Bioactive gelatin cryogels with BMP-2 biomimetic peptide and VEGF:A potential scaffold for synergistically induced osteogenesis

A poor biocompatibility and bioactivity of invasive materials remains major problems for biomaterialbased therapy. In this study, we introduced gelatin scaffolds carrying both bone morphogenetic protein-2(BMP-2) biomimetic peptide and vascular endothelial growth factor-165(VEGF) that achieved controlled release, cell attachment, proliferation and differentiation. To promote osteogenesis with VEGF, we designed the BMP-2 biomimetic peptide that comprised BMP-2 core sequence oligopeptide(SSVPT), ph...     

Integration exosomes with MOF-modified multifunctional scaffold for accelerating vascularized bone regeneration

Designing a multifunctional scaffold with osteogenic and angiogenic properties holds promise for ideal bone regeneration. Innovative scaffold was here constructed by immobilizing exosomes derived from human bone mesenchymal stem cells (hBMSCs) onto porous polymer meshes which developed by PLGA and Cu-based MOF (PLGA/CuBDC@Exo). The synthesized exosome-laden scaffold capable of providing a dual cooperative controllable release of bioactive copper ions and exosomes that promote osteogenesis and angiogenesis, thereby achieving cell-free bone regeneration. In vitro assay revealed the composite stent not only substantially upregulated the expression of osteogenic-related proteins (ALP, Runx2, Ocn) and VEGF in hBMSCs, but promoted the migration and tube formation of the human umbilical vein endothelial cells (HUVECs). In vivo evaluation further confirmed this scaffold dramatically stimulated bone regeneration and angiogenesis in critical-sized defects in rats. Altogether, this composite scaffold carrying therapeutic exosomes had an osteogenic-angiogenic coupling effect and offered a new idea for cell-free bone tissue engineering.     

Biomimetic hybrid scaffold containing niosomal deferoxamine promotes angiogenesis in full-thickness wounds

Effective management of full-thickness wounds faces significant challenges due to poor angiogenesis and impaired healing. Biomimetic tissue-engineered scaffolds with angiogenic properties can, however, enhance the regeneration capacity of the damaged skin. Here, we developed a hybrid double-layer nanofibrous scaffold, comprised of egg white (EW) and polyvinyl alcohol (PVA), loaded with niosomal Deferoxamine (NDFO) for enhanced angiogenesis and wound healing features. The hybrid scaffold showed enhanced mechanical properties with comparable modulus and shape-recovery behavior of the human skin. Thanks to the porous morphology and uniform distribution of NDFO within the nanofibers, in vitro drug release studies indicated controlled and sustained release of DFO for up to 9 days. The constructs also promoted a significant increase in vascular sprouting area in vitro and enhanced vascular branches ex vivo. In vivo, implantation of the hybrid scaffold in full-thickness wounds in rats revealed early angiogenic response, a higher number of neo-formed vessels, a faster healing rate and complete epithelialization as early as day 10, compared to the control groups. Thus, the presented biomimetic hybrid scaffold with DFO control release features holds great promise in accelerated full-thickness wound healing and soft tissue regeneration.     

Nanosilica-Anchored Polycaprolactone/Chitosan Nanofibrous Bioscaffold to Boost Osteogenesis for Bone Tissue Engineering

The strategy of incorporating bioactive inorganic nanomaterials without side effects as osteoinductive supplements is promising for bone regeneration. In this work, a novel biomass nanofibrous scaffold synthesized by electrospinning silica (SiO₂) nanoparticles into polycaprolactone/chitosan (PCL/CS) nanofibers was reported for bone tissue engineering. The nanosilica-anchored PCL/CS nanofibrous bioscaffold (PCL/CS/SiO₂) exhibited an interlinked continuous fibers framework with SiO₂ nanoparticles embedded in the fibers. Compact bone-derived cells (CBDCs), the stem cells derived from the bone cortex of the mouse, were seeded to the nanofibrous bioscaffolds. Scanning electron microscopy and cell counting were used to observe the cell adhesion. The Counting Kit-8 (CCK-8) assay was used. Alkaline phosphatase (ALP), Alizarin red staining, real-time Polymerase Chain Reaction and Western blot tests were performed to confirm the osteogenesis of the CBDCs on the bioscaffolds. The research results demonstrated that the mechanical property of the PCL together with the antibacterial and hydrophilic properties of the CS are conducive to promoting cell adhesion, growth, migration, proliferation and differentiation. SiO₂ nanoparticles, serving as bone induction factors, effectively promote the osteoblast differentiation and bone regeneration. This novel SiO₂-anchored nanofibrous bioscaffold with superior bone induction activity provides a better way for bone tissue regeneration.     

Improved efficacy of bio‐mineralization of human mesenchymal stem cells on modified PLLA nanofibers coated with bioactive materials via enhanced expression of integrin α2β1

Current therapeutic interventions in bone defects are mainly focused on finding the best bioactive materials for inducing bone regeneration via activating the related intracellular signaling pathways. Integrins are trans‐membrane receptors that facilitate cell‐extracellular matrix (ECM) interactions and activate signal transduction. To develop a suitable platform for supporting human bone marrow mesenchymal stem cells (hBM‐MSCs) differentiation into bone tissue, electrospun poly L‐lactide (PLLA) nanofiber scaffolds were coated with nano‐hydroxyapatite (PLLA/nHa group), gelatin nanoparticles (PLLA/Gel group), and nHa/Gel nanoparticles (PLLA/nHa/Gel group) and their impacts on cell proliferation, expression of osteoblastic biomarkers, and bone differentiation were examined and compared. MTT data showed that proliferation of hBM‐MSCs on PLLA/nHa/Gel scaffolds was significantly higher than other groups (P < .05). Alkaline phosphatase activity was also more increased in hBM‐MSCs cultured under osteogenic media on PLLA/nHa/Gel scaffolds compared to others. Gene expression evaluation confirmed up‐regulation of integrin α2β1 as well as the osteogenic genes BGLAP, COL1A1, and RUNX2. Following use of integrin α2β1 blocker antibody, the protein level of integrin α2β1 in cells seeded on PLLA/nHa/Gel scaffolds was decreased compared to control, which confirmed that most of the integrin receptors were bound to gelatin molecules on scaffolds and could activate the integrin α2β1/ERK axis. Collectively, PLLA/nHa/Gel scaffold is a suitable platform for hBM‐MSCs adhesion, proliferation, and osteogenic differentiation in less time via activating integrin α2β1/ERK axis, and thus it might be applicable in bone tissue engineering.     

A collagen(Col)/nano-hydroxyapatite (nHA) biological composite bone scaffold with double multi-level interface reinforcement

IntroductionBone scaffold is expected to possess excellent mechanical and biological properties similar to natural bone tissues. In this study, we aimed to prepare a biomineralized Col and hydroxyapatite composite scaffold consisting of biomimetic bone components and multi-level bionic bone structure to strengthen its mechanical properties.MethodsWe prepared a Col/nano-hydroxyapatite biological composite scaffold with multi-level structure (from nanofibers to micron bionic bone motif to bionc bone scaffold) of biomimetic bone tissue, and biomineralized the scaffold in simulated body fluid (SBF) preheated to 37 °C. X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and Scanning electron microscope, were used to characterize the biomineralized products.ResultsMorphological study confirmed in situ deposition of nHA in the multi-scale hierarchical structure of the biomineralized scaffold. We explored the biomineralization nucleation mechanism of the scaffolds at the atomic level based on the first principles and the mechanisms for growth of mineralized nHA crystal array in its multi-scale structure, and how the double multiscales structure strengthened the mechanical properties of the material.ConclusionsThis synthetic bone scaffold, with bionic bone composition and double multi-level interface reinforcement, provides a new strategy for synthesizing bioactive bone scaffolds with enhanced biomechanical properties.     

Biomimetic strengthening polylactide scaffold materials for bone tissue engineering

In this paper, a new polylactide (PLA)-based scaffold composite by biomimetic synthesis was designed. The novel composite mainly consists of nano-hydroxyapatite (n-HA), which is the main inorganic content in natural bone tissue for the PLA. The crystal degree of the n-HA in the composite is low and the crystal size is very small, which is similar to that of natural bone. The compressive strength of the composite is higher than that of the PLA scaffold. Using the osteoblast culture technique, we detected cell behaviors on the biomaterial in vitro by SEM, and the cell affinity of the composite was found to be higher than that of the PLA scaffold. The biomimetic three-dimensional porous composite can serve as a kind of excellent scaffold material for bone tissue engineering because of its microstructure and properties. Translated from Journal of Hunan University (Natural Sciences), 2006, 33(2) (in Chinese)     

Tantalum nanoparticles enhance the osteoinductivity of multiscale composites based on poly(lactide-co-glycolide) electrospun fibers embedded in a gelatin hydrogel

Bioresorbable polymeric materials have risen great interest as implants for bone tissue regeneration, since they show substantial advantages with respect to conventional metal devices, including biodegradability, flexibility, and the possibility to be easily modified to introduce specific functionalities. In the present work, an innovative nanocomposite scaffold, properly designed to show biomimetic and osteoinductive properties for potential application in bone tissue engineering, was developed. The scaffold is characterized by a multi-layer structure, completely different with respect to the so far employed polymeric implants, consisting in a poly(d,l-lactide-co-glycolide)/polyethylene glycol electrospun nanofibrous mat sandwiched between two hydrogel gelatin layers enriched with tantalum nanoparticles (NPs). The composition of the electrospun fibers, containing 10 wt% of polyethylene glycol, was selected to ensure a proper integration of the fibers in the gel phase, essential to endow the composite with flexibility and to prevent delamination between the layers. The scaffold maintained its structural integrity after six weeks of soaking in physiological solutions, albeit the gelatin phase was partially released. The combined use of gelatin, bioresorbable electrospun fibers and tantalum NPs endows the final device with biomimetic and osteoinductive properties. Indeed, results of the in vitro tests demonstrate that the obtained scaffolds clearly represent a favorable milieu for normal human bone-marrow derived mesenchymal stem cells viability and osteoblastic differentiation; moreover, inclusion of tantalum NPs in the scaffold improves cell performance with particular regard to early and late markers of osteoblastic differentiation.     

Natural and Synthetic Polymer Scaffolds Comprising Upconversion Nanoparticles as a Bioimaging Platform for Tissue Engineering

Modern biocompatible materials of both natural and synthetic origin, in combination with advanced techniques for their processing and functionalization, provide the basis for tissue engineering constructs (TECs) for the effective replacement of specific body defects and guided tissue regeneration. Here we describe TECs fabricated using electrospinning and 3D printing techniques on a base of synthetic (polylactic-co-glycolic acids, PLGA) and natural (collagen, COL, and hyaluronic acid, HA) polymers impregnated with core/shell β-NaYF₄:Yb³⁺,Er³⁺/NaYF₄ upconversion nanoparticles (UCNPs) for in vitro control of the tissue/scaffold interaction. Polymeric structures impregnated with core/shell β-NaYF₄:Yb³⁺,Er³⁺/NaYF₄ nanoparticles were visualized with high optical contrast using laser irradiation at 976 nm. We found that the photoluminescence spectra of impregnated scaffolds differ from the spectrum of free UCNPs that could be used to control the scaffold microenvironment, polymer biodegradation, and cargo release. We proved the absence of UCNP-impregnated scaffold cytotoxicity and demonstrated their high efficiency for cell attachment, proliferation, and colonization. We also modified the COL-based scaffold fabrication technology to increase their tensile strength and structural stability within the living body. The proposed approach is a technological platform for “smart scaffold” development and fabrication based on bioresorbable polymer structures impregnated with UCNPs, providing the desired photoluminescent, biochemical, and mechanical properties for intravital visualization and monitoring of their behavior and tissue/scaffold interaction in real time.     

Sustainable Development of Chitosan/Calotropis procera-Based Hydrogels to Stimulate Formation of Granulation Tissue and Angiogenesis in Wound Healing Applications

The formation of new scaffolds to enhance healing magnitude is necessarily required in biomedical applications. Granulation tissue formation is a crucial stage of wound healing in which granulation tissue grows on the surface of a wound by the formation of connective tissue and blood vessels. In the present study, porous hydrogels were synthesized using chitosan incorporating latex of the Calotropis procera plant by using a freeze–thaw cycle to stimulate the formation of granulation tissue and angiogenesis in wound healing applications. Structural analysis through Fourier transform infrared (FTIR) spectroscopy confirmed the interaction between chitosan and Calotropis procera. Latex extract containing hydrogel showed slightly higher absorption than the control during water absorption analysis. Thermogravimetric analysis showed high thermal stability of the 60:40 combination of chitosan (CS) and Calotropis procera as compared to all other treatments and controls. A fabricated scaffold application on a chick chorioallantoic membrane (CAM) showed that all hydrogels containing latex extract resulted in a significant formation of blood vessels and regeneration of cells. Overall, the formation of connective tissues and blood capillaries and healing magnitude decreased in ascending order of concentration of extract.     

Production and characterization of elastomeric cardiac tissue-like patches for Myocardial Tissue Engineering

Cardiovascular disease remains the leading cause of death. Damaged heart muscle is the etiology of heart failure. Heart failure is the most frequent cause of hospital and emergency room admissions. As a differentiated organ, current therapeutics and techniques can not repair or replace the damaged myocardial tissue. Myocardial tissue engineering is one of the promising treatment modalities for repairing damaged heart tissue in patients with heart failure. In this work, random Polylactic acid (PLA), Polylactic acid/Polyethylene glycol (PLA/PEG) and random and aligned Polylactic acid/Polyethylene glycol/Collagen (PLA/PEG/COL) nanofiber patches were successfully produced by the electrospinning technique. In vitro cytotoxic test (MTT), morphological (SEM), molecular interactions between the components (FT-IR), thermal analysis (DSC), tensile strength and physical analysis were carried out after production. The resulting nanofiber patches exhibited beadless and smooth structures. When the fiber diameters were examined, it was observed that the collagen doped random nanofiber patches had the lowest fiber diameter value (755 nm). Mechanical characterization results showed that aligned nanofiber patches had maximum tensile strength (5.90 MPa) values compared to PLA, PLA/PEG, and PLA/PEG/COL (random). In vitro degradation test reported that aligned patch had the highest degradation ratio. The produced patches displayed good alignment with tissue on cardiomyocyte cell morphology studies. In conclusion, newly produced patches have noticeable potential as a tissue-like cardiac patch for regeneration efforts after myocardial infarction.     

A study on biomineralization behavior of N-methylene phosphochitosan scaffolds

Biomimetic growth of calcium phosphate over natural polymer may be an effective approach to constituting an organic/inorganic composite scaffold for bone tissue engineering. In this work, N-methylene phosphochitosan (NMPCS) was prepared via formaldehyde addition and condensation with phosphoric acid in a step that allowed homogeneous modification without obvious deterioration in chitosan (CS) properties. The NMPCS obtained was characterized by using FT-IR and elemental analysis. The macroporous scaffolds were fabricated through a freeze-drying technique. A comparative study on NMPCS and CS scaffold biomimetic mineralization was carried out in different media, i.e, a simulated body fluid (SBF) or alternative CaCl(2) and Na(2)HPO(4) solutions respectively. Apatite formation within NMPCS and CS scaffolds was identified with FT-IR, scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) and X-ray diffractometery (XRD). The results revealed alternate soaking of the scaffolds in CaCl(2) and Na(2)HPO(4) solutions was better than soaking in SBF solution alone in relation to apatite deposition on the scaffold pore walls. Biomineralization provides an approach to improve nature derived materials, e.g., chitosan derivative NMPCS properties e.g., compressive modulus, etc. SEM image of a NMPCS/apatite composite scaffold.     

Biofunctional properties of polyester fibers grafted with chitosan and collagen

Poly(ethylene terephthalate) (PET) fiber was treated with ⁶⁰Co-γ-ray and grafted with acrylic acid (AA). The resulting fibers were further grafted with chitosan (CS) via esterification. Afterward collagen (COL) was immobilized onto CS-grafting fibers. The antibacterial activity of CS against Staphylococus aureus, Escherichia coli, and Pseudomonas aeruginosa was preserved after COL-immobilization. After immobilizing COL, the L929 fibroblasts cell proliferation was promoted than CS-grafting PET fiber. The results indicate that by grafting with CS and immobilizing with COL, PET fibers exhibited both antibacterial activity against four pathological bacteria and improvement in the proliferation of fibroblast. Copyright © 2007 John Wiley & Sons, Ltd.     

Preparation of enzymatically cross-linked sulfated chitosan hydrogel and its potential application in thick tissue engineering

For the requirement of preliminary vascularization, the scaffolds for thick tissue engineering should possess not only good cell affinity, but also anticoagulant ability. In this paper, an enzymatically crosslinked hydrogel scaffold based on sulfated chitosan (SCTS) was prepared. Firstly, sulfated chitosan-hydroxyphenylpionic acid (SCTS-HPA) conjugate was synthesized, and its structure was identified by FITR and ¹H NMR. And then an enzymatically crosslinked hydrogel was prepared in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂). The gelation time, mechanical property, morphology and cytotoxicity to human umbilical vein endothelial cells (HUVECs) of the hydrogel was evaluated in vitro, the tissue compatibility of SCTS scaffold was studied in vivo. The results showed that the gelation time, mechanical property, morphology of the dehydrated hydrogel could be controlled by the HRP and H₂O₂ concentration. The cytotoxicity test showed that the hydrogel extracts had no cytotoxicity to HUVECs. The in vivo assay indicated that SCTS-HPA scaffold showed good tissue compatibility, and no thrombus formation. All these results indicated that the SCTS-HPA scaffold could be used as thick tissue engineering scaffold.     

Laponite–Gelatin Nanofibrous Microsphere Promoting Human Dental Follicle Stem Cells Attachment and Osteogenic Differentiation for Noninvasive Stem Cell Transplantation

Nanofibrous microspheres (NFM) are emerging as prominent next-generation biomimetic injectable scaffold system for stem cell delivery and different tissue regeneration where nanofibrous topography facilitates ECM-like stem cells niches. Addition of osteogenic bioactive nanosilicate platelets within NFM can provide osteoconductive cues to facilitate matrix mediated osteogenic differentiation of stem cells and enhance the efficiency of bone tissue regeneration. In this study, gelatin nanofibrous microspheres are prepared containing fluoride-doped laponite XL21 (LP) using the emulsion mediated thermal induce phase separation (TIPS) technique. Systematic studies are performed to understand the effect of physicochemical properties of biomimicking NFM alone and with different concentrations of LP on human dental follicle stem cells (hDFSCs), their cellular attachment, proliferation, and osteogenic differentiation. The study highlights the effect of LP nanosilicate with biomimicking nanofibrous injectable scaffold system aiding in enhancing stem cell differentiation under normal physiological conditions compared to NFM without LP. The laponite–NFM shows suitability as excellent injectable biomaterials system for stem cell attachment, proliferation and osteogenic differentiation for stem cell transplantation and bone tissue regeneration.     

与胶原特异性结合的BMP2模拟肽/PLGA 3D打印复合支架的制备及成骨诱导活性

将胶原绑定结构域(CBD)多肽序列与骨形态发生蛋白2模拟肽(BMP2-MP)序列连接制备具有胶原绑定能力的CBD-BMP2-MP, 再将CBD-BMP2-MP与聚丙交酯-乙交酯/胶原(PLGA/COL)3D打印支架相结合, 以支架表面的胶原成分为媒介, 将CBD-BMP2-MP更有效地固定于骨修复材料上, 达到对其进行改性的目的. 利用扫描电子显微镜(SEM)、 电子万能试验机和接触角测量仪对复合支架表面形貌、 力学强度和亲水性等材料学性能进行评价. 用荧光成像法评测 CBD-BMP2-MP及BMP2-MP与支架材料的结合能力. 在各组支架材料表面接种MC3T3-E1细胞进行体外培养, 采用CCK-8、 鬼笔环肽荧光染色、 茜素红染色及qPCR综合评价细胞在材料表面的黏附、 增殖和成骨分化等细胞行为, 研究CBD-BMP2-MP修饰的3D多孔PLGA/COL复合支架的生物学性能. 研究结果表明, 利用3D打印技术制备的多孔支架具有形貌可控的孔隙结构, 为细胞生长创造更有利的细胞微环境, 支架表面胶原成分的加入提高了支架材料的亲水性, 同时对支架材料本身的力学性能无任何影响, 提高了复合支架本身的生物相容性. 与普通BMP2-MP相比, CBD-BMP2-MP具有更好的胶原绑定能力, 与复合支架的结合更稳定, 提高了PLGA/COL复合支架对BMP2-MP的负载能力. 支架表面负载CBD-BMP2-MP后具有极强的促细胞成骨分化能力. MC3T3-E1细胞表现出更高的钙沉积能力, 并且成骨分化相关基因Runx2, ALP, COL-I及OPN等水平也有了明显提升. 表明CBD-BMP2-MP多孔复合支架具有良好的生物相容性和成骨诱导活性, 在骨组织修复领域具有良好的应用前景.     

Novel 3D Neuron Regeneration Scaffolds Based on Synthetic Polypeptide Containing Neuron Cue

Neural tissue engineering has become a potential technology to restore the functionality of damaged neural tissue with the hope to cure the patients with neural disorder and to improve their quality of life. This paper reports the design and synthesis of polypeptides containing neuron stimulate, glutamic acid, for the fabrication of biomimetic 3D scaffold in neural tissue engineering application. The polypeptides are synthesized by efficient chemical reactions. Monomer γ‐benzyl glutamate‐N‐carboxyanhydride undergoes ring‐opening polymerization to form poly(γ‐benzyl‐l ‐glutamate), then hydrolyzes into poly(γ‐benzyl‐l ‐glutamate)‐r‐poly(glutamic acid) random copolymer. The glutamic acid amount is controlled by hydrolysis time. The obtained polymer molecular weight is in the range of 200 kDa for good quality of fibers. The fibrous 3D scaffolds of polypeptides are fabricated using electrospinning techniques. The scaffolds are biodegradable and biocompatible. The biocompatibility and length of neurite growth are improved with increasing amount of glutamic acid in scaffold. The 3D scaffold fabricated from aligned fibers can guide anisotropic growth of neurite along the fiber and into 3D domain. Furthermore, the length of neurite outgrowth is longer for scaffold made from aligned fibers as compared with that of isotropic fibers. This new polypeptide has potential for the application in the tissue engineering for neural regeneration.     

Bioorganometallic chemistry: biocatalytic oxidation reactions with biomimetic NAD/NADH co-factors and [Cp*Rh(bpy)H] for selective organic synthesis

The biocatalytic, regioselective hydroxylation of 2-hydroxybiphenyl to the corresponding catechol was accomplished utilizing the monooxygenase 2-hydroxybiphenyl 3-monooxygenase (HbpA). The necessary natural 1,4-dihydronicotinamde adenine dinucleotide (NADH) co-factor for this biocatalytic process was replaced by a biomimetic co-factor, N-benzyl-1,4-dihydronicotinamide, 1b. The interaction between the flavin (FAD) containing HbpA enzyme and the corresponding biomimetic NADH compound, N-benzyl-1,4-dihdronicotinamide, 1b, for hydride transfer, was shown to readily occur. The in situ recycling of the reduced NADH biomimic 1b from 1a was accomplished with [Cp*Rh(bpy)H](Cl); however, productive coupling of this regeneration reaction to the enzymatic hydroxylation reaction was not totally successful, due to a deactivation process concerning the HbpA enzyme peripheral groups; i.e., -SH or -NH₂ possibly reacting with the precatalyst, [Cp*Rh(bpy)(H₂O)](Cl)₂, and thus inhibiting the co-factor regeneration process. The deactivation mechanism was studied, and a promising strategy of derivatizing these peripheral -SH or -NH₂ groups with a polymer containing epoxide was successful in circumventing the undesired interaction between HbpA and the precatalyst. This latter strategy allowed tandem co-factor regeneration using 1a or 2a, [Cp*Rh(bpy)(H₂O)](Cl)₂, and formate ion, in conjunction with the polymer bound, FAD containing HbpA enzyme to provide the catechol product.     

L-Arginine based polyester amide/hyaluronic acid hybrid hydrogel with dual anti-inflammation and antioxidant functions for accelerated wound healing

Nowadays, there are still many challenges to skin regeneration. As a new type of skin substitute, hydrogel has emerging gradually with its excellent properties. However, it is still a challenge to combine with biological active agents to facilitate skin regeneration. Under the circumstance, we synthesized argininebased poly(ester amide)(Arg-PEA) and hyaluronic acid(HA-MA), and combined them into new hybrid hydrogels via photo-crosslinking. We found that the internal structure and physicochemical...     

Fabrication and Characterization of an Electro-Compacted Collagen/Elastin/Hyaluronic Acid Sheet as a Potential Skin Scaffold

The development of biomimetic structures with integrated extracellular matrix (ECM) components represents a promising approach to biomaterial fabrication. Here, an artificial ECM, comprising the structural protein collagen I and elastin (ELN), as well as the glycosaminoglycan hyaluronan (HA), is reported. Specifically, collagen and ELN are electrochemically aligned to mimic the compositional characteristics of the dermal matrix. HA is incorporated into the electro-compacted collagen-ELN matrices via adsorption and chemical immobilization, to give a final composition of collagen/ELN/HA of 7:2:1. This produces a final collagen/ELN/hyaluronic acid scaffold (CEH) that recapitulates the compositional feature of the native skin ECM. This study analyzes the effect of CEH composition on the cultivation of human dermal fibroblast cells (HDFs) and immortalized human keratinocytes (HaCaTs). It is shown that the CEH scaffold supports dermal regeneration by promoting HDFs proliferation, ECM deposition, and differentiation into myofibroblasts. The CEH scaffolds are also shown to support epidermis growth by supporting HaCaTs proliferation, differentiation, and stratification. A double-layered epidermal-dermal structure is constructed on the CEH scaffold, further demonstrating its ability in supporting skin cell function and skin regeneration.