Skin Tissue Engineering Research Articles

Bioprinting-By-Design of Hydrogel-Based Biomaterials for In Situ Skin Tissue Engineering

Burns are one of the most common trauma injuries worldwide and have detrimental effects on the entire body. However, the current standard of care is autologous split thickness skin grafts (STSGs), which induces additional injuries to the patient. Therefore, the development of alternative treatments to replace traditional STSGs is critical, and bioprinting could be the future of burn care. Specifically, in situ bioprinting offers several advantages in clinical applications compared to conventional in vitro bioprinting, primarily due to its ability to deposit bioink directly onto the wound. This review provides an in-depth discussion of the aspects involved in in situ bioprinting for skin regeneration, including crosslinking mechanisms, properties of natural and synthetic hydrogel-based bioinks, various in situ bioprinting methods, and the clinical translation of in situ bioprinting. The current limitations of in situ bioprinting is the ideal combination of bioink and printing mechanism to allow multi-material dispensing or to produce well-orchestrated constructs in a timely manner in clinical settings. However, extensive ongoing research is focused on addressing these challenges, and they do not diminish the significant potential of in situ bioprinting for skin regeneration.

Electrospun scaffold with bioactive polyurethane shell infused with propolis and starch-hyaluronic acid core: An advanced therapeutic platform for skin tissue engineering.

Biological macromolecules such as polysaccharides and proteins, due to their excellent biocompatibility and biodegradability, are ideal for promoting Skin Tissue Engineering (STE) both in vitro and in vivo. In this study, a core-shell electrospun scaffold was fabricated using the coaxial electrospinning method, with Polyurethane (PU) forming the shell and a mixture of Starch (ST), Propolis Extract (PE), and Hyaluronic Acid (HA) forming the core. The scaffold's morphology was characterized by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM), confirming the successful formation of a well-defined core-shell structure. The scaffold exhibited a contact angle of 56.7°, reflecting its favorable hydrophilic properties for cellular attachment. Mechanical testing revealed Young's modulus of 8.12MPa and a strain at break of 46%, indicating an optimal balance of mechanical strength and elasticity for STE. Antibacterial tests demonstrated that the core-shell structure exhibited strong antimicrobial activity against Staphylococcus aureus and Escherichia coli, making them a potential candidate. Cytotoxicity assessments showed no toxicity, with L929 fibroblast cells demonstrating enhanced adhesion and proliferation on the core-shell structure compared to control samples. These findings suggest that the PU-shell and ST/PE/HA-core electrospun scaffold represents a promising multifunctional platform for advanced STE and regenerative medicine applications.

Development of Recombinant Human Collagen-Based Porous Scaffolds for Skin Tissue Engineering: Enhanced Mechanical Strength and Biocompatibility

Development of Recombinant Human Collagen-Based Porous Scaffolds for Skin Tissue Engineering: Enhanced Mechanical Strength and Biocompatibility

Nanoparticles Perspective in Skin Tissue Engineering: Current Concepts and Future Outlook.

Nanotechnology seems to provide solutions to the unresolved complications in skin tissue engineering. According to the broad function of nanoparticles, this review article is intended to build a perspective for future success in skin tissue engineering. In the present review, recent studies were reviewed, and essential benefits and challenging issues regarding the application of nanoparticles in skin tissue engineering were summarized. Previous studies indicated that nanoparticles can play essential roles in the improvement of engineered skin. Bio-inspired design of an engineered skin structure first needs to understand the native tissue and mimic that in laboratory conditions. Moreover, a fundamental comprehension of the nanoparticles and their related effects on the final structure can guide researchers in recruiting appropriate nanoparticles. Attention to essential details, including the designation of nanoparticle type according to the scaffold, how to prepare the nanoparticles, and what concentration to use, is critical for the application of nanoparticles to become a reality. In conclusion, nanoparticles were applied to promote scaffold characteristics and angiogenesis, improve cell behavior, provide antimicrobial conditions, and cell tracking.

The role of biomaterials-based scaffolds in advancing skin tissue construct.

Despite extensive clinical studies and therapeutic interventions, addressing significant skin wounds remains challenging, necessitating novel approaches for effective regeneration therapy. In the current review, we analyzed and evaluated the application, advancements, and future directions of biomaterials-based scaffolds for skin tissue construct. In addition, we investigated the role of other biological substitutes in promoting wound healing and skin tissue regeneration. The review highlights the impact of biomaterial-based scaffolds on skin tissue regeneration and wound healing. After presenting the physiological process of skin tissue regeneration, the review emphasizes the different biochemical components significant for skin healing and regeneration. Subsequently, it delves into the role of scaffolds in skin tissue engineering. Recent advancements in nanotechnology are also highlighted with a specific focus on the utilization of nanomaterials for enhancing healing, facilitating tissue regeneration, and promoting skin reconstruction. Biomaterial scaffolds have emerged as a potential intervention for wound healing forming the foundation of skin tissue regeneration. These scaffolds, intricate three-dimensional frameworks, serve as carriers for cells, medications, and genes, facilitating their delivery into the body. The integration of degradable porous scaffolds with biological cells offers a promising avenue for tissue repair. Biomaterials play a crucial role in tissue engineering, providing temporary mechanical support and facilitating cellular processes to augment skin tissue regeneration.

Piezoelectric hydrogels for accelerating healing of diverse wound types.

The skin, as the body's largest organ, plays a crucial role in protecting against mechanical forces and infections, maintaining fluid balance, and regulating body temperature. Therefore, skin wounds can significantly threaten human health and cause a heavy economic burden on society. Recently, bioelectric fields and electrical stimulation (ES) have been recognized as a promising pathway for modulating tissue engineering and regeneration of wounded skin. However, conventional hydrogel dressing lacks electrical generation capabilities and usually requires external stimuli to initiate the cell regeneration process, and the role of ES in different stages of healing is not fully understood. Therefore, to endow hydrogel-based wound dressings with piezoelectric properties, which can accelerate wound healing and potentially suppress infection via introducing ES, piezoelectric hydrogels (PHs) have emerged recently, combining the advantages of both piezoelectric nanomaterials and hydrogels beneficial for wound healing. Given the scarcity of systematic literature on the application of PHs in wound healing, this paper systematically discusses the principles of the piezoelectric effects, the design and fabrication of PHs, their piezoelectric properties, the way PHs trigger ES and the mechanisms by which they promote wound healing. Additionally, it summarizes the recent applications of PHs in various types of wounds, including traumatic wounds, pressure injuries, diabetic wounds, and infected wounds. Finally, the paper proposes future directions and challenges for the development of PH wound dressings for wound healing.

Enzyme-crosslinked hyaluronic acid hydrogel scaffolds for BMSCs microenvironment and wound healing.

Tissue engineering utilizing hydrogel scaffolds in combination with exogenous stem cells holds significant potential for promoting wound regeneration. However, the microenvironment provided by existing skin tissue engineering scaffold materials is often inadequate. Herein, we demonstrate an enzyme-crosslinked hyaluronic acid hydrogel to provide a growth microenvironment for exogenous bone marrow mesenchymal stem cells and promote acute wound healing. This material is developed by grafting dopamine onto hyaluronic acid, followed by enzyme crosslinking using horseradish peroxidase and hydrogen peroxide, which creates a loose, porous structure. The hydrogel possesses adhesive and self-healing properties, offering a microenvironment with excellent cell compatibility for exogenous BMSCs. In vivo studies showed that this hydrogel significantly accelerated the healing of acute full-thickness skin wounds, resulting in the formation of appendages such as hair follicles and minimal scarring. This study not only presents a novel skin tissue engineering scaffold but also offers a promising clinical strategy for achieving scar-minimized wound healing.

Skin Necrosis: Pathophysiology and innovations in tissue regeneration

Skin, the largest organ in the human body, serves as a crucial barrier against environmental threats. However, larger skin defects or compromised wound healing can result in persistent wounds, sometimes requiring skin substitutes. Skin tissue engineering aims to create materials that can replace skin functions temporarily or permanently. The skin comprises several tissue types, including epithelial, connective, muscular, nervous, and vascular tissues. Keratinocytes, for instance, undergo a specialized process to form the cornified layer, which differentiates from apoptosis, a type of programmed cell death. Pathogenic processes often involve necrosis, a form of tissue death caused by insufficient blood supply, infections, or trauma. There are various types of necrosis, including coagulation, liquefactive, gangrenous, caseous, fat, and fibrinoid necrosis, each defined by the tissue changes and underlying causes. Necrosis can result from external factors like mechanical trauma, thermal damage, or ischemia, and internal factors such as infection or certain diseases. Necrosis is linked to autoimmune conditions, vascular diseases, and toxic exposures. Risk factors include age, alcohol abuse, infections, and conditions like diabetes and HIV. Treatment for necrosis involves removing dead tissue (debridement), managing infections, and restoring blood flow, often requiring surgery or amputation. Additional treatments like antibiotics, hyperbaric oxygen therapy, and wound dressings support healing. Alternative approaches, including homeopathy and Ayurveda, focus on stimulating natural healing processes through herbs and detoxification.

Innovations in Epidermal Tissue Engineering

This paper reviews recent advances and challenges in epidermal medical engineering and scaffold material research. The basic elements of tissue engineering include seed cells, scaffold materials and bioactive factors. Current skin tissue engineering techniques offer innovative therapeutic avenues for the repair of large wounds, mainly through suitable tissue scaffolds. The paper also discusses the principles of skin regeneration, including skin structure and function, the process of skin regeneration, and explores the potential of stem cells and exosomes in scar-free healing. Future research directions will focus on developing high-performance biomaterials and scaffolds, optimising stem cell delivery methods, finding optimal stem cell sources and maintaining stem cell activity. In particular, the combined use of natural polymers such as filipin proteins and sodium alginate is expected to create composites that more closely resemble extracellular matrices, thus better promoting cell proliferation and differentiation. In addition, the study of stem cells and exosomes offers new ways to achieve scar-free healing, potentially improving healing efficiency and reducing scar formation when combined with bioscaffolds.

Decellularized Green and Brown Macroalgae as Cellulose Matrices for Tissue Engineering.

Scaffolds resembling the extracellular matrix (ECM) provide structural support for cells in the engineering of tissue constructs. Various material sources and fabrication techniques have been employed in scaffold production. Cellulose-based matrices are of interest due to their abundant supply, hydrophilicity, mechanical strength, and biological inertness. Terrestrial and marine plants offer diverse morphologies that can replicate the ECM of various tissues and be isolated through decellularization protocols. In this study, three marine macroalgae species-namely Durvillaea poha, Ulva lactuca, and Ecklonia radiata-were selected for their morphological variation. Low-intensity, chemical treatments were developed for each species to maintain native cellulose structures within the matrices while facilitating the clearance of DNA and pigment. Scaffolds generated from each seaweed species were non-toxic for human dermal fibroblasts but only the fibrous inner layer of those derived from E. radiata supported cell attachment and maturation over the seven days of culture. These findings demonstrate the potential of E. radiata-derived cellulose scaffolds for skin tissue engineering and highlight the influence of macroalgae ECM structures on decellularization efficiency, cellulose matrix properties, and scaffold utility.

Cotton cellulose nanofiber/chitosan scaffolds for skin tissue engineering and wound healing applications

Chitosan (CS) is a promising polymeric biomaterial for use in scaffolds forin vitroskin models and wound dressings, owing to its non-antigenic and antimicrobial properties. However, CS often exhibits insufficient physicochemical properties, mechanical strength, and bioactivity, limiting its efficacy in demanding applications. To address these challenges, cotton cellulose nanofibers (CNFs) represent a promising nanomaterial for enhancing CS-based scaffolds in tissue engineering. CNF offers superior stiffness, and mechanical properties that enhance cellular adhesion and proliferation, both crucial for effective tissue regeneration and healing. This study aimed to develop and characterize a scaffold combining cotton CNF and CS, focusing on its cytocompatibility with human fibroblasts and keratinocytes. The cotton CNF/CS scaffold was fabricated using the casting technique, and its physicochemical properties and cellular compatibility were assessedin vitro. The results demonstrated that incorporating cotton CNF significantly enhanced the stability of the CS matrix. The CS scaffold with 1000 μg ml-1of cotton CNF exhibited increased roughness and reduced rupture strain compared to the pure CS scaffold. The cotton CNF/CS scaffold effectively promoted the adhesion, viability, proliferation, migration, and collagen synthesis of skin cells. Notably, increased cell viability was observed in human fibroblasts cultured on scaffolds with higher concentrations of cotton CNF (100 and 1000 μg ml-1). Based on the findings, the cotton CNF/CS scaffold demonstrates enhanced physicochemical properties and bioactivity, making it a promising candidate for the development ofin vitrohuman skin models and wound healing dressings.

Development of New Chitosan-Based Complex with Bioactive Molecules for Regenerative Medicine

Background/Objectives: The development of new materials incorporating bioactive molecules for tissue regeneration is a growing area of interest. The objective of this study was to develop a new complex specifically designed for bone and skin tissue engineering, combining chitosan, ascorbic acid-2-magnesium phosphate (ASAP), and β-tricalcium phosphate (β-TCP). Methods: Chitosan and the complexes chitosan/ASAP and chitosan/ASAP/β-TCP were prepared in membrane form, macerated to a particulate format, and then subjected to characterization through Fourier transform infrared (FTIR) spectroscopy, optical and scanning electron microscopy (SEM), zeta potential, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Cell viability was evaluated through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and with fluorescein diacetate (FDA) and propidium iodide (PI) staining in stem cells obtained from deciduous teeth. Statistical analyses were performed using analysis of variance (ANOVA), followed by Tukey’s test. Results: The FTIR results indicated the characteristic bands in the chitosan group and the complexation between chitosan, ASAP, and β-TCP. Microscopic characterization revealed a polydisperse distribution of micrometric particles. Zeta potential measurements demonstrated a reduction in surface charge upon the addition of ASAP and β-TCP to the chitosan matrix. TGA and DSC analyses further indicated complexation between the three components and the successful formation of a cross-linked structure in the chitosan matrix. Stem cells cultured with the particulate biomaterials demonstrated their biocompatibility. Statistical analysis revealed a significant increase in cell viability for the chitosan/ASAP and chitosan/ASAP/β-TCP groups compared to the chitosan control. Conclusions: Therefore, the chitosan/ASAP complex demonstrated potential for skin regeneration, while the chitosan/ASAP/β-TCP formulation showed promise as a biomaterial for bone regeneration due to the presence of β-tricalcium phosphate.

Fabrication of Thymol-loaded Isabgol/Konjac Glucomannan-based Microporous Scaffolds with Enriched Antioxidant and Antibacterial Properties for Skin Tissue Engineering Applications.

An antioxidant, antibacterial, and biocompatible biomaterial is essential to repair skin wounds effectively. Here, we have employed two natural biopolymers, isabgol (ISAB) and konjac glucomannan (KGM), to prepare microporous scaffolds by freezing and lyophilization. The scaffolds are loaded with thymol (THY) to impart potent antioxidant and antibacterial activities. The physicochemical properties of the ISAB+KGM+THY scaffold, like porosity (41.8±2.4 %), swelling, and biodegradation, were optimal for tissue regeneration application. Compared to the control, ISAB+KGM+THY scaffolds promote attachment, migration, and proliferation of L929 fibroblasts. The antioxidant activity of the ISAB+KGM+THY scaffold was significantly improved after loading THY. This would protect the tissues from oxidative damage. The antibacterial activity of the ISAB+KGM+THY scaffold was significantly higher than that of the control, which would help prevent bacterial infection. The vascularization ability of the ISAB+KGM scaffold was not altered by incorporating THY in the ISAB+KGM scaffold. Therefore, a strong antioxidant, antibacterial, and biocompatible nature of the ISAB+KGM+THY scaffold could be useful for various biomedical applications.

Development and characterization of electrospun curcumin-loaded PVA/gelatin based nanofibers scaffolds for skin tissue engineering

Chronic skin wounds have a profound impact on the global population, affecting over 40 million individuals and resulting in healthcare expenditures exceeding $20 billion annually by 2025. Researchers have developed wound dressings using biocompatible polymers that possess bioactive properties to combat this pressing issue. The present research focuses on fabricating a nanofiber-based composite structure made of Polyvinyl alcohol (PVA) and Gelatin, incorporating varying concentrations of curcumin (0.25, 0.5, and 0.75 mg/ml). The fabrication process employed electrospinning techniques to create nanofiber-based scaffolds that closely mimic the native structure of the extracellular matrix (ECM) found in the skin. The developed nanofiber mats underwent comprehensive characterization through a sequence of in-vitro experiments, encompassing SEM imaging, Fourier transform infrared spectroscopy (FTIR), in-vitro release studies, and evaluation of tensile strength, swelling, and degradation. SEM images revealed a notable reduction in the mean fiber diameter, swelling potential and extent of degradation following the addition of curcumin. Regarding drug release, curcumin demonstrated a biphasic release profile in phosphate buffer (pH 7.4) and Tween 80 solutions. The PVA/gelatin (PG) mats containing curcumin displayed strong antimicrobial effects against Gram-negative E. coli and Gram-positive S. aureus. The biocompatibility of the membranes was further confirmed through cytocompatibility testing utilizing the L929 cell line. Overall, this research indicates that wound dressings made from nanofibers composed of polyvinyl alcohol (PVA) and gelatin, incorporating curcumin, exhibit considerable potential for treating cutaneous wounds. However, additional research is necessary to determine the effectiveness of these dressings in vivo.

A Layer-by-Layer Polycaprolactone/Chitosan-Based Biomimetic Hybrid Nanofibroporous Scaffold for Enhanced Skin Tissue Regeneration: Integrating Solution Blow Spinning and Freeze Casting Techniques.

Nanofibers, with their high surface area-to-volume ratio, elasticity, and mechanical strength, significantly enhance scaffold structures for skin tissue engineering. The present study introduces a unique method of combining solution blow spinning (SBS) and freeze casting to fabricate biomimetic hybrid nanofibroporous scaffolds (BHNS) using polycaprolactone (PCL) and chitosan (CH). The developed scaffolds mimic the fibrous porous natural extracellular matrix (ECM) architecture, promoting cell adhesion, proliferation, and matrix deposition. The combined SBS and freeze-casting processes resulted in scaffolds with high porosity and optimal mechanical strength, crucial for effective skin regeneration. Scanning electron microscopy (SEM) confirmed the uniform, nonwoven, and beadless architecture of the PCL fibers and the fibroporous nature of the PCL/CH scaffolds. The scaffolds exhibited excellent swelling behavior, controlled degradation rates, and enhanced mechanical properties. In vitro cell studies demonstrated scaffold cell-supportive properties in terms of cell attachment, proliferation, and migration. This innovative layer-by-layer fabrication technique, integrating nanofibers with freeze-cast scaffolds, represents a significant advancement in skin tissue engineering, promising improved outcomes in wound healing and regenerative medicine.

Enhanced chitosan fibres for skin regeneration: solution blow spinning and incorporation with platelet lysate and tannic acid

Abstract In this study, we developed and characterised enhanced chitosan/polyethylene oxide (PEO) nanofibre scaffolds using solution blow spinning (SBS) for potential application in skin tissue engineering. SBS enabled the efficient and scalable production of fibre matrices with precise morphology control, facilitating the integration of PEO to improve spinnability, 100X the speed of electron spinning. Following fabrication, fibres were subjected to potassium carbonate neutralisation to reduce PEO content, improving chitosan stability in aqueous environments. Characterisation by scanning electron microscopy (SEM) and attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) confirmed structural integrity post-neutralisation and the successful incorporation with bioactive additives. Platelet lysate (PL) was incorporated to introduce growth factors, and tannic acid (TA) was added for antibacterial properties and enhanced mechanical stability through potential crosslinking. Mechanical testing showed that the optimised PL- and TA-enriched scaffolds exhibited the highest mechanical performance, with Young’s modulus of 7.0 ± 0.6 MPa, an ultimate tensile strength of 26.4 ± 2.3 MPa, elongation at break of 16.5 ± 1.7%, and toughness of 3.0 ± 0.3 MJ m−3 which is within the range of human skin. At the same time, SEM and ATR-FTIR analyses confirmed the stability and distribution of these functional agents within the fibre network. Biocompatibility tests with normal human dermal fibroblasts (NHDF) indicated low cytotoxicity, appropriate cell adhesion and proliferation over 14 days in culture, suggesting these scaffolds as promising candidates for wound healing and skin regeneration applications.

328 Tissue-engineered human skin model allows monitoring of arboviral cutaneous infections introduced by live mosquitoes

328 Tissue-engineered human skin model allows monitoring of arboviral cutaneous infections introduced by live mosquitoes

Review on Hydrogel Based Systems and their use in Drug Delivery for Wound Healing & Wound Management

Abstract: The largest organ of the human body, the skin, shields the body from the outside environment. Despite having a great capacity for regeneration, major skin abnormalities cannot heal on their own and must be covered with artificial skin. In recent years, significant advancements have been achieved in the area of skin tissue engineering to create novel skin replacements. Because of their porous as well as moisturized polymeric structural composition, hydrogels are one of the choices with the greatest ability to imitate the natural skin microenvironment. Naturally derived polymers, synthesized polymers, polymerizable synthetic monomolecules, as well as mixtures of natural and synthesized polymers, can all be used to create hydrogels. They can be used to assist in the regeneration as well as repair of the wounded dermis, epidermis or else both by dressing various wounds permanently or temporarily. Hydrogels possess distinct properties like lightweight, stretchable, biocompatible, and biodegradable; they have the potential to be incorporated as flexible solutions for the care of chronic wounds. Additionally, these characteristics make hydrogels appropriate for use in the pharmaceutical and medical industries. Physical, chemical, and hybrid bonding are all involved in the creation of hydrogels. Several processes, including solution casting, solution mixing, bulk crosslinking polymerization, the free radical mechanism, radiation therapy, and the development of interpenetrating networks, are used to create the bonding. This review primarily focuses on the type of wounds with phases in wound healing and the many kinds of hydrogels based on cross-linking, ionic charge, physical properties, source etc., and it also describes potential fabrication techniques for hydrogel design in biomedical applications, drug delivery as well as wound management hydrogel systems. Hydrogel-based systems for wound recovery and management are described, as well as current research & future prospective of hydrogel-based drug delivery systems in wound healing for topical applications.

In vitro evaluation of decellularized floral scaffold with surface nanotopography for skin tissue engineering

Despite substantial advancements in developing scaffolds for skin tissue engineering, the scarcity to manage the 'cost to heal factor' still presents demanding concerns. In this regard, synthetic scaffolds with nanotopographical features have been popular as they provide anchoring sites for cellular adherence and mimic the natural nanotopographic cues present in the native extracellular matrix (ECM) of skin. However, complicated nanofabrication techniques and the associated high cost of production limits their commercial success. Similar to mammalian skin ECM, floral plant tissues also contain nanotopographic features in their ECM which can be explored for developing tissue engineering scaffold in a sustainable and cost-effective manner. Herein, we have carefully decellularized floral Bougainvillea bract to preserve the acellular nanotopographic matrix (average height: 122.37 ± 19.46 nm) and utilized it as a scaffold for growing skin cells in vitro. Without incorporation of any cell-adhesion moiety, the nanotopographic surface of the decellularized bract exhibits significant adhesion, migration, proliferation and differentiation of skin cells. Moreover, expression of characteristic epidermal and dermal protein markers indicates that the decellularized floral scaffold is able to provide suitable nanoenvironment niche to the skin cells, enabling them to secrete their own ECM proteins on the scaffold.

Optimization and characterization of electrospun bilayered PVA/collagen nanofibers loaded with quercetin for tissue engineering applications

Bilayered electrospun membranes for skin tissue engineering and wound dressings were developed using Poly vinyl alcohol (PVA), collagen (COLL), chitosan (CH), and a tamarind seed polysaccharide (TSP) are crosslinked with quercetin (QU). To maintain a sustained release of drug from the membrane we have developed a novel crosslinked two layered stable PVA fibrous mat, top layer composed of PVA/CH/TSP and quercetin and the bottom layer is composed of PVA/CH/COLL. Developed bilayered scaffolds were characterized using Field Emission Scanning Electron Microscope (FE-SEM) and their surface morphologies exhibited random fibrous orientation with porous morphology. Cross sectional images showed the junction of the bilayered scaffold with different fiber morphology between the layers. The results revealed fibrous bilayer separation confirming the bilayered scaffold with uniform porosity which is beneficial for tissue engineering application, moreover the PVA fibrous mats are stable after crosslinking it with quercetin, more than 24 h. Invitro biological studies results also showed desirable cell viability on fibroblast cells with increased proliferation and adhesion on the bilayer material making it potential for targeted tissue engineering application.