PLA nanofibrous bioactive scaffolds for cardiac tissue engineering

Journal Pre-proof Photoluminescent functionalized carbon quantum dots loaded electroactive Silk fibroin/PLA nanofibrous bioactive scaffolds for cardiac tissue engineering and nursing care application

Yuexia Ren, Xiaoyu Sun, Limin Jin, Xiaoli Liu, Huiling Chen, Kangjun Wang, Man Yu, Yonghui Zhao PII:

S1011-1344(19)31294-1

DOI:

https://doi.org/10.1016/j.jphotobiol.2019.111680

Reference:

JPB 111680

To appear in:

Journal of Photochemistry & Photobiology, B: Biology

Received date:

27 September 2019

Revised date:

23 October 2019

Accepted date:

30 October 2019

Please cite this article as: Y. Ren, X. Sun, L. Jin, et al., Photoluminescent functionalized carbon quantum dots loaded electroactive Silk fibroin/PLA nanofibrous bioactive scaffolds for cardiac tissue engineering and nursing care application, Journal of Photochemistry & Photobiology, B: Biology(2019), https://doi.org/10.1016/ j.jphotobiol.2019.111680

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

© 2019 Published by Elsevier.

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Photoluminescent functionalized carbon quantum dots loaded electroactive Silk

fibroin/PLA nanofibrous

bioactive scaffolds for cardiac

tissue

engineering and nursing care application

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Yuexia Ren1, Xiaoyu Sun1, Limin Jin2, Xiaoli Liu3 , Huiling Chen1 , Kangjun Wang4, Man

1

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Yu1,*, Yonghui Zhao 1,*

Department of Cardiology, Henan Provincial People's Hospital;

Department of Neurology, First Affiliated Hospital of Zhengzhou University. 3

Department of Laboratory, Henan Provincial People's Hospital.

Provincial Committee Health Care Room, the Second Outpatient Department,

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4

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2

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Fuwai Central Cardiovascular Hospital.

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Direct authority of Henan Province.

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Conflict of interest statement

The authors declare no conflict of interest *Author for correspondence: Dr. Man Yu, No. 1 Fuwai Avenue, Zhengdong New District, Zhengzhou 45000, China.

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Abstract Tissue engineering and stem cell rehabilitation are the hopeful aspects that are being investigated for the management of Myocardial Infarction (MI); cardiac patches have been used to start myocardial rejuvenation. In this study, we engineered p-phenylenediamine surface functionalized (modif-CQD) into the Silk fibroin/PLA (SF/PLA) nanofibrous bioactive scaffolds

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with improved physico-chemical abilities, mechanical and cytocompatibility to cardiomyocytes.

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The micrograph results visualized the morphological improved spherical modif-CQD have been The fabricated

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equivalently spread throughout the SF/PLA bioactive cardiac scaffolds.

CQD@SF/PLA nanofibrous bioactive scaffolds were highly porous with fully consistent pores;

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effectively improved young modulus and swelling asset for the suitability and effective

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implantation efficacy. The scaffolds were prepared with rat cardiomyocytes and cultured for up

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to 7 days, without electrical incentive. After 7 days of culture, the scaffold pores all over the construct volume were overflowing with cardiomyocytes. The metabolic activity and viability of

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the cardiomyocytes in CQD@SF/PLA scaffolds were significantly higher than cardiomyocytes

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in Silk fibroin /PLA scaffolds. The integration of CQD also influenced greatly and increases the expression of cardiac- marker genes. The results of the present investigations evidently recommended that well-organized cardiac nanofibrous scaffold with greater cardiac related mechanical abilities and biocompatibilities for cardiac tissue engineering and nursing care applications. Keywords: Scaffolds; Carbon Quantum Dots; Silk fibroin; PLA

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1. Introduction Stem cell transplantation and tissue engineering therapies have the possible to necessarily adjust the conservative therapy of Myocardial Infarction (MI) by inspiring the rejuvenation of injured myocardium[1]. The stem cell niche is exceptionally necessary for the differentiation of

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stem cells and tissue regeneration. Stem cell rehabilitation has shown excellent remedial outcomes for MI in several studies but remains scanty for patient-contact experience[2,3]. Earlier

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investigations adopted different sites of conveyance ways [4–6], such as intra- myocardial

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injection[6–8] and transendocardial injection[9], have exposed that in excess of 90% of the

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implanted stem cells underwent extermination in a week after cell conveyance. The poor

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survivability and lower retention of implanted stem cells are the most important problems to achieve the perfect remedial outcomes. The enhancement of implanted stem cell viability is a

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most significant problem in stem cell therapy[10].

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Fabricating stem cells on bio-designed tissue scaffolds can able to deal with the major

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problems that presently edge the of cardiac stem cell based therapy[11]. Several scaffolds have been maximized with regard their mechanical and physical aspects[12–18]. Electrical implanting polymers such as polyaniline and polypyrrole have been investigated[19], recently, attention has been increasing in carbon based materials for bio-medical usages including biosensors[20], nanovehicles for drug delivery and cell delivery agents[21–24]. While, the new element of the "nanoparticle world," Carbon Quantum Dots (CQD) have been widely characterized using various analytical techniques[25–28]. Moreover, since CQD show attractive optical properties and capable of conducting electricity, several studies have designed to reveal the mechanisms accountable for the photophysical phenomena connected with the carbon nanoparticles[29–31]. 3

Journal Pre-proof Fibroin is the water-soluble glue-like protein of silk fibers that combine the fibroin fibers together[32]. It has been demonstrated that silk fibroin has greater exceptionality, including striking mechanical properties, biocompatibility, humidity and oxyge n permeability, enhance proliferation of human skin fibroblasts and human keratinocytes[25,32]. In addition, silk fibroin can be used to make a gel, film, non-woven mats and porous material. Therefore, the silk fibroin has been prepared as a key material in the fields of drug delivery, biomaterials, and scaffolds for

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tissue engineering[33–35]. While, poly (L-lactic acid) (PLA), a Food and Drug Administration

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(FDA)-approved polymer, can be electrospun to fabricate arbitrary nanofiber scaffolds[36].

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The present study, an attempt has been made to construct an electroactive CQD

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incorporated SF/PLA nanofibrous bioactive scaffolds on the conveyance of cardiomyocytes for

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cardiac tissue engineering and nursing care application. We have successfully developed the SF/PLA nanofibrous bioactive scaffolds with vastly distributed and globular morphological

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surface properties of CQD to examin the effect of electroactive CQD incorporated SF/PLA

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nanofibrous bioactive scaffolds on the cardiomyocytes.

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2. Experimental procedures

2.1. Fabrication of electroactive CQD integrated Silk fibroin /PLA nanofibrous bioactive scaffolds All chemicals were analytical grade and purchased from Sigma-Aldrich. The electrochemical method was used for the synthesis of CQD. The electrolyte for the electrochemical development is combination ethanol/H2O (100ml; Volume ratio = 99.5: 0.5) with (0.2-0.4g) NaOH. CQD were synthesized by graphite rods (diameter about 0.5 cm) as together anode and cathode with a current intensity in the range of 100-200 mA cm -2 . In general, 4

Journal Pre-proof the rate of CQD fabrication is about 10mg per hour for each setting. CQD was separated by column chromatography. Thereafter, the raw CQD solution with MgSO 4 (5-7wt %), stirred for 20 minutes, then store for 24 hours to eradicate salt and water. Then, the purified CQD solution was separated by silica- gel column chromatography with an suitable developing solvent (a mixture of 1:1 petroleum ether: diethyl ether) The CQD loaded SF/PLA nanofibrous bioactive scaffolds was fabricated by the subsequent steps: Generally, 60wt% Silk fibroin (6 g; Aldrich-

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Sigma) and 30 wt% of PLA (3 g; Aldrich-Sigma) mix was primed by progressively totaling with

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a definite quantity of diluted hydrochloric acid (HCL, 0.1M) solution, which was stirred for 12 h

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in an oil bath at 100 °C and assorted into a glass apparatus.

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The CQD was supplemented in to the SF/PLA mix to fabricate different amount fractions

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from 0 to 2 wt%, as described earlier[20]. The electrical assets were investigated by a conductivity meter (High Resistance / Low Conductance Meter (HRLC), AlphaLab, USA),

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wherever it was exposed that there was an opposite relationship connecting CQD concentration

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and resistance; the 2 wt% sample had the lowest resistance with a value of 7x10 -6 Ω. More than 2 wt% the values began to plateau. As a product a 2 wt% CQD@Silk fibroin /PLA mix was

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prepared to electrospin the erratically adapted nanofiber scaffolds, by a voltage of15 kV and a feed rate of 0.05mL min1, with the collector screen is 15 cm from the syringe needle. While a technique of manage electrospun recovered adapted Silk fibroin /PLA nanofiber scaffolds were also synthesized not including CQD. The fairly accurate schematic illustration of scaffold development is given in the Fig.1.

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2.2. Analytical methods The spectral analysis methods of Shimadzu FTIR spectroscopic and Photoluminescence spectroscopic methods were used to evaluate the photoactive and surface interaction of CQD onto the natural polymers. The exterior morphological surface and microporous behaviors of

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CQD loaded SF/PLA nanofibrous bioactive scaffolds were studied under JSM 6460 LA JEOL

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SEM and Philips CM100 TEM micrograph techniques. For TEM study, fabricated fragments

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were equipped by dipping 10 µl of CQD@SF/PLA nanofibrous bioactive scaffolds diffusions coated on copper plates. The element size allocation of CQD nanoparticles were examined by

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using Malvern Zetasizer DLS. To measure the young's modulus of CQD nanofibrous bioactive

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scaffolds assembles, 100 µm thick distended scaffolds in PBS were examined by an atomic force

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2.3. Cell viability

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microscopy (AFM).

Cell proliferation and viability of fabricated scaffolds were performed as per the

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approved institutional ethical clearance and cell conducting procedures. The quantitative and qualitative analysis of cell experiments were evaluated by using 3-(4,5-Dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay and Confocal Laser Scanning Microscopy (CLSM) methods. The fabricated scaffolds were sterilized with UV light and ethanol for cell viability study and they had been immersed in PBS for 24 hrs. Scaffold presence and absence of CQD were put in 24 well plates and the H9C2 cell line in Dulbecco's modified eagle medium (DMEM) with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin were inoculated on the scaffold presence and absence of CQD, 6

Journal Pre-proof subsequently incubated at 37°C in 95% humidity and 5% CO 2 . At 1st, 3rd, 5th and 7th days, after that culture medium were discarded and culture plates with cells were washed with PBS; then, the MTT solution (5 mg/ml) was poured on the scaffold presence and absence of CQD/ cells changed the yellow tetrazole to purple formazan (4h at 37°C), followed by exclusion of the culture medium. The produced formazan crystals were dissolved by dropping 1 ml dimethyl sulfoxide (DMSO) and by shaking it in an orbital shaker for 20 min. after which the amount of

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absorbance of the formazan was calculated on a microplate reader (biokit, ELx800 READER,

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Spain) at 570 nm.

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2.4. Gene Expression. (Real time-qPCR).

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The gene expression levels of specific-cardiac markers: Troponin C Type 1 (Tnnc1);

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Troponin T Type 2 (Tnnt2); Connexin-43 (Cx43); Atrial natriuretic factor (Anf) and calcium transporting ATPase (Atp2a2) were examined by real- time quantitative PCR. Caridomyocytes

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of cardiac genes.

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from scaffolds were collected after 7 days of culture to estimate the expression of mRNA levels

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The RNA isolation and real-time PCR method was carried out as previously reported[37]. RNA was isolated by TRIzol reagent (Invitrogen, Life Technology) PrimescriptTM 1st Strand cDNA Synthesis Kit (TaKaRa, Dalian, China) was applied to reverse total RNA (1 µg) transcription to synthesize cDNA. Reverse transcription was achieved with a specific stem- loop real-time PCR miRNA kit (RiboBio, Guangzhou, China). Real time PCR process was achieved with SYBR® Premix Ex TaqTM II (Tli RNaseH Plus) (TaKaRa, Dalian, China) on a 7500 Fast Real Time PCR system (Applied Biosystems, Foster City, CA, USA). The expression levels of the genes were normalized to those of β-actin, 7

Journal Pre-proof which was employed as an internal control, and calculated using the standard 2-ΔΔCT method. The primers were listed in Table. 2.5. Statistical analysis Values were expressed as mean ± SE. Student's t-test was performed to detect significance in comparisons of two groups (n=5) of data. One-way analysis of variance followed by Tukey's

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post test was performed for inter group comparisons of more than three groups (n=5) of data. All

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data were repeated at least three times. All data were analyzed using Statistical Package for Social Sciences (SPSS-version 17.0) statistical software. The statistics were prepared by using

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Graph Pad Prism 5. Differences were considered statistically significant when P ≤ 0.05.

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3. Results and Discussion

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3.1. Analysis of Surface structure and Morphology The Photoluminescent excitations of CQD and p-phenylenediamine functionalized CQD

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in different wavelengths were evaluated by the PL spectroscopic technique as shown in Figure 1.

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The as-prepared CQD have high amount of COOH groups and its was functionalized with introduction of -NH2 (p-phenyldiamine) could be led to new avenues for the improving conjugation efficiency with biomolecules. The PL spectral results exhibited that each sample (CQD and Modif-CQD) have one strong PL peak and one optimal excitation wavelength, implying the most leading emission sites of CQD. The strong emission peaks were observed at around 425 and 465 for the CQD and Modif-CQD, respectively. The PL spectral data of the prepared samples have outstanding emission shift in different excitations, demonstrating that the redshift degree of CQD is highly proportional to the enhancement of the excitation wavelength. FTIR spectral results are exhibited the structural interactions of prepared CQD and SF/PLA 8

Journal Pre-proof molecules and distinguish the probable chemical modifications of the synthesized scaffolds. Fig. 2 shows the FTIR spectra of CQD, SF/PLA, and CQD@SF/PLA. Figure 2(a) shows the spectrum of the CQD, which implying that existence of C=O well-established band at the range of 1686 cm-1 , authenticating the occurrence of carboxylic groups onto the structure of functionalized CQD. The spectral data of prepared SF/PLA in the absence of CQD [Figure 2 (b)] exhibits multiple peaks of C-O stretching (1176 cm-1 ), C=O stretching (1649 cm-1 ) and C=C

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aromatic stretching (1449 cm-1 ), which confirms the multiple hydrogen binding and electrostatic

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interaction among the Silk fibroin and PLA molecules are chemically cross-linked. In addition,

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the characteristic hydrogen-bonded peaks of OH also presented at the range of ~3000 cm-1 . The

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FTIR spectrum of CQD@SF/PLA [Figure 2(c)] shows peaks are a little shifts to a lower wave numbers, because of interaction of CQD nanoparticles through functional groups of SF/PLA

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molecules; additional N-H winding peak at 1541 cm-1 and a C-N extending band at 1246 cm-1 ,

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also representing that new amide bonds were created among the carboxylic and amine groups. The electrostatic interactions and elemental compositions of the CQD embedded SF/PLA

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nanofibrous scaffolds was evaluated by XPS survey spectrum (Fig. 2b). The decreasing

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characteristic N1s peak of CQD@SF/PLA nanofibrous scaffolds was established that the successful interactions of QDs and PLA molecules into the silk proteins. To study the morphology structure of constructed bioactive scaffold, we scanned the inner structure of the prepared CQD and SF/PLA nanofibrous bioactive scaffold loaded with CQD via microscopic (TEM and SEM) examination. The presented superior nano morphology and size distributions of CQD (Fig. A & B) was refined by HR-TEM micrograph examination and also it exhibits evidently reporting of CQD in to the nanofibrous bioactive scaffold (Fig 3 (F)). The morphology structure exhibits the healthy prearranged PLA and SF/PLA scaffold 9

Journal Pre-proof structure in the absence of Carbon QDs that visualized an even and softly consistent with smooth and porous surface structure as shown in Fig. 3 (C & D). The prepared modif-CQD were accumulated equivalently into the surface of SF/PLA scaffold (Fig. 3 E & F), the microstructure showed more solid and healthy connection with the quantum dots without modulating its finetuned morphology of bio-scaffold. As revealed, the round structured CQD were dispersed in to the SF/PLA nanofibrous bioactive scaffold without troubling their original exterior morphology.

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The occurrence of CQD on the scaffold microstructure has been involved a significant role for

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the improvement of electroactive assets[38], physiological solidity and mechanical potency of

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the SF/PLA nanofibrous bioactive scaffold systems. SF was set up to encourage cell adhesion

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and increase type I collagen due to the elevated level of exterior area and a constructive setting for cells to attach[39]. Furthermore, the inclusion of CQD in the bioactive scaffold produced in

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enhanced cell proliferation and adhesion qualities than SF/PLA scaffold.

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3.2. Physical characterization of fabricated scaffolds

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Moreover, raising the ratio of prepared modif-CQD let to construct the bio-scaffolds as

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favorable mechanical properties for the cardiac tissue engineering and nursing care application. The physical characterizations of fabricated scaffolds are important factors to have an effect on nutrients and a gas exchange to the cell growth inside the cardiac assembles[40]. The consistent integration of CQD on to the SF/PLA nanofibrous bioactive scaffold system allow to amplify the young modulus value from the 466 to young modulus from 466 kPa to a highest value of 1610 kPa with correlated to the amount of CQD are revealed on Fig. 4 (A). The well- tuned structured CQD are to the highest degree strengthen with nanofibrous bioactive scaffolds greatly enhanced the mechanical constancy at the higher ratios (10 and 15 Wt% ) of CQD. As confirmed in Fig. 4 (B), incorporation of CQD at the higher ratios of CQD (10 and 15 Wt% ) into the SF/PLA 10

Journal Pre-proof scaffold matrix going to a significantly reduce the swelling ratio from 63 ± 6 % for SF/PLA scaffold to the lowest of near 24 ± 4% for the 10 and 15 Wt% of CQD@SF/PLA scaffolds. The swelling value decrease are correlated to the falling pore size of the CQD@Silk fibroin/ PLA scaffolds as comparable to the SF/PLA scaffolds in the lack of CQD, ultimately manage the water substance for the cardiac purpose. While incorporation of CQD to specified exceptional benefits in reduce pore size to encouraging for nutrient and gas exchanges into the

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CQD@SF/PLA scaffolds. The physical properties, for example swelling performance, porosity

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and compressive modulus of the CQD incorporated nanofibrous bioactive scaffold have been

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examined.

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3.3. Cell viability on CQD@SF/PLA nanofibrous bioactive scaffolds

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To estimate the suitability of CQD@SF/PLA scaffolds for the cardiac tissue engineering and nursing care application by H9C2 cell line. The adhesion of cardiomyocytes on the scaffolds

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and cell viability was studied as well as responsibility proportional examines by the SF/PLA

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scaffolds without CQD. The cell viability of CQD@SF/PLA nanofibrous bioactive scaffolds was

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expressively advanced than those on SF/PLA scaffolds (Fig. 5). The cell proliferations have visualized by CLSM microscopic images as exhibited in Figure 5 (A). Several studies have been carried out using scaffolds to study cell viability[41–46]. Since these studies have used different biomaterials and cells. Tomecka et al[36]. reported that polymeric nanofibers (poly (L- lactic acid) and polyurethane) are better substrates for cardiac cell culture than polystyrene surface and they enable cultivating these cells under conditions more similar to in vivo environment. The suitability of TiO2-PEG/CTS composite hydrogel for the fabrication of cardiac repairs by using neonatal rat cardiomyocytes and

cell viability have revealed that TiO2 nanoparticles are

promoted cell adhesion, elongation and spreading of cells and its given superior activity and 11

Journal Pre-proof favorable for cell attachment and compatibility comparable to the hydrogels without nanoparticles (Liu et al., 2018). The outcome of the present viability study has recommended to facilitate CQD are improved elongation and scattering of cells; cell adhesion and its agreed higher action and encouraging in favor of cell adhesion and suitability when compare to the scaffolds without CQD nanoparticles.

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3.4. Gene Expression (Real Time-qPCR)

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The mRNA expression levels of cardiac genes were tested for cardiomyocytes cultured in

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SF/PLA and CQD@SF/PLA scaffolds, to study the influence of CQD on the mRNA level of particular cardiac marker genes. All genes were increased mRNA expression in cells on

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CQD@SF/PLA scaffolds after 7 days of culture. Cardiomyocytes in the scaffolds communicate

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by electrical impulses in the course of gap junctions. This capability was improved through the occurrence of CQD nanoparticles in SF/PLA scaffolds, as confirmed via significantly higher

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mRNA expression of Cx43 (Essential for conduction of electrical signals) after 7 days (Figure

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6). The elevated Cx43 mRNA level, in the absence of electrical supply, recommends to the CQD

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influence physiology alone of probable corresponding property of the exterior electrical field. The higher mRNA expression also found in Tnnc1, Tnnc2, Anf, and Atpa2a genes subsequent to 7 days (Figure 6). Anf is a indicator of cardiomyocyte differentiation; a influential vasodilator [47]. The present study also the mRNA expression of Anf were significantly higher in rat cardiomyocytes after 7days. The mRNA expression and action of ATPase 2a has been examined to decline in cardiomyocytes in a failure heart, and the over expression Atpa2a can bring back the cardiac

function

in heart

failure by enhancing calcium management

in the

cardiomyocytes[48]. Significantly higher expression of ATP2a2 was found in CQD@SF/PLA scaffolds than control (SF/PLA scaffolds) after 7 days culture as exhibited in Figure 6. Martins et 12

Journal Pre-proof al[49]. demonstrated up regulation of Tnnc1 and Cx43 mRNA levels in chitosan/carbon/cell constructs after 7 days of culture and 14 days of culture. The myocardial matrix hydrogel on the CPC gene expression profile, quantitative PCR analysis was performed at days 4 and 7 post encapsulation and compared to the collagen hydrogel group and reported that a naturally derived, cardiac-specific hydrogel enhanced the cardiogenic marker genes when compared to a collagen gel[50]. Quantitative real time qPCR therefore authenticates that the incorporation of CQD in

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SF/PLA scaffolds improved the cardiogenic marker genes mRNA expression after 7 days, in the

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absence of exterior electrical supply revealed, these scaffolds may be an appropriate material for

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cardiac tissue engineering and nursing care applications.

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4. Conclusion

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In this study, we constructed CQD loaded SF/PLA nanofibrous bioactive scaffolds as a superior cardiac material to improve functional activity of cardiomyocytes. The fabricated CQD

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are equivalently scattered and estimably cross- linked on the exterior of SF/PLA scaffolds. The

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synthesized bioactive scaffolds have been showed enhanced compressive modulus and positive

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swelling values when compare to SF/PLA scaffolds in the lack of CQD. Mainly, the cell viability of cardiomyocytes on the CQD@SF/PLA scaffolds has improved comparable to lack of CQD. The outcomes of cardiac marker genes (Tnnc1, Tnnc2, Cx4, Anf, and Atpa2a) were increased on the CQD@SF/PLA scaffolds revealed more strong and improved activity as compared to the SF/PLA scaffolds. In conclusion, our data recognized that the CQD loaded SF/PLA scaffolds with estimable properties provide a appropriate material for cardiac tissue engineering and nursing care application.

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Figure captions and legends Scheme 1. Schematic diagram of CQD loaded SF/PLA nanofibrous bioactive scaffolds. Figure 1. Photoluminescent of CQD and modified CQD Figure 2. FT-IR spectra of (a) CQD nanoparticles, (b) SF/PLA and (c) CQD@SF/PLA samples;

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XPS survey spectra of (a) CQD nanoparticles, (b) SF/PLA and (c) CQD@SF/PLA samples.

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Figure 3. The morphology (SEM and TEM images) of synthesized SF/PLA (A) and CQD@SF/PLA (B & C) nanofibrous bioactive scaffolds under SEM. TEM images of

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synthesized SF/PLA (D) and CQD@SF/PLA (E & F) nanofibrous bioactive scaffolds [CQD

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nanoparticles (inserted image in C and F)].

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Figure 4. (A) Swelling ratio percentage and (B) Young modulus of CQD@SF/PLA nanofibrous bioactive scaffolds in the different weight percentages (%).

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Figure 5. In vitro fluorescence cell viability images and Quantified cell viability of the Silk

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fibroin/PLA in the presence and absence of CQD nanoparticles at 1,3,5 and 7 days of culture.

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Figure 6. mRNA transcript levels of cardiac genes (Tnnc1; Tnnt2; Cx43; Anf and Atp2a2) were tested for cardiomyocytes cultured in Silk fibroin/PLA and CQD@SF/PLA scaffolds after incubation at 37 °C in 95% humidity and 5% CO2 for 7 days.

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Scheme 1.

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Figure 1.

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Figure 2.

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Figure 3.

Figure 4.

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Figure 5.

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Figure 6.

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Title: Photoluminescent functionalized carbon quantum dots loaded electroactive Silk fibroin/PLA nanofibrous bioactive scaffolds for cardiac tissue engineering and nursing care application Highlights Constructed Modif-CQDs into the Silk fibroin/PLA nanofibrous bioactive scaffolds

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The scaffolds exhibited highly porous improved mechanical abilities.

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The cell viability and cardiomyocytes proliferation were significantly greater with

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The incorporated CQD nanoparticles scaffolds were enhances the expression of cardiac-

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marker genes.

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scaffolds.

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