Biocompatibility and sub-chronic toxicity studies of phlorotannin/polycaprolactone coated trachea tube for advancing medical device applications.

The phlorotannin-polycaprolactone-coated endotracheal tube (PP tube) has been developed with the aim of preventing tracheal stenosis that can result from endotracheal intubation, a factor that can lead to a serious airway obstruction. Its preventive efficacy has been assessed through both in vitro and in vivo investigations. However, there is a lack of studies concerning its biocompatibility and sub-chronic toxicity in animal models, a crucial factor to ensure the safety of its usage as a functional endotracheal tube. Thus, this study aimed to evaluate the biocompatibility and sub-chronic (13 weeks) toxicity of the PP tube through L929 cell line and diverse in vivo models. The cytotoxicity testing was performed using the extracts of PP tube on L929 cells for 72 h. Furthermore, other tests conducted on animal models, including ICR mice (acute systemic toxicity), New Zealand white rabbit (intradermal reactivity and pyrogen tests), guinea pig (maximization sensitization), and Sprague Dawley rats (sub-chronic toxicity). In both biocompatibility and sub-chronic toxicity analyses, no significant adverse effects are observed in the groups exposed to the PP tube, when compared to control group. Altogether, the findings suggested that the PP tube exhibits relative non-toxic and safety, supporting its suitability for clinical usage. However, extended periods of intubation may produce mild irritant responses, highlighting the clinical caution of limiting intubation duration to less than 13 weeks.

A literature review of bioactive substances for the treatment of periodontitis: In vitro, in vivo and clinical studies.

Periodontitis is a common chronic inflammatory disease of the supporting tissues of the tooth that involves a complex interaction of microorganisms and various cell lines around the infected site. To prevent and treat this disease, several options are available, such as scaling, root planning, antibiotic treatment, and dental surgeries, depending on the stage of the disease. However, these treatments can have various side effects, including additional inflammatory responses, chronic wounds, and the need for secondary surgery. Consequently, numerous studies have focused on developing new therapeutic agents for more effective periodontitis treatment. This review explores the latest trends in bioactive substances with therapeutic effects for periodontitis using various search engines. Therefore, this study aimed to suggest effective directions for therapeutic approaches. Additionally, we provide a summary of the current applications and underlying mechanisms of bioactive substances, which can serve as a reference for the development of periodontitis treatments.

Poly(vinyl alcohol)/chitosan hydrogel incorporating chitooligosaccharide-gentisic acid conjugate with antioxidant and antibacterial properties as a potential wound dressing.

The design and development of wound dressing with antioxidant and antibacterial properties to accelerate wound healing remain challenging. In this study, we synthesize a chitooligosaccharide-gentisic acid (COS-GSA) conjugate using the free-radical grafting method, and fabricate a poly(vinyl alcohol) (PVA)/chitosan (CH)/COS-GSA (PVA/CH/CG) hydrogel using a freeze-thaw method. We characterize the synthesized COS-GSA conjugates using through polyphenol assay, absorbance, and 1H NMR spectroscopy and evaluate their antioxidant properties. The COS-GSA conjugates are successfully synthesized and exhibit better antioxidant properties than pristine COSs. Subsequently, the fabricated hydrogel is characterized based on its morphological analysis, rheological properties, water contact angle, swelling, degradation, water retention properties, and COS-GSA release profiles. Finally, the biocompatibility of the fabricated hydrogel is evaluated on HDF and HaCaT cells through indirect and direct cytotoxicity. The PVA/CH/CG hydrogel exhibited significantly higher antioxidant properties (DPPH, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydrogen peroxide (H2O2) scavenging activities) and antibacterial activities (Staphylococcus aureus and Pseudomonas aeruginosa) compared to other fabricated hydrogels such as PVA, PVA/CH, and PVA/CH/COS (PVA/CH/C). These results provide evidence that PVA/CH/CG hydrogels with antioxidant, antibacterial, and non-cytotoxic properties have great potential for wound-dressing applications.

Structure-Based In Silico Screening of Marine Phlorotannins for Potential Walrus Calicivirus Inhibitor.

A new calicivirus isolated from a walrus was reported in 2004. Since unknown marine mammalian zoonotic viruses could pose great risks to human health, this study aimed to develop therapeutic countermeasures to quell any potential outbreak of a pandemic caused by this virus. We first generated a 3D model of the walrus calicivirus capsid protein and identified compounds from marine natural products, especially phlorotannins, as potential walrus calicivirus inhibitors. A 3D model of the target protein was generated using homology modeling based on two publicly available template sequences. The sequence of the capsid protein exhibited 31.3% identity and 42.7% similarity with the reference templates. The accuracy and reliability of the predicted residues were validated via Ramachandran plotting. Molecular docking simulations were performed between the capsid protein 3D model and 17 phlorotannins. Among them, five phlorotannins demonstrated markedly stable docking profiles; in particular, 2,7-phloroglucinol-6,6-bieckol showed favorable structural integrity and stability during molecular dynamics simulations. The results indicate that the phlorotannins are promising walrus calicivirus inhibitors. Overall, the study findings showcase the rapid turnaround of in silico-based drug discovery approaches, providing useful insights for developing potential therapies against novel pathogenic viruses, especially when the 3D structures of the viruses remain experimentally unknown.

Purification and Molecular Docking Study on the Angiotensin I-Converting Enzyme (ACE)-Inhibitory Peptide Isolated from Hydrolysates of the Deep-Sea Mussel Gigantidas vrijenhoeki.

The objective of this study was to prepare an angiotensin I-converting enzyme (ACE)-inhibitory peptide from the hydrothermal vent mussel, Gigantidas vrijenhoeki. The G. vrijenhoeki protein was hydrolyzed by various hydrolytic enzymes. The peptic hydrolysate exhibited the highest ACE-inhibitory activity and was fractionated into four molecular weight ranges by ultrafiltration. The <1 kDa fraction exhibited the highest ACE inhibitory activity and was found to have 11 peptide sequences. Among the analyzed peptides, KLLWNGKM exhibited stronger ACE inhibitory activity and an IC50 value of 0.007 µM. To investigate the ACE-inhibitory activity of the analyzed peptides, a molecular docking study was performed. KLLWNGKM exhibited the highest binding energy (-1317.01 kcal/mol), which was mainly attributed to the formation of hydrogen bonds with the ACE active pockets, zinc-binding motif, and zinc ion. These results indicate that G. vrijenhoeki-derived peptides can serve as nutritional and pharmacological candidates for controlling blood pressure.

Anti-inflammatory effect of polydeoxyribonucleotides (PDRN) extracted from red alga (Porphyra sp.) (Ps-PDRN) in RAW 264.7 macrophages stimulated with Escherichia coli lipopolysaccharides: A comparative study with commercial PDRN.

Polydeoxyribonucleotide (PDRN) is a DNA-derived drug extracted from the sperm cells of Oncorhynchus mykiss or O. keta. PDRN exhibits wound healing and anti-inflammatory activities by activating adenosine A2A receptor and salvage pathways. However, commercial PDRN products (e.g., Placentex, Rejuvenex, and HiDr) have limitations as they are exclusively extracted O. mykiss and O. keta, which are expensive and can only be used as extraction sources during a specific period when their sperm cells are activated. Therefore, this study aimed to extract PDRN from Porphyra sp. (Ps-PDRN) and investigate whether it has anti-inflammatory activity through a comparative study with commercial product. The results indicated that Ps-PDRN had an anti-inflammatory effect on Escherichia coli lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophages. It inhibited nitric oxide production and inducible nitric oxygen synthase protein expression by suppressing phosphorylation of p38 and ERK, without cytotoxicity. Furthermore, Ps-PDRN promoted cell proliferation and collagen production in human dermal fibroblast. In conclusion, our study confirms that Ps-PDRN exhibits both anti-inflammatory and cell proliferative effects. These results indicated that Ps-PDRN has the potential as a bioactive drug for tissue engineering.

Anti-Cancer Effect of Chlorophyllin-Assisted Photodynamic Therapy to Induce Apoptosis through Oxidative Stress on Human Cervical Cancer.

Photodynamic therapy is an alternative approach to treating tumors that utilizes photochemical reactions between a photosensitizer and laser irradiation for the generation of reactive oxygen species. Currently, natural photosensitive compounds are being promised to replace synthetic photosensitizers used in photodynamic therapy because of their low toxicity, lesser side effects, and high solubility in water. Therefore, the present study investigated the anti-cancer efficacy of chlorophyllin-assisted photodynamic therapy on human cervical cancer by inducing apoptotic response through oxidative stress. The chlorophyllin-assisted photodynamic therapy significantly induced cytotoxicity, and the optimal conditions were determined based on the results, including laser irradiation time, laser power density, and chlorophyllin concentration. In addition, reactive oxygen species generation and Annexin V expression level were detected on the photodynamic reaction-treated HeLa cells under the optimized conditions to evaluate apoptosis using a fluorescence microscope. In the Western blotting analysis, the photodynamic therapy group showed the increased protein expression level of the cleaved caspase 8, caspase 9, Bax, and cytochrome C, and the suppressed protein expression level of Bcl-2, pro-caspase 8, and pro-caspase 9. Moreover, the proposed photodynamic therapy downregulated the phosphorylation of AKT1 in the HeLa cells. Therefore, our results suggest that the chlorophyllin-assisted photodynamic therapy has potential as an antitumor therapy for cervical cancer.

Combinatorial prophylactic effect of phlorotannins with photobiomodulation against tracheal stenosis.

Several conventional treatments are used to manage tracheal stenosis after intubation and surgical procedures; however, patients are at risk of restenosis because of the absence of effective preventative therapy. In this study, we evaluate the biomodulatory effect of PT-combined blue light (BL) PBM in tracheostomal stenosis-induced animal models. The PT-combined BL group showed a significant decrease in the fibrotic protein synthesis by downregulating the release of stenosis-triggering fibrotic signals, without cytotoxicity or thermal damage. Moreover, the combined treatment ameliorated excessive granulation and collagen formation, and consequently preserved the opening of the tracheostoma ten days after fenestration. The current study demonstrated the biomodulatory effect of PT-combined BL on human tracheal fibroblasts and tracheal fenestration rodent models. Hence, PT-combined BL has the potential to be an effective preventative treatment for tracheal stenosis but also as an alternative option for fibrotic disorders.

Stimulatory effects of wavelength-dependent photobiomodulation on proliferation and angiogenesis of colorectal cancer.

In recent decades, the laser treatment of cancer has been introduced as a promising treatment option. Because of the maldistribution of optical energy and an ambiguous boundary between the normal and tumor tissues, laser irradiation can stimulate residual cancer cells, leading to a cancer regrowth. As photobiomodulation (PBM) is involved in an extensive range of cellular responses, profound comprehension of photo-stimulated mechanisms against the cancer cells is required to establish a safety margin for PBM. Therefore, we aimed to identify the stimulant effects of PBM at various wavelengths against the tumor cells to establish a safety margin for the laser treatment. CT26 murine colon cancer cells were exposed to either 405 (BL), 635 (VIS), or 808 (NIR) nm laser lights at the fluences of 0, 10, 30, and 50 J/cm2. In addition, CT26 tumor-bearing mice were irradiated with BL, VIS, or NIR at a fluence of 30 J/cm2. Both the proliferation and angiogenesis potential of the CT26 cells and tumors were evaluated using the MTT assay, western blot, and immunohistochemistry (IHC) staining analyses. Although cell viability was not statistically significant, BL significantly induced p-ERK upregulation in the CT26 cells, indicating that PBM with BL can stimulate proliferation. In vivo tests showed that the NIR group exhibited the maximum relative tumor volume, and BL yielded a slight increase compared to the control. In the IHC staining and western blot analyses, both BL and NIR increased the expression of EGFR, VEGF, MMP-9, and HIF-1α, which are related to the proliferation and angiogenesis-related factors. Further investigations will be pursued to clarify the molecular pathways that depend on the cancer cell types and laser wavelengths for the establishment of safety guidelines in clinical environments.

A 3D-Printed Polycaprolactone/Marine Collagen Scaffold Reinforced with Carbonated Hydroxyapatite from Fish Bones for Bone Regeneration.

In bone tissue regeneration, extracellular matrix (ECM) and bioceramics are important factors, because of their osteogenic potential and cell-matrix interactions. Surface modifications with hydrophilic material including proteins show significant potential in tissue engineering applications, because scaffolds are generally fabricated using synthetic polymers and bioceramics. In the present study, carbonated hydroxyapatite (CHA) and marine atelocollagen (MC) were extracted from the bones and skins, respectively, of Paralichthys olivaceus. The extracted CHA was characterized using Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analysis, while MC was characterized using FTIR spectroscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The scaffolds consisting of polycaprolactone (PCL), and different compositions of CHA (2.5%, 5%, and 10%) were fabricated using a three-axis plotting system and coated with 2% MC. Then, the MC3T3-E1 cells were seeded on the scaffolds to evaluate the osteogenic differentiation in vitro, and in vivo calvarial implantation of the scaffolds was performed to study bone tissue regeneration. The results of mineralization confirmed that the MC/PCL, 2.5% CHA/MC/PCL, 5% CHA/MC/PCL, and 10% CHA/MC/PCL scaffolds increased osteogenic differentiation by 302%, 858%, 970%, and 1044%, respectively, compared with pure PCL scaffolds. Consequently, these results suggest that CHA and MC obtained from byproducts of P. olivaceus are superior alternatives for land animal-derived substances.

In Silico Virtual Screening of Marine Aldehyde Derivatives from Seaweeds against SARS-CoV-2.

Coronavirus disease 2019, caused by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global pandemic that poses an unprecedented threat to the global economy and human health. Several potent inhibitors targeting SARS-CoV-2 have been published; however, most of them have failed in clinical trials. This study aimed to assess the therapeutic compounds among aldehyde derivatives from seaweeds as potential SARS-CoV-2 inhibitors using a computer simulation protocol. The absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties of the compounds were analyzed using a machine learning algorithm, and the docking simulation of these compounds to the 3C-like protease (Protein Data Bank (PDB) ID: 6LU7) was analyzed using a molecular docking protocol based on the CHARMm algorithm. These compounds exhibited good drug-like properties following the Lipinski and Veber rules. Among the marine aldehyde derivatives, 4-hydroxybenzaldehyde, 3-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, and 5-bromoprotocatechualdehyde were predicted to have good absorption and solubility levels and non-hepatotoxicity in the ADME/Tox prediction. 3-hydroxybenzaldehyde and 3,4-dihydroxybenzaldehyde were predicted to be non-toxic in TOPKAT prediction. In addition, 3,4-dihydroxybenzaldehyde was predicted to exhibit interactions with the 3C-like protease, with binding energies of -71.9725 kcal/mol. The computational analyses indicated that 3,4-dihydroxybenzaldehyde could be regarded as potential a SARS-CoV-2 inhibitor.

A phlorotannins-loaded homogeneous acellular matrix film modulates post-implantation inflammatory responses.

Peritendinous adhesion mainly occurs between proliferating fibrous tissues and adjacent normal organs after surgery. Many physical barriers are applied to the implanted site to prevent peritendinous adhesion. However, these barriers often trigger inflammatory responses. Therefore, our study sought to develop phlorotannins-loaded cartilage acellular matrix (CAM) films as a physical barrier and investigate their inhibitory effect on inflammatory responses, which are associated with the induction of postoperative peritendinous adhesion (PAA). Our findings indicated that incorporating phlorotannin into the CAM film did not affect its unique characteristics including its thermal and spectroscopic properties. Moreover, the phlorotannins-loaded CAM films suppressed the expression of inflammatory mediators on RAW 264.7 macrophages stimulated using Escherichia coli lipopolysaccharides and exhibited an anti-inflammatory effect when implanted subcutaneously in rats. Therefore, our results highlight the potential of phlorotannins-loaded CAM films as a promising physical barrier to prevent PAA.

Dieckol induces cell cycle arrest by down-regulating CDK2/cyclin E in response to p21/p53 activation in human tracheal fibroblasts.

The phlorotannin derivative dieckol isolated from Ecklonia cava has been shown to exhibit anti-inflammatory, anti-bacterial, anti-oxidative anti-adipogenic and anti-stenosis activity. However, the role of dieckol in cyclin-dependent kinase 2 (CDK2)/cyclin E signalling, which regulates fibrosis development, has not yet been determined. In this study, we report that dieckol-suppressed cell proliferation through the cell cycle arrest of Hs680.Tr human tracheal fibroblasts. Following consecutive purification, dieckol was identified as a potent bioactive compound. The results showed that dieckol had significant anti-proliferative activity against Hs680.Tr human tracheal fibroblastsWestern blotting analysis also found that dieckol dose-dependently induced the cell cycle arrest of Hs680.Tr fibroblasts in the G0/G1 phase, accompanied by the downregulation of CDK2 and cyclin E and the upregulation of p21 and p53. As attested by molecular docking study, the dieckol interacted with the core interface residues in transforming growth factor-ß receptor with high affinity. These findings suggest that dieckol from E. cava inhibits the cell proliferation of Hs680.Tr, potentially through p21- and p53-mediated G0/G1 cell cycle arrest.

Anti-Allergic Effect of Low Molecular Weight Digest from Abalone Viscera on Atopic Dermatitis-Induced NC/Nga.

Abalone viscera (AV) is one of the byproducts of the seafood processing industry. The low molecular weight (<5 kDa) peptides (LMW-AV) obtained from gastrointestinal digestion of AV could suppress allergenic responses on activated HMC-1 human mast cells in our previous study. Regarding the allergenic response of LMW-AV, in the present study, we further investigated the potential of oral administration of LMW-AV against atopic dermatitis (AD) in a dermatitis-induced model stimulated with Dermatophagoides farinae. The results demonstrated that the LMW-AV reduced a number of clinical symptoms, such as the severity of the dermatitis and serum immunoglobulin E levels. Moreover, LMW-AV could inhibit the expression of chemokines and cytokines. The histological analysis indicated that the LMW-AV has suppressed the eosinophil count and the mast cell infiltration into the upper dermis. The results suggest that LMW-AV can be considered as a promising candidate for AD treatment.

Wound healing properties of triple cross-linked poly (vinyl alcohol)/methacrylate kappa-carrageenan/chitooligosaccharide hydrogel.

To develop an effective and mechanically robust wound dressing, a poly (vinyl alcohol) (PVA)/methacrylate kappa-carrageenan (κ-CaMA) composite hydrogel encapsulated with a chitooligosaccharide (COS) was prepared in a cassette via repeated freeze/thaw cycles, photo-crosslinking, and chemical cross-linking. The chemical, physical, mechanical, in vitro biocompatibility, in vivo wound-healing properties, and antibacterial activity of triple-crosslinked hydrogel were subsequently characterized. The results showed that the PVA/κ-CaMA/COS (Pκ-CaC) hydrogel had a uniformly thick, highly porous three-dimensional architecture with uniformly distributed pores, a high fluid absorption, and retention capacity without disturbing its mechanical stability, and good in vitro biocompatibility. Macroscopic images from the full-thickness skin wound model revealed that the wounds dressed with the proposed Pκ-CaC hydrogel were completely healed by day 14, while the histomorphological results confirmed full re-epithelization and rapid skin-tissue remodeling. This study thus indicates that the composite Pκ-CaC hydrogel has significant potential for use as a wound dressing.

Applications of Marine Organism-Derived Polydeoxyribonucleotide: Its Potential in Biomedical Engineering.

Polydeoxyribonucleotides (PDRNs) are a family of DNA-derived drugs with a molecular weight ranging from 50 to 1500 kDa, which are mainly extracted from the sperm cells of salmon trout or chum salmon. Many pre-clinical and clinical studies have demonstrated the wound healing and anti-inflammatory properties of PDRN, which are mediated by the activation of adenosine A2A receptor and salvage pathways, in addition to promoting osteoblast activity, collagen synthesis, and angiogenesis. In fact, PDRN is already marketed due to its therapeutic properties against various wound healing- and inflammation-related diseases. Therefore, this review assessed the most recent trends in marine organism-derived PDRN using the Google Scholar search engine. Further, we summarized the current applications and pharmacological properties of PDRN to serve as a reference for the development of novel PDRN-based technologies.

Erratum: Phan, T.T.V., et al. Spontaneous Hinge-Bending Motions of Angiotensin I Converting Enzyme: Role in Activation and Inhibition. Molecules 2020, 25, 1288.

The authors wish to make the following corrections to the paper [...].

Electrospun porous bilayer nano-fibrous fish collagen/PCL bio-composite scaffolds with covalently cross-linked chitooligosaccharides for full-thickness wound-healing applications.

The development of tissue-engineered biodegradable artificial tissue substitutes with extracellular matrix-mimicking properties that govern the interaction between the material and biological environment is of great interest in wound-healing applications. In the present study, novel bilayer nanofibrous scaffolds composed of fish collagen (FC) and poly(ε-caprolactone) (PCL) were fabricated using electrospinning, with the covalent attachment of chitooligosaccharides (COS) via carbodiimide chemistry. The architecture and fiber diameter of the non-cross-linked nanofibrous scaffolds remained consistent irrespective of the polymer ratio under different electrospinning conditions, but the fiber diameter changed after cross-linking in association with the FC content. Fourier-transform infrared spectroscopy analysis indicated that the blend of biomaterials was homogenous, with an increase in COS levels with increasing FC content in the nanofibrous scaffolds. Based on cytocompatibility analysis (i.e., the cellular response to the nanofibrous scaffolds and their interaction), the nanofibrous scaffolds with high FC content were functionally active in response to normal human dermal fibroblast­neonatal (NHDF-neo) and HaCaT keratinocyte cells, leading to the generation of a very effective tissue-engineered implant for full-thickness wound-healing applications. In addition to these empirical results, an assessment of the hydrophilicity, swelling, and mechanical integrity of the proposed COS-containing FC-rich FC/PCL (FCP) nanofibrous scaffolds confirmed that they have significant potential for use as tissue-engineered skin implants for rapid skin regeneration.

3D PCL/fish collagen composite scaffolds incorporating osteogenic abalone protein hydrolysates for bone regeneration application: in vitro and in vivo studies.

Three-dimensional (3 D) printing is an effective technology that has shown considerable potential for use in tissue regeneration. Of the many materials that have been proposed for this purpose, poly (ε-caprolactone) (PCL) 3 D scaffolds have been received significant attention in the bone tissue engineering field due to its advantageous mechanical properties and biocompatibility. In this study, a novel method was developed for tissue-engineered bone that combines PCL 3 D scaffolds with fish collagen (Col) and the osteogenic abalone intestine gastro-intestinal digests (AIGIDs) from Haliotis discus hannai. And then, mouse mesenchymal stem cells (MSCs) were seeded onto the fabricated scaffolds. After in vitro culturing, the proliferation of the MSCs on the scaffolds, alkaline phosphatase (ALP) activity, and the amount of deposited calcium were investigated. The results indicated that the ALP activity and mineralization in PCL/AIGIDs/Col was higher than that of the other scaffolds. In an in vivo experiment, the two fabricated scaffolds were implanted in a rabbit tibia. PCL/AIGIDs/Col group exhibited strong osteoinduction capability in the rabbit tibia defect model. These stimulated biological responses in vitro and in vivo suggest that the PCL/AIGIDs/Col scaffold are promising material for use in tissue implants and bone regeneration.

Recent advances in biological macromolecule based tissue-engineered composite scaffolds for cardiac tissue regeneration applications.

Tissue engineering has become a primary research topic for the treatment of diseased or damaged cardiac tissue, which is a global healthcare concern. Current tissue engineering strategies utilise biomimetic scaffolds and cells that promote healthy growth and regeneration of cardiac tissue. Successful cardiac tissue engineering (CTE) requires scaffolds that mimic the natural anisotropy and microstructure of native tissues, while simultaneously supporting proliferation and differentiation and acting as a natural extracellular matrix (ECM) substitute until it is replaced by the body's residing cells. Among the various types of scaffolding materials, naturally occurred biological macromolecules, synthetic polymers, electroconductive polymers and electroconductive nanoparticles are utilised due to their unique biological and physicochemical properties. In this context, naturally occurred biological macromolecules has gained significant attention in designing tissue engineered composite scaffolds for cardiac tissue regeneration applications due to their excellent biocompatibility, cytocompatibility, biodegradability, and low immunogenicity. The objective of this review is to summarize the micro and macro architecture of the heart and its functional properties and provides a firm summarization of recent progress in biological macromolecules based composites scaffolds with innovative fabrication techniques so that it may help the design of novel substitutes for cardiac tissue regeneration application.