Scaffolds For Tissue Engineering Research Articles

Construction and performance evaluation of fully biomimetic hyaline cartilage matrix scaffolds for joint defect regeneration

Due to the absence of nerves and blood vessels in articular cartilage, its regeneration and repair present a significant and complex challenge in osteoarthritis treatment. Developing a specialized physical and chemical microenvironment supporting cell growth has been difficult in cartilage grafting, especially when aiming for comprehensive biomimetic solutions. Based on previous research, we have designed a tissue-engineered decellularized living hyaline cartilage graft (dLhCG). The study developed a method to improve the hydrophilicity and stiffness of scaffolds by employing chemical grafting techniques and designed a decellularized hyaline cartilage phenotype matrix scaffold for tissue engineering. Here, we reported a method using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride /N-hydroxysuccinimide (EDC/NHS) to achieve the grafting of chondroitin sulfate (CS) onto dLhCG, ultimately producing a tissue-engineered hyaline cartilage graft with the CS (dLhCG/CS). Young's modulus measurements revealed that the cross-linked scaffolds exhibited enhanced mechanical properties. We implanted the cross-linked dLhCG/CS scaffolds into the trochlear region of rat joints and evaluated their functionality through histological analysis and biomechanical tests. After 12 weeks, the dLhCG/CS scaffolds demonstrated excellent bioinductive activity comparable to dLhCG. The regenerated tissue effectively maintained a hyaline cartilage phenotype and exhibited similar mechanical properties, playing a crucial role in cartilage regeneration.

Integrated environmental and health economic assessments of novel xeno-keratografts addressing a growing public health crisis

Tissue scarcity poses global challenges for corneal transplantation and public health. Xeno-keratoplasty using animal-derived tissues offers a potential solution, but its environmental and economic implications remain unclear. This study evaluated two xeno-keratoplasty procedures at a single institution: (1) native corneas (Option 1) and (2) tissue-engineered corneal scaffolds derived from slaughterhouse waste (Option 2). Life cycle assessment (LCA) quantified environmental impacts across 18 midpoint indicators, while cost-effectiveness analysis (CEA) incorporated cost and environmental impact using two approaches. Option 1 exhibited significantly lower environmental impact than Option 2 across most indicators, primarily due to the energy and equipment demands of cell culture in Option 2. Both CEA approaches (carbon offset pricing and utility decrement) demonstrated cost-effectiveness dominance for Option 1. Xeno-keratoplasty using native corneas (Option 1) appears more environmentally and economically favorable than tissue-engineered scaffolds (Option 2) in the current analysis. Future studies could explore diverse xeno-keratoplasty techniques for optimizing sustainability.

Poly(HEMA-co-MMA) Hydrogel Scaffold for Tissue Engineering with Controllable Morphology and Mechanical Properties Through Self-Assembly

Poly(2-hydroxyethyl methacrylate) (PHEMA) has been widely used in medical materials for several decades. However, the poor mechanical properties of this material have limited its application in the field of tissue engineering. The purpose of this study was to fabricate a scaffold with suitable mechanical properties and in vitro cell responses for soft tissue by using poly(HEMA-co-MMA) with various concentration ratios of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA). To customize the concentration ratio of HEMA and MMA, the characteristics of the fabricated scaffold with various concentration ratios were investigated through structural morphology, FT-IR, mechanical property, and contact angle analyses. Moreover, in vitro cell responses were observed according to the various concentration ratios of HEMA and MMA. Consequently, various morphologies and pore sizes were observed by changing the HEMA and MMA ratio. The mechanical properties and contact angle of the fabricated scaffolds were measured according to the HEMA and MMA concentration ratio. The results were as follows: compressive maximum stress: 254.24–932.42 KPa; tensile maximum stress: 4.37–30.64 KPa; compressive modulus: 16.14–38.80 KPa; tensile modulus: 0.5–2 KPa; and contact angle: 36.89–74.74°. In terms of the in vitro cell response, the suitable cell adhesion and proliferation of human dermal fibroblast (HDF) cells were observed in the whole scaffold. Therefore, a synthetic hydrogel scaffold with enhanced mechanical properties and suitable fibroblast cell responses could be easily fabricated for use with soft tissue using a specific HEMA and MMA concentration ratio.

A facile method for carbon nanotube/carbon fiber‐reinforced polylactic acid composites

AbstractThe mechanical strength of polylactic acid (PLA) can be improved by carbon fiber (CF) compositing to expand its application in tissue engineering scaffolds. However, the mechanical strength of CF‐reinforced polylactic acid (CFRPLA) composites is compromised due to weak interfacial interaction resulting from the chemically inert surface of CF. In the article, carbon nanotube (CNT) with poly(diallyldimethylammonium chloride) (PDDA) as a coupling agent was covered on CF to improve the chemical activity and roughness of the surface of CF, and then the as‐prepared CF‐PCNT were further incorporated into PLA via melt compounding. The yield strength, modulus, and thermal conductivity of PLA/CF‐PCNT were 14.09%, 7.65%, and 5.24% higher than those of PLA/CF, respectively, and the volume resistivity was 99.74% lower at a 10 wt% loading. The enhancement for the mechanical properties of PLA/CF‐PCNT composites could be ascribed to the mechanical locking, hydrogen bonds and covalent bonds between CF and matrix through the interface modulation of CNT and PDDA. This facile and non‐destructive method offers a novel strategy for the modification of CF fillers.Highlights CF was modified by PDDA and CNT through a facile and non‐destructive method. The active functional groups and roughness on the surface of CF were increased. The surfaces of CFs were characterized by FT‐IR, Raman spectra, XPS and SEM. The interface was improved by mechanical locking, covalent, and hydrogen bonds. The mechanical strength, electrical and thermal conductivity of composites were improved.

Human amniotic membrane scaffold enhances adipose mesenchymal stromal cell mitochondrial bioenergetics promoting their regenerative capacities.

The human amniotic membrane (hAM) has been applied as a scaffold in tissue engineering to sustain stem cells and enhance their regenerative capacities. We investigated the molecular and biochemical regulations of mesenchymal stromal cells (MSCs) cultured on hAM scaffold in a three-dimensional (3D) setting. Culture of adipose-MSCs (AMSCs) on decellularized hAM showed significant improvement in their viability, proliferative capacity, resistance to apoptosis, and enhanced MSC markers expression. These cultured MSCs displayed altered expression of markers associated with pro-angiogenesis and inflammation and demonstrated increased potential for differentiation into adipogenic and osteogenic lineages. The hAM scaffold modulated cellular respiration by upregulating glycolysis in MSCs as evidenced by increased glucose consumption, cellular pyruvate and lactate production, and upregulation of glycolysis markers. These metabolic changes modulated mitochondrial oxidative phosphorylation (OXPHOS) and altered the production of reactive oxygen species (ROS), expression of OXPHOS markers, and total antioxidant capacity. They also significantly boosted the urea cycle and altered the mitochondrial ultrastructure. Similar findings were observed in bone marrow-derived MSCs (BMSCs). Live cell imaging of BMSCs cultured in the same 3D environment revealed dynamic changes in cellular activity and interactions with its niche. These findings provide evidence for the favorable properties of hAM as a biomimetic scaffold for enhancing the in vitro functionality of MSCs and supporting their potential usefulness in clinical applications.

The induction of bone formation by 3D-printed PLGA microsphere scaffolds in a calvarial orthotopic mouse model: a pilot study

Polymeric biodegradable microspheres are readily utilized to support targeted drug delivery for various diseases clinically. 3D printed tissue engineering scaffolds from polymer filaments with embedded microspheres or nanoparticles, as well as bulk microsphere scaffolds, have been investigated for regenerative medicine and tissue engineering. However, 3D printed scaffolds consisting only of a homogenous microsphere size with an optimized architecture that includes a unique micro- and macroporosity, have been challenging to produce and hence, have not been assessed in the literature yet. Utilizing our recently established 3D-MultiCompositional Microsphere-Adaptive Printing (3D-McMap) method, the present study evaluated the effectiveness of 3D-printed poly (lactic-co-glycolic acid) (PLGA) microsphere scaffolds, consisting of microsphere sizes 50, 100, or 200 μm, on the induction of bone formation when implanted in the calvarial murine regeneration model. Our results showed that PLGA microsphere scaffolds possess unique properties that support bone regeneration by supporting osteoconduction and stimulating, in our opinion, true spontaneous osteoinduction. The study demonstrated that PLGA microsphere-based scaffolds support bone growth in the absence of additional growth factors and promote osteogenesis primarily via their unique geometric configuration. The larger the microspheres were, the greater de novo bone formation was. This proves that bone tissue engineering scaffolds 3D printed from microspheres, enabled by the 3D-McMap method, are superior over bulk material printed scaffolds, as they possess the unique capability of spontaneous induction of new bone formation. With the addition of encapsulated modulatory bone-forming biomolecules they can substantially improve the spatiotemporal control of tissue morphogenesis, potentially leading to new innovative clinical tissue repair therapies that regenerate bone in large defects correctly and fully.

Enhanced Mechanical Properties and Degradation Control of Poly(Lactic) Acid/Hydroxyapatite/Reduced Graphene Oxide Composites for Advanced Bone Tissue Engineering Application

This study explores the enhancement of poly(lactic acid) (PLA) matrix using calcium hydroxyapatite (cHAP) and reduced graphene oxide (rGO) for developing composite scaffolds aimed at bone regeneration applications. The PLA composites were fabricated through solvent evaporation and melt extrusion and characterized by various techniques, including thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and mechanical testing. The incorporation of cHAP and rGO significantly improved the thermal, mechanical, and morphological properties of the PLA matrix. Mechanical testing revealed that adding 10% cHAP and varying amounts of rGO (0.1%, 0.3%, 0.5%) enhanced tensile and compressive strengths, with the highest improvements observed at 0.5% rGO content. Thermal analysis showed increased thermal stability with higher degradation temperatures for the composites. Spectroscopic analyses confirmed the effective integration of cHAP and rGO into the PLA matrix with characteristic peaks of the fillers identified in the composite spectra. In vitro, degraded action tests in phosphate-buffered saline (PBS) at pH 7.4 over 12 months indicated that composites with higher rGO content exhibited lower mass loss and better mechanical stability. Furthermore, finite element analysis (FEA) simulations were performed to validate the experimental results, demonstrating a strong correlation between simulated and experimental compressive strengths. This novel approach demonstrates the potential of PLA/cHAP/rGO composites in creating effective and biocompatible scaffolds for tissue engineering, providing a comprehensive analysis of the synergistic effects of cHAP and rGO on the PLA matrix and offering a promising material for bone regeneration applications.

Double-Network Hydrogel 3D BioPrinting Biocompatible with Fibroblast Cells for Tissue Engineering Applications

The present study examines the formulation of a biocompatible hydrogel bioink for 3D bioprinting, integrating poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA) using a double-network approach. These materials were chosen for their synergistic qualities, with PEGDA contributing to mechanical integrity and SA ensuring biocompatibility. Fibroblast cells were included in the bioink and printed with a Reg4Life bioprinter employing micro-extrusion technology. The optimisation of printing parameters included needle size and flow velocities. This led to precise structure development and yielded results with a negligible deviation in printed angles and better control of line widths. The rheological characteristics of the bioink were evaluated, demonstrating appropriate viscosity and shear-thinning behaviour for efficient extrusion. The mechanical characterisation revealed an average compressive modulus of 0.38 MPa, suitable for tissue engineering applications. The printability of the bioink was further confirmed through the evaluations of morphology and diffusion rates, confirming structural integrity. Biocompatibility assessments demonstrated a high cell viability rate of 82.65% following 48 h of incubation, supporting the bioink’s suitability for facilitating cell survival. This study introduced a reliable technique for producing tissue-engineered scaffolds that exhibit outstanding mechanical characteristics and cell viability, highlighting the promise of PEGDA–SA hydrogels in bioprinting applications.

Application of electrospinning and 3D-printing based bilayer composite scaffold in the skull base reconstruction during transnasal surgery

Skull base defects are a common complication after transsphenoidal endoscopic surgery, and their commonly used autologous tissue repair has limited clinical outcomes. Tissue-engineered scaffolds prepared by advanced techniques of electrostatic spinning and three-dimensional (3D) printing was an effective way to solve this problem. In this study, soft tissue scaffolds consisting of centripetal nanofiber mats and 3D-printed hard tissue scaffolds consisting of porous structures were prepared, respectively. And the two layers were combined to obtain bilayer composite scaffolds. The physicochemical characterization proved that the nanofiber mat prepared by polylactide-polycaprolactone (PLCL) electrospinning had a uniform centripetal nanofiber structure, and the loaded bFGF growth factor could achieve a slow release for 14 days and exert its bioactivity to promote the proliferation of fibroblasts. The porous scaffolds prepared with polycaprolactone (PCL), and hydroxyapatite (HA) 3D printing have a 300 μm macroporous structure with good biocompatibility. In vivo experiments results demonstrated that the bilayer composite scaffold could promote soft tissue repair of the skull base membrane through the centripetal nanofiber structure and slow-release of bFGF factor. It also played the role of promoting the regeneration of the skull base bone tissue. In addition, the centripetal nanofiber structure also had a promotional effect on the regeneration of skull base bone tissue.

Biomimetic Mineralized Organic–Inorganic Hybrid Scaffolds From Microfluidic 3D Printing for Bone Repair

AbstractBone defect is a common clinical orthopedic disease. The trend in this field is to develop tissue engineering scaffolds with appropriately designed components and structures for bone repair. Herein, inspired by the organic and inorganic components of bone matrix and the natural biomineralization mechanism, a MgSiO3@Fe3O4 nanoparticle composite polycaprolactone (PCL) hybrid mineralized scaffold for bone repair is developed by microfluidic 3D printing. The incorporation of MgSiO3@Fe3O4 within the PCL scaffold can effectively improve the bioactivity. In addition, a biomimetic mineralized layer is prepared on the surface of the scaffold, which endowed it with unique microstructural characteristics, enhanced cell adhesion and osteogenic activity, and thus improved the bone repair performance. Owing to these advantages, both in vivo and in vitro experiments have demonstrated that the designed scaffold has outstanding biocompatibility and bone repair performance. These features indicate that the organic–inorganic biomineralized hybrid scaffold can be a potential bone graft substitute for clinical bone repair.

Scaffold-based tissue engineering strategies for urethral repair and reconstruction.

Urethral strictures are common in urology; however, the reconstruction of long urethral strictures is still a major challenge. There are still unavoidable limitations in clinical application of grafts for urethral injuries, which has facilitated the advancement of urethral tissue engineering. Tissue-engineered urethral scaffolds that combine cells or bioactive factors with a biomaterial to mimic the native microenvironment of the urethra, offer a promising approach to urethral reconstruction. Despite the recent rapid development of tissue engineering materials and techniques, a consensus on the optimal strategy for urethral repair and reconstruction is still lacking. This review aims to collect the achievements of urethral tissue engineering in recent years and to categorize and summarize them in order to shed new light on their design. Finally, we visualize several important future directions for urethral repair and reconstruction.

Unraveling hierarchically ordered melt electro-written tissue engineering scaffolds: Morphological and mechanical insights

Addressing critical tissue defects treatment remains a pressing challenge in medicine and bioengineering. Tissue engineering (TE) scaffolds, characterized by porous architectures suitable to cell growth, is a pivotal solution. Recent advances in additive techniques have revolutionized scaffold fabrication, enabling precise control over complex porous structures. This study conducts a comprehensive analysis of hierarchically ordered melt electrospun written (MEW) TE scaffolds, elucidating the relationships between fabrication parameters and their morphological and mechanical properties. Leveraging the phenomenon of melt jet deposit buckling, characteristic hierarchically ordered porous architectures were attained. The study explores the fabrication potential of hierarchically ordered porous MEW architectures across varied voltages, feed rates, and needle sizes. Morphometric parameters, including percent porosity, density of fiber intersections, and fiber diameter, were identified. It was revealed that for feed rates exceeding 20 mm/s, resultant fiber diameters were unaffected by voltage. However, increasing voltage leads to noticeable reduction of mesh stiffness due to the coiled fibers presence. Exceptions occur at the feed rate of 20 mm/s and for needle G24, where stiffness surpasses those of regular primary pattern, which could be attributed to increased number of fiber interconnections.

Current advances in the development of microRNA-integrated tissue engineering strategies: a cornerstone of regenerative medicine

Regenerative medicine is an innovative scientific field focused on repairing, replacing, or regenerating damaged tissues and organs to restore their normal functions. A central aspect of this research arena relies on the use of tissue-engineered scaffolds, which serve as structural supports that mimic the extracellular matrix, providing an environment that orchestrates cell growth and tissue formation. Remarkably, the therapeutic efficacy of these scaffolds can be improved by harnessing the properties of other molecules or compounds that have crucial roles in healing and regeneration pathways, such as phytochemicals, enzymes, transcription factors, and non-coding RNAs (ncRNAs). In particular, microRNAs (miRNAs) are a class of tiny (20–24 nt), highly conserved ncRNAs that play a critical role in the regulation of gene expression at the post-transcriptional level. Accordingly, miRNAs are involved in a myriad of biological processes, including cell differentiation, proliferation, and apoptosis, as well as tissue regeneration, angiogenesis, and osteogenesis. On this basis, over the past years, a number of research studies have demonstrated that miRNAs can be integrated into tissue-engineered scaffolds to create advanced therapeutic platforms that precisely modulate cellular behavior and offer a controlled and targeted release of miRNAs to optimize tissue repair and regeneration. Therefore, in this current review, we discuss the most recent advances in the development of miRNA-loaded tissue-engineered scaffolds and provide an overview of the future outlooks that should be aborded in this area of study in order to lay the groundwork for the clinical translation of these tissue engineering approaches.

Plant-based scaffolds and osteogenesis: a systematic review

Objective: To enhance the understanding and usefulness of decellularised plant tissues as scaffolds for bone tissue engineering, and to review the recent advances in plant-based scaffolds for bone regeneration. Method: The systematic review was conducted from February to June 2022, and comprised literature search on PubMed and Science Direct databases for articles published in the English language between 2013 and June, 2022. The search was conducted using key words ‘plant-based scaffolds and osteogenesis’ and ‘decellularised plant and scaffolds and bone tissue engineering’ and ‘plant root-based scaffold and bone formation’. Full-text articles and short communication covering both in vitro and in vivo studies focussing on plant-based scaffolds for osteogenesis were included. Additional references that satisfied the inclusion criteria were found on Google Scholar and included in the review. Quality evaluation of the studies included was done independently by two researchers, and the risk of bias was calculated and categorised as low, medium and high risk. Results: Of the 564 articles, 10(1.77 %) were included; 6(60%) purely in vitro studies, and 4(40%) studies having both in vitro and in vivo components. Decellularized plant tissue alone was used as three-dimensional scaffold materials in 5(50%) studies, but in 4(40%) studies, plant-based composite scaffolds were used. The risk of bias was medium in 7(70%) studies. Conclusions: Plant-based scaffolds promote osteogenesis, but more in vivo research on plant-based studies is needed to label it as suitable scaffolds for bone tissue engineering. Key Words: Plant-based scaffolds, Osteogenesis, Decellularised Plant, bone tissue engineering, Plant root-based scaffold, Bone formation.

Exploiting the Potential of Decellularized Extracellular Matrix (ECM) in Tissue Engineering: A Review Study.

While significant progress has been made in creating polymeric structures for tissue engineering, the therapeutic application of these scaffolds remains challenging owing to the intricate nature of replicating the conditions of native organs and tissues. The use of human-derived biomaterials for therapeutic purposes closely imitates the properties of natural tissue, thereby assisting in tissue regeneration. Decellularized extracellular matrix (dECM) scaffolds derived from natural tissues have become popular because of their unique biomimetic properties. These dECM scaffolds can enhance the body's ability to heal itself or be used to generate new tissues for restoration, expanding beyond traditional tissue transfers and transplants. Enhanced knowledge of how ECM scaffold materials affect the microenvironment at the injury site is expected to improve clinical outcomes. In this review, recent advancements in dECM scaffolds are explored and relevant perspectives are offered, highlighting the development and application of these scaffolds in tissue engineering for various organs, such as the skin, nerve, bone, heart, liver, lung, and kidney.

Advances and Functional Integration of Hydrogel Composites as Drug Delivery Systems in Contemporary Dentistry.

This study explores the recent advances of and functional insights into hydrogel composites, materials that have gained significant attention for their versatile applications across various fields, including contemporary dentistry. Hydrogels, known for their high water content and biocompatibility, are inherently soft but often limited by mechanical fragility. Key areas of focus include the customization of hydrogel composites for biomedical applications, such as drug delivery systems, wound dressings, and tissue engineering scaffolds, where improved mechanical properties and bioactivity are critical. In dentistry, hydrogels are utilized for drug delivery systems targeting oral diseases, dental adhesives, and periodontal therapies due to their ability to adhere to the mucosa, provide localized treatment, and support tissue regeneration. Their unique properties, such as mucoadhesion, controlled drug release, and stimuli responsiveness, make them ideal candidates for treating oral conditions. This review highlights both experimental breakthroughs and theoretical insights into the structure-property relationships within hydrogel composites, aiming to guide future developments in the design and application of these multifunctional materials in dentistry. Ultimately, hydrogel composites represent a promising frontier for advancing materials science with far-reaching implications in healthcare, environmental technology, and beyond.

Seaweed-derived etherified carboxymethyl cellulose for sustainable tissue engineering

Biodegradability, biocompatibility, abundant supply from renewable sources, and affordability are the outstanding properties of cellulose that have prompted substantial studies into its potential in biomedical applications. Beyond terrestrial sources of cellulose, seaweeds have attracted much attention as a potential source of cellulose because they are widely available. Cellulose and its byproducts may be extracted from various macroalgae species, including red, green, and brown algae. The extracted cellulose's qualities vary depending on the algae species, age, and extraction process utilized. Cellulose's characteristics are enhanced through chemical modifications, specifically etherification and esterification, which substitute functional groups for hydroxyl groups, yielding a range of products, including cellulose acetate (CA), cellulose nitrate, cellulose sulfate, methylcellulose, and carboxymethyl cellulose (CMC). The ability to modify CMC characteristics for particular applications is explored through techniques including grafting processes mixing, and cross-linking with other polymers. Moreover, tissue engineering is given significant consideration in the growing use of CMC and its altered forms in biological applications. These alterations allow for the production of scaffolds that promote tissue regeneration and cell proliferation, enabling CMC-based scaffolds for various tissue engineering uses. This review provides a comprehensive overview of CMC's properties, modifications, and potential in tissue engineering.

Applications of hydroxyapatite-based polymeric scaffolds in bone tissue engineering: An update

Bone tissue is a comprising of an organic and inorganic environment, in which the collagen element and the mineral part are structured into complex and spongy constructions. Hydroxyapatite (HAp) is the chief inorganic constituent of human bone. HAp is extensively utilized in bone tissue regeneration for its bioactivity and biocompatibility, and a rising number of investigators are discovering ways to recover the physical belongings and biological roles of HAp. However, this biomimetic material has poor mechanical properties, such as low tensile and compressive strength, which make it not suitable for bone tissue engineering (BTE). For this reason, HA is frequently utilized in a mixture with diverse polymers to increase their mechanical strengths and the general performance of the implantable biomaterials advanced for orthopedic usage. In this review, we attempt to contribute a brief and inclusive outline of HAp-based natural and synthetic polymer materials as reinforcing components and their applications in bone tissue engineering.

Advances of natural hydrogel-based vascularization strategies for soft tissue repair

Regeneration of soft tissues, especially those requiring complex vascularization, is a major challenge in the field of tissue engineering. The current types of tissue engineering scaffolds include sponges, electric spinning silk, hydrogels, and 3D printed biomaterials. Among them, hydrogels have the unique property of mimicking extracellular matrix (ECM), which can provide a relatively stable microenvironment for cellular activities and facilitate cell adhesion, proliferation, and differentiation; thus, have become a promising scaffold. In this paper, we present a review of the commonly used types of natural hydrogels and their applications as scaffolds in tissue vascularization. First, we enumerate the importance and advantages of several types of commonly used hydrogels of natural origin in terms of fabricating vascularized tissues or organs. Second, we discuss two different formation modalities of blood vessels, as well as natural hydrogel-based vascularization strategies, including carrying growth factors, stem cell delivery, special scaffold structures and pharmaceutical-enhanced strategy. In addition, we describe the crosslinking strategies of hydrogels as scaffolds for regeneration of vascularized soft tissues, as well as the factors affecting it. Finally, new insights are provided for the development of natural hydrogel-based vascularized soft tissue regeneration research.

Fabrication and characterization of bioresorbable, electroactive and highly regular nanomodulated cell interfaces

Biomaterial-based implantable scaffolds capable of promoting physical and functional reconnection of injured spinal cord and nerves represent the latest frontier in neural tissue engineering. Here, we report the fabrication and characterization of self-standing, biocompatible and bioresorbable substrates endowed with both controlled nanotopography and electroactivity, intended for the design of transient implantable scaffolds for neural tissue engineering. In particular, we obtain conductive and nano-modulated poly(D,L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) free-standing films by simply iterating a replica moulding process and coating the polymer with a thin layer of poly(3,4-ethylendioxythiophene) polystyrene sulfonate. The capability of the substrates to retain both surface patterning and electrical properties when exposed to a liquid environment has been evaluated by atomic force microscopy, electrochemical impedance spectroscopy and thermal characterizations. In particular, we show that PLA-based films maintain their surface nano-modulation for up to three weeks of exposure to a liquid environment, a time sufficient for promoting axonal anisotropic sprouting and growth during neuronal cell differentiation. In conclusion, the developed substrates represent a novel and easily-tunable platform to design bioresorbable implantable devices featuring both topographic and electrical cues.