3D-printed Scaffolds Research Articles

Cartilage Tissue Construct from Human Adipose-Derived Mesenchymal Stem Cells on 3D-Printed Polylactic Acid Scaffold

Cartilage Tissue Construct from Human Adipose-Derived Mesenchymal Stem Cells on 3D-Printed Polylactic Acid Scaffold

3D Printing Hierarchical Porous Nanofibrous Scaffold for Bone Regeneration.

Current limitations in 3D printing pose significant challenges for the fabrication of hierarchical 3D scaffolds with nanofibrous structures that simulate the natural bone extracellular matrix (ECM) for enhanced bone regeneration. This study presents an innovative approach to 3D printing customized hierarchical porous scaffolds with nanofiber structures using biodegradable nanofibrous microspheres as the bio-ink. In vitro investigations demonstrate that the hierarchical porous architecture substantially enhances cell infiltration and proliferation rates, while the nanofiber topology provides physical cues to guide osteogenic differentiation and ECM deposition. When serving as a cell carrier, the 3D-printed nanofibrous scaffold promotes bone tissue regeneration and integration in vivo. Additionally, the facile and versatile chemical modification facilitates the precise tailoring of the scaffold's functionality. Using nanofibrous microspheres with highly biomimetic and versatile modification properties as the foundational constituent in this universal 3D printing methodology enables comprehensive manipulation of scaffolding biological properties, spanning from macroscopic external morphology to molecular-scale biochemical kinetics, thereby addressing a diverse spectrum of clinical requisites.

Micro-thin hydrogel coating integrated in 3D printing for spatiotemporal delivery of bioactive small molecules

Three-dimensional (3D) printing incorporated with controlled delivery is an effective tool for complex tissue regeneration. Here, we explored a new strategy for spatiotemporal delivery of bioactive cues by establishing a precise-controlled micro-thin coating of hydrogel carriers on 3D-printed scaffolds. We optimized the printing parameters for three hydrogel carriers, fibrin cross-linked with genipin, methacrylate hyaluronic acid, and multidomain peptides, resulting in homogenous micro-coating on desired locations in 3D printed polycaprolactone microfibers at each layer. Using the optimized multi-head printing technique, we successfully established spatial-controlled micro-thin coating of hydrogel layers containing profibrogenic small molecules (SMs), Oxotremorine M and PPBP maleate, and a chondrogenic cue, Kartogenin. The delivered SMs showed sustained releases up to 28 d and guided regional differentiation of mesenchymal stem cells, thus leading to fibrous and cartilaginous tissue matrix formation at designated scaffold regionsin vitroandin vivo. Our micro-coating of hydrogel carriers may serve as an efficient approach to achieve spatiotemporal delivery of various bioactive cues through 3D printed scaffolds for engineering complex tissues.

DNAR-04. TUMOUR TREATING FIELDS (TTFIELDS) AND DNA DAMAGE RESPONSE (DDR) INHIBITORS ENHANCE GLIOMA CELL DEATH THROUGH CHEMO-/RADIOSENSITISATION

Abstract High grade gliomas are the most common primary brain cancer malignancies with ~300,000 global diagnoses each year with glioblastomas (WHO grade IV) conferring the worst prognoses. This arises from their treatment resistance, rationalised by the presence of glioma stem cell-like (GSC) tumour sub-regions and high intratumoural spatio-heterogeneity. TTFields are clinically approved alternating electric fields of intermediate frequency that exert anti-mitotic effects and invoke downregulation of the DDR. Therefore, TTFields alongside clinically developed, and blood brain barrier (BBB) penetrating DDR inhibitors (DDRi) could boost cell death and overcome treatment resistance through chemo-/radiosensitisation. Primary GSC cell lines were derived from surgically resected and clinically defined tumour core and invasive edge regions and grown in more biologically relevant 3D-printed AlvetexTM scaffolds, offering highly clinically relevant models. Cells were then pre-treated with DDRi, subjected to chemo-/radiotherapy and then incubated under TTFields (200 kHz, 72 hrs) with their survival measured by clonogenic assays after 3 weeks. Immunofluorescence and western blot analysis were used to analyse the combination treatment effects on the DDR. In multiple 3D-grown core/edge GSC models, western blot analyses revealed that the DDR was altered by TTFields and clonogenic survival assays revealed that TTFields alongside DDRi led to significant chemo-/radiosensitisation. TTFields alongside DDRi effectively enhances cell death by significant treatment sensitisation effects in clinically relevant 3D GSCs which exhibit extensive intra and intertumoral spatio-heterogeneity. Given that all the DDRi used are BBB penetrable and are either clinically approved or in clinical trials, TTFields could additionally compliment these treatment regimens in gliomas to boost their efficacy.

3D-Printed Gelatin-Based Scaffold Crosslinked by Genipin: Evaluation of Mechanical Properties and Biological Effect.

In this study, scaffolds based on natural polymer gelatin A, blended with polyvinylpyrrolidone were crosslinked by genipin (0.5 and 1 wt%), in order to investigate their mechanical performance and potential for biomedical application. Semi-solid extrusion (SSE) 3D printing technique was used, enabling insitu crosslinking of the blend during processing. Swelling test showed that the swelling ratio reduces with higher concentration of genipin due to an increased crosslinking. The FTIR analysis confirmed the crosslinking of scaffolds by genipin. DSC analysis and mechanical testing have shown improved thermal and mechanical properties. Morphological analysis of scaffolds by FESEM showed increased toughening of the material with the crosslinking. Tensile strength and microhardness showed a significant rise in scaffolds with the increase in genipin content, which was up to 93.8% and 125.3%, respectively. These findings were in accordance with morphological features present in samples. The biological effect of the scaffold matrix system was evaluated by qualitative and quantitative cytotoxicity assessment invitro, demonstrating the absence of cytotoxicity in tested preparations in a direct test. The cytotoxicity index based on the metabolic activity of cells in an indirect test showed up to 20% reduction of viability compared with the control, confirming the absence of cytotoxicity, which was additionally verified by propidium iodine staining of the cells exposed to scaffolds. The presented gelatin-based crosslinked scaffolds obtained by 3D printing represent good candidates for biomedical application and future research that includes further invitro and invivo analysis.

3D-Printed Bifunctional Scaffold for Treatment of Critical Bone Defects Based on Osteoimmune Microenvironment Regulation and Osteogenetic Effects.

The critical-sized bone defect resulting from trauma, tumor resection, and congenital deformity fails to undergo spontaneous healing due to its substantial size, while the ensuing inflammatory process and hypoxic environment further impede the regenerative process. Therefore, it has consistently presented a significant clinical challenge. In the present study, we incorporate a glycyrrhizic acid (GA)-functionalized hydrogel onto the surface of a Hydroxyapatite (Hap)-modified Polycaprolactone (PCL) scaffold to fabricate a composite scaffold. The composed scaffold showed favorable anti-inflammatory and antioxidative capabilities by modulating macrophage polarization and scavenging reactive oxygen species (ROS); the modification of Hap enhanced its osteogenic ability. An in vivo rat skull defect model confirmed that the composed scaffold efficiently promotes bone regeneration. In general, the composed scaffold with the ability of osteoimmune microenvironment regulation can effectively repair critical-sized bone defects. This strategy provides a promising method for the reconstruction of large segmental bone defects.

Three-Dimensional Bioprinting of Tarsal Plates with Adipose-Derived Mesenchymal Stem Cells: Evaluation of Meibomian Gland Reconstruction in a Rat Model

Background: The aim of this study was to develop 3D-bioprinted scaffolds embedded with human adipose-derived stem cells (hADSCs) to reconstruct the tarsal plate in a rat model. Methods: Scaffolds were printed using a 3D bioprinter with a bioink composed of atelocollagen and alginate. hADSCs (5 × 105 cells/mL) were embedded within the bioink. A total of 30 male Sprague Dawley (SD) rats (300 g) were divided into three groups: group 1 (normal control, n = 10), group 2 (3D-bioprinted scaffolds, n = 10), and group 3 (3D-bioprinted scaffolds with hADSCs, n = 10). Four weeks after surgery, a histopathological analysis was performed using hematoxylin and eosin (H&E) staining, Masson’s trichrome (MT) staining, and immunofluorescence staining. Gene expression of SREBP-1, PPAR-γ, FADS-2, and FAS was assessed via real-time polymerase chain reaction (PCR). Results: No abnormalities were observed in the operated eyelids of any of the 30 rats. The histopathological analysis revealed lipid-secreting cells resembling meibocytes in both group 2 and group 3, with more pronounced meibocyte-like cells in group 3. Immunofluorescence staining for phalloidin expression showed a significant increase in group 3. Additionally, the RNA expression of SREBP-1, PPAR-γ, FADS-2, and FAS, all related to lipid metabolism, was elevated in group 3. Conclusions: The 3D-printed scaffolds combined with hADSCs were effective for tarsal plate reconstruction, with the hADSCs notably contributing to the generation of cells associated with lipid metabolism.

Mechanical Behavior of 3D-Printed Schwarz Diamond-Structured Scaffolds for Tissue Engineering Applications

Mechanical Behavior of 3D-Printed Schwarz Diamond-Structured Scaffolds for Tissue Engineering Applications

Lost in translation: the lack of agreement between surgeons and scientists regarding biomaterials research and innovation for treating bone defects

BackgroundWith over 2 million grafts performed annually, bone ranks second only to blood in the frequency of transplants. This high demand is primarily driven by the persistent challenges posed by bone defects, particularly following trauma or surgical interventions such as tumour excision. The demand for effective and efficient treatments has increased exponentially in the twenty-first century. Limitations associated with autologous bone grafts drive exploration into replacements, including allografts, synthetic substitutes, and 3D-printed scaffolds. This research aimed to unravel disparities in the knowledge and evaluation of current and future bone defect treatments between surgeons and biomaterial scientists.MethodsA prospective cross-sectional survey, pre-registered with the OSF (https://osf.io/y837m/?view_only=fab29e24df4f4adf897353ac70aa3361) and conducted online from October 2022 to March 2023, collected data on surgeons’ views (n = 337) and scientists (n = 99) on bone defect treatments.ResultsScientists were significantly more optimistic than surgeons regarding the future replacement of autologous bone grafts with synthetic or tissue-engineered substitutes (p < 0.001). Accordingly, scientists foresee a paradigm shift from autologous bone grafts to biomaterial and tissue-engineered solutions, reflecting their confidence in the ongoing advancements within this field.Furthermore, regulatory trepidations for 3D-printed bone scaffolds were acknowledged, with scientists emphasizing the need for a more significant focus on clinical relevance in preclinical studies and regulatory clarity. In a ranked categorical assessment, witnessing the technology in action was deemed most influential in adopting new bone regeneration methods by both scientists and surgeons.ConclusionsTo conclude, this study was conducted through a web-based survey, highlighting a substantial translational gap. It underscores the immediate need (“call to action”) for meaningful interdisciplinary collaboration between surgeons and scientists, often referred to as the need to “walk the talk”. The findings underscore the critical importance of aligning clinical needs, research outcomes, and regulatory frameworks to improve the development and implementation of biomaterial-based bone graft substitutes that demonstrate efficacy and efficiency in bone defect treatment.

Incorporating Hydrogel (with Low Polymeric Content) into 3D-Printed PLGA Scaffolds for Local and Sustained Release of BMP2 in Repairing Large Segmental Bone Defects.

Treating large bone defects remains a considerable challenge for clinicians: bone repair requires scaffolds with mechanical properties and bioactivities. Herein, based on crosslinking o-phthalaldehyde (OPA) with amine groups, 4-arm polyethylene glycol (4armPEG)-OPA/Gelatin hydrogel loaded with bone morphogenetic protein 2 (BMP2) is prepared and a three dimensional (3D)-printed poly (lactic-co-glycolic acid) (PLGA) porous scaffold is filled with the hydrogel solution. The composite scaffold, with a compression modulus of 0.68 ±0.097GPa similar to the cancellous bone, has a porosity of 56.67 ± 4.72% and a pore size of about 380µm, promoting bone growth. The hydrogel forms a porous network at low concentrations, aiding protein release and cell migration. The hydrogel degrades in approximately three weeks, and the scaffold takes five months, matching bone repair timelines. BMP2 release experiment shows a sustained BMP2 release with a 72.4 ± 0.53% release ratio. The ALP activity test and alizarin red staining shows effective osteogenic promotion, while RT-PCR confirms BMP2@Gel enhanced COL-1 and OPN expression. Animal experiments further validate the composite scaffold's bone repair efficacy. This study demonstrates the effectiveness of the hydrogel in releasing BMP2 and the mechanical support of the 3D-printed PLGA porous scaffold, providing a new treatment for bone defects.

Highly porous sildenafil loaded polylactic acid/polyvinylpyrrolidone based 3D printed scaffold containing forsterite nanoparticles for craniofacial reconstruction

Tissue engineering has emerged as a promising substitute for traditional tissue repair methods. Nowadays, advancements in 3D printing technology have enabled the fabrication of customized scaffolds to support tissue regeneration. In the present study, a polylactic acid-polyvinylpyrrolidone 3D-printed scaffold containing 10 % forsterite was fabricated. Subsequently, lyophilized fucoidan microstructures loaded with sildenafil were filled the channels of this 3D-printed scaffold. The fabricated scaffold loaded with sildenafil was thoroughly characterized, revealing that 97.46 % of the loaded sildenafil was released in a sustained manner over 28 days. Furthermore, the biocompatibility of MG63 was evaluated through cell viability and adhesion tests. The findings indicated a direct and favorable influence on cell behavior. Based on the chicken chorioallantoic membrane assay, the fabricated scaffold significantly increases angiogenesis due to the sustained release of sildenafil. Moreover, in-vivo studies conducted on a rat model demonstrated that the 3D-printed scaffold was able to stimulate and accelerate the repair of calvarial defects within 8 weeks, and the amount of new bone tissue formation was significantly higher than that of other experimental groups. Based on the comprehensive in-vitro and in-vivo assessments, the scaffold with a macro- and microporous structure combined with the ability to release sildenafil is suggested as a potential candidate for repairing bone tissue, especially in the context of skull defects.

3D-printed porous calcium silicate scaffolds with hydroxyapatite/graphene oxide hybrid coating for guided bone regeneration

Calcium silicate (CS) is a suitable bone repair material due to its bioactivity and biocompatibility. However, its rapid degradation rate and poor cell response affect the bone regeneration process. Surface modification of implants represents a potent strategy for enhancing the performance of biomaterials. Here, we present a novel method combining hydrothermal treatment and chemical grafting to tailor the surface morphology and composition of 3D-printed calcium silicate porous scaffolds. The resulting scaffold surface features hydroxyapatite (HA) nanosheets and graphene oxide (GO) sheet structures. Surface modification significantly reduced the degradation rate of CS scaffolds and decreased the Si ion concentration after PBS immersion, which was more conducive to cell survival. Our findings reveal that the CS/HA/GO scaffold exhibits superior biocompatibility and significantly enhances cell adhesion, proliferation, and osteogenic differentiation. In vivo studies demonstrate that the CS/HA/GO scaffold markedly promotes the regeneration of defective bone tissue. This work highlights the potential of HA and GO coatings on interconnected porous scaffolds to induce bone tissue regeneration, offering a promising strategy for orthopedic applications.

Deferoxamine functionalized alginate-based collagen composite material enhances the integration of metal implant and bone interface

Poor osseointegration markedly compromises the longevity of prostheses. To enhance the stability of titanium implants, surface functionalization is a proven strategy to promote prosthesis-bone integration. This study developed a hydrogel coating capable of simultaneous osteoangiogenesis and vascularization by incorporating deferoxamine (DFO) into a sodium alginate mineralized collagen composite hydrogel. The physicochemical properties of this hydrogel were thoroughly analyzed. In vivo and in vitro experiments confirmed the hydrogel scaffold's osteogenic and angiogenic capabilities. Results indicated that sodium alginate notably enhanced the mechanical characteristics of the mineralized collagen, allowing it to fully infiltrate the interstices of the 3D-printed titanium scaffold. Furthermore, as the hydrogel degraded, collagen, calcium ion, phosphate ion, and DFO were gradually released around the scaffolds, altering the local osteogenic microenvironment and strongly inducing new bone tissue growth. These findings offer novel perspectives for the creation and utilization of functionalized bone implant materials.

Osteoinductively Functionalized 3D-Printed Scaffold for Vertical Bone Augmentation in Beagle Dogs.

To evaluate the efficacy of 3D-printed scaffolds that were osteoinductively functionalized with a bone morphogenetic protein 2 (BMP-2)-incorporated biomimetic calcium phosphate particles (BMP-2-inc. BpNcCaP)/hyaluronic acid (HA) composite gel in vertical bone augmentation in beagle dogs. Four Beagle dogs were used in this study. Three months after the extraction of 1st, 2nd, 3rd, and 4th premolars at both sides of the lower jaws of Beagle dogs, one or two critical-size vertical bone defects (4 mm vertical bone defect without buccal and lingual bone) on each sidewere surgically created. The defects were randomly subjected to the following groups: (1) Control (without bone-defect-filling materials); (2) 3D scaffold; (3) BMP2-inc. BpNcCaP/HA-functionalized 3D scaffold. Six weeks post-surgery, samples were harvested and subjected to micro-CT and histomorphometric analyses. The struts of the BMP2-inc. BpNcCaP/HA-func. 3D scaffold were covered by a thick layer of cemented irregular particles with an average pore size at 327 ± 27 μm. The BpNcCaP/HA-func. 3D scaffold group bore significantly higher bone volume, bone volume fraction, trabecular number, trabecular thickness, bone mineral density, connectivity density, and bone volumes in three directions (mesiodistal, buccolingual, and apicocoronal) when compared with the groups of Control and 3D scaffold. Moreover, the BMP2-inc. BpNcCaP/HA-func. 3D scaffold group bore significantly lower trabecular separation and exhibited significantly higher bone-to-scaffold contact percentage and newly formed bone area percentage within pores in comparison with 3D scaffold. BMP2-inc. BpNcCaP/HA-func. 3D scaffold dramatically enhanced vertical alveolar bone augmentation, which suggests a promising application potential of BMP2-inc. BpNcCaP/HA-func. 3D scaffold in dental clinic.

The Potential Applications of Stem Cell Conditioned Medium Secretome in Knee Cartilage Regeneration: A Systematic Review

Background: Articular cartilage injuries often result from trauma, genetic predisposition, and degeneration. These injuries lack inherent regeneration mechanisms due to the absence of blood vessels and limited progenitor cell entry. Osteoarthritis is characterized by gradual cartilage deterioration. Mesenchymal stem cells (MSCs), particularly their secretome including exosomes, hold promise as a regenerative therapy. This review explores the application of MSCs and their secretome to address cartilage defects.Methods: This review was conducted based on PRISMA guidelines. Animal model studies focusing on the use of stem cell secretomes for cartilage regeneration were explored. The search, encompassing PubMed, MEDLINE, the Cochrane Library, Scopus, Web of Science, and Science Direct from January 10, 2023, to July 27, 2023, was conducted utilizing Google Chrome as the search engine. Studies with outcomes based on OARSI or ICRS scores, as well as any additional outcomes related to MSC secretome utilization, cartilage regeneration, and proliferation, were included.Results: Our systematic review identified six studies using MSCs in vivo and in vitro. Synovial membrane-derived MSCs significantly enhanced cartilage regeneration by elevating chondrogenic capabilities. Hydrogel-based systems techniques and 3D-printed scaffolds have emerged for innovative delivery. Specific microRNAs, such as miR-92a-3p, have been recognized for enhancing cartilage regeneration. Strategies for the effective targeting of MSC exosomes to the precise cartilage damage site have been explored.Conclusions: The studies demonstrate the potential of MSC-derived secretomes and exosomes for knee cartilage regeneration in animal models. Further research and clinical trials are needed to refine these approaches for practical application.

3D-printed scaffolds with controlled-releasing compounds for ectopic activation of dormant ovarian follicles

Throughout a woman&amp;rsquo;s reproductive life, hundreds of functioning follicles are activated for development, while thousands of dormant follicles remain in the ovaries. Dormant follicle activation in vitro is an effective clinical strategy for women with fertility needs who suffer from ovarian dysfunction. However, activating dormant follicles in vivo is still a challenge due to difficulties such as delivering stimulators to local sites. Here, we developed a compound-preloaded microporous scaffold by combining three-dimensional (3D) printing techniques with pharmacological activators to support and stimulate the activation and development of primordial follicles. The gelatin/alginate composite scaffolds exhibited exceptional mechanical properties and biological compatibility, effectively supporting the survival of ovarian granulosa cells for more than 7 days, which is essential for oocyte development. Furthermore, the ovarian tissue-scaffold complex successfully survived after transplantation under the mouse kidney capsule, demonstrating its excellent biocompatibility. After pre-mixing widely used clinical activators into the bio-ink, the scaffold had the ability to gradually release the mixture of compounds, effectively activating primordial follicles. By transplanting the ovary-scaffold complex containing activators into the mouse abdominal subcutaneous pocket, dormant follicles could be activated subcutaneously and developed into growing follicles. The number of growing follicles is approximately three times higher compared to the group without activators. In conclusion, by integrating biomaterials, activators, and 3D printing technology, we have developed 3D-printed biological scaffolds that can ectopically support primordial follicle activation and development in vivo. This novel approach could provide a promising strategy for treating ovarian insufficiency and endocrine disorders in the clinic, without the need for in situ ovarian tissue grafting.

Three-Dimensional Scaffolds Designed and Printed Using CAD/CAM Technology: A Systematic Review

The objective of this work is to review the literature on the use of three-dimensional scaffolds obtained by printing for the regeneration of bone defects in the maxillofacial area. The research question asked was: what clinical experiences exist on the use of bone biomaterials manufactured by CAD/CAM in the maxillofacial area? Prospective and retrospective studies and randomized clinical trials in humans with reconstruction area in the maxillofacial and intraoral area were included. The articles had to obtain scaffolds for bone reconstruction that were designed by computer processing and printed in different materials. Clinical cases, case series, in vitro studies and those that were not performed in humans were excluded. Six clinical studies were selected that met the established inclusion criteria. The selected studies showed heterogeneity in their objectives, materials used and types of regenerated bone defects. A high survival rate was found for dental implants placed on 3D-printed scaffolds, with rates ranging from 94.3% to 98%. The materials used included polycaprolactone, coral-derived hydroxyapatite, biphasic calcium phosphate (BCP) and bioceramics. The use of CAD/CAM technology is seen as key for satisfying variations in the shapes and requirements of different fabrics and size variations between different individuals. Furthermore, the possibility of using the patient’s own stem cells could revolutionize the way bone defects are currently treated in oral surgery. The results indicate a high survival rate of dental implants placed on 3D-printed scaffolds, suggesting the potential of this technology for bone regeneration in the maxillofacial mass.

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 200μm, 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.

A promising pullulan/PLA composite: Influence of pullulan in the scaffolds morphology constructed by 3D printing

AbstractManufacturing three‐dimensional scaffolds with significant rough and porous structures is advantageous in tissue regeneration approaches influencing cell growth. Thus, this work aims to study the effect of using different Pullulan contents (PULL) in the poly(lactic) acid (PLA) matrix for 3D printing scaffolds. PLA composites filler with PULL (5 and 10% wt.) were prepared in a thermokinetic mixer, extruded in a machine, and then used to print samples using a fused deposition modeling (FDM) 3D printer. The prepared filaments and scaffolds were characterized using Field emission scanning electron microscopy (FESEM), Fourier‐transform infrared spectroscopy (FTIR), thermogravimetry analyses (TGA), water contact angle (WCA), differential scanning calorimetry (DSC), and hardness techniques. The insertion of PULL into the PLA matrix influenced the increase in diameter and roughness, and density reduction of the composite filaments compared to pristine PLA. Furthermore, the filler promoted an increase in thermal stability, shore hardness, and the development of promising morphological characteristics for cell growth because the walls of the scaffolds are more robust and have more regular‐sized holes. The scaffold fabrication reinforced with 10% PULL presented high surface roughness (up to 1022% if compared with pristine PLA), and open pores can be confirmed successfully compared to pristine PLA. Thus, the use of PULL as a filler in a PLA matrix guarantees the development of composite scaffolds with improved morphological and hardness properties, which could allow the possibility of future research into the application of the proposed material (10% wt. PULL) as an ecologically correct and biocompatible alternative for application in tissue engineering.

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.