bims-biprem 2024-03-31 papers

bims-biprem

Biomed News

on Bioprinting for regenerative medicine

Issue of 2024–03–31
twelve papers selected by
Seerat Maqsood, University of Teramo

Recent Developments in Bio-Ink Formulations Using Marine-Derived Biomaterials for Three-Dimensional (3D) Bioprinting.
Advancements in 3D-printable polysaccharides, proteins, and synthetic polymers for wound dressing and skin scaffolding - A review.
3D Bioprinting-Based Dopamine-Coupled Flexible Material for Nasal Cartilage Repair.
Three-Dimensional Printing Methods for Bioceramic-Based Scaffold Fabrication for Craniomaxillofacial Bone Tissue Engineering.
High Hopes for the Biofabrication of Articular Cartilage-What Lies beyond the Horizon of Tissue Engineering and 3D Bioprinting?
3D bioprinted tumor model: a prompt and convenient platform for overcoming immunotherapy resistance by recapitulating the tumor microenvironment.
Towards Precision Ophthalmology: The Role of 3D Printing and Bioprinting in Oculoplastic Surgery, Retinal, Corneal, and Glaucoma Treatment.
Designing of a Multifunctional 3D-Printed Biomimetic Theragenerative Aerogel Scaffold via Mussel-Inspired Chemistry: Bioactive Glass Nanofiber-Incorporated Self-Assembled Silk Fibroin with Antibacterial, Antiosteosarcoma, and Osteoinductive Properties.
3D Printed Materials for Permanent Restorations in Indirect Restorative and Prosthetic Dentistry: A Critical Review of the Literature.
Preparation and properties of a 3D printed nHA/PLA bone tissue engineering scaffold loaded with a β-CD-CHX combined dECM hydrogel.
Biodegradable poly(caprolactone fumarate) 3D printed scaffolds for segmental bone defects within the Masquelet technique.
3D-Printed Chitosan-Based Scaffolds with Scutellariae baicalensis Extract for Dental Applications.

Mar Drugs. 2024 Mar 16. pii: 134. [Epub ahead of print]22(3):

Recent Developments in Bio-Ink Formulations Using Marine-Derived Biomaterials for Three-Dimensional (3D) Bioprinting.

Zied Khiari.

  3D bioprinting is a disruptive, computer-aided, and additive manufacturing technology that allows the obtention, layer-by-layer, of 3D complex structures. This technology is believed to offer tremendous opportunities in several fields including biomedical, pharmaceutical, and food industries. Several bioprinting processes and bio-ink materials have emerged recently. However, there is still a pressing need to develop low-cost sustainable bio-ink materials with superior qualities (excellent mechanical, viscoelastic and thermal properties, biocompatibility, and biodegradability). Marine-derived biomaterials, including polysaccharides and proteins, represent a viable and renewable source for bio-ink formulations. Therefore, the focus of this review centers around the use of marine-derived biomaterials in the formulations of bio-ink. It starts with a general overview of 3D bioprinting processes followed by a description of the most commonly used marine-derived biomaterials for 3D bioprinting, with a special attention paid to chitosan, glycosaminoglycans, alginate, carrageenan, collagen, and gelatin. The challenges facing the application of marine-derived biomaterials in 3D bioprinting within the biomedical and pharmaceutical fields along with future directions are also discussed.

Keywords:  3D bioprinting; bio-ink; marine biomaterials; polysaccharides; proteins

DOI:  https://doi.org/10.3390/md22030134
Int J Biol Macromol. 2024 Mar 27. pii: S0141-8130(24)02012-9. [Epub ahead of print] 131207

Advancements in 3D-printable polysaccharides, proteins, and synthetic polymers for wound dressing and skin scaffolding - A review.

Ali Sadeghianmaryan, Nivad Ahmadian, Sydney Wheatley, Hamed Alizadeh Sardroud, Seyyed Ahmad Seyyed Nasrollah, Emad Naseri, Ali Ahmadi.

  This review investigates the most recent advances in personalized 3D-printed wound dressings and skin scaffolding. Skin is the largest and most vulnerable organ in the human body. The human body has natural mechanisms to restore damaged skin through several overlapping stages. However, the natural wound healing process can be rendered insufficient due to severe wounds or disturbances in the healing process. Wound dressings are crucial in providing a protective barrier against the external environment, accelerating healing. Although used for many years, conventional wound dressings are neither tailored to individual circumstances nor specific to wound conditions. To address the shortcomings of conventional dressings, skin scaffolding can be used for skin regeneration and wound healing. This review thoroughly investigates polysaccharides (e.g., chitosan, Hyaluronic acid (HA)), proteins (e.g., collagen, silk), synthetic polymers (e.g., Polycaprolactone (PCL), Poly lactide-co-glycolic acid (PLGA), Polylactic acid (PLA)), as well as nanocomposites (e.g., silver nano particles and clay materials) for wound healing applications and successfully 3D printed wound dressings. It discusses the importance of combining various biomaterials to enhance their beneficial characteristics and mitigate their drawbacks. Different 3D printing fabrication techniques used in developing personalized wound dressings are reviewed, highlighting the advantages and limitations of each method. This paper emphasizes the exceptional versatility of 3D printing techniques in advancing wound healing treatments. Finally, the review provides recommendations and future directions for further research in wound dressings.

Keywords:  3D-printing; Polysaccharides; Proteins; Skin scaffolding; Wound dressing

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.131207
Aesthetic Plast Surg. 2024 Mar 25.

3D Bioprinting-Based Dopamine-Coupled Flexible Material for Nasal Cartilage Repair.

Wendan Jia, Zixian Liu, Zhuwei Ma, Peiyi Hou, Yanyan Cao, Zhizhong Shen, Meng Li, Hulin Zhang, Xing Guo, Shengbo Sang.

   INTRODUCTION: Since 3D printing can be used to design implants according to the specific conditions of patients, it has become an emerging technology in tissue engineering and regenerative medicine. How to improve the mechanical, elastic and adhesion properties of 3D-printed photocrosslinked hydrogels is the focus of cartilage tissue repair and reconstruction research.
MATERIALS AND METHODS: We established a strategy for toughening hydrogels by mixing GelMA-DOPA (GD), which is prepared by coupling dopamine (DA) with GelMA, with HAMA, bacterial cellulose (BC) to produce composite hydrogels (HB-GD). HB-GD hydrogel scaffolds were characterized in vitro by scanning electron microscopy (SEM), Young's modulus, swelling property and rheological property tests. And biocompatibility and chondrogenic ability were tested by live/dead staining, DNA quantitative analysis and immunofluorescence staining. Combined with 3D bioprinting technology, mouse chondrocytes (ADTC5) were added to form a biological chain to construct an in vitro model, and the feasibility of the model for nasal cartilage regeneration was verified by cytology evaluation.
RESULTS: With the increase of GD concentration, the toughness of the composite hydrogel increased (47.0 ± 2.7 kPa (HB-5GD)-158 ± 3.2 kPa (HB-20GD)), and it had excellent swelling properties, rheological properties and printing properties. The HB-GD composite hydrogel promoted the proliferation and differentiation of ATDC5. Cells in 3D printed scaffolds had higher survival rates (> 95%) and better protein expression than the encapsulated cultures.
CONCLUSION: The HB-10GD hydrogel can be made into a porous scaffold with precise shape, good internal pore structure, high mechanical strength and good swelling rate through extrusion 3D printing.
NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Keywords:  3D bioprinting; BC; Cartilage repair; DA; GelMA; HAMA

DOI:  https://doi.org/10.1007/s00266-024-03982-7
J Funct Biomater. 2024 Mar 01. pii: 60. [Epub ahead of print]15(3):

Three-Dimensional Printing Methods for Bioceramic-Based Scaffold Fabrication for Craniomaxillofacial Bone Tissue Engineering.

Zeeshan Sheikh, Vasudev Vivekanand Nayak, Umer Daood, Anupreet Kaur, Hanan Moussa, Abbas Canteenwala, Pierre-Luc Michaud, Ísis de Fátima Balderrama, Edisa de Oliveira Sousa, Nick Tovar, Andrea Torroni, Michael Glogauer, Huzefa Talib, Paulo G Coelho, Lukasz Witek.

  Three-dimensional printing (3DP) technology has revolutionized the field of the use of bioceramics for maxillofacial and periodontal applications, offering unprecedented control over the shape, size, and structure of bioceramic implants. In addition, bioceramics have become attractive materials for these applications due to their biocompatibility, biostability, and favorable mechanical properties. However, despite their advantages, bioceramic implants are still associated with inferior biological performance issues after implantation, such as slow osseointegration, inadequate tissue response, and an increased risk of implant failure. To address these challenges, researchers have been developing strategies to improve the biological performance of 3D-printed bioceramic implants. The purpose of this review is to provide an overview of 3DP techniques and strategies for bioceramic materials designed for bone regeneration. The review also addresses the use and incorporation of active biomolecules in 3D-printed bioceramic constructs to stimulate bone regeneration. By controlling the surface roughness and chemical composition of the implant, the construct can be tailored to promote osseointegration and reduce the risk of adverse tissue reactions. Additionally, growth factors, such as bone morphogenic proteins (rhBMP-2) and pharmacologic agent (dipyridamole), can be incorporated to promote the growth of new bone tissue. Incorporating porosity into bioceramic constructs can improve bone tissue formation and the overall biological response of the implant. As such, employing surface modification, combining with other materials, and incorporating the 3DP workflow can lead to better patient healing outcomes.

Keywords:  3D-printing; bioceramics; bone tissue engineering; scaffold fabrication

DOI:  https://doi.org/10.3390/jfb15030060
Biomedicines. 2024 Mar 15. pii: 665. [Epub ahead of print]12(3):

High Hopes for the Biofabrication of Articular Cartilage-What Lies beyond the Horizon of Tissue Engineering and 3D Bioprinting?

Yordan Sbirkov, Murad Redzheb, Nico Forraz, Colin McGuckin, Victoria Sarafian.

  Technologies and biomaterials for 3D bioprinting have been developing extremely quickly in the past decade as they hold great potential in tissue engineering. This, together with the possibility to differentiate stem cells of different origin into any cell type, raises the hopes in regenerative medicine once again after the initial breakthrough with stem cells in the 1980s. Nevertheless, three decades of 3D bioprinting experiments have shown that the production of functional tissues would take a longer time than anticipated. Cartilage, one of the simplest tissues in the body, consists of only one cell type. It is not vascularised and innervated and does not have lymphatic vessels either, which makes it a perfect target tissue for successful implantation. The tremendous amount of work since the beginning of this century, combining the efforts of bioengineers, material scientists, biologists, and physicians, has culminated in multiple proof-of-concept constructs that have been implanted in animals. However, there is no single reproducible, standardised, widely accessible and accepted strategy that can be readily applied in the clinic. In this review, we focus on the current progress in the field of the 3D biofabrication of articular cartilage and critically assess failures and future challenges.

Keywords:  3D bioprinting; articular cartilage; regenerative medicine; tissue engineering

DOI:  https://doi.org/10.3390/biomedicines12030665
Cell Oncol (Dordr). 2024 Mar 23.

3D bioprinted tumor model: a prompt and convenient platform for overcoming immunotherapy resistance by recapitulating the tumor microenvironment.

Zhangyi Zhang, Xuebo Chen, Sujie Gao, Xuedong Fang, Shengnan Ren.

   BACKGROUND: Cancer immunotherapy is receiving worldwide attention for its induction of an anti-tumor response. However, it has had limited efficacy in some patients who acquired resistance. The dynamic and sophisticated complexity of the tumor microenvironment (TME) is the leading contributor to this clinical dilemma. Through recapitulating the physiological features of the TME, 3D bioprinting is a promising research tool for cancer immunotherapy, which preserves in vivo malignant aggressiveness, heterogeneity, and the cell-cell/matrix interactions. It has been reported that application of 3D bioprinting holds potential to address the challenges of immunotherapy resistance and facilitate personalized medication.
CONCLUSIONS AND PERSPECTIVES: In this review, we briefly summarize the contributions of cellular and noncellular components of the TME in the development of immunotherapy resistance, and introduce recent advances in 3D bioprinted tumor models that served as platforms to study the interactions between tumor cells and the TME. By constructing multicellular 3D bioprinted tumor models, cellular and noncellular crosstalk is reproduced between tumor cells, immune cells, fibroblasts, adipocytes, and the extracellular matrix (ECM) within the TME. In the future, by quickly preparing 3D bioprinted tumor models with patient-derived components, information on tumor immunotherapy resistance can be obtained timely for clinical reference. The combined application with tumoroid or other 3D culture technologies will also help to better simulate the complexity and dynamics of tumor microenvironment in vitro. We aim to provide new perspectives for overcoming cancer immunotherapy resistance and inspire multidisciplinary research to improve the clinical application of 3D bioprinting technology.

Keywords:  Acquired resistance; Bioprinting; Cancer immunotherapy; In vitro tumor model; Personalized medication

DOI:  https://doi.org/10.1007/s13402-024-00935-9
Biomimetics (Basel). 2024 Feb 27. pii: 145. [Epub ahead of print]9(3):

Towards Precision Ophthalmology: The Role of 3D Printing and Bioprinting in Oculoplastic Surgery, Retinal, Corneal, and Glaucoma Treatment.

Kevin Y Wu, Adrian Tabari, Éric Mazerolle, Simon D Tran.

  In the forefront of ophthalmic innovation, biomimetic 3D printing and bioprinting technologies are redefining patient-specific therapeutic strategies. This critical review systematically evaluates their application spectrum, spanning oculoplastic reconstruction, retinal tissue engineering, corneal transplantation, and targeted glaucoma treatments. It highlights the intricacies of these technologies, including the fundamental principles, advanced materials, and bioinks that facilitate the replication of ocular tissue architecture. The synthesis of primary studies from 2014 to 2023 provides a rigorous analysis of their evolution and current clinical implications. This review is unique in its holistic approach, juxtaposing the scientific underpinnings with clinical realities, thereby delineating the advantages over conventional modalities, and identifying translational barriers. It elucidates persistent knowledge deficits and outlines future research directions. It ultimately accentuates the imperative for multidisciplinary collaboration to enhance the clinical integration of these biotechnologies, culminating in a paradigm shift towards individualized ophthalmic care.

Keywords:  3D printing; biomimetics; bioprinting; clinical translation; corneal transplantation; glaucoma; oculoplastic surgery; ophthalmology; retinal tissue engineering; surgical simulation; tissue engineering

DOI:  https://doi.org/10.3390/biomimetics9030145
ACS Appl Mater Interfaces. 2024 Mar 28.

Designing of a Multifunctional 3D-Printed Biomimetic Theragenerative Aerogel Scaffold via Mussel-Inspired Chemistry: Bioactive Glass Nanofiber-Incorporated Self-Assembled Silk Fibroin with Antibacterial, Antiosteosarcoma, and Osteoinductive Properties.

Nahal Abie, Ceyda Ünlü, Ana Rita Pinho, Maria C Gomes, Torsten Remmler, Marc Herb, Daniela Grumme, Ehsan Tabesh, Mohammad-Ali Shahbazi, Sanjay Mathur, João F Mano, Hajar Maleki.

  Biomaterial-mediated bone tissue engineering (BTE) offers an alternative, interesting approach for the restoration of damaged bone tissues in postsurgery osteosarcoma treatment. This study focused on synthesizing innovative composite inks, integrating self-assembled silk fibroin (SF), tannic acids (TA), and electrospun bioactive glass nanofibers 70SiO2-25CaO-5P2O5 (BGNF). By synergistically combining the unique characteristics of these three components through self-assembly and microextrusion-based three-dimensional (3D) printing, our goal was to produce durable and versatile aerogel-based 3D composite scaffolds. These scaffolds were designed to exhibit hierarchical porosity along with antibacterial, antiosteosarcoma, and bone regeneration properties. Taking inspiration from mussel foot protein attachment chemistry involving the coordination of dihydroxyphenylalanine (DOPA) amino acids with ferric ions (Fe3+), we synthesized a tris-complex catecholate-iron self-assembled composite gel. This gel formation occurred through the coordination of oxidized SF (SFO) with TA and polydopamine-modified BGNF (BGNF-PDA). The dynamic nature of the coordination ligand-metal bonds within the self-assembled SFO matrix provided excellent shear-thinning properties, allowing the SFO-TA-BGNF complex gel to be extruded through a nozzle, facilitating 3D printing into scaffolds with outstanding shape fidelity. Moreover, the developed composite aerogels exhibited multifaceted features, including NIR-triggered photothermal antibacterial and in vitro photothermal antiosteosarcoma properties. In vitro studies showcased their excellent biocompatibility and osteogenic features as seeded cells successfully differentiated into osteoblasts, promoting bone regeneration in 21 days. Through comprehensive characterizations and biological validations, our antibacterial scaffold demonstrated promise as an exceptional platform for concurrent bone regeneration and bone cancer therapy, setting the stage for their potential clinical application.

Keywords:  3D printing; aerogels; antibacterial properties; bioactive glass; bioinspired materials; bone tissue engineering; hydrogel; mussel-inspired chemistry; osteogenic properties; osteosarcoma therapy; photothermal therapy

DOI:  https://doi.org/10.1021/acsami.4c00065
Materials (Basel). 2024 Mar 18. pii: 1380. [Epub ahead of print]17(6):

3D Printed Materials for Permanent Restorations in Indirect Restorative and Prosthetic Dentistry: A Critical Review of the Literature.

Dario Balestra, Morgan Lowther, Cecilia Goracci, Mauro Mandurino, Silvia Cortili, Gaetano Paolone, Chris Louca, Alessandro Vichi.

  The objective of this study was to review the scientific evidence currently available on 3D printable materials and 3D printing technologies used for the fabrication of permanent restorations, focusing on material properties that are clinically relevant. A literature search was performed on four databases (MEDLINE/PubMed, Scopus, Cochrane Library, Web of Science) for articles published from January 2013 until November 2023, using a combination of free words: (restorative dentistry OR prosthetic dentistry) AND (3D printing OR additive manufacturing OR rapid prototyping) AND materials. Two reviewers screened titles and/or abstracts of 2.468 unique studies. In total, 83 studies were selected for full-text reading, from which 36 were included in the review. The assessed variables were mechanical properties, reporting in most of the cases positive results, dimensional accuracy and fit, reporting conflicting results with a predominance of positive, aesthetic properties, with positive reports but scarcely addressed, and biological properties, almost unexplored in independent studies. Despite numerous studies with positive results in favor, papers with negative outcomes were also retrieved. Aesthetic and biological properties are conversely still mostly unexplored. There remains a lack of conclusive evidence for viable 3D printable restorative and prosthodontic materials for permanent restorations. Research should be strengthened by defining international standards for laboratory testing and, where pre-clinical data are promising, conducting clinical trials.

Keywords:  3D printing; additive manufacturing; prosthodontics; rapid prototyping

DOI:  https://doi.org/10.3390/ma17061380
RSC Adv. 2024 Mar 20. 14(14): 9848-9859

Preparation and properties of a 3D printed nHA/PLA bone tissue engineering scaffold loaded with a β-CD-CHX combined dECM hydrogel.

Shangbo Li, Zijian Liu, Xiaohan Gao, Lidi Cheng, Zexian Xu, Li Li, Yaru Diao, Liqiang Chen, Yanshan Liu, Jian Sun.

Jaw defects, which can result from a multitude of causes, significantly affect the physical well-being and psychological health of patients. The repair of these infected defects presents a formidable challenge in the clinical and research fields, owing to their intricate and diverse nature. This study aims to develop a personalized bone tissue engineering scaffold that synergistically offers antibacterial and osteogenic properties for treating infected maxillary defects. This study engineered a novel temperature-sensitive, sustained-release hydrogel by amalgamating β-cyclodextrin (β-CD) with chlorhexidine (CHX) and a decellularized extracellular matrix (dECM). This hydrogel was further integrated with a polylactic acid (PLA)-nano hydroxyapatite (nHA) scaffold, fabricated through 3D printing, to form a multifaceted composite scaffold (nHA/PLA/dECM/β-CD-CHX). Drug release assays revealed that this composite scaffold ensures prolonged and sustained release. Bacteriological studies confirmed that the β-CD-CHX loaded scaffold exhibits persistent antibacterial efficacy, thus effectively inhibiting bacterial growth. Moreover, the scaffold demonstrated robust mechanical strength. Cellular assays validated its superior biocompatibility, attributed to dECM and nHA components, significantly enhancing the proliferation, adhesion, and osteogenic differentiation of osteogenic precursor cells (MC3T3-E1). Consequently, the nHA/PLA/dECM/β-CD-CHX composite scaffold, synthesized via 3D printing technology, shows promise in inducing bone regeneration, preventing infection, and facilitating the repair of jaw defects, positioning itself as a potential breakthrough in bone tissue engineering.

DOI: https://doi.org/10.1039/d4ra00261j
J Orthop Res. 2024 Mar 24.

Biodegradable poly(caprolactone fumarate) 3D printed scaffolds for segmental bone defects within the Masquelet technique.

Maria D Astudillo Potes, Indranath Mitra, Kari Hanson, Emily T Camilleri, Bipin Gaihre, Mahnoor Shafi, Abdelrahman Hamouda, Lichun Lu, Benjamin D Elder.

  Segmental bone defects, often clinically treated with nondegradable poly(methylmethacrylate) (PMMA) in multistage surgeries, present a significant clinical challenge. Our study investigated the efficacy of 3D printed biodegradable polycaprolactone fumarate (PCLF)/PCL spacers in a one-stage surgical intervention for these defects, focusing on early bone regeneration influenced by spacer porosities. We compared nonporous PCLF/PCL and PMMA spacers, conventionally molded into cylinders, with porous PCLF/PCL spacers, 3D printed to structurally mimic segmental defects in rat femurs for a 4-week implantation study. Histological analysis, including tissue staining and immunohistochemistry with bone-specific antibodies, was conducted for histomorphometry evaluation. The PCLF/PCL spacers demonstrated compressive properties within 6 ± 0.5 MPa (strength) and 140 ± 15 MPa (modulus). Both porous PCLF/PCL and Nonporous PMMA formed collagen-rich membranes (PCLF/PCL: 92% ± 1.3%, PMMA: 86% ± 1.5%) similar to those induced in the Masquelet technique, indicating PCLF/PCL's potential for one-stage healing. Immunohistochemistry confirmed biomarkers for tissue regeneration, underscoring PCLF/PCL's regenerative capabilities. This research highlights PCLF/PCL scaffolds' ability to induce membrane formation in critical-sized segmental bone defects, supporting their use in one-stage surgery. Both solid and porous PCLF/PCL spacers showed adequate compressive properties, with the porous variants exhibiting BMP-2 expression and woven bone formation, akin to clinical standard PMMA. Notably, the early ossification of the membrane into the pores of porous scaffolds suggests potential for bone interlocking and regeneration, potentially eliminating the need for a second surgery required for PMMA spacers. The biocompatibility and biodegradability of PCLF/PCL make them promising alternatives for treating critical bone defects, especially in vulnerable patient groups.

Keywords:  Masquelet technique; biodegradable scaffolds; guided bone regeneration; poly(caprolactone fumarate) spacer

DOI:  https://doi.org/10.1002/jor.25839
Pharmaceutics. 2024 Mar 04. pii: 359. [Epub ahead of print]16(3):

3D-Printed Chitosan-Based Scaffolds with Scutellariae baicalensis Extract for Dental Applications.

Magdalena Paczkowska-Walendowska, Ioanna Koumentakou, Maria Lazaridou, Dimitrios Bikiaris, Andrzej Miklaszewski, Tomasz Plech, Judyta Cielecka-Piontek.

  The plant material Scutellariae baicalensis radix, which is rich in flavones (baicalin), possesses antibacterial, antifungal, antioxidant, and anti-inflammatory properties. This work aimed to develop a 3D-printed chitosan-based hydrogel rich in Scutellariae baicalensis extract as an innovative approach for the personalized treatment of periodontal diseases. Chitosan-based hydrogels were prepared, and the printability of the prepared hydrogels was determined. The hydrogel with 2.5% w/v of high molecular-weight chitosan (CS), 2% w/v gelatin (Gel), and 10% w/w of extract (Ex) presented the best printability, producing smooth and uniform scaffolds. It was proved that the CS/Gel/Ex hydrogel was stabilized by hydrogen bonds and remained in amorphous dispersion in the 3D-printed structures (confirmed by ATR-FTIR and XRPD). Due to the amorphization of the active substance, a significant increase in the release of baicalin in vitro was observed. It was demonstrated that there was an initial burst release and a continuous release profile (n = 3). Higuchi kinetic was the most likely baicalin release kinetic. The second fit, the Korsmeyer-Peppas kinetics model, showed coupled diffusion of the active ingredient in the hydrated matrix and polymer relaxation regulated release, with n values ranging from 0.45 to 0.89. The anti-inflammatory properties of 3D-printed scaffolds were assessed as the ability to inhibit the activity of the hyaluronidase enzyme. Activity was assessed as IC50 = 63.57 ± 4.98 mg hydrogel/mL (n = 6). Cytotoxicity tests demonstrated the biocompatibility of the material. After 24 h of exposure to the 2.5CS/2Gel/10Ex scaffold, fibroblasts migrated toward the scratch, closed the "wound" by 97.1%, and significantly accelerated the wound healing process. The results render the 3D-printed CS/Gel/extract scaffolds as potential candidates for treating periodontal diseases.

Keywords:  3D printing; Scutellariae baicalensis extract; chitosan; gelatin

DOI:  https://doi.org/10.3390/pharmaceutics16030359