Evaluating osteogenic potential of a 3D-printed bioceramic-based scaffold for critical-sized defect treatment: an in vivo and in vitro investigation.

The integration of precision medicine principles into bone tissue engineering has ignited a wave of research focused on customizing intricate scaffolds through advanced 3D printing techniques. Bioceramics, known for their exceptional biocompatibility and osteoconductivity, have emerged as a promising material in this field. This article aims to evaluate the regenerative capabilities of a composite scaffold composed of 3D-printed gelatin combined with hydroxyapatite/tricalcium phosphate bioceramics (G/HA/TCP), incorporating human dental pulp-derived stem cells (hDPSCs). Using 3D powder printing, we created cross-shaped biphasic calcium phosphate scaffolds with a gelatin layer. The bone-regenerating potential of these scaffolds, along with hDPSCs, was assessed through in vitro analyses and in vivo studies with 60 rats and critical-sized calvarial defects. The assessment included analyzing cellular proliferation, differentiation, and alkaline phosphatase activity (ALP), and concluded with a detailed histological evaluation of bone regeneration. Our study revealed a highly favorable scenario, displaying not only desirable cellular attachment and proliferation on the scaffolds but also a notable enhancement in the ALP activity of hDPSCs, underscoring their pivotal role in bone regeneration. However, the histological examination of calvarial defects at the 12-wk mark yielded a rather modest level of bone regeneration across all experimental groups. The test and cell group exhibited significant bone formation compared to all other groups except the control and cell group. This underscores the complexity of the regenerative process and paves the way for further in-depth investigations aimed at improving the potential of the composite scaffolds.

Reconstructing Critical-Sized Mandibular Defects in a Rabbit Model: Enhancing Angiogenesis and Facilitating Bone Regeneration via a Cell-Loaded 3D-Printed Hydrogel-Ceramic Scaffold Application.

In this study, we propose a spatially patterned 3D-printed nanohydroxyapatite (nHA)/beta-tricalcium phosphate (ß-TCP)/collagen composite scaffold incorporating human dental pulp-derived mesenchymal stem cells (hDP-MSCs) for bone regeneration in critical-sized defects. We investigated angiogenesis and osteogenesis in a rabbit critical-sized mandibular defect model treated with this engineered construct. The critical and synergistic role of collagen coating and incorporation of stem cells in the regeneration process was confirmed by including a cell-free uncoated 3D-printed nHA/ß-TCP scaffold, a stem cell-loaded 3D-printed nHA/ß-TCP scaffold, and a cell-free collagen-coated 3D-printed nHA/ß-TCP scaffold in the experimental design, in addition to an empty defect. Posteuthanasia evaluations through X-ray analysis, histological assessments, immunohistochemistry staining, histomorphometry, and reverse transcription-polymerase chain reaction (RT-PCR) suggest the formation of substantial woven and lamellar bone in the cell-loaded collagen-coated 3D-printed nHA/ß-TCP scaffolds. Histomorphometric analysis demonstrated a significant increase in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization compared to that observed in the control group. Conversely, a significant decrease in fibroblasts/fibrocytes and connective tissue was observed in this group compared to that in the control group. RT-PCR indicated a significant upregulation in the expression of osteogenesis-related genes, including BMP2, ALPL, SOX9, Runx2, and SPP1. The findings suggest that the hDP-MSC-loaded 3D-printed nHA/ß-TCP/collagen composite scaffold is promising for bone regeneration in critical-sized defects.

Deep eutectic solvent-based ferrofluid for highly efficient preconcentration and determination of metronidazole by vortex-assisted liquid-phase microextraction under experimental design optimization.

To determine metronidazole in water samples, we developed an environmentally friendly, efficient, and straightforward ferrofluid-based liquid-liquid microextraction sample pretreatment technique. It is coupled with a high-performance liquid chromatography-ultraviolet analytical technique known for its sensitivity, speed, and precision. The magnetic separation of metronidazole-containing ferrofluid from the matrix was effortlessly achieved through the application of an external magnetic field, eliminating the need for centrifugation. Response surface optimization was employed to systematically determine the key experimental parameters influencing extraction efficiency, including pH, NaCl concentration, ferrofluid volume, and vortex duration. With a low detection limit (0.116 ng mL-1), a broad linear range between 0.5 and 700 ng mL-1 was achieved at optimal conditions. Additionally, acceptable spiking recoveries (94.3-97.3 %) and RSD values (≤3.7 %) for intra- and inter-day precision were attained in water samples. In conclusion, the effectiveness of the vortex and ferrofluid combination, along with the convenience of collection and elimination of the need for centrifugation, bestows a highly valuable technique for determining metronidazole in water samples.

Studying the electrical, mechanical, and biological properties of BCZT-HA composites.

The piezoelectric properties of natural bone and their influence on bone growth have inspired researchers to study a range of bio-piezoelectric composite materials. By exploring these materials, researchers aim to understand better, how piezoelectricity can be controlled to promote bone growth and tissue regeneration. In this work, the prominent piezoelectric material, (Ba, Zr) TiO3 -x(Ba,Ca)TiO3 , abbreviated as BCZT, was selected as a possible bone growth enhancer in hydroxyapatite (HA) scaffolds. Initially, BCZT and hydroxyapatite (HA) powders were synthesized using the sol-gel method. Subsequently, various composite samples of BCZT-xHA were prepared using the conventional solid-state method. After sintering the samples at 1300°C, the phase structure, microstructure, density, and electrical properties were characterized. The samples' compressive strength was determined by analyzing the outcomes of basic compression tests. The biological behavior of the samples in terms of in vitro simulated body fluid immersion and MTT tests were evaluated. Our results revealed that among the BCZT-xHA samples, the BCZT-20HA sample had the best composition, considering its electrical, mechanical, and biological properties. A d33 value of 10 pC/N, dielectric permittivity of 110, and the g33 equal to 10.27 mV m/N resulted in the output voltage of 1.03 V. The results of the MTT assay test confirmed the noncytotoxic nature of the samples with the highest optical density in the BCZT-20HA sample.

The Need for Smart Materials in an Expanding Smart World: MXene-Based Wearable Electronics and Their Advantageous Applications.

As a result of the transformation of inflexible electronic structures into flexible and stretchy devices, wearable electronics now provide great advantages in a variety of fields, including mobile healthcare sensing and monitoring, human-machine interfaces, portable energy storage and harvesting, and more. Because of their enriched surface functionalities, large surface area, and high electrical conductivity, transition metal nitrides and carbides (also known as MXenes) have recently come to be extensively considered as a group of functioning two-dimensional nanomaterials as well as exceptional fundamental elements for forming flexible electronics devices. This Review discusses the most recent advancements that have been made in the field of MXene-enabled flexible electronics for wearable electronics. The emphasis is placed on extensively established nonstructural features in order to highlight some MXene-enabled electrical devices that were constructed on a nanometric scale. These attributes include devices configured in three dimensions: printed materials, bioinspired structures, and textile and planar substrates. In addition, sample applications in electromagnetic interference (EMI) shielding, energy, healthcare, and humanoid control of machinery illustrate the exceptional development of these nanodevices. The increasing potential of MXene nanoparticles as a new area in next-generation wearable electronic technologies is projected in this Review. The design challenges associated with these electronic devices are also discussed, and possible solutions are presented.

Magnetic hydrogel applications in articular cartilage tissue engineering.

Articular cartilage defects afflict millions of individuals worldwide, presenting a significant challenge due to the tissue's limited self-repair capability and anisotropic nature. Hydrogel-based biomaterials have emerged as promising candidates for scaffold production in artificial cartilage construction, owing to their water-rich composition, biocompatibility, and tunable properties. Nevertheless, conventional hydrogels typically lack the anisotropic structure inherent to natural cartilage, impeding their clinical and preclinical applications. Recent advancements in tissue engineering (TE) have introduced magnetically responsive hydrogels, a type of intelligent hydrogel that can be remotely controlled using an external magnetic field. These innovative materials offer a means to create the desired anisotropic architecture required for successful cartilage TE. In this review, we first explore conventional techniques employed for cartilage repair and subsequently delve into recent breakthroughs in the application and utilization of magnetic hydrogels across various aspects of articular cartilage TE.

Enhancing bone tissue engineering with 3D-Printed polycaprolactone scaffolds integrated with tragacanth gum/bioactive glass.

Tissue-engineered bone substitutes, characterized by favorable physicochemical, mechanical, and biological properties, present a promising alternative for addressing bone defects. In this study, we employed an innovative 3D host-guest scaffold model, where the host component served as a mechanical support, while the guest component facilitated osteogenic effects. More specifically, we fabricated a triangular porous polycaprolactone framework (host) using advanced 3D printing techniques, and subsequently filled the framework's pores with tragacanth gum-45S5 bioactive glass as the guest component. Comprehensive assessments were conducted to evaluate the physical, mechanical, and biological properties of the designed scaffolds. Remarkably, successful integration of the guest component within the framework was achieved, resulting in enhanced bioactivity and increased strength. Our findings demonstrated that the scaffolds exhibited ion release (Si, Ca, and P), surface apatite formation, and biodegradation. Additionally, in vitro cell culture assays revealed that the scaffolds demonstrated significant improvements in cell viability, proliferation, and attachment. Significantly, the multi-compartment scaffolds exhibited remarkable osteogenic properties, indicated by a substantial increase in the expression of osteopontin, osteocalcin, and matrix deposition. Based on our results, the framework provided robust mechanical support during the new bone formation process, while the guest component matrix created a conducive micro-environment for cellular adhesion, osteogenic functionality, and matrix production. These multi-compartment scaffolds hold great potential as a viable alternative to autografts and offer promising clinical applications for bone defect repair in the future.

The Potential Therapeutic Effects of Platelet-Derived Biomaterials on Osteoporosis: A Comprehensive Review of Current Evidence.

Osteoporosis is a chronic multifactorial condition that affects the skeletal system, leading to the deterioration of bone microstructure and an increased risk of bone fracture. Platelet-derived biomaterials (PDBs), so-called platelet concentrates, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), have shown potential for improving bone healing by addressing microstructural impairment. While the administration of platelet concentrates has yielded positive results in bone regeneration, the optimal method for its administration in the clinical setting is still debatable. This comprehensive review aims to explore the systemic and local use of PRP/PRF for treating various bone defects and acute fractures in patients with osteoporosis. Furthermore, combining PRP/PRF with stem cells or osteoinductive and osteoconductive biomaterials has shown promise in restoring bone microstructural properties, treating bony defects, and improving implant osseointegration in osteoporotic animal models. Here, reviewing the results of in vitro and in vivo studies, this comprehensive evaluation provides a detailed mechanism for how platelet concentrates may support the healing process of osteoporotic bone fractures.

Clinical Trials of Mesenchymal Stem Cells for the Treatment of COVID 19.

Mesenchymal Stem Cells (MSCs) are being investigated as a treatment for a novel viral disease owing to their immunomodulatory, anti-inflammatory, tissue repair and regeneration characteristics, however, the exact processes are unknown. MSC therapy was found to be effective in lowering immune system overactivation and increasing endogenous healing after SARS-CoV-2 infection by improving the pulmonary microenvironment. Many studies on mesenchymal stem cells have been undertaken concurrently, and we may help speed up the effectiveness of these studies by collecting and statistically analyzing data from them. Based on clinical trial information found on clinicaltrials. gov and on 16 November 2020, which includes 63 clinical trials in the field of patient treatment with COVID-19 using MSCs, according to the trend of increasing studies in this field, and with the help of meta-analysis studies, it is possible to hope that the promise of MSCs will one day be realized. The potential therapeutic applications of MSCs for COVID-19 are investigated in this study.

Data-driven supervised machine learning to predict the compressive response of porous PVA/Gelatin hydrogels and in-vitro assessments: Employing design of experiments.

The purpose of this study is to design and evaluate a series of porous hydrogels by considering three independent variables using the Box-Behnken method. Accordingly, concentrations of the constituent macromolecules of the hydrogels, Polyvinyl Alcohol and Gelatin, and concentration of the crosslinking agent are varied to fabricate sixteen different porous samples utilizing the lyophilization process. Subsequently, the porous hydrogels are subjected to a battery of tests, including Fourier Transform Infrared spectroscopy, morphology assessment, pore-size study, porosimetry, uniaxial compression, and swelling measurements. Additionally, in-vitro cell assessments are performed by culturing mouse fibroblast cells (L-929) on the hydrogels, where viability, proliferation, adhesion, and morphology of the L-929 cells are monitored over 24, 48, and 72 h to evaluate the biocompatibility of these biomaterials. To better understand the mechanical behavior of the hydrogels under compressive loadings, Deep Neural Networks (DNNs) are implemented to predict and capture their compressive stress-strain responses as a function of the constituent materials' concentrations and duration of the performed mechanical tests. Overall, this study emphasizes the importance of considering multiple variables in the design of porous hydrogels, provides a comprehensive evaluation of their mechanical and biological properties, and, particularly, implements DNNs in the prediction of the hydrogels' stress-strain responses.

Vascular endothelial growth factor (VEGF) delivery approaches in regenerative medicine.

The utilization of growth factors in the process of tissue regeneration has garnered significant interest and has been the subject of extensive research. However, despite the fervent efforts invested in recent clinical trials, a considerable number of these studies have produced outcomes that are deemed unsatisfactory. It is noteworthy that the trials that have yielded the most satisfactory outcomes have exhibited a shared characteristic, namely, the existence of a mechanism for the regulated administration of growth factors. Despite the extensive exploration of drug delivery vehicles and their efficacy in delivering certain growth factors, the development of a reliable predictive approach for the delivery of delicate growth factors like Vascular Endothelial Growth Factor (VEGF) remains elusive. VEGF plays a crucial role in promoting angiogenesis; however, the administration of VEGF demands a meticulous approach as it necessitates precise localization and transportation to a specific target tissue. This process requires prolonged and sustained exposure to a low concentration of VEGF. Inaccurate administration of drugs, either through off-target effects or inadequate delivery, may heighten the risk of adverse reactions and potentially result in tumorigenesis. At present, there is a scarcity of technologies available for the accurate encapsulation of VEGF and its subsequent sustained and controlled release. The objective of this review is to present and assess diverse categories of VEGF administration mechanisms. This paper examines various systems, including polymeric, liposomal, hydrogel, inorganic, polyplexes, and microfluidic, and evaluates the appropriate dosage of VEGF for multiple applications.

Fabrication and evaluation of PLA/MgAl2O4 scaffolds manufactured through 3D printing method.

In this study, we synthesized magnesium aluminate spinel (MgAl2O4) with a particle size ranging from 35 to 70 nm using a facile combustion approach. Then, we used a 3D printing (FDM) machine to produce PLA/x wt% MgAl2O4 (x = 0, 2, 4, 6, and 8) scaffolds. To investigate the crystal structure, microstructure, biodegradability, and thermal characteristics of the produced materials, we employed X-ray diffraction analysis (XRD), field emission scanning electron microscope (FESEM), Inductively Coupled Plasma (ICP), Simultaneous Thermal Analysis (STA), and compressive strength analyses. The results showed that PLA/6 wt% MgAl2O4 scaffolds possess the highest amounts of compressive strength. We evaluated the bio-activation and biodegradability of scaffolds by immersing them in simulated body fluid (SBF) for four weeks. Interestingly, the highest strength was achieved in PLA/6 wt% MgAl2O4 scaffolds, while the improper dispersion of ceramic particles happened on the polymer substrate in cases where x>6. ICP analysis showed that the addition of spinel nanoparticles to PLA increased the biodegradability of the scaffolds. Our FESEM results supported this finding and also revealed that the dispersion of ceramic particles on the polymer substrate was not uniform in cases where x>6. Also, according to the results of STA, the presence of MgAl2O4 nanoparticles effectively reduces the rate of thermal decomposition from 95 to 85 percent.

3D-bioprinting of patient-derived cardiac tissue models for studying congenital heart disease.

Introduction: Congenital heart disease is the leading cause of death related to birth defects and affects 1 out of every 100 live births. Induced pluripotent stem cell technology has allowed for patient-derived cardiomyocytes to be studied in vitro. An approach to bioengineer these cells into a physiologically accurate cardiac tissue model is needed in order to study the disease and evaluate potential treatment strategies. Methods: To accomplish this, we have developed a protocol to 3D-bioprint cardiac tissue constructs comprised of patient-derived cardiomyocytes within a hydrogel bioink based on laminin-521. Results: Cardiomyocytes remained viable and demonstrated appropriate phenotype and function including spontaneous contraction. Contraction remained consistent during 30 days of culture based on displacement measurements. Furthermore, tissue constructs demonstrated progressive maturation based on sarcomere structure and gene expression analysis. Gene expression analysis also revealed enhanced maturation in 3D constructs compared to 2D cell culture. Discussion: This combination of patient-derived cardiomyocytes and 3D-bioprinting represents a promising platform for studying congenital heart disease and evaluating individualized treatment strategies.

Moving beyond nanotechnology to uncover a glimmer of hope in diabetes medicine: Effective nanoparticle-based therapeutic strategies for the management and treatment of diabetic foot ulcers.

Hyperglycemia, a distinguishing feature of diabetes mellitus that might cause a diabetic foot ulcer (DFU), is an endocrine disorder that affects an extremely high percentage of people. Having a comprehensive understanding of the molecular mechanisms underlying the pathophysiology of diabetic wound healing can help researchers and developers design effective therapeutic strategies to treat the wound healing process in diabetes patients. Using nanoscaffolds and nanotherapeutics with dimensions ranging from 1 to 100 nm represents a state-of-the-art and viable therapeutic strategy for accelerating the wound healing process in diabetic patients, particularly those with DFU. Nanoparticles can interact with biological constituents and infiltrate wound sites owing to their reduced diameter and enhanced surface area. Furthermore, it is noteworthy that they promote the processes of vascularization, cellular proliferation, cell signaling, cell-to-cell interactions, and the formation of biomolecules that are essential for effective wound healing. Nanomaterials possess the ability to effectively transport and deliver various pharmacological agents, such as nucleic acids, growth factors, antioxidants, and antibiotics, to specific tissues, where they can be continuously released and affect the wound healing process in DFU. The present article elucidates the ongoing endeavors in the field of nanoparticle-mediated therapies for the management of DFU.

3D Printing of Hybrid-Hydrogel Materials for Tissue Engineering: a Critical Review.

Purpose: Key natural polymers, known as hydrogels, are an important group of materials in design of tissue-engineered constructs that can provide suitable habitat for cell attachment and proliferation. However, in comparison to tissues within the body, these hydrogels display poor mechanical properties. Such properties cause challenges in 3D printing of hydrogel scaffolds as well as their surgical handling after fabrication. For this reason, the purpose of this study is to critically review the 3D printing processes of hydrogels and their characteristics for tissue engineering application. Methods: A search of Google Scholar and PubMed has been performed from 2003 to February 2022 using a combination of keywords. A review of the types of 3D printing is presented. Additionally, different types of hydrogels and nano-biocomposite materials for 3D printing application are critically reviewed. The rheological properties and crosslinking mechanisms for the hydrogels are assessed. Results: Extrusion-based 3D printing is the most common practice for constructing hydrogel-based scaffolds, and it allows for the use of varying types of polymers to enhance the properties and printability of the hydrogel-based scaffolds. Rheology has been found to be exceedingly important in the 3D printing process; however, shear-thinning and thixotropic characteristics should also be present in the hydrogel. Despite these features of extrusion-based 3D printing, there are limitations to its printing resolution and scale. Conclusion: Combining natural and synthetic polymers and a variety of nanomaterials, such as metal, metal oxide, non-metal, and polymeric, can enhance the properties of hydrogel and provide additional functionality to their 3D-printed constructs.

Lithium metasilicate glass-ceramic fabrication using spark plasma sintering.

Background: The digital dentistry, requires materials with wo opposite properties of machining ability and also enough hardness. The main objective of this experimental study was to investigate the fabrication feasibility of the lithium metasilicate glass-ceramic in partially crystalized stated using the spark plasma sintering (SPS) method. Materials and Methods: In this study, SPS for the first time was used to fabricate primary lithium metasilicate glass-ceramic (LMGC) blocks. The raw materials were mixed and melted and then quenched in water and the resulted frits were grinded. The resulting powder was sintered by SPS at 660, 680, and 700°C. Results: Scanning Electron Microscope (SEM), X-ray diffraction (XRD), and Vicker's microhardness assay were used to evaluate the properties of samples. Statistical comparison of the obtained data was performed by ANOVA, followed by the post hoc test of Duncan. Microstructural studies by SEM and XRD showed that all samples were composed of lithium metasilicate phase in a glassy matrix. With increasing the sintering temperature, the number and size of lithium metasilicate particles increased and higher mechanical properties have been achieved. However, the sintered sample at 700°C has less processing ability than the samples sintered at 660 and 680°C. Conclusion: The optimum sintering temperature for glass frit consolidation was determined by SPS at 680°C.

Potential advantages of genetically modified mesenchymal stem cells in the treatment of acute and chronic liver diseases.

Liver damage caused by toxicity can lead to various severe conditions, such as acute liver failure (ALF), fibrogenesis, and cirrhosis. Among these, liver cirrhosis (LC) is recognized as the leading cause of liver-related deaths globally. Unfortunately, patients with progressive cirrhosis are often on a waiting list, with limited donor organs, postoperative complications, immune system side effects, and high financial costs being some of the factors restricting transplantation. Although the liver has some capacity for self-renewal due to the presence of stem cells, it is usually insufficient to prevent the progression of LC and ALF. One potential therapeutic approach to improving liver function is the transplantation of gene-engineered stem cells. Several types of mesenchymal stem cells from various sources have been suggested for stem cell therapy for liver disease. Genetic engineering is an effective strategy that enhances the regenerative potential of stem cells by releasing growth factors and cytokines. In this review, we primarily focus on the genetic engineering of stem cells to improve their ability to treat damaged liver function. We also recommend further research into accurate treatment methods that involve safe gene modification and long-term follow-up of patients to increase the effectiveness and reliability of these therapeutic strategies.

Effect of Pore Characteristics and Alkali Treatment on the Physicochemical and Biological Properties of a 3D-Printed Polycaprolactone Bone Scaffold.

Polycaprolactone scaffolds were designed and 3D-printed with different pore shapes (cube and triangle) and sizes (500 and 700 µm) and modified with alkaline hydrolysis of different ratios (1, 3, and 5 M). In total, 16 designs were evaluated for their physical, mechanical, and biological properties. The present study mainly focused on the pore size, porosity, pore shapes, surface modification, biomineralization, mechanical properties, and biological characteristics that might influence bone ingrowth in 3D-printed biodegradable scaffolds. The results showed that the surface roughness in treated scaffolds increased compared to untreated polycaprolactone scaffolds (R a = 2.3-10.5 nm and R q = 17- 76 nm), but the structural integrity declined with an increase in the NaOH concentration especially in the scaffolds with small pores and a triangle shape. Overall, the treated polycaprolactone scaffolds particularly with the triangle shape and smaller pore size provided superior performance in mechanical strength similar to that of cancellous bone. Additionally, the in vitro study showed that cell viability increased in the polycaprolactone scaffolds with cubic pore shapes and small pore sizes, whereas mineralization was enhanced in the designs with larger pore sizes. Based on the results obtained, this study demonstrated that the 3D-printed modified polycaprolactone scaffolds exhibit a favorable mechanical property, biomineralization, and better biological properties; therefore, they can be applied in bone tissue engineering.

Structural parameters of nanoparticles affecting their toxicity for biomedical applications: a review.

Rapidly growing interest in using nanoparticles (NPs) for biomedical applications has increased concerns about their safety and toxicity. In comparison with bulk materials, NPs are more chemically active and toxic due to the greater surface area and small size. Understanding the NPs' mechanism of toxicity, together with the factors influencing their behavior in biological environments, can help researchers to design NPs with reduced side effects and improved performance. After overviewing the classification and properties of NPs, this review article discusses their biomedical applications in molecular imaging and cell therapy, gene transfer, tissue engineering, targeted drug delivery, Anti-SARS-CoV-2 vaccines, cancer treatment, wound healing, and anti-bacterial applications. There are different mechanisms of toxicity of NPs, and their toxicity and behaviors depend on various factors, which are elaborated on in this article. More specifically, the mechanism of toxicity and their interactions with living components are discussed by considering the impact of different physiochemical parameters such as size, shape, structure, agglomeration state, surface charge, wettability, dose, and substance type. The toxicity of polymeric, silica-based, carbon-based, and metallic-based NPs (including plasmonic alloy NPs) have been considered separately.

3D-Printed Soft Membrane for Periodontal Guided Tissue Regeneration.

OBJECTIVES: The current study aimed to perform an in vivo examination using a critical-size periodontal canine model to investigate the capability of a 3D-printed soft membrane for guided tissue regeneration (GTR). This membrane is made of a specific composition of gelatin, elastin, and sodium hyaluronate that was fine-tuned and fully characterized in vitro in our previous study. The value of this composition is its potential to be employed as a suitable replacement for collagen, which is the main component of conventional GTR membranes, to overcome the cost issue with collagen. METHODS: Critical-size dehiscence defects were surgically created on the buccal surface of the roots of canine bilateral mandibular teeth. GTR treatment was performed with the 3D-printed membrane and two commercially available collagen membranes (Botiss Jason® and Smartbrane-Regedent membranes) and a group without any membrane placement was considered as the control group. The defects were submerged with tension-free closure of the gingival flaps. Histologic and histometric analyses were employed to assess the periodontal healing over an 8-week experimental period. RESULTS: Histometric evaluations confirmed higher levels of new bone formation in the 3D-printed membrane group. Moreover, in all defects treated with the membranes, the formation of periodontal tissues, bone, periodontal ligaments, and cementum was observed after 8 weeks, while in the control group, only connective tissue was found in the defect sites. There was no clinical sign of inflammation or recession of gingiva in any of the groups. SIGNIFICANCE: The 3D-printed gelatin/elastin/sodium hyaluronate membrane can be safe and effective for use in GTR for periodontal tissue regeneration therapies, with better or comparable results to the commercial collagen membranes.