bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–11–24
eleven papers selected by
Seerat Maqsood, University of Teramo
  1. Recent advances in 3D bioprinted polysaccharide hydrogels for biomedical applications: A comprehensive review.
  2. 3D Printing-Based Hydrogel Dressings for Wound Healing.
  3. Advancements in 3D skin bioprinting: processes, bioinks, applications and sensor integration.
  4. 3D Printing Hierarchical Porous Nanofibrous Scaffold for Bone Regeneration.
  5. Enhancing vaginal reconstruction through 3D bioprinted scaffolds using a novel vECM-GelMA-SF bioink.
  6. 3D-printing of dipyridamole/thermoplastic polyurethane materials for bone regeneration.
  7. Nanostructured polymer composites for bone and tissue regeneration.
  8. Carboxymethyl chitosan-enhanced multi-level microstructured composite hydrogel scaffolds for bone defect repair.
  9. Strontium-Substituted Nanohydroxyapatite Containing Biodegradable 3D Printed Composite Scaffolds for Bone Regeneration.
  10. Three-dimensional tissue engineered skeletal muscle modelling facioscapulohumeral muscular dystrophy.
  11. Biomaterials for bone tissue engineering: achievements to date and future directions.
  1. Carbohydr Polym. 2025 Jan 15. pii: S0144-8617(24)01071-3. [Epub ahead of print]348(Pt B): 122845
    Recent advances in 3D bioprinted polysaccharide hydrogels for biomedical applications: A comprehensive review.
    Fouad Damiri, Ahmed Fatimi, Yang Liu, Adina Magdalena Musuc, André R Fajardo, B H Jaswanth Gowda, Lalitkumar K Vora, Armin Shavandi, Oseweuba V Okoro.
      Polysaccharide hydrogels, which can mimic the natural extracellular matrix and possess appealing physicochemical and biological characteristics, have emerged as significant bioinks for 3D bioprinting. They are highly promising for applications in tissue engineering and regenerative medicine because of their ability to enhance cell adhesion, proliferation, and differentiation in a manner akin to the natural cellular environment. This review comprehensively examines the fabrication methods, characteristics, and applications of polysaccharide hydrogel-driven 3D bioprinting, underscoring its potential in tissue engineering, drug delivery, and regenerative medicine. To contribute pertinent knowledge for future research in this field, this review critically examines key aspects, including the chemistry of carbohydrates, manufacturing techniques, formulation of bioinks, and characterization of polysaccharide-based hydrogels. Furthermore, this review explores the primary advancements and applications of 3D-printed polysaccharide hydrogels, encompassing drug delivery systems with controlled release kinetics and targeted therapy, along with tissue-engineered constructs for bone, cartilage, skin, and vascular regeneration. The use of these 3D bioprinted hydrogels in innovative research fields, including disease modeling and drug screening, is also addressed. Despite notable progress, challenges, including modulating the chemistry and properties of polysaccharides, enhancing bioink printability and mechanical properties, and achieving long-term in vivo stability, have been highlighted.
    Keywords:  Additive manufacturing; Bioinks; Bioprinting; Polysaccharide modification; Regenerative medicine; Tissue engineering
    DOI:  https://doi.org/10.1016/j.carbpol.2024.122845
  2. Adv Sci (Weinh). 2024 Nov 18. e2404580
    3D Printing-Based Hydrogel Dressings for Wound Healing.
    Xuan Zhou, Xunzhou Yu, Tingting You, Baohua Zhao, Lanlan Dong, Can Huang, Xiaoqing Zhou, Malcolm Xing, Wei Qian, Gaoxing Luo.
      Skin wounds have become an important issue that affects human health and burdens global medical care. Hydrogel materials similar to the natural extracellular matrix (ECM) are one of the best candidates for ideal wound dressings and the most feasible choices for printing inks. Distinct from hydrogels made by traditional technologies, which lack bionic and mechanical properties, 3D printing can promptly and accurately create hydrogels with complex bioactive structures and the potential to promote tissue regeneration and wound healing. Herein, a comprehensive review of multi-functional 3D printing-based hydrogel dressings for wound healing is presented. The review first summarizes the 3D printing techniques for wound hydrogel dressings, including photo-curing, extrusion, inkjet, and laser-assisted 3D printing. Then, the properties and design approaches of a series of bioinks composed of natural, synthetic, and composite polymers for 3D printing wound hydrogel dressings are described. Thereafter, the application of multi-functional 3D printing-based hydrogel dressings in a variety of wound environments is discussed in depth, including hemostasis, anti-inflammation, antibacterial, skin appendage regeneration, intelligent monitoring, and machine learning-assisted therapy. Finally, the challenges and prospects of 3D printing-based hydrogel dressings for wound healing are presented.
    Keywords:  3D printing; bioinks; hydrogel dressings; multi‐function; wound healing
    DOI:  https://doi.org/10.1002/advs.202404580
  3. Int J Extrem Manuf. 2025 Feb 01. 7(1): 012009
    Advancements in 3D skin bioprinting: processes, bioinks, applications and sensor integration.
    I Deniz Derman, Taino Rivera, Laura Garriga Cerda, Yogendra Pratap Singh, Shweta Saini, Hasan Erbil Abaci, Ibrahim T Ozbolat.
      This comprehensive review explores the multifaceted landscape of skin bioprinting, revolutionizing dermatological research. The applications of skin bioprinting utilizing techniques like extrusion-, droplet-, laser- and light-based methods, with specialized bioinks for skin biofabrication have been critically reviewed along with the intricate aspects of bioprinting hair follicles, sweat glands, and achieving skin pigmentation. Challenges remain with the need for vascularization, safety concerns, and the integration of automated processes for effective clinical translation. The review further investigates the incorporation of biosensor technologies, emphasizing their role in monitoring and enhancing the wound healing process. While highlighting the remarkable progress in the field, critical limitations and concerns are critically examined to provide a balanced perspective. This synthesis aims to guide scientists, engineers, and healthcare providers, fostering a deeper understanding of the current state, challenges, and future directions in skin bioprinting for transformative applications in tissue engineering and regenerative medicine.
    Keywords:  3D bioprinting; biofabrication; biosensors; skin models; skin tissue engineering
    DOI:  https://doi.org/10.1088/2631-7990/ad878c
  4. Small. 2024 Nov 16. e2405406
    3D Printing Hierarchical Porous Nanofibrous Scaffold for Bone Regeneration.
    Zhiai Hu, Hengyi Lin, Zhenming Wang, Yating Yi, Shujuan Zou, Hao Liu, Xianglong Han, Xin Rong.
      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.
    Keywords:  3D printing; bone regeneration; gelatin; microspheres; nanofiber
    DOI:  https://doi.org/10.1002/smll.202405406
  5. Biofabrication. 2024 Nov 21.
    Enhancing vaginal reconstruction through 3D bioprinted scaffolds using a novel vECM-GelMA-SF bioink.
    Jiahua Zheng, Xuemei Zhang, Kaixuan Guo, Liman Yan, Xiaotong Xu, Wenxin Shi, Jingkun Zhang, Yanfang Du, Mingle Zhang, Xianghua Huang.
      Overcoming the low cell survival rates and insufficient neovascularization associated with tissue engineering of the vagina is crucial for advancing the vaginal reconstruction. In this research, we have developed a unique bioink composed of porcine vaginal extracellular matrix (vECM), gelatin methacrylamide (GelMA), and silk fibroin (SF) to facilitate the bioprinting of a vaginal scaffold. The vECM-GelMA-SF bioink effectively replicates the in vivo microenvironment, supporting the in vitro cultivation of 3D bioprinted vaginal scaffolds. It promotes stem cell viability and enhances neovascularization by harnessing the mechanical properties of GelMA/SF and the tissue specificity of vECM. In vivo orthotopic studies have demonstrated that the use of 3D bioprinted vaginal scaffolds significantly improves the functionality of reconstructed vaginas, promoting angiogenesis, rapid epithelialization, muscle regeneration, glycogen secretion, and nerve repair. The reconstructed vaginal tissues in the 3D cell-loaded scaffold group closely resemble natural vaginal tissues. Differential proteomics analysis has provided insights into the genetic functions and biological pathways involved in vaginal reconstruction. Our study successfully optimized the composition of the vECM-GelMA-SF bioink, achieving a balance between biocompatibility and printability. This bioink is suitable for constructing 3D bioprinted vaginal scaffolds of various dimensions, transplantable in situ in animal models with different degrees of vaginal absence. The bioink may find applications in clinical settings, improving the overall effectiveness and safety of in vivo vaginal reconstruction procedures.
    Keywords:  3D bioprinting; Bioink; Vaginal extracellular matrix; Vaginal reconstruction
    DOI:  https://doi.org/10.1088/1758-5090/ad95bf
  6. Drug Deliv Transl Res. 2024 Nov 22.
    3D-printing of dipyridamole/thermoplastic polyurethane materials for bone regeneration.
    Masoud Adhami, Anushree Ghosh Dastidar, Qonita Kurnia Anjani, Usanee Detamornrat, Quim Tarrés, Marc Delgado-Aguilar, Jonathan G Acheson, Krishnagoud Manda, Susan A Clarke, Natalia Moreno-Castellanos, Eneko Larrañeta, Juan Domínguez-Robles.
      Tissue engineering combines biology and engineering to develop constructs for repairing or replacing damaged tissues. Over the last few years, this field has seen significant advancements, particularly in bone tissue engineering. 3D printing has revolutionised this field, allowing the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration, thus providing a personalised approach that offers unique control over the shape, size, and structure of 3D-printed constructs. Accordingly, thermoplastic polyurethane (TPU)-based 3D-printed scaffolds loaded with dipyridamole (DIP) were manufactured to evaluate their in vitro osteogenic capacity. The fabricated DIP-loaded TPU-based scaffolds were fully characterised, and their physical and mechanical properties analysed. Moreover, the DIP release profile, the biocompatibility of scaffolds with murine calvaria-derived pre-osteoblastic cells, and the intracellular alkaline phosphatase (ALP) assay to verify osteogenic ability were evaluated. The results suggested that these materials offered an attractive option for preparing bone scaffolds due to their mechanical properties. Indeed, the addition of DIP in concentrations up to 10% did not influence the compression modulus. Moreover, DIP-loaded scaffolds containing the highest DIP cargo (10% w/w) were able to provide sustained drug release for up to 30 days. Furthermore, cell viability, proliferation, and osteogenesis of MC3T3-E1 cells were significantly increased with the highest DIP cargo (10% w/w) compared to the control samples. These promising results suggest that DIP-loaded TPU-based scaffolds may enhance bone regeneration. Combined with the flexibility of 3D printing, this approach has the potential to enable the creation of customized scaffolds tailored to patients' needs at the point of care in the future.
    Keywords:  3D printing; Bone regeneration; Dipyridamole; Flexible materials; Fused deposition modelling; Thermoplastic polyurethane
    DOI:  https://doi.org/10.1007/s13346-024-01744-1
  7. Int J Biol Macromol. 2024 Nov 20. pii: S0141-8130(24)08644-6. [Epub ahead of print] 137834
    Nanostructured polymer composites for bone and tissue regeneration.
    E Venkata Prathyusha, Shyam Sudhakar Gomte, Hafiz Ahmed, A Prabakaran, Mukta Agrawal, Naveen Chella, Amit Alexander.
      Nanostructured polymer composites have gained significant attention in recent years for their remarkable potential in bone and tissue regeneration. Moreover, with the integration of 3D printing technology, these composites hold promise for use in personalized medicine, where patient-specific scaffolds can be tailored to enhance therapeutic outcomes. Therefore, this review article aims to provide a comprehensive overview of the latest advancements in the development and application of nanostructured polymeric composites within the field of tissue engineering and bone regeneration. Here, the potential of biopolymers, natural polymers, and 3D-printed polymers to craft biocompatible, non-toxic, and mechanically robust composites is discussed in brief. Further, the fabrication techniques for 3D scaffolds and various forms of nanocomposites, including nanoparticles, nanocapsules, nanofibers, nanogels, and micelles for bone and tissue regeneration, are listed. Also, particular emphasis is placed on the role of nano-scaffolds and in situ hydrogels in bone and tissue regeneration. Overall, this review provides a concise and authoritative summary of the current state-of-the-art in nanostructured polymer composites for regenerative medicine, highlighting future directions and potential clinical applications.
    Keywords:  3D scaffolds; Bone regeneration; Polymeric composites; Polysaccharides; Tissue engineering
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.137834
  8. Carbohydr Polym. 2025 Jan 15. pii: S0144-8617(24)01073-7. [Epub ahead of print]348(Pt B): 122847
    Carboxymethyl chitosan-enhanced multi-level microstructured composite hydrogel scaffolds for bone defect repair.
    Yilong Wang, Xingyu Zhou, Junhui Jiang, Tianhao Zhao, Junbo Dang, Ruibo Hu, Chen Shen, Qiaochu Fan, Dahui Sun, Mei Zhang.
      Critical-sized bone defects (CSBDs) necessitate interventions like bone grafts or tissue engineering scaffolds to surpass the body's limited spontaneous healing capacity and ensure effective bone regeneration. A multi-level microstructured composite hydrogel 3D scaffold was fabricated for enhanced bone defect repair, integrating a 3D-printed macroporous polylactic acid (PLA) scaffold with polydopamine treatment and filled with a sodium alginate/nano hydroxyapatite/carboxymethyl chitosan (SA/nHA/CMCS) micrometer-scale porous composite hydrogel. The incorporation of nano hydroxyapatite (nHA) nanoparticles enhanced hydrogel crosslinking and osteogenic activity. A systematic evaluation of CMCS concentration demonstrated its pivotal role in enhancing hydrogel cross-linking and mineralization, regulating degradation rate adapted to the osteogenic cycle, endowing the scaffold with a bioactive micrometer-scale porous structure. In vitro studies confirmed the osteogenic effectiveness of the composite hydrogel 3D scaffold, particularly those with CMCS, which boosted bone mesenchymal stem cells (BMSCs) adhesion, proliferation, and differentiation. The rabbit tibial bone defect model further confirmed that, compared to the DAPLA (dopamine modified PLA) scaffold, the bone trabecular number of the DSHC (DAPLA-SA/nHA/CMCS) scaffold increases 2.06-fold. In conclusion, this study expanded the application of hydrogel scaffolds in bone tissue engineering and provided an effective strategy for the development of hydrogel implant materials.
    Keywords:  3D printed scaffold; Bone defect repair; Carboxymethyl chitosan; Composite hydrogel; Multi-level microstructure
    DOI:  https://doi.org/10.1016/j.carbpol.2024.122847
  9. ACS Appl Mater Interfaces. 2024 Nov 18.
    Strontium-Substituted Nanohydroxyapatite Containing Biodegradable 3D Printed Composite Scaffolds for Bone Regeneration.
    Shazia Shaikh, Shreya Mehrotra, Bas van Bochove, Arun Kumar Teotia, Prerna Singh, Isabella Laurén, Nina C Lindfors, Jukka Seppälä, Ashok Kumar.
      Treatment of large-size bone defects is difficult, and acquiring autografts may be challenging due to limited availability. A synthetic patient-specific bone substitute can be developed by using 3D printing technologies in such cases. In the present study, we have developed photocurable composite resins with poly(trimethylene carbonate) (PTMC) containing a high percentage of biodegradable bioactive strontium-substituted nanohydroxyapatite (SrHA, size 30-70 nm). These photocurable resins have then been employed to develop high-surface-area 3D-printed bone substitutes using the digital light processing (DLP) technique. To enhance the surface area of the 3D-printed substitute, cryogels alone and functionalized with bioactive components of bone morphogenetic protein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed scaffold/substitute. The scaffolds were tested in vitro for biocompatibility and functionality in vivo in two therapeutically relevant rat models with large bone defects (4 mm). The porosities of 3D printed scaffolds were found to be 60.1 ± 0.9%, 72.9 ± 0.5%, and 74.3 ± 1.6% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the range of cancellous bone (50-95%). The thermogravimetric analysis demonstrated the fabrication of 3D printed composites with HA and SrHA concentrations of 51.5 and 57.4 wt %, respectively, in the PTMC matrix. The tensile Young's modulus (E), compressive moduli, and wettability increased post incorporation of SrHA and HA in the PTMC matrix. In vitro and in vivo results revealed that SrHA integrated into the PTMC matrix exhibited good physicochemical and biological properties. Furthermore, the osteoactive molecule-functionalized 3D printed composite scaffolds were found to have an adequate osteoconductive and osteoinductive surface that has shown increased bone regeneration and defect repair in both tibial and cranial bone defects. Our findings thus support the use of PTMC-SrHA composites as next-generation patient-specific synthetic bioactive biodegradable bone substitutes.
    Keywords:  3D-printing; bioactive molecules; bone regeneration; digital light processing; poly(trimethylene carbonate); strontium substituted nanohydroxyapatite
    DOI:  https://doi.org/10.1021/acsami.4c16195
  10. Brain. 2024 Nov 18. pii: awae379. [Epub ahead of print]
    Three-dimensional tissue engineered skeletal muscle modelling facioscapulohumeral muscular dystrophy.
    Marnix Franken, Erik van der Wal, Dongxu Zheng, Bianca den Hamer, Patrick J van der Vliet, Richard J L F Lemmers, Anita van den Heuvel, Alexandra L Dorn, Cas G A Duivenvoorden, Stijn L M In't Groen, Christian Freund, Bert Eussen, Rabi Tawil, Baziel G M van Engelen, Pim W W M P Pijnappel, Silvère M van der Maarel, Jessica C de Greef.
      Facioscapulohumeral muscular dystrophy (FSHD) is caused by sporadic misexpression of the transcription factor double homeobox 4 (DUX4) in skeletal muscles. So far, monolayer cultures and animal models have been used to study the FSHD disease mechanism and for FSHD therapy development, but these models do not fully recapitulate the disease and there is a lack of knowledge on how DUX4 misexpression leads to skeletal muscle dysfunction. To overcome these barriers, we have developed a three-dimensional tissue engineered skeletal muscle (3D-TESM) model by generating genetically matched myogenic progenitors (MPs) from human induced pluripotent stem cells of three mosaic FSHD patients. 3D-TESMs derived from genetically affected MPs recapitulate pathological features including DUX4 and DUX4 target gene expression, smaller myofiber diameters, and reduced absolute forces upon electrical stimulation. RNA sequencing data illustrates increased expression of DUX4 target genes in 3D-TESMs compared to two-dimensional (2D) myotubes, and cellular differentiation was improved by 3D culture conditions. Treatment of 3D-TESMs with three different small molecules identified in drug development screens in 2D muscle cultures showed no improvements, and sometimes even declines, in contractile force and sarcomere organization. These results suggest that these compounds either have a detrimental effect on the formation of 3D-TESMs, an effect that might have been overlooked or was challenging to detect in 2D cultures and in vivo models, and/or that further development of the 3D-TESM model is needed. In conclusion, we have developed a 3D skeletal muscle model for FSHD that can be employed for preclinical research focusing on DUX4 expression and downstream pathways of FSHD in relation to contractile properties. In the future, we expect that this model can also be used for preclinical drug screening.
    Keywords:  3D tissue engineering; DUX4; FSHD; disease modelling; hiPSC; mosaic
    DOI:  https://doi.org/10.1093/brain/awae379
  11. Biomed Mater. 2024 Nov 22.
    Biomaterials for bone tissue engineering: achievements to date and future directions.
    Adithya Garimella, Subrata Bandhu Ghosh, Sanchita B Ghosh.
      Advancement in medicine and technology has resulted into prevention of countless deaths and increased life span. However, it is important to note that, the modern lifestyle has altered the food habits, witnessed increased life-style stresses and road accidents leading to several health complications and one of the primary victims is the bone health. More often than ever, healthcare professionals encounter cases of massive bone fracture, bone loss and generation of critical sized bone defects. Surgical interventions, through the use of bone grafting techniques are necessary in such cases. Natural bone grafts (allografts, autografts and xenografts) however, have major drawbacks in terms of delayed rehabilitation, lack of appropriate donors, infection and morbidity that shifted the focus of several investigators to the direction of synthetic bone grafts. By employing biomaterials that are based on bone tissue engineering, synthetic bone grafts provide a more biologically acceptable approach to establishing the phases of bone healing. The current review article provides the critical insights on several biomaterials that could yield to revolutionary improvements in orthopaedic medical fields. The introduction section of this article focuses on the statistical information on the requirements of various bone scaffolds globally and its impact on economy. In the later section, anatomy of the human bone, defects and diseases pertaining to human bone, and limitations of natural bone scaffolds and synthetic bone scaffolds were detailed. Biopolymers, bioceramics, and biometals-based biomaterials were discussed in further depth in the sections that followed. The article then concludes with a summary addressing the current trends and the future prospects of potential bone transplants.&#xD.
    Keywords:  Biomaterials; Bone grafts; bioceramics; biometals; biopolymer; bone repair; bone tissue engineering
    DOI:  https://doi.org/10.1088/1748-605X/ad967c
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