μL of fresh DMEM medium and 150 μL of MTT solution (2 mg/mL in DMEM) were added to each well and incubated at 37 °C for 4 h. After that, the MTT and DMEM mediums were removed, and 200 μL of dimethyl sulfoxide (DMSO) was added to each well. The MTT was decreased by normally metabolizing cells’ mitochondrial dehydrogenase and DMSO was added into each well to dissolve the formazan crystals, generating a purple color that showed high optical density at 570 nm and was measured using an ELISA reader (Awareness Technologies Stat Fax 2100 Microplate Reader).

2.4.2 Alizarin Red S assay

Alizarin Red S is utilized to determine the presence of calcific deposition in osteogenic lineage cells. Alizarin Red S forms a complex in the extracellular matrix with Ca2+, leading to the display of bright orange-red stains. 34 Scaffolds containing cells were washed twice with PBS and fixed with ice-cold 70 % ethanol at room temperature for 1 h. After that, the scaffolds were stained with an Alizarin Red S solution (40 mmol L−1, pH = 4.2) at room temperature for 20 min. The scaffolds were rinsed with deionized water three times at room temperature to observe calcium deposition and subjected to cetylpyridinium chloride 10 % (w.v−1) for 30 min. Ultimately, the absorbance of the solution was measured at 540 nm on a Victor 3TMV (PerkinElmer).

2.5 Statistical analysis

The t-test and One-way ANOVA were used to compare the different groups. For statistical significance, P < 0.05 was considered. All experiments were performed in triplicate in three independent experiments.

3 Results and discussion

This research study involved the fabrication of gelatin methacrylate and polycaprolactone-polyethylene glycol-polycaprolactone (GelMA-PCEC) composites. GelMA hydrogel is prepared from the reaction of methacrylate units present in GelMA chains and this photochemical reaction is activated by EosinY when it absorbs blue-green light between 450 and 550 nm. It has lately been described that blue-green light is much safer than UV ranges and the Irgacure 2,959. 35

3.1 Morphology

The freeze-dried scaffold exhibited a dense structure with a flat surface, less thickness, and a puffy state, as shown in Figure 1A. On the other hand, the 3D-printed scaffold possessed larger holes and greater thickness (Figure 1B). The porosity of the hydrogel is a critical factor in its interaction with cells and tissues, and the 3D-printed scaffold exhibited higher porosity than the freeze-dried scaffold.

Figure 1: GelMA-PCEC composite scaffold in this study: (A) GelMA-PCEC freeze-dried; (B) extrusion-based 3D-printing scaffolds of GelMA-PCEC; (C) SEM image of freeze-dried scaffold without seeded cells; (D) SEM image of 3D-printed scaffold without seeded cells.
Figure 1:

GelMA-PCEC composite scaffold in this study: (A) GelMA-PCEC freeze-dried; (B) extrusion-based 3D-printing scaffolds of GelMA-PCEC; (C) SEM image of freeze-dried scaffold without seeded cells; (D) SEM image of 3D-printed scaffold without seeded cells.

To evaluate the scaffold’s structural characteristics such as pore size, shape, and surface morphology the SEM images were obtained (Figure 1C and D) and analyzed. The pore size of the designed scaffolds was suitable for cell adhesion and proliferation. Additionally, both scaffolds possessed suitable size distributions, which are crucial for their effectiveness in promoting tissue regeneration.

3.2 Molecular structure

FTIR analysis provides details regarding functional groups in the structure of molecules. The FTIR spectra recorded for the obtained samples are presented in Figure 2. The absorption bands in 1,100 cm−1 and 1,417.41 cm−1 are related to C–O–C tensile vibration and C–O–C asymmetric tensile vibration of PEG polymer, respectively. The peak at 1,570.36 cm−1 is associated with the carboxylic ester (C=O) group of PCL polymer. The characteristic absorption bands of the functional group from the gelatin methacrylate at 3,448 cm−1 demonstrate a peak related to the tensile vibrations of the OH groups. 36 The 3,200 to 3,400 cm−1 bands are associated with the presence of NH tensile vibration and likewise, in the area of 3,000 cm−1 is the relevant presence of CH tensile vibration of GelMA hydrogel. Peaks 1,625 cm−1, 1,571.44 cm−1 and 1,417.73 cm−1, respectively, correspond to the presence of the C=O stretching, N–H bending, and C–N stretching plus N–H bending of GelMA hydrogel. 37 , 38 The analysis results indicate the effective formation of the GelMA-PCEC composite (in Figure 2).

Figure 2: FTIR spectra of the GelMA-PCEC composite.
Figure 2:

FTIR spectra of the GelMA-PCEC composite.

The structure of the GelMA-PCEC composite was confirmed using 1H-NMR analysis and Figure 3 reveals the GelMA-PCEC composite 1H-NMR spectra.

Figure 3: 1H-NMR spectra of the GelMA-PCEC composite.
Figure 3:

1H-NMR spectra of the GelMA-PCEC composite.

Peaks associated with methylene groups of PCL were observed in the areas of 1.25, 1.5, 2.35, 4.18 ppm. Peaks of the methylene groups of PEG appeared in the 3.68 ppm area. Peaks in area, 2 ppm and 5.5 ppm belong to CH3–C=CH2 and =CH2 groups of GelMA.

3.3 Swelling

The swelling behavior of the fabricated scaffolds was evaluated over a period of 144 h, and the results are presented in Figure 4. Both scaffolds exhibited an increase in swelling over time. The swelling ratio of the freeze-dried scaffold increased from 4.5 to 13.5, while that of the 3D printed scaffold increased from 9 to 24.5.

Figure 4: Swelling behavior of the scaffolds in PBS.
Figure 4:

Swelling behavior of the scaffolds in PBS.

The freeze-dried scaffold had a lower swelling capacity, which may be attributed to its smaller pore size and dense structure. In contrast, the 3D-printed scaffold absorbed water at a rate 1.82 times higher than the freeze-dried scaffold, likely due to its larger pore size and three-dimensional structure. On the other hand, the high porosity and network structure in the 3D-printed scaffold resulted in more significant swelling than the freeze-dried scaffold (Figure 4).

3.4 Mechanical properties

The scaffold’s mechanical properties were evaluated through a tensile test, 39 and the results are illustrated in Figure 5. The Young’s modulus of the scaffolds was determined from the stress–strain curves. The results indicated that, at a 0.2 % strain for several min, the 3D-printed scaffold maintained its structure. However, when the strain intensity or time increased (0.0201626 MP), the structure of the 3D-printed scaffold was compromised. The Young’s modulus of the 3D-printed and freeze-dried scaffolds was 0.0224 and 0.0049, respectively.

Figure 5: Stress–strain curves of GelMA-PCEC 3D-printed and freeze-dried scaffolds.
Figure 5:

Stress–strain curves of GelMA-PCEC 3D-printed and freeze-dried scaffolds.

As strain accumulated, both scaffolds experienced a reduction in their strength. However, the 3D-printed scaffold exhibited higher resistance than the freeze-dried scaffold. It is worth noting that the mechanical properties of hydrogels depend on the concentration of polymer, initiator, and the amount of exposure to blue–green light. The results of the mechanical test demonstrated that the 3D-printed scaffold had a higher Young’s modulus compared to the freeze-dried scaffold (Figure 5).

3.5 Cell adhesion and proliferation study

HDPSCs were seeded onto GelMA-PCEC 3D-printed and freeze-dried scaffolds and cell proliferation was evaluated after 3, 7, and 14 days. The MTT assay was used to measure cell proliferation in scaffolds (Figure 6). 3D-printed Scaffolds possessed enhanced proliferation of hDPSCs compared to the control group. The cell viability in 3D-printed scaffolds was 86 % and in freeze-dried scaffolds was 63 %. As Figure 6 shows, cells viability was much higher on day 14 than day 7 for both scaffolds.

Figure 6: In vitro cytotoxic effects of the GelMA-PCEC scaffolds on hDPSCs.
Figure 6:

In vitro cytotoxic effects of the GelMA-PCEC scaffolds on hDPSCs.

The obtained results could be due to the 3D-printed scaffolds' network structure and better porosity, which trigger higher cell proliferation. 40 , 41

3.6 SEM analysis of cell seeded scaffolds

Cell adhesion was evaluated using SEM images after 14 days. The results were shown in Figure 7. HDPSCs presented high adhesion in 3D-printed and freeze-dried scaffolds. However, in the GelMA-PCEC freeze-dried scaffold, the cells were located only on the surface of the scaffold (Figure 7B). Such results could be arised from the higher porosity of 3D-printed scaffolds (Figure 7A) while lower adhesion to the freeze-dried scaffold could be a result of the insufficient porosity.

Figure 7: SEM images of hDPSCs seeded on the (A) GelMA-PCEC 3D-printed scaffold, and also (B) GelMA-PCEC freeze-dried scaffold.
Figure 7:

SEM images of hDPSCs seeded on the (A) GelMA-PCEC 3D-printed scaffold, and also (B) GelMA-PCEC freeze-dried scaffold.

3.7 Osteoclast differentiation

Scaffolds containing hDPSCs were treated with the bone differentiation medium and cultured for 14 days. The medium was renewed every three days. To evaluate the osteoblastic differentiation of hDPSCs on 3D-printed and freeze-dried scaffolds, Alizarin Red S was performed as a late indicator of osteogenesis. After 14 days of cell culture, the intensity of Alizarin Red S in the 3D-printed scaffolds was higher than the freeze-dried scaffolds and formed a compact calcified matrix with calcium deposits confirmed by specific alizarin red staining (Figure 8).

Figure 8: Representative images of Alizarin Red S for hDPSCs cultured with: (A) GelMA-PCEC 3D-printed scaffold on days 14 and (B) GelMA-PCEC freeze-dried scaffold on days 14.
Figure 8:

Representative images of Alizarin Red S for hDPSCs cultured with: (A) GelMA-PCEC 3D-printed scaffold on days 14 and (B) GelMA-PCEC freeze-dried scaffold on days 14.

Average absorbance values for osteodifferentiation in freeze-dried and 3D-printed scaffolds were 0.58 ± 0.02 and 0.74 ± 0.02, respectively (Figure 9). The results show that the amount of calcium deposition on the 3D-printed scaffold (Figure 8A) is higher than that on the freeze-dried scaffold (Figure 8B) and consequently, the 3D-printed scaffolds have a higher capacity for promoting osteogenic differentiation than the freeze-dried scaffolds.

Figure 9: Quantitative results of calcium deposits in GelMA-PCEC 3D-printed and freeze-dried scaffolds.
Figure 9:

Quantitative results of calcium deposits in GelMA-PCEC 3D-printed and freeze-dried scaffolds.

According to the results the cell viability in the GelMA-PCEC composite was significantly enhanced on days 14 compared to days 7 and 3 post-seeding (Figure 6). Calcium deposition in Alizarin Red S test results confirmed the differentiation of hDPSCs cells right into the bone. Figures 8 and 9 demonstrate that both scaffolds were effective in promoting differentiation. However, there was a significant difference in the amount of ossification observed between the two scaffolds, with the 3D-printed scaffold exhibiting a greater degree of ossification compared to the freeze-dried scaffold.

Its known that the UV light photons cause radical formation in methacrylate groups which quickly combine in their vicinity, leading to a crosslinked network. To avoid this, we used EosinY in combination with visible light (400 nm < λ < 700 nm) as an alternative UV photoinitiation. After exiting EosinY from the base state to the triplet state, blue-green light leads to separates hydrogen from TEA amine functional initiators. Lastly, deprotonated TEA radicals form the radical center on the GelMA methacrylate groups. 42 Visible light polymerization requires VC monomers to produce sufficient radicals and accelerate the gelation process. In this study, we assessed the swelling effect of GelMA-PCEC hydrogel on both freeze-dried scaffolds and 3D-printed scaffolds.

Methacrylated gelatin (GelMA) has been widely used as a tissue-engineered scaffold material, However, exclusively low-concentration GelMA hydrogels were found to be promising cell-laden bioinks with excellent cell viability. 21 , 43 , 44 3D printed hybrid scaffolds were fabricated utilizing PCL and GelMA was shown to support osteoinductivity, while the PCL provided the mechanical strength required to mimic the bone tissue. 45 Our design and fabrication of GelMA/PCEC extensively extend the applications of GelMA hydrogels for bone regeneration, in which GelMA improves cell viability and PCL increases strength.

4 Conclusions

Current study involved the fabrication of a novel polymer material “GelMA-PCEC” using freeze-drying and 3D printing techniques. The obtained results highlighted the potential of GelMA-PCEC for bone regeneration. GelMA-PCEC scaffolds were prepared by visibile light assisted crosslinking of GelMA hydrogel. Insite polymerization and crosslinking using visible light of GelMA hydrogel, make it suitable for lithography-based platforms.

The obtained hydrogels were freeze-dried or 3D-printed and the results indicated that both scaffolds possessed suitable mechanical properties while the 3D-printed scaffolds showed a three-dimensional network structure, which improved the proliferation and growth of hDPSCs cells.

Corresponding author: Soodabeh Davaran, Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, 1476651664 Tabriz, Iran; and Drug Applied Research Center, Tabriz University of Medical Sciences, 5165665811 Tabriz, Iran, E-mail:

Funding source: Iran National Science Foundation

Award Identifier / Grant number: 940002

Acknowledgments

This report is based on the database from a PhD thesis registered at Tabriz University of Medical Sciences (registration number 60992).

  1. Research ethics: The study, conducted at Tabriz University of Medical Sciences, adhered to the Code of Ethics and received ethical approval from the university’s ethics committee (Approval ID: IR.TBZMED.VCR.REC.1397.307).

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: Roghayeh Khoeini, Leila Roshangar, Marziyeh Aghazadeh, Saeideh Soltani, Somaieh Soltani, Hossein Danafar, Rasoul Hosseinpour, Soodabeh Davaran “The authors have accepted responsibility for the entire content of this manuscript and approved its submission.”

  4. Use of Large Language Models, AI and Machine Learning Tools: The authors of this manuscript, hereby declare that no large language models, artificial intelligence (AI), or machine learning tools were used in the creation of this work.

  5. Conflict of interest: All other authors state no conflict of interest.

  6. Research funding: The present study has received support in the form of funding from the Iran National Science Foundation (INSF), covered by grant number 940002.

  7. Data availability: The raw data can be obtained on request from thecorresponding author.

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Received: 2024-03-27
Accepted: 2024-09-04
Published Online: 2024-11-04
Published in Print: 2024-11-26

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Material Properties
  3. Effect of epoxidized soybean oil on melting behavior of poly(l-lactic acid) and poly(d-lactic acid) blends after isothermal crystallization
  4. An experimental investigation on the influence of pore foaming agent particle size on cell morphology, hydrophobicity, and acoustic performance of open cell poly (vinylidene fluoride) polymeric foams
  5. Reinforcement of recycled polypropylene by nano lanthana with improved thermal, mechanical and antimicrobial properties
  6. Microstructure-mechanical property relationships of polymer nanocomposite reinforced with lyophilized montmorillonite/carbon nanotubes hybrid particles
  7. Preparation and Assembly
  8. Preparation and dynamic simulation of a hemin reversible associated copolymer with self-healing properties
  9. Molecularly imprinted polymer for the selective removal of direct violet 51 from wastewater: synthesis, characterization, and environmental applications
  10. Engineering and Processing
  11. Comparative analysis of 3D-printed and freeze-dried biodegradable gelatin methacrylate/ poly‐ε‐caprolactone- polyethylene glycol-poly‐ε‐caprolactone (GelMA/PCL-PEG-PCL) hydrogels for bone applications
  12. Thermally conductive and electrically insulated DGEBA-epoxy nano-composite fabricated by integrating GO/h-BN and rGO/h-BN hybrid for thermal management applications: a comparative analysis
https://doi.org/10.1515/polyeng-2024-0063
Keywords for this article
tissue engineering; biomaterials; scaffold

Articles in the same Issue

  1. Frontmatter
  2. Material Properties
  3. Effect of epoxidized soybean oil on melting behavior of poly(l-lactic acid) and poly(d-lactic acid) blends after isothermal crystallization
  4. An experimental investigation on the influence of pore foaming agent particle size on cell morphology, hydrophobicity, and acoustic performance of open cell poly (vinylidene fluoride) polymeric foams
  5. Reinforcement of recycled polypropylene by nano lanthana with improved thermal, mechanical and antimicrobial properties
  6. Microstructure-mechanical property relationships of polymer nanocomposite reinforced with lyophilized montmorillonite/carbon nanotubes hybrid particles
  7. Preparation and Assembly
  8. Preparation and dynamic simulation of a hemin reversible associated copolymer with self-healing properties
  9. Molecularly imprinted polymer for the selective removal of direct violet 51 from wastewater: synthesis, characterization, and environmental applications
  10. Engineering and Processing
  11. Comparative analysis of 3D-printed and freeze-dried biodegradable gelatin methacrylate/ poly‐ε‐caprolactone- polyethylene glycol-poly‐ε‐caprolactone (GelMA/PCL-PEG-PCL) hydrogels for bone applications
  12. Thermally conductive and electrically insulated DGEBA-epoxy nano-composite fabricated by integrating GO/h-BN and rGO/h-BN hybrid for thermal management applications: a comparative analysis
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