bims-biprem 2024-12-22 papers

bims-biprem

Biomed News

on Bioprinting for regenerative medicine

Issue of 2024–12–22
twelve papers selected by
Seerat Maqsood, University of Teramo

Photocrosslinkable Biomaterials for 3D Bioprinting: Mechanisms, Recent Advances, and Future Prospects.
Bioprinting extracellular vesicles as a "cell-free" regenerative medicine approach.
3D extrusion bioprinting of microbial inks for biomedical applications.
3D Bioprinting and Artificial Intelligence-Assisted Biofabrication of Personalized Oral Soft Tissue Constructs.
3D printing for controlled release Pharmaceuticals: Current trends and future directions.
Self-healing, 3D printed bioinks from self-assembled peptide and alginate hybrid hydrogels.
Advances and Challenges in Polymer-Based Scaffolds for Bone Tissue Engineering: A Path Towards Personalized Regenerative Medicine.
Alkaline etching assisted polydopamine coating for enhanced cell-material interactions on 3D printed polylactic acid scaffolds.
Hierarchically porous 3D-printed ceramic scaffolds for bone tissue engineering.
Functionalization of 3D printed poly(lactic acid)/graphene oxide/β-tricalcium phosphate (PLA/GO/TCP) scaffolds for bone tissue regeneration application.
3D printed PCL-nHAp composite implants for the treatment of segmental bone defects: in vivo application in a rabbit model.
Tissue Engineering 3D-Printed Scaffold Using Allograft/Alginate/Gelatin Hydrogels Coated With Platelet-Rich Fibrin or Adipose Stromal Vascular Fraction Induces Osteogenesis In Vitro.

Int J Mol Sci. 2024 Nov 22. pii: 12567. [Epub ahead of print]25(23):

Photocrosslinkable Biomaterials for 3D Bioprinting: Mechanisms, Recent Advances, and Future Prospects.

Yushang Lai, Xiong Xiao, Ziwei Huang, Hongying Duan, Liping Yang, Yuchu Yang, Chenxi Li, Li Feng.

  Constructing scaffolds with the desired structures and functions is one of the main goals of tissue engineering. Three-dimensional (3D) bioprinting is a promising technology that enables the personalized fabrication of devices with regulated biological and mechanical characteristics similar to natural tissues/organs. To date, 3D bioprinting has been widely explored for biomedical applications like tissue engineering, drug delivery, drug screening, and in vitro disease model construction. Among different bioinks, photocrosslinkable bioinks have emerged as a powerful choice for the advanced fabrication of 3D devices, with fast crosslinking speed, high resolution, and great print fidelity. The photocrosslinkable biomaterials used for light-based 3D printing play a pivotal role in the fabrication of functional constructs. Herein, this review outlines the general 3D bioprinting approaches related to photocrosslinkable biomaterials, including extrusion-based printing, inkjet printing, stereolithography printing, and laser-assisted printing. Further, the mechanisms, advantages, and limitations of photopolymerization and photoinitiators are discussed. Next, recent advances in natural and synthetic photocrosslinkable biomaterials used for 3D bioprinting are highlighted. Finally, the challenges and future perspectives of photocrosslinkable bioinks and bioprinting approaches are envisaged.

Keywords:  3D bioprinting; hydrogel; photocrosslinkable biomaterials

DOI:  https://doi.org/10.3390/ijms252312567
Extracell Vesicles Circ Nucl Acids. 2023 ;4(2): 218-239

Bioprinting extracellular vesicles as a "cell-free" regenerative medicine approach.

Kexin Jiao, Chun Liu, Saraswat Basu, Nimal Raveendran, Tamaki Nakano, Sašo Ivanovski, Pingping Han.

  Regenerative medicine involves the restoration of tissue or organ function via the regeneration of these structures. As promising regenerative medicine approaches, either extracellular vesicles (EVs) or bioprinting are emerging stars to regenerate various tissues and organs (i.e., bone and cardiac tissues). Emerging as highly attractive cell-free, off-the-shelf nanotherapeutic agents for tissue regeneration, EVs are bilayered lipid membrane particles that are secreted by all living cells and play a critical role as cell-to-cell communicators through an exchange of EV cargos of protein, genetic materials, and other biological components. 3D bioprinting, combining 3D printing and biology, is a state-of-the-art additive manufacturing technology that uses computer-aided processes to enable simultaneous patterning of 3D cells and tissue constructs in bioinks. Although developing an effective system for targeted EVs delivery remains challenging, 3D bioprinting may offer a promising means to improve EVs delivery efficiency with controlled loading and release. The potential application of 3D bioprinted EVs to regenerate tissues has attracted attention over the past few years. As such, it is timely to explore the potential and associated challenges of utilizing 3D bioprinted EVs as a novel "cell-free" alternative regenerative medicine approach. In this review, we describe the biogenesis and composition of EVs, and the challenge of isolating and characterizing small EVs - sEVs (< 200 nm). Common 3D bioprinting techniques are outlined and the issue of bioink printability is explored. After applying the following search strategy in PubMed: "bioprinted exosomes" or "3D bioprinted extracellular vesicles", eight studies utilizing bioprinted EVs were found that have been included in this scoping review. Current studies utilizing bioprinted sEVs for various in vitro and in vivo tissue regeneration applications, including angiogenesis, osteogenesis, immunomodulation, chondrogenesis and myogenesis, are discussed. Finally, we explore the current challenges and provide an outlook on possible refinements for bioprinted sEVs applications.

Keywords:  3D bioprinting; bioprinted sEVs; regenerative medicine; small extracellular vesicles

DOI:  https://doi.org/10.20517/evcna.2023.19
Adv Drug Deliv Rev. 2024 Dec 17. pii: S0169-409X(24)00327-2. [Epub ahead of print] 115505

3D extrusion bioprinting of microbial inks for biomedical applications.

Nicolas Burns, Arjun Rajesh, Avinash Manjula-Basavanna, Anna Duraj-Thatte.

  In recent years, the field of 3D bioprinting has witnessed the intriguing development of a new type of bioink known as microbial inks. Bioinks, typically associated with mammalian cells, have been reimagined to involve microbes, enabling many new applications beyond tissue engineering and regenerative medicine. This review presents the latest advancements in microbial inks, including their definition, types, composition, salient characteristics, and biomedical applications. Herein, microbes are genetically engineered to produce 1) extrudable bioink and 2) life-like functionalities such as self-regeneration, self-healing, self-regulation, biosynthesis, biosensing, biosignaling, biosequestration, etc. We also discuss some of the promising applications of 3D extrusion printed microbial inks, such as 1) drugs and probiotics delivery, 2) metabolite production, 3) tissue engineering, 4) bioremediation, 5) biosensors and bioelectronics, 6) biominerals and biocomposites, and 7) infectious disease modeling. Finally, we describe some of the current challenges of microbial inks that needs to be addressed in the coming years, to make a greater impact in health science and technology and many other fields.

Keywords:  3D Printing; Additive Manufacturing; Bioinks; Bioprinting; Engineered Living Materials; Extrusion; Microbial Inks

DOI:  https://doi.org/10.1016/j.addr.2024.115505
Adv Healthc Mater. 2024 Dec 17. e2402727

3D Bioprinting and Artificial Intelligence-Assisted Biofabrication of Personalized Oral Soft Tissue Constructs.

Yichen Dai, Peter Wang, Apurva Mishra, Kui You, Yuheng Zong, Wen Feng Lu, Edward Kai-Hua Chow, Philip M Preshaw, Dejian Huang, Jacob Ren Jie Chew, Dean Ho, Gopu Sriram.

  Regeneration of oral soft tissue defects, including mucogingival defects associated with the recession or loss of gingival and/or mucosal tissues around teeth and implants, is crucial for restoring oral tissue form, function, and health. This study presents a novel approach using three-dimensional (3D) bioprinting to fabricate individualized grafts with precise size, shape, and layer-by-layer cellular organization. A multicomponent polysaccharide/fibrinogen-based bioink is developed, and bioprinting parameters are optimized to create shape-controlled oral soft tissue (gingival) constructs. Rheological, printability, and shape-fidelity assays, demonstrated the influence of thickener concentration and print parameters on print resolution and shape fidelity. Artificial intelligence (AI)-derived tool enabled streamline the iterative bioprinting parameter optimization and analysis of the interaction between the bioprinting parameters. The cell-laden polysaccharide/fibrinogen-based bioinks exhibited excellent cellular viability and shape fidelity of shape-controlled, full-thickness gingival tissue constructs over the 18-day culture period. While variations in thickener concentrations within the bioink minimally impact the cellular organization and morphogenesis (gingival epithelial, connective tissue, and basement membrane markers), they influence the shape fidelity of the bioprinted constructs. This study represents a significant step toward the biofabrication of personalized soft tissue grafts, offering potential applications in the repair and regeneration of mucogingival defects associated with periodontal disease and dental implants.

Keywords:  artificial intelligence; bioink; bioprinting; fibrin; periodontal disease; personalized grafts; polysaccharides; soft tissue grafts

DOI:  https://doi.org/10.1002/adhm.202402727
Int J Pharm. 2024 Dec 16. pii: S0378-5173(24)01323-1. [Epub ahead of print] 125089

3D printing for controlled release Pharmaceuticals: Current trends and future directions.

Mingyue Deng, Siyi Wu, Meiying Ning.

  In recent years, 3D printers have grown strongly in drug delivery and personalised medicine, being used more and more widely. In medicine, 3DP technology can advance personalised medicine and design dosage forms to regulate the drug release rate. This review gives an overview of the 3D printing for controlled-release pharmaceuticals, detailing the technical principles, common types (including extrusion, powder, liquid, and sheet lamination-based systems), drug release control mechanisms (e.g., dissolution and diffusion, osmosis, and swelling, partitioning and erosion, and targeting), and the advantages, status, and challenges. It discusses the future direction of the technology, including multidisciplinary cross-fertilisation and the advancement of personalised medicine. The technology has potential but faces many challenges such as cost, production capacity, materials, regulations, and quality control.

Keywords:  3D printed tablets; 3D printing; Controlled-released pharmaceuticals; Personalized medications

DOI:  https://doi.org/10.1016/j.ijpharm.2024.125089
Biomater Adv. 2024 Dec 08. pii: S2772-9508(24)00388-1. [Epub ahead of print]169 214145

Self-healing, 3D printed bioinks from self-assembled peptide and alginate hybrid hydrogels.

Emily H Field, Julian Ratcliffe, Chad J Johnson, Katrina J Binger, Nicholas P Reynolds.

  There is a pressing need for new cell-laden, printable, biomaterials that are rigid and highly biocompatible. These materials can mimic stiffer tissues such as cartilage, fibrotic tissue and cancer microenvironments, and thus have exciting applications in regenerative medicine, wound healing and cancer research. Self-assembled peptides (SAPs) functionalised with aromatic groups such as Fluorenyl-9-methoxycarbonyl (Fmoc) show promise as components of these biomaterials. However, the harsh basic conditions often used to solubilise SAPs leads to issues with toxicity and reproducibility. Here, we have designed a hybrid material comprised of self-assembled Fmoc-diphenylalanine (Fmoc-FF) assemblies dispersed throughout a sodium alginate matrix and investigated the influence of different organic solvents as peptide solubilising agents. Bioinks fabricated from peptides dissolved in 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) showed improved biocompatibility compared to those made from Dimethyl Sulfoxide (DMSO) peptide stocks, due to the increased volatility and reduced surface tension of HFIP, allowing for more efficient expulsion from the system. Through optimisation of assembly and solvent conditions we can generate hybrid bioinks with stiffnesses up to 8 times greater than sodium alginate alone that remain highly printable, even when laden with high concentrations of cells. In addition, the shear-thinning nature of the self-assembled peptide assemblies gave the hybrid bioinks highly desirable self-healing capabilities. Our developed hybrid materials allow the bioprinting of materials previously considered too stiff to extrude without causing shear induced cytotoxicity with applications in tissue engineering and biosensing.

Keywords:  3D bioprinting; 3D cell culture; Bioengineering; Biomaterials; Fmoc-FF; Hydrogel

DOI:  https://doi.org/10.1016/j.bioadv.2024.214145
Polymers (Basel). 2024 Nov 26. pii: 3303. [Epub ahead of print]16(23):

Advances and Challenges in Polymer-Based Scaffolds for Bone Tissue Engineering: A Path Towards Personalized Regenerative Medicine.

Samira Farjaminejad, Rosana Farjaminejad, Melika Hasani, Franklin Garcia-Godoy, Majid Abdouss, Anand Marya, Ari Harsoputranto, Abdolreza Jamilian.

  Polymers have become essential in advancing bone tissue engineering, providing adaptable bone healing and regeneration solutions. Their biocompatibility and biodegradability make them ideal candidates for creating scaffolds that mimic the body's natural extracellular matrix (ECM). However, significant challenges remain, including degradation by-products, insufficient mechanical strength, and suboptimal cellular interactions. This article addresses these challenges by evaluating the performance of polymers like poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), and polylactic acid (PLA) in scaffold development. It also explores recent innovations, such as intelligent polymers, bioprinting, and the integration of bioactive molecules to enhance scaffold efficacy. We propose that overcoming current limitations requires a combination of novel biomaterials, advanced fabrication techniques, and tailored regulatory strategies. The future potential of polymer-based scaffolds in personalised regenerative medicine is discussed, focusing on their clinical applicability.

Keywords:  bone regeneration; polymers; regenerative medicine; scaffolds; tissue engineering

DOI:  https://doi.org/10.3390/polym16233303
J Biomater Sci Polym Ed. 2024 Dec 15. 1-26

Alkaline etching assisted polydopamine coating for enhanced cell-material interactions on 3D printed polylactic acid scaffolds.

Athira Murali, Ramesh Parameswaran.

  The implant surface chemistry and topography are primary factors regulating the success and survival of bone scaffold. Surface modification is a promising alternative to enhance the biocompatibility and tissue response to augment the osteogenic functionalities of polyesters like PLA. The study employed the synergistic effect of alkaline hydrolysis and polydopamine (PDA) functionalization to enhance the cell-material interactions on 3D printed polylactic acid (PLA) scaffold. Comprehensive characterization of the modified PLA highlights the improvements in the physical, chemical and cell-material interactions upon two-step surface modification. The X-ray photoelectron spectroscopy (XPS) analysis substantiated enhanced PDA deposition with a ∼8.2% increase in surface N composition after surface etching due to homogeneous PDA deposition compared to the non-etched counterpart. The changes in surface chemistry and morphology upon dual surface modification complemented the human osteoblast (HOS) attachment and proliferation, with distinct cell morphology and spreading on PDA coated etched PLA (Et-PLAPDA) scaffolds. Moreover, substantial improvement in osteogenic differentiation of UMR-106 cells on etched PLA (Et-PLA) and Et-PLAPDA highlights the suitability of alkali etching-mediated PDA deposition to improve mineralization on PLA. Overall, the present work opens insights to modify scaffold surface composition, topography, hydrophilicity and roughness to regulate local cell adhesion to improve the osteogenic potential of PLA.

Keywords:  Cell–material interaction; alkaline etching; hydrophilicity; osteoblast adhesion; surface roughness

DOI:  https://doi.org/10.1080/09205063.2024.2436691
Biomater Adv. 2024 Dec 09. pii: S2772-9508(24)00392-3. [Epub ahead of print]169 214149

Hierarchically porous 3D-printed ceramic scaffolds for bone tissue engineering.

Shareen S L Chan, Jay R Black, George V Franks, Daniel E Heath.

  Sacrificial templating offers the ability to create interconnected pores within 3D printed filaments and to control pore morphology. Beta-tricalcium phosphate (TCP) bone tissue engineering (BTE) scaffolds were fabricated with multiscale porosity: (i) macropores from direct ink writing (DIW, a material extrusion 3D printing technique), (ii) micropores from oil templating, and (iii) smaller micropores from partial sintering. The hierarchically porous scaffolds possessed a total porosity of 58-70 %, comprising 54-63 % interconnected open pores. The in vitro results demonstrated that scaffolds with macroporosity promoted human osteoblast growth more than scaffolds with only microporosity. The elongated pores from the capillary suspension filament microstructure induced greater cell spreading than the sphere-like pores from the emulsion. Overall, the hierarchically porous scaffold with capillary suspension TCP filaments provided a superior microenvironment for significantly higher cell viability and proliferation than the other scaffolds, including a poly(ε-caprolactone) (PCL) control, a material currently used clinically as porous BTE scaffolds. The cellular response was further enhanced when macropore size was in the range of 570-590 μm. Therefore, the hierarchically porous scaffolds in this study are promising as BTE scaffolds, and the reported process of DIW of oil-templated colloidal pastes is a feasible strategy with potential for further customization.

Keywords:  3D printing; Bone tissue engineering; Calcium phosphate; Direct ink writing; Hierarchical porosity; Osteoblasts

DOI:  https://doi.org/10.1016/j.bioadv.2024.214149
RSC Adv. 2024 Dec 17. 14(54): 39804-39819

Functionalization of 3D printed poly(lactic acid)/graphene oxide/β-tricalcium phosphate (PLA/GO/TCP) scaffolds for bone tissue regeneration application.

Angela Sánchez-Cepeda, M Carolina Pazos, Prieto-Abello Leonardo, Silva-Cote Ingrid, Luz Stella Correa-Araujo, Chávez García María de Lourdes, Ricardo Vera-Graziano.

The challenge of bone tissue regeneration implies the use of new advanced technologies for the manufacture of polymeric matrices, with 3D printing technology being a suitable option for tissue engineering due to its low processing cost, its simple operation and the wide use of biomaterials in biomedicine. Among the biopolymers used to obtain porous scaffolds, poly(lactic acid) (PLA) stands out due its mechanical and biodegradability properties, although its low bioactivity to promote bone regeneration is a great challenge. In this research, a 3D scaffold based on PLA reinforced with bioceramics such as graphene oxide (GO) and β-tricalcium phosphate (TCP) was designed and characterized by FTIR, XRD, DSC, SEM and mechanical tests. The in vitro biocompatibility, viability, and cell proliferation of the poly-l-lysine (POLYL) functionalized scaffold were investigated using Wharton Jelly mesenchymal stem cells (hWJ-MSCs) and confirmed by XPS. The incorporation of GO/TCP bioceramics into the PLA polymer matrix increased the mechanical strength and provided a thermal barrier during the fusion treatments that the polymeric material undergoes during its manufacturing. The results show that the functionalization of the scaffold with POLYL allows improving the cell adhesion, proliferation and differentiation of hWJ-MSCs. The resulting scaffold PLA/GO/TCP/POLYL exhibits enhanced structural integrity and osteogenic cues, rendering it a promising candidate for biomedical applications.

DOI: https://doi.org/10.1039/d4ra05889e
Biofabrication. 2024 Dec 16.

3D printed PCL-nHAp composite implants for the treatment of segmental bone defects: in vivo application in a rabbit model.

Deniz Başöz, Muhammed İlkay Karaman, Senem Büyüksungur, Deniz Yucel, Nesrin Hasırcı, Barıs Kocaoglu, Vasif Hasirci.

  The management and treatment of long bone defects are challenging clinical problems. In this study, in order to address the need for load bearing segmental defects, 3D printed cylindrical implants of poly(-caprolactone) (PCL) and nanohydroxyapatite (nHAp) composites were prepared and applied as lateral segments to the femurs of New Zealand white rabbits. The results obtained after 6 weeks of implantation were compared with the autografts. Although the maximum load determined in the 3-point bending tests for the autografts (93±56 N) was higher than the composite implants (57±5 N), histological studies demonstrated similar new bone formation in both test groups. Also, a sizeable callus formation around the autografts and bone ingrowth to the 3D printed implants were observed, and X-ray studies confirmed the formation of the callus. An increase in the bone density around the defect site was detected for both test groups. SEM revealed close interaction between the newly formed bone tissue and the struts of the 3D printed implant. mRUST values, which is an indicator of tissue healing, increased continuously during 6 weeks. In conclusion, 3D printed, 1.5 cm long cylindrical nHAp-PCL implants exhibited excellent bone healing and biomechanical stability in the large lateral segmental bone defects of the rabbits even in a relatively short implantation time as 6 weeks. We believe that these implants could serve as an alternative to autografts in the treatment of long bone defects.

Keywords:  3D print; Segmental bone defect; biodegradable; composite implant; hydroxyapatite; poly(ε-caprolactone)

DOI:  https://doi.org/10.1088/1758-5090/ad9fe1
J Cell Physiol. 2024 Dec 19.

Tissue Engineering 3D-Printed Scaffold Using Allograft/Alginate/Gelatin Hydrogels Coated With Platelet-Rich Fibrin or Adipose Stromal Vascular Fraction Induces Osteogenesis In Vitro.

Sahar Baniameri, Hossein Aminianfar, Niusha Gharehdaghi, Amir-Ali Yousefi-Koma, Sadra Mohaghegh, Hanieh Nokhbatolfoghahaei, Arash Khojasteh.

Incorporating autologous patient-derived products has become imperative to enhance the continually improving outcomes in bone tissue engineering. With this objective in mind, this study aimed to evaluate the osteogenic potential of 3D-printed allograft-alginate-gelatin scaffolds coated with stromal vascular fraction (SVF) and platelet-rich fibrin (PRF). The primary goal was to develop a tissue-engineered construct capable of facilitating efficient bone regeneration through the utilization of biomaterials with advantageous properties and patient-derived products. To achieve this goal, 3D-printed gelatin, allograft, and alginate scaffolds were utilized, along with stem cells derived from the buccal fat pad and human-derived components (PRF, SVF). Cells were seeded onto scaffolds, both with and without SVF/PRF, and subjected to comprehensive assessments including adhesion, proliferation, differentiation (gene expression and protein secretion levels), penetration, and gene expression analysis over 14 days. The data was reported as mean ± standard deviation (SD). Two-way or one-way analysis of variance (ANOVA) was performed, followed by a Tukey post hoc test for multiple comparisons. Statistical significance was determined as a p value below 0.05. The scaffolds demonstrated structural integrity, and the addition of PRF coatings significantly enhanced cellular adhesion, proliferation, and differentiation compared to other groups. Gene expression analysis showed increased expression of osteogenic and angiogenic markers in the PRF-coated scaffolds. These findings highlight the promising role of PRF-coated scaffolds in promoting osteogenesis and facilitating bone tissue regeneration. This study emphasizes the development of patient-specific tissue-engineered constructs as a valuable approach for effective bone regeneration.

DOI: https://doi.org/10.1002/jcp.31497