bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–06–16
six papers selected by
Seerat Maqsood, University of Teramo



  1. Front Bioeng Biotechnol. 2024 ;12 1363483
      Diabetes is a metabolic disorder characterized by high blood sugar. Uncontrolled blood glucose affects the circulatory system in an organism by intervening blood circulation. The high blood glucose can lead to macrovascular (large blood vessels) and microvascular (small blood vessels) complications. Due to this, the vital organs (notably brain, eyes, feet, heart, kidneys, lungs and nerves) get worsen in diabetic patients if not treated at the earliest. Therefore, acquiring treatment at an appropriate time is very important for managing diabetes and other complications that are caused due to diabetes. The root cause for the occurrence of various health complications in diabetic patients is the uncontrolled blood glucose levels. This review presents a consolidated account of the applications of various types of three-dimensional (3D) printing and bioprinting technologies in treating diabetes as well as the complications caused due to impaired blood glucose levels. Herein, the development of biosensors (for the diagnosis), oral drug formulations, transdermal drug carriers, orthotic insoles and scaffolds (for the treatment) are discussed. Next to this, the fabrication of 3D bioprinted organs and cell-seeded hydrogels (pancreas engineering for producing insulin and bone engineering for managing bone defects) are explained. As the final application, 3D bioprinting of diabetic disease models for high-throughput screening of ant-diabetic drugs are discussed. Lastly, the challenges and future perspective associated with the use of 3D printing and bioprinting technologies against diabetes and its related chronic complications have been put forward.
    Keywords:  3D bioprinting; 3D printing; cell-seeded hydrogels; chronic complications; diabetes; diabetic disease models; diagnosis; treatment
    DOI:  https://doi.org/10.3389/fbioe.2024.1363483
  2. Adv Mater. 2024 Jun 11. e2403641
      The repair and functional reconstruction of bone defects resulting from severe trauma, surgical resection, degenerative disease, and congenital malformation pose significant clinical challenges. Bone tissue engineering (BTE) holds immense potential in treating these severe bone defects, without incurring prevalent complications associated with conventional autologous or allogeneic bone grafts. Three-dimensional (3D) printing technology enables control over architectural structures at multiple length scales and has been extensively employed to process biomimetic scaffolds for BTE. In contrast to inert and functional bone grafts, next-generation smart scaffolds possess remarkable ability to mimic the dynamic nature of native extracellular matrix (ECM), thereby facilitating bone repair and regeneration. Additionally, they can generate tailored and controllable therapeutic effects, such as antibacterial or antitumor properties, in response to exogenous and/or endogenous stimuli. This review provides a comprehensive assessment of the progress of 3D-printed smart scaffolds for BTE applications. It begins with an introduction to bone physiology, followed by an overview of 3D printing technologies utilized for smart scaffolds. Notable advances in various stimuli-responsive strategies, therapeutic efficacy, and applications of 3D-printed smart scaffolds are discussed. Finally, the review highlights the existing challenges in the development and clinical implementation of smart scaffolds, as well as emerging technologies in this field. This article is protected by copyright. All rights reserved.
    Keywords:  3D printing; additive manufacturing; bone tissue engineering; smart scaffold
    DOI:  https://doi.org/10.1002/adma.202403641
  3. Chin Clin Oncol. 2024 May 28. pii: cco-24-4. [Epub ahead of print]
       BACKGROUND AND OBJECTIVE: Oncology is increasingly adopting three-dimensional (3D) printing, a method of creating objects through additive manufacturing using various techniques and materials. This technology, divided into conventional 3D printing (using non-biological materials like thermoplastics or titanium) and bioprinting (involving living cells and tissues), has shown potential in surgical planning, implant creation, and radiotherapy. However, despite promising preclinical and clinical applications, its clinical integration faces challenges such as a lack of strong evidence, standardized guidelines, and detailed data on costs and scalability. This study reviews the current use of 3D printing in oncology, aiming to differentiate between practical and experimental applications, thereby guiding clinicians interested in incorporating this technology.
    METHODS: A literature search was conducted to gather comments, reviews, and preclinical and clinical studies focusing on the use of 3D printing in oncology, with publications dated before December 1, 2023. The search for pertinent studies involved utilizing PubMed and Google Scholar Review. The selection process for articles was based on a unanimous consensus among all authors. We excluded topics related to bioprinting and the technical nuances of 3D printing.
    KEY CONTENT AND FINDINGS: The review comprehensively describes the utilization of 3D printing in radiation oncology, surgical oncology, orthopedic oncology, medical oncology, hyperthermia, and patients' education. However, 3D printing faces several limitations that are related to unpredictable costs, difficult scalability, very complex regulations and lack of standardization.
    CONCLUSIONS: 3D printing is increasingly useful in oncology for diagnostics and treatment, yet remains experimental and case-based. Despite growing literature, it focuses mostly on pre-clinical studies and case reports, with few clinical studies involving small samples. Thus, extensive research is needed to fully evaluate its efficacy and application in larger patient groups.
    Keywords:  3D printing; 3D-printed bolus; custom-made prosthesis; implants; personalization
    DOI:  https://doi.org/10.21037/cco-24-4
  4. Biomed Mater. 2024 Jun 10.
      Chronic skin wounds pose a global clinical challenge, necessitating effective treatment strategies. This study explores the potential of 3D printed Poly Lactic Acid (PLA) scaffolds, enhanced with Whey Protein Concentrate (WPC) at varying concentrations (25, 35, and 50% wt), for wound healing applications. PLA's biocompatibility, biodegradability, and thermal stability make it an ideal material for medical applications. The addition of WPC aims to mimic the skin's extracellular matrix and enhance the bioactivity of the PLA scaffolds. Fourier Transform Infrared Spectroscopy (FTIR) results confirmed the successful loading of WPC into the 3D printed PLA-based scaffolds. Scanning Electron Microscopy (SEM) images revealed no significant differences in pore size between PLA/WPC scaffolds and pure PLA scaffolds. Mechanical strength tests showed similar tensile strength between pure PLA and PLA with 50% WPC scaffolds. However, scaffolds with lower WPC concentrations displayed reduced tensile strength. Notably, all PLA/WPC scaffolds exhibited increased strain at break compared to pure PLA. Swelling capacity was highest in PLA with 25% WPC, approximately 130% higher than pure PLA. Scaffolds with higher WPC concentrations also showed increased swelling and degradation rates. Drug release was found to be prolonged with increasing WPC concentration. After seven days of incubation, cell viability significantly increased in PLA with 50% WPC scaffolds compared to pure PLA scaffolds. This innovative approach could pave the way for personalized wound care strategies, offering tailored treatments and targeted drug delivery. However, further studies are needed to optimize the properties of these scaffolds and validate their effectiveness in clinical settings.&#xD.
    Keywords:  3D printing; Tissue engineering scaffolds; Whey Protein Concentrate; Wound healing
    DOI:  https://doi.org/10.1088/1748-605X/ad565d
  5. Regen Biomater. 2024 ;11 rbae055
      Clinical bone-morphogenetic protein 2 (BMP2) treatment for bone regeneration, often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems, necessitates research into improved biomaterials for better BMP2 stability and retention. To tackle this challenge, we introduced a groundbreaking bone-targeted, lipoplex-loaded, three-dimensional bioprinted bilayer scaffold, termed the polycaprolactone-bioink-nanoparticle (PBN) scaffold, aimed at boosting bone regeneration. We encapsulated BMP2 within the fibroin nanoparticle based lipoplex (Fibroplex) and functionalized it with DSS6 for bone tissue-specific targeting. 3D printing technology enables customized, porous PCL scaffolds for bone healing and soft tissue growth, with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex, shown to support effective nutrient exchange and cell growth at specific pore sizes. The PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue, a finding validated by in vitro osteogenic differentiation assays. The PBN scaffold was evaluated for critical calvarial defects, focusing on sustained BMP2 delivery, prevention of soft tissue cell infiltration and controlled fiber membrane pore size in vivo. The PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge, promoting osteogenic differentiation and bone regeneration in a calvarial defect animal. Our findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation, thereby reducing the risk of heterotopic ossification.
    Keywords:  3D bioprinting; BMP2; bone regeneration; bone-targeting lipoplex
    DOI:  https://doi.org/10.1093/rb/rbae055
  6. Int J Biol Macromol. 2024 Jun 08. pii: S0141-8130(24)03843-1. [Epub ahead of print] 133038
      Bone defects persist as a significant challenge in the field of clinical orthopedics. This study focuses on the fabrication and characterization of 3D-printed composite hydrogel scaffolds composed of sodium alginate, gelatin, and α-tricalcium phosphate (α-TCP) with varying ratios of Strontium ions (Sr2+). These scaffolds aim to address the clinical challenges associated with bone defect repair by providing mechanical support and promoting bone formation and vascularization. The degradation, swelling, mechanical properties, and release profiles of Sr2+ from the hydrogel scaffolds were comprehensively characterized. In vitro tests were conducted to assess cell viability and proliferation, as well as osteogenic and angiogenic gene expression, to investigate the osteogenic and pro-angiogenic potential of the composite hydrogel scaffolds. Furthermore, skull defect simulations were performed, and composite scaffolds with varying Sr2+ ratios were implanted to evaluate their effectiveness in bone repair. This research establishes a foundation for advancing bone tissue engineering through composite scaffolds containing biological macromolecules and strontium, with alginate serving as a key element in enhancing performance and expanding clinical applicability.
    Keywords:  3D-printing scaffold; Alginate; Bone defect repair; Strontium
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.133038