Design of Collagen and Gelatin-based Electrospun Fibers for Biomedical Purposes: An Overview.

Collagen and gelatin are essential natural biopolymers commonly utilized in biomaterials and tissue engineering because of their excellent physicochemical and biocompatibility properties. They can be used either in combination with other biomacromolecules or particles or even exclusively for the enhancement of bone regeneration or for the development of biomimetic scaffolds. Collagen or gelatin derivatives can be transformed into nanofibrous materials with porous micro- or nanostructures and superior mechanical properties and biocompatibility using electrospinning technology. Specific attention was recently paid to electrospun mats of such biopolymers, due to their high ratio of surface area to volume, as well as their biocompatibility, biodegradability, and low immunogenicity. The fiber mats with submicro- and nanometer scale can replicate the extracellular matrix structure of human tissues and organs, making them highly suitable for use in tissue engineering due to their exceptional bioaffinity. The drawbacks may include rapid degradation and complete dissolution in aqueous media. The use of gelatin/collagen electrospun nanofibers in this form is thus greatly restricted for biomedicine. Therefore, the cross-linking of these fibers is necessary for controlling their aqueous solubility. This led to enhanced biological characteristics of the fibers, rendering them excellent options for various biomedical uses. The objective of this review is to highlight the key research related to the electrospinning of collagen and gelatin, as well as their applications in the biomedical field. The review features a detailed examination of the electrospinning fiber mats, showcasing their varying structures and performances resulting from diverse solvents, electrospinning processes, and cross-linking methods. Judiciously selected examples from literature will be presented to demonstrate major advantages of such biofibers. The current developments and difficulties in this area of research are also being addressed.

Evaluating the osteogenic properties of polyhydroxybutyrate-zein/multiwalled carbon nanotubes (MWCNTs) electrospun composite scaffold for bone tissue engineering applications.

In this investigation, the electrospun nanocomposite scaffolds were developed utilizing poly-3-hydroxybutyrate (PHB), zein, and multiwalled carbon nanotubes (MWCNTs) at varying concentrations of MWCNTs including 0.5 and 1 wt%. Based on the SEM evaluations, the scaffold containing 1 wt% MWCNTs (PZ-1C) exhibited the lowest fiber diameter (384 ± 99 nm) alongside a suitable porosity percentage. The presence of zein and MWCNT in the chemical structure of the scaffold was evaluated by FTIR. Furthermore, TEM images revealed the alignment of MWCNTs with the fibers. Adding 1 % MWCNTs to the PHB-zein scaffold significantly enhanced tensile strength by about 69 % and reduced elongation by about 31 %. Hydrophilicity, surface roughness, crystallinity, and biomineralization were increased by incorporating 1 wt% MWCNTs, while weight loss after in vitro degradation was decreased. The MG-63 cells exhibited enhanced attachment, viability, ALP secretion, calcium deposition, and gene expression (COLI, RUNX2, and OCN) when cultivated on the scaffold containing MWCNTs compared to the scaffolds lacking MWCNTs. Moreover, the study found that MWCNTs significantly reduced platelet adhesion and hemolysis rates below 4 %, indicating their favorable anti-hemolysis properties. Regarding the aforementioned results, the PZ-1C electrospun composite scaffold is a promising scaffold with osteogenic properties for bone tissue engineering applications.

Peptide direct growth on poly(acrylic acid)/poly(vinyl alcohol) electrospun fibers coated with branched poly(ethylenimine): A solid-phase approach for scaffolds biofunctionalization.

Due to their resemblance to the fibrillar structure of the extracellular matrix, electrospun nanofibrous meshes are currently used as porous and mechanically stable scaffolds for cell culture. In this study, we propose an innovative methodology for growing peptide sequences directly onto the surface of electrospun nanofibers. To achieve this, electrospun fibers were produced from a poly(acrylic acid)/poly(vinyl alcohol) blend that was thermally crosslinked and subjected to a covalent coating of branched poly(ethylenimine). The exposed amino functionalities on the fiber surface were then used for the direct solid-phase synthesis of the RGD peptide sequence. In contrast to established strategies, mainly involving the grafting of pre-synthesized peptides onto the polymer chains before electrospinning or onto the nanofibers surface, this method allows for the concurrent synthesis and anchoring of peptides to the substrate, with potential applications in combinatorial chemistry. The incorporation of this integrin-binding motive significantly enhanced the nanofibers' ability to capture human cervical carcinoma (HeLa) cells, selected as a proof of concept to assess the functionalities of the developed material.

Improved Recovery of Complete Spinal Cord Transection by a Plasma-Modified Fibrillar Scaffold.

Complete spinal cord injury causes an irreversible disruption in the central nervous system, leading to motor, sensory, and autonomic function loss, and a secondary injury that constitutes a physical barrier preventing tissue repair. Tissue engineering scaffolds are presented as a permissive platform for cell migration and the reconnection of spared tissue. Iodine-doped plasma pyrrole polymer (pPPy-I), a neuroprotective material, was applied to polylactic acid (PLA) fibers and implanted in a rat complete spinal cord transection injury model to evaluate whether the resulting composite implants provided structural and functional recovery, using magnetic resonance (MR) imaging, diffusion tensor imaging and tractography, magnetic resonance spectroscopy, locomotion analysis, histology, and immunofluorescence. In vivo, MR studies evidenced a tissue response to the implant, demonstrating that the fibrillar composite scaffold moderated the structural effects of secondary damage by providing mechanical stability to the lesion core, tissue reconstruction, and significant motor recovery. Histologic analyses demonstrated that the composite scaffold provided a permissive environment for cell attachment and neural tissue guidance over the fibers, reducing cyst formation. These results supply evidence that pPPy-I enhanced the properties of PLA fibrillar scaffolds as a promising treatment for spinal cord injury recovery.

AI-Driven Optimization of PCL/PEG Electrospun Scaffolds for Enhanced In Vivo Wound Healing.

Here, an artificial intelligence (AI)-based approach was employed to optimize the production of electrospun scaffolds for in vivo wound healing applications. By combining polycaprolactone (PCL) and poly(ethylene glycol) (PEG) in various concentration ratios, dissolved in chloroform (CHCl3) and dimethylformamide (DMF), 125 different polymer combinations were created. From these polymer combinations, electrospun nanofiber meshes were produced and characterized structurally and mechanically via microscopic techniques, including chemical composition and fiber diameter determination. Subsequently, these data were used to train a neural network, creating an AI model to predict the optimal scaffold production solution. Guided by the predictions and experimental outcomes of the AI model, the most promising scaffold for further in vitro analyses was identified. Moreover, we enriched this selected polymer combination by incorporating antibiotics, aiming to develop electrospun nanofiber scaffolds tailored for in vivo wound healing applications. Our study underscores three noteworthy conclusions: (i) the application of AI is pivotal in the fields of material and biomedical sciences, (ii) our methodology provides an effective blueprint for the initial screening of biomedical materials, and (iii) electrospun PCL/PEG antibiotic-bearing scaffolds exhibit outstanding results in promoting neoangiogenesis and facilitating in vivo wound treatment.

Transmucosal Delivery of Peptides and Proteins Through Nanofibers: Current Status and Emerging Developments.

Advancements in recombinant DNA technology have made proteins and peptides available for diagnostic and therapeutic applications, but their effectiveness when taken orally leads to poor patient compliance, requiring clinical administration. Among the alternative routes, transmucosal delivery has the advantage of being noninvasive and bypassing hepato-gastrointestinal clearance. Various mucosal routes-buccal, nasal, pulmonary, rectal, and vaginal-have been explored for delivering these macromolecules. Nanofibers, due to their unique properties like high surface-area-to-volume ratio, mechanical strength, and improved encapsulation efficiency, serve as promising carriers for proteins and peptides. These nanofibers can be tailored for quick dissolution, controlled release, enhanced encapsulation, targeted delivery, and improved bioavailability, offering superior pharmaceutical and pharmacokinetic performance compared to conventional methods. This leads to reduced dosages, fewer side effects, and enhanced patient compliance. Hence, nanofibers hold tremendous potential for protein/peptide delivery, especially through mucosal routes. This review focuses on the therapeutic application of proteins and peptides, challenges faced in their conventional delivery, techniques for fabricating different types of nanofibers and, various nanofiber-based dosage forms, and factors influencing nanofiber generation. Insights pertaining to the precise selection of materials used for fabricating nanofibers and regulatory aspects have been covered. Case studies wherein the use of specific protein/peptide-loaded nanofibers and delivered via oral/vaginal/nasal mucosa for diagnostic/therapeutic use and related preclinical and clinical studies conducted have been included in this review.

In Vitro Modulation of Spontaneous Activity in Embryonic Cardiomyocytes Cultured on Poly(vinyl alcohol)/Bioglass Type 58S Electrospun Scaffolds.

Because of the physiological and cardiac changes associated with cardiovascular disease, tissue engineering can potentially restore the biological functions of cardiac tissue through the fabrication of scaffolds. In the present study, hybrid nanofiber scaffolds of poly (vinyl alcohol) (PVA) and bioglass type 58S (58SiO2-33CaO-9P2O5, Bg) were fabricated, and their effect on the spontaneous activity of chick embryonic cardiomyocytes in vitro was determined. PVA/Bg nanofibers were produced by electrospinning and stabilized by chemical crosslinking with glutaraldehyde. The electrospun scaffolds were analyzed to determine their chemical structure, morphology, and thermal transitions. The crosslinked scaffolds were more stable to degradation in water. A Bg concentration of 25% in the hybrid scaffolds improved thermal stability and decreased degradation in water after PVA crosslinking. Cardiomyocytes showed increased adhesion and contractility in cells seeded on hybrid scaffolds with higher Bg concentrations. In addition, the effect of Ca2+ ions released from the bioglass on the contraction patterns of cultured cardiomyocytes was investigated. The results suggest that the scaffolds with 25% Bg led to a uniform beating frequency that resulted in synchronous contraction patterns.

Polycaprolactone/graphene oxide/acellular matrix nanofibrous scaffolds with antioxidant and promyelinating features for the treatment of peripheral demyelinating diseases.

Peripheral demyelinating diseases entail damage to axons and Schwann cells in the peripheral nervous system. Because of poor prognosis and lack of a cure, this group of diseases has a global impact. The primary underlying cause of these diseases involves the inability of Schwann cells to remyelinate the damaged insulating myelin around axons, resulting in neuronal death over time. In the past decade, extensive research has been directed in the direction of Schwann cells focusing on their physiological and neuroprotective effects on the neurons in the peripheral nervous system. One cause of dysregulation in the remyelinating function of Schwann cells has been associated with oxidative stress. Tissue-engineered biodegradable scaffolds that can stimulate remyelination response in Schwann cells have been proposed as a potential treatment strategy for peripheral demyelinating diseases. However, strategies developed to date primarily focussed on either remyelination or oxidative stress in isolation. Here, we have developed a multifunctional nanofibrous scaffold with material and biochemical cues to tackle both remyelination and oxidative stress in one matrix. We developed a nanofibrous scaffold using polycaprolactone (PCL) as a foundation loaded with antioxidant graphene oxide (GO) and coated this bioscaffold with Schwann cell acellular matrix. In vitro studies revealed both antioxidant and remyelination properties of the developed bioscaffold. Based on the results, the developed multifunctional bioscaffold approach can be a promising biomaterial approach for treating demyelinating diseases.

Novel Nanostructured Scaffolds of Poly(butylene trans-1,4-cyclohexanedicarboxylate)-Based Copolymers with Tailored Hydrophilicity and Stiffness: Implication for Tissue Engineering Modeling.

Here, we present novel biocompatible poly(butylene trans-1,4-cyclohexanedicarboxylate) (PBCE)-based random copolymer nanostructured scaffolds with tailored stiffness and hydrophilicity. The introduction of a butylene diglycolate (BDG) co-unit, containing ether oxygen atoms, along the PBCE chain remarkably improved the hydrophilicity and chain flexibility. The copolymer containing 50 mol% BDG co-units (BDG50) and the parent homopolymer (PBCE) were synthesized and processed as electrospun scaffolds and compression-molded films, added for the sake of comparison. We performed thermal, wettability, and stress-strain measures on the PBCE-derived scaffolds and films. We also conducted biocompatibility studies by evaluating the adhesion and proliferation of multipotent mesenchymal/stromal cells (hBM-MSCs) on each polymeric film and scaffold. We demonstrated that solid-state properties can be tailored by altering sample morphology besides chemical structure. Thus, scaffolds were characterized by a higher hydrophobicity and a lower elastic modulus than the corresponding films. The three-dimensional nanostructure conferred a higher adsorption protein capability to the scaffolds compared to their film counterparts. Finally, the PBCE and BDG50 scaffolds were suitable for the long-term culture of hBM-MSCs. Collectively, the PBCE homopolymer and copolymer are good candidates for tissue engineering applications.

The ad hoc chemical design of random PBS-based copolymers influences the activation of cardiac differentiation while altering the HYPPO pathway target genes in hiPSCs.

Cardiac tissue engineering is a cutting-edge technology aiming to replace irreversibly damaged cardiac tissue and restore contractile functionality. However, cardiac tissue engineering porous and perfusable scaffolds to enable oxygen supply in vitro and eventually promote angiogenesis in vivo are still desirable. Two fully-aliphatic random copolymers of poly(butylene succinate) (PBS), poly(butylene succinate/Pripol), P(BSBPripol), and poly(butylene/neopentyl glycol succinate), P(BSNS), containing two different subunits, neopentyl glycol and Pripol 1009, were successfully synthesized and then electrospun in tridimentional fibrous mats. The copolymers show different thermal and mechanical behaviours as result of their chemical structure. In particular, copolymerization led to a reduction in crystallinity and consequently PBS stiffness, reaching values of elastic modulus very close to those of soft tissues. Then, to check the biological suitability, human induced Pluripotent Stem Cells (hiPSCs) were directly seeded on both PBS-based copolymeric scaffolds. The results confirmed the ability of both the scaffolds to sustain cell viability and to maintain their stemness during cell expansion. Furthermore, gene expression and immunofluorescence analysis showed that P(BSBPripol) scaffold promoted an upregulation of the early cardiac progenitor and later-stage markers with a simultaneously upregulation of HYPPO pathway gene expression, crucial for mechanosensing of cardiac progenitor cells. These results suggest that the correct ad-hoc chemical design and, in turn, the mechanical properties of the matrix, such as substrate stiffness, together with surface porosity, play a critical role in regulating the behaviour of cardiac progenitors, which ultimately offers valuable insights into the development of novel bio-inspired scaffolds for cardiac tissue regeneration.

Investigation of osteogenesis and angiogenesis in perfusion bioreactors using improved multi-layer PCL-nHA-nZnO electrospun scaffolds.

PURPOSE: Bone tissue engineering aims to create a three-dimensional, matured, angiogenic scaffold with a suitable thickness that resembles a natural bone matrix. On the other hand, electrospun fibers, which researchers have considered due to their good biomimetic properties, are considered 2D structures. Due to the highly interwoven network and small pore size, achieving the desired thickness for bone lesions has always been challenging. In bone tissue engineering, bioreactors are crucial for achieving initial tissue maturity and introducing certain signals as flow parameters for differentiation. METHODS: In the present study, Human bone marrow mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) were co-cultured in a perfusion bioreactor on treated (improved pore size by gelatin sacrification and subsequent ultrasonication) 5-layer polycaprolactone-nano hydroxyapatite-nano zinc oxide (T-PHZ) scaffolds to investigate osteogenesis and angiogenesis simultaneously. The flow parameters and stresses on the cells were studied using two patterns of parallel and vertical scaffolds relative to the flow of the culture medium. In dynamic vertical flow (DVF), the culture medium flows perpendicular to the scaffolds, and in dynamic parallel flow (DPF), the culture medium flows parallel to the scaffolds. In all evaluations, static samples (S) served as the control group. RESULTS: Live/dead, and MTT assays demonstrated the biocompatibility of the 5-layer scaffolds and the suitability of the bioreactor's functional conditions. ALP activity, EDAX analysis, and calcium content measurements exhibited greater osteogenesis for T-PHZ scaffolds in DVF conditions. Calcium content increased by a factor of 2.2, 1.8, and 1.6 during days 7 to 14 of culture under DVF, DPF and S conditions, respectively. After 21 days of co-culturing, an immunohistochemistry (IHC) test was performed to investigate angiogenesis and osteogenesis. Five antibodies were investigated in DVF, CD31, VEGFA, and VEGFR2 for angiogenesis, osteocalcin, and RUNX2 for osteogenesis. Compressive stress applied in DVF mode has increased osteogenic activity compared to DPF. CONCLUSION: The results indicated the development of ideal systems for osteogenesis and angiogenesis on the treated multilayer electrospun scaffolds in the perfusion bioreactor.

Development of Mucoadhesive Electrospun Scaffolds for Intravaginal Delivery of Lactobacilli spp., a Tenside, and Metronidazole for the Management of Bacterial Vaginosis.

Bacterial vaginosis (BV) is an infection of the vagina associated with thriving anaerobes, such as Gardnerella vaginitis and other associated pathogens. These pathogens form a biofilm responsible for the recurrence of infection after antibiotic therapy. The aim of this study was to develop a novel mucoadhesive polyvinyl alcohol and polycaprolactone electrospun nanofibrous scaffolds for vaginal delivery, incorporating metronidazole, a tenside, and Lactobacilli. This approach to drug delivery sought to combine an antibiotic for bacterial clearance, a tenside biofilm disruptor, and a lactic acid producer to restore healthy vaginal flora and prevent the recurrence of bacterial vaginosis. F7 and F8 had the least ductility at 29.25% and 28.39%, respectively, and this could be attributed to the clustering of particles that prevented the mobility of the crazes. F2 had the highest at 93.83% due to the addition of a surfactant that increased the affinity of the components. The scaffolds exhibited mucoadhesion between 31.54 ± 0.83% and 57.86 ± 0.95%, where an increased sodium cocoamphoacetate concentration led to increased mucoadhesion. F6 showed the highest mucoadhesion at 57.86 ± 0.95%, as compared to 42.67 ± 1.22% and 50.89 ± 1.01% for the F8 and F7 scaffolds, respectively. The release of metronidazole via a non-Fickian diffusion-release mechanism indicated both swelling and diffusion. The anomalous transport within the drug-release profile pointed to a drug-discharge mechanism that combined both diffusion and erosion. The viability studies showed a growth of Lactobacilli fermentum in both the polymer blend and the nanofiber formulation that was retained post-storage at 25 °C for 30 days. The developed electrospun scaffolds for the intravaginal delivery of Lactobacilli spp., along with a tenside and metronidazole for the management of bacterial vaginosis, provide a novel tool for the treatment and management of recurrent vaginal infection.

Collagen Functionalization of Polymeric Electrospun Scaffolds to Improve Integration into Full-Thickness Wounds.

BACKGROUND: Electrospun fibers are widely studied in regenerative medicine for their ability to mimic the extracellular matrix (ECM) and provide mechanical support. In vitro studies indicated that cell adhesion and migration is superior on smooth poly(L-lactic acid) (PLLA) electrospun scaffolds and porous scaffolds once biofunctionalized with collagen. METHODS: The in vivo performance of PLLA scaffolds with modified topology and collagen biofunctionalization in full-thickness mouse wounds was assessed by cellular infiltration, wound closure and re-epithelialization and ECM deposition. RESULTS: Early indications suggested unmodified, smooth PLLA scaffolds perform poorly, with limited cellular infiltration and matrix deposition around the scaffold, the largest wound area, a significantly larger panniculus gape, and lowest re-epithelialization; however, by day 14, no significant differences were observed. Collagen biofunctionalization may improve healing, as collagen-functionalized smooth scaffolds were smallest overall, and collagen-functionalized porous scaffolds were smaller than non-functionalized porous scaffolds; the highest re-epithelialization was observed in wounds treated with collagen-functionalized scaffolds. CONCLUSION: Our results suggest that limited incorporation of smooth PLLA scaffolds into the healing wound occurs, and that altering surface topology, particularly by utilizing collagen biofunctionalization, may improve healing. The differing performance of the unmodified scaffolds in the in vitro versus in vivo studies demonstrates the importance of preclinical testing.

Biodegradable Scaffolds for Vascular Regeneration Based on Electrospun Poly(L-Lactide-co-Glycolide)/Poly(Isosorbide Sebacate) Fibers.

Vascular regeneration is a complex process, additionally limited by the low regeneration potential of blood vessels. Hence, current research is focused on the design of artificial materials that combine biocompatibility with a certain rate of biodegradability and mechanical robustness. In this paper, we have introduced a scaffold material made of poly(L-lactide-co-glycolide)/poly(isosorbide sebacate) (PLGA/PISEB) fibers fabricated in the course of an electrospinning process, and confirmed its biocompatibility towards human umbilical vein endothelial cells (HUVEC). The resulting material was characterized by a bimodal distribution of fiber diameters, with the median of 1.25 µm and 4.75 µm. Genotyping of HUVEC cells collected after 48 h of incubations on the surface of PLGA/PISEB scaffolds showed a potentially pro-angiogenic expression profile, as well as anti-inflammatory effects of this material. Over the course of a 12-week-long hydrolytic degradation process, PLGA/PISEB fibers were found to swell and disintegrate, resulting in the formation of highly developed structures resembling seaweeds. It is expected that the change in the scaffold structure should have a positive effect on blood vessel regeneration, by allowing cells to penetrate the scaffold and grow within a 3D structure of PLGA/PISEB, as well as stabilizing newly-formed endothelium during hydrolytic expansion.

Construction of spider silk protein small-caliber tissue engineering vascular grafts based on dynamic culture and its performance evaluation.

Tissue engineering is an alternative method for preparing small-caliber (<6 mm) vascular grafts. Dynamic mechanical conditioning is being researched as a method to improve mechanical properties of tissue engineered blood vessels. This method attempts to induce unique reaction in implanted cells that regenerate the matrix around them, thereby improving the overall mechanical stability of the grafts. In this study, we used a bioreactor to seed endothelial cells and smooth muscle cells into the inner and outer layers of the electrospun spider silk protein scaffold respectively to construct vascular grafts. The cell proliferation, mechanical properties, blood compatibility and other indicators of the vascular grafts were characterized in vitro. Furthermore, the vascular grafts were implanted in Sprague Dawley rats, and the vascular grafts' patency, extracellular matrix formation, and inflammatory response were evaluated in vivo. We aimed to construct spider silk protein vascular grafts with the potential for in vivo implantation by using a pulsating flow bioreactor. The results showed that, when compared with the static culture condition, the dynamic culture condition improved cell proliferation on vascular scaffolds and enhanced mechanical function of vascular scaffolds. In vivo experiments also showed that the dynamic culture of vascular grafts was more beneficial for the extracellular matrix deposition and anti-thrombogenesis, as well as reducing the inflammatory response of vascular grafts. In conclusion, dynamic mechanical conditioning aid in the resolution of challenges impeding the application of electrospun scaffolds and have the potential to construct small-caliber blood vessels with regenerative function for cardiovascular tissue repair.

Multi-responsive on-demand drug delivery PMMA-co-PDEAEMA platform based on CO2, electric potential, and pH switchable nanofibrous membranes.

This study investigated the release characteristics of curcumin (CUR)-loaded switchable poly(methyl methacrylate)-co-poly(N,N-diethylaminoethyl methacrylate) (PMMA-co-PDEAEMA) membranes following the application of various stimuli, as well as the platform's applicability in wound dressing and tissue engineering applications. The free-radical polymerization method was used to synthesize the PMMA-co-PDEAEMA copolymer. The drug-loaded nanofibrous membrane with electric potential (EP)-, CO2-, and pH-responsive properties was developed by the electrospinning of PMMA-co-PDEAEMA and CUR. The resulted structure was characterized by a scanning electron microscope (SEM) coupled with X-ray energy dispersive spectroscopy and wide-angle X-ray scattering measurements. The release characteristics of the CUR-loaded wound covering were analyzed in various simulated environments at varying voltages, alternated CO2/N2 gas bubbling, and at two different pH values; the results demonstrated high drug release controllability. Loaded CUR displayed high stability and better solubility compared with free CUR. The CUR-loaded tissue also exhibited high antibacterial activity against Escherichia coli and staphylococcus aureus bacteria. In addition, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay depicted high biocompatibility of up to 95% in the CUR-loaded membrane. This platform could be a promising candidate for usage in tissue engineering and medical applications such as targeted drug delivery, biodetection, reversible cell capture-and-release systems, and biosensors.

Differential Foreign Body Reactions between Branched and Linear Glucomannan Scaffolds.

The extent and patterns of foreign body reaction (FBR) influence the function and feasibility of biomaterials. Polysaccharides, as an important biomaterial category, have received increasing attention in diverse biomaterials design and biomedical applications due to their excellent polymeric and biocompatible characteristics. Their biological effects are usually associated with their monosaccharide composition or functional groups, yet the contribution of their glycan structure is still unknown. Herein, two glucomannans, similar in composition and molecular weight with differences in glycan structure, linear-chain (Konjac glucomannan, KGM), and branched-chain (Bletilla striata polysaccharide, BSP), were adopted to explore the host-biomaterials interaction. After acetyl modification, these polysaccharides were fabricated into electrospun scaffolds to reduce the impacts derived from the physical properties and surface morphology. According to a systematic study of their biological effects on immune cells and host response in a subcutaneous implantation model in vivo, it was revealed that acetyl KGM (acKGM) scaffolds caused a stronger FBR than acetyl BSP materials. Additionally, acKGM could stimulate macrophages to release pro-inflammatory cytokines, suggesting the influence of sugar chain arrangement on FBR and providing clues for the fine regulation of immune response and novel biomaterials design.

Pulsed Vacuum Arc Deposition of Nitrogen-Doped Diamond-like Coatings for Long-Term Hydrophilicity of Electrospun Poly(ε-caprolactone) Scaffolds.

The surface hydrophobicity of poly(ε-caprolactone) electrospun scaffolds prevents their interactions with cells and tissue integration. Although plasma treatment of scaffolds enhances their hydrophilicity, this effect is temporary, and the hydrophobicity of the scaffolds is restored in about 30 days. In this communication, we report a method for hydrophilization of poly(ε-caprolactone) electrospun scaffolds for more than 6 months. To that end, diamond-like coating was deposited on the surface of the scaffolds in a nitrogen atmosphere using pulsed vacuum arc deposition with sputtering of graphite target. This approach allows for a single-side hydrophilization of the scaffold (water contact angle of 22 ± 3° vs. 126 ± 2° for pristine PCL scaffold) and preserves its structure. With increased nitrogen pressure in the chamber, sp3-hybridized carbon content decreased twice (sp2/sp3 ratio decreased from 1.06 to 0.52), which demonstrates the possibility of tailoring the content of carbon in sp2 and sp3 hybridization state. Nitrogen content in the deposited coatings was found at 16.1 ± 0.9 at.%. In vitro tests with fibroblast cell culture did not reveal any cytotoxic compounds in sample extracts.

From In Vitro to Perioperative Vascular Tissue Engineering: Shortening Production Time by Traceable Textile-Reinforcement.

BACKGROUND: The production of tissue-engineered vascular graft (TEVG) usually involves a prolonged bioreactor cultivation period of up to several weeks to achieve maturation of extracellular matrix and sufficient mechanical strength. Therefore, we aimed to substantially shorten this conditioning time by combining a TEVG textile scaffold with a recently developed copolymer reinforced fibrin gel as a cell carrier. We further implemented our grafts with magnetic resonance imaging (MRI) contrast agents to allow the in-vitro monitoring of the TEVG's remodeling process. METHODS: Biodegradable polylactic-co-glycolic acid (PLGA) was electrospun onto a non-degradable polyvinylidene fluoride scaffold and molded along with copolymer-reinforced fibrin hydrogel and human arterial cells. Mechanical tests on the TEVGs were performed both instantly after molding and 4 days of bioreactor conditioning. The non-invasive in vitro monitoring of the PLGA degradation and the novel imaging of fluorinated thermoplastic polyurethane (19F-TPU) were performed using 7T MRI. RESULTS: After 4 days of close loop bioreactor conditioning, 617 ± 85 mmHg of burst pressure was achieved, and advanced maturation of extracellular matrix (ECM) was observed by immunohistology, especially in regards to collagen and smooth muscle actin. The suture retention strength (2.24 ± 0.3 N) and axial tensile strength (2.45 ± 0.58 MPa) of the TEVGs achieved higher values than the native arteries used as control. The contrast agents labeling of the TEVGs allowed the monitorability of the PLGA degradation and enabled the visibility of the non-degradable textile component. CONCLUSION: Here, we present a concept for a novel textile-reinforced TEVG, which is successfully produced in 4 days of bioreactor conditioning, characterized by increased ECM maturation and sufficient mechanical strength. Additionally, the combination of our approach with non-invasive imaging provides further insights into TEVG's clinical application.

Effect of cellulose nanofibers on polyhydroxybutyrate electrospun scaffold for bone tissue engineering applications.

The choice of materials and preparation methods are the most important factors affecting the final characteristics of the scaffolds. In this study, cellulose nanofibers (CNFs) as a nano-additive reinforcer were selected to prepare a polyhydroxybutyrate (PHB) based nanocomposite mat. The PHB/CNF (PC) scaffold properties, created via the electrospinning method, were investigated and compared with pure PHB. The obtained results, in addition to a slight increment of crystallinity (from ≃46 to 53 %), showed better water contact angle (from ≃120 to 96°), appropriate degradation rate (up to ≃25 % weight loss in two months), prominent biomineralization (Ca/P ratio about 1.50), and ≃89 % increment in toughness factor of PC compare to the neat PHB. Moreover, the surface roughness as an affecting parameter on cell behavior was also increased up to ≃43 % in the presence of CNFs. Eventually, not only the MTT assay revealed better human osteoblast MG63 cell viability on PC samples, but also DAPI staining and SEM results confirmed the more plausible cell spreading in the presence of cellulose nano-additive. These improvements, along with the appropriate results of ALP and Alizarin red, authenticate that the newly PC nanocomposite composition has the required efficiency in the field of bone tissue engineering.