bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024‒03‒03
ten papers selected by
Seerat Maqsood, University of Teramo

  1. Drug Discov Today. 2024 Feb 22. pii: S1359-6446(24)00049-7. [Epub ahead of print] 103924
      Cancer remains one of the most devastating diseases, necessitating innovative and precise therapeutic solutions. The emergence of 3D bioprinting has revolutionized the platform of cancer therapy by offering bespoke solutions for drug screening, tumor modeling, and personalized medicine. The utilization of 3D bioprinting enables the fabrication of complex tumor models that closely mimic the in vivo microenvironment, facilitating more accurate drug testing and personalized treatment strategies. Moreover, 3D bioprinting also provides a platform for the development of implantable scaffolds as a therapeutic solution to cancer. In this review, we highlight the application of 3D bioprinting for cancer therapy along with current advancements in cancer 3D model development with recent case studies.
    Keywords:  3D bioprinting; cancer therapy; immunotherapy; tumor microenvironment; tumor model
  2. Ann Biomed Eng. 2024 Feb 28.
      The emergence of bone tissue engineering as a trend in regenerative medicine is forcing scientists to create highly functional materials and scaffold construction techniques. Bone tissue engineering uses 3D bio-printed scaffolds that allow and stimulate the attachment and proliferation of osteoinductive cells on their surfaces. Bone grafting is necessary to expedite the patient's condition because the natural healing process of bones is slow. Fused deposition modeling (FDM) is therefore suggested as a technique for the production process due to its simplicity, ability to create intricate components and movable forms, and low running costs. 3D-printed scaffolds can repair bone defects in vivo and in vitro. For 3D printing, various materials including metals, polymers, and ceramics are often employed but polymeric biofilaments are promising candidates for replacing non-biodegradable materials due to their adaptability and environment friendliness. This review paper majorly focuses on the fused deposition modeling approach for the fabrication of 3D scaffolds. In addition, it also provides information on biofilaments used in FDM 3D printing, applications, and commercial aspects of scaffolds in bone tissue engineering.
    Keywords:  3D printing; Biofilaments; Bone tissue engineering; Polymers; Scaffolds
  3. ACS Omega. 2024 Feb 20. 9(7): 7375-7392
      Three-dimensional bioprinting is an emerging technology that has high potential application in tissue engineering and regenerative medicine. Increasing advancement and improvement in the decellularization process have led to an increase in the demand for using a decellularized extracellular matrix (dECM) to fabricate tissue engineered products. Decellularization is the process of retaining the extracellular matrix (ECM) while the cellular components are completely removed to harvest the ECM for the regeneration of various tissues and across different sources. Post decellularization of tissues and organs, they act as natural biomaterials to provide the biochemical and structural support to establish cell communication. Selection of an effective method for decellularization is crucial, and various factors like tissue density, geometric organization, and ECM composition affect the regenerative potential which has an impact on the end product. The dECM is a versatile material which is added as an important ingredient to formulate the bioink component for constructing tissue and organs for various significant studies. Bioink consisting of dECM from various sources is used to generate tissue-specific bioink that is unique and to mimic different biometric microenvironments. At present, there are many different techniques applied for decellularization, and the process is not standardized and regulated due to broad application. This review aims to provide an overview of different decellularization procedures, and we also emphasize the different dECM-derived bioinks present in the current global market and the major clinical outcomes. We have also highlighted an overview of benefits and limitations of different decellularization methods and various characteristic validations of decellularization and dECM-derived bioinks.
  4. Sci Technol Adv Mater. 2023 ;24(1): 2273803
      In biomedical imaging, it is desirable that custom-made accessories for restraint, anesthesia, and monitoring can be easily cleaned and not interfere with the imaging quality or analyses. With the rise of 3D printing as a form of rapid prototyping or manufacturing for imaging tools and accessories, it is important to understand which printable materials are durable and not likely to interfere with imaging applications. Here, 15 3D printable materials were evaluated for radiodensity, optical properties, simulated wear, and capacity for repeated cleaning and disinfection. Materials that were durable, easily cleaned, and not expected to interfere with CT, PET, or optical imaging applications were identified.
    Keywords:  3D printing; Biomedical imaging; material science; polymer characterization; prototyping
  5. Curr Opin Biotechnol. 2024 Feb 24. pii: S0958-1669(24)00016-8. [Epub ahead of print]86 103080
      Collagen is a primary constituent of the tissue extracellular matrix. As a result, collagen has been a common component of tissue engineering biomaterials, including those to promote bone regeneration or to investigate cell-material interactions in the context of bone homeostasis or disease. This review summarizes key considerations regarding current state-of-the-art design and use of collagen biomaterials for these applications. We also describe strategic opportunities for collagen biomaterials to address a new era of challenges, including immunomodulation and appropriate consideration of sex and other patient characteristics in biomaterial design.
  6. Biomater Adv. 2024 Feb 22. pii: S2772-9508(24)00047-5. [Epub ahead of print]159 213804
      Although several bioactive 3D-printed bone scaffolds loaded with multiple kinds of biomolecules for enhanced bone regeneration have been recently developed, the manipulation of on-demand release profiles of different biomolecules during bone regeneration remains challenging. Herein, a 3D-printed dual-drug-loaded biomimetic scaffold to regulate the host stem cell recruitment and osteogenic differentiation in a two-stage process for bone regeneration was successfully fabricated. First, a chemotactic small-molecule drug, namely, simvastatin (SIM) was directly incorporated into the hydroxyapatite/collagen bioink for printing and could be rapidly released during the early stage of bone regeneration. Further, near-infrared (NIR)-light-responsive polydopamine-coated hydroxyapatite nanoparticles were designed to deliver the osteogenic drug, i.e., pargyline (PGL) in a controllable manner. Together, our scaffold displayed an on-demand sequential release of those two drugs and could optimize their therapeutic effects to align with the stem cell recruitment and osteoblastic differentiation, thereby promoting bone regeneration. The results confirmed the suitable mechanical strength, high photothermal conversion efficiency, good biocompatibility of our scaffold. The scaffold loaded with SIM could efficiently accelerate the migration of stem cells. In addition, the scaffold with on-demand sequential release promoted alkaline phosphatase (ALP) activity, significantly upregulated gene expression levels of osteogenesis-related markers, and enhanced new-bone-formation capabilities in rabbit cranial defect models. Altogether, this scaffold not only offers a promising strategy to control the behavior of stem cells during bone regeneration but also provides an efficient strategy for controllable sequential release of different biomolecule in bone tissue engineering.
    Keywords:  3D-printed scaffolds; Bone tissue engineering; NIR-light-responsive; On-demand release; Small-molecule drugs
  7. Int J Pharm. 2024 Feb 23. pii: S0378-5173(24)00175-3. [Epub ahead of print] 123941
      Developing safe and effective formulations for the geriatric and pediatric population is a challenging task due to issues of swallowability and palatability. The lack of standardized procedures for pediatric formulations further complicates the process. Manipulating adult formulations for children can lead to suboptimal efficacy and safety concerns. To overcome these challenges, minitablets or spinklets are preferred for the geriatric and pediatric population due to their smaller size and flexible dose adjustment. The aim of this study is the development of a 3D printed spinklets formulation of celecoxib, a nonsteroidal anti-inflammatory drug, using hot melt extrusion to address the limitations of traditional manufacturing methods. Three different formulations of celecoxib were prepared using Poly-2-ethyl-tetra-oxazoline (Aquazol) with and without surfactant. Subsequently, the mechanical properties and solubility of the drug-loaded filaments were evaluated. Solid state characterization confirmed the drug conversion into an amorphous form during the extrusion process, Computer-aided design software facilitate sprinklets design for fused deposition modeling and scanning electron microscopy assess the surface morphology. Sophorolipids plasticize better than TPGS, resulting in lowering processing temperatures during melt extrusion. In vitro drug release showed successful enhancements in the dissolution of oral medications for pediatric patients, considering their distinctive physiological characteristics. Overall, this study demonstrates the successful development of PEtOx-based 3D printed celecoxib sprinklets by coupling hot-melt extrusion and 3D printing technology. Future exploration holds the potential to revolutionize pharmaceutical production and advance personalized medication formulations.
    Keywords:  3D sprinklets; Amorphous solid dispersion; Fused deposition modeling; Personalized medicine; Poly-2-ethyl-tetra-oxazoline
  8. Biomed Mater. 2024 Feb 29.
      Macrophage-mediated bone immune responses significantly influence the repair of bone defects when utilizing tissue-engineered scaffolds. Notably, the scaffolds' physical structure critically impacts macrophage polarization. The optimal pore size for facilitating bone repair remains a topic of debate due to the imprecision of traditional methods in controlling scaffold pore dimensions and spatial architecture. In this investigation, we utilized fused deposition modeling (FDM) technology to fabricate high-precision porous polycaprolactone (PCL) scaffolds, aiming to elucidate the impact of pore size on macrophage polarization. We assessed the scaffolds' mechanical attributes and biocompatibility. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression levels of macrophage-related genes, and enzyme linked immunosorbent assay (ELISA) for cytokine secretion levels. In vitro osteogenic capacity was determined through alkaline phosphatase (ALP) and alizarin red staining (ARS). Our findings indicated that macroporous scaffolds enhanced macrophage adhesion and drove their differentiation towards the M2 phenotype. This led to the increased production of anti-inflammatory factors and a reduction in pro-inflammatory agents, highlighting the scaffolds' immunomodulatory capabilities. Moreover, conditioned media from macrophages cultured on these macroporous scaffolds bolstered the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), exhibiting superior osteogenic differentiation potential. Consequently, FDM-fabricated PCL scaffolds, with precision-controlled pore sizes, present promising prospects as superior materials for bone tissue engineering, leveraging the regulation of macrophage polarization.
    Keywords:  3D printing; bone regeneration; bone tissue engineering; macrophage polarization; polycaprolactone; pore size
  9. Childs Nerv Syst. 2024 Mar 01.
      PURPOSE: 3D printing technologies have become an integral part of modern life, and the most routinely used materials in reconstructive surgery in children are biodegradable materials. The combination of these two technologies opens up new possibilities for the application of innovative methods in neurosurgery and a patient-centered approach in medical care. The aim of the study was to determine whether a physician without specialized programming and printing skills could independently create materials in a clinical setting for the treatment of patients.METHODS: We conducted a preclinical study on 15 male Balb-C mice. Cylindrical materials made of polylactic acid (PLA) plastic were 3D printed. Sterilization of the obtained material was performed using a cold plasma sterilizer with hydrogen peroxide vapor and its plasma. The sterile material was implanted subcutaneously into the mice for 30 days, followed by histological examination. Using open-source software for modeling and printing, plates and screws made of PLA plastic were manufactured. The produced components were tested in the biomedical laboratory of the institute.
    RESULTS: The histological material showed that no inflammatory changes were observed at the implantation site during the entire observation period. The cellular composition is mainly represented by macrophages and fibroblasts. There was a gradual resolution of the material and its replacement by native tissues. Research conducted to assess the effectiveness of material sterilization in a cold plasma sterilizer demonstrated its high bactericidal efficiency.
    CONCLUSION: The method we developed for obtaining biodegradable plates and fixation elements on a 3D printer is easy to use and has demonstrated safety in a preclinical study on an animal model.
    Keywords:  3D printer; Additive technologies; Children; Fixation devices; Neurosurgery; Polylactide materials