bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–03–17
nine papers selected by
Seerat Maqsood, University of Teramo



  1. Polymers (Basel). 2024 Mar 05. pii: 706. [Epub ahead of print]16(5):
      The treatment of bone defects has always posed challenges in the field of orthopedics. Scaffolds, as a vital component of bone tissue engineering, offer significant advantages in the research and treatment of clinical bone defects. This study aims to provide an overview of how 3D printing technology is applied in the production of bone repair scaffolds. Depending on the materials used, the 3D-printed scaffolds can be classified into two types: single-component scaffolds and composite scaffolds. We have conducted a comprehensive analysis of material composition, the characteristics of 3D printing, performance, advantages, disadvantages, and applications for each scaffold type. Furthermore, based on the current research status and progress, we offer suggestions for future research in this area. In conclusion, this review acts as a valuable reference for advancing the research in the field of bone repair scaffolds.
    Keywords:  3D-printed scaffold; ceramic material; gelatin composite scaffolds; polycaprolactone composite scaffolds
    DOI:  https://doi.org/10.3390/polym16050706
  2. Methods Mol Biol. 2024 ;2783 221-233
      Three-dimensional (3D) cell culture techniques have become a valuable tool to mimic the complex interactions of cells with each other and their surrounding extracellular matrix as they occur in vivo. In this respect, 3D spheroids are widely acknowledged as self-assembled cellular aggregates that can be generated from a variety of cell types without the need for exogenous material while being highly reproducible, easy to handle, and cost-effective. Furthermore, due to their capacity to be developed into microtissues, spheroids represent potential building blocks for various tissue engineering applications, including 3D bioprinting approaches for tissue model development. Adipose-derived stromal/stem cells (ASCs), due to their ease of isolation, multipotent nature, and secretory capacity, represent an attractive cell source employed in numerous tissue engineering studies and other cell-based therapy approaches. In this chapter, we describe two procedures for robust spheroid generation, namely the liquid overlay technique, either using agarose-coated 96-well plates or employing agarose-cast micromolds. Furthermore, we show, in principle, the generation of ASC spheroids with subsequent adipogenic differentiation and the spheroid generation using adipogenically differentiated ASCs, as well as the morphological characterization of generated spheroids.
    Keywords:  3D cell culture; Adipocytes; Adipose-derived stromal/stem cells; Bioprinting; Co-culture; Spheroids; Tissue engineering
    DOI:  https://doi.org/10.1007/978-1-0716-3762-3_15
  3. Int J Biol Macromol. 2024 Mar 12. pii: S0141-8130(24)01631-3. [Epub ahead of print] 130827
      The treatment of large craniofacial bone defects requires more advanced and effective strategies than bone grafts since such defects are challenging and cannot heal without intervention. In this regard, 3D printing offers promising solutions through the fabrication of scaffolds with the required shape, porosity, and various biomaterials suitable for specific tissues. In this study, 3D-printed polycaprolactone (PCL)-based scaffolds containing up to 30 % tricalcium silicate (TCS) were fabricated and then modified by incorporation of decellularized bone matrix- oxidized sodium alginate (DBM-OA). The results showed that the addition of 20 % TCS increased compressive modulus by 4.5-fold, yield strength by 12-fold, and toughness by 15-fold compared to pure PCL. In addition, the samples containing TCS revealed the formation of crystalline phases with a Ca/P ratio near that of hydroxyapatite (1.67). Cellular experiment results demonstrated that TCS have improved the biocompatibility of PCL-based scaffolds. On day 7, the scaffolds modified with DBM and 20 % TCS exhibited 8-fold enhancement of ALP activity of placenta-derived mesenchymal stem/stromal cells (P-MSCs) compared to pure PCL scaffolds. The present study's results suggest that the incorporation of TCS and DBM-OA into the PCL-based scaffold improves its mechanical behavior, bioactivity, biocompatibility, and promotes mineralization and early osteogenic activity.
    Keywords:  3D printing; Bone tissue engineering; Decellularized bone matrix; Oxidized sodium alginate; Tricalcium silicate
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.130827
  4. bioRxiv. 2024 Mar 01. pii: 2024.02.26.582070. [Epub ahead of print]
      3D printed biomaterial implants are revolutionizing personalized medicine for tissue repair, especially in orthopedics. In this study, a radiopaque Bi 2 O 3 doped polycaprolactone ( PCL ) composite is developed and implemented to enable the use of diagnostic X-ray technologies, especially photon counting X-ray computed tomography ( PCCT ), for comprehensive in vivo device monitoring. PCL filament with homogeneous Bi 2 O 3 nanoparticle ( NP ) dispersion (0.8 to 11.7 wt%) are first fabricated. Tissue engineered scaffolds ( TES ) are then 3D printed with the composite filament, optimizing printing parameters for small feature size and severely overhung geometries. These composite TES are characterized via micro-computed tomography ( µ CT ), tensile testing, and a cytocompatibility study, with Bi 2 O 3 mass fractions as low as 2 wt% providing excellent radiographic distinguishability, improved tensile properties, and equivalent cytocompatibility of neat PCL. The excellent radiographic distinguishability is validated in situ by imaging 4 and 7 wt% TES in a mouse model with µCT, showing excellent agreement with in vitro measurements. Subsequently, CT image-derived swine menisci are 3D printed with composite filament and re-implanted in their corresponding swine legs ex vivo . Re-imaging the swine legs via clinical CT allows facile identification of device location and alignment. Finally, the emergent technology of PCCT unambiguously distinguishes implanted menisci in situ.
    DOI:  https://doi.org/10.1101/2024.02.26.582070
  5. Neurosci Lett. 2024 Mar 09. pii: S0304-3940(24)00101-0. [Epub ahead of print] 137724
      Dorsal root avulsion injuries lead to loss of sensation and to reorganization of blood vessels (BVs) in the injured area. The inability of injured sensory axons to re-enter the spinal cord results in permanent loss of sensation, and often also leads to the development of neuropathic pain. Approaches that restore connection between peripheral sensory axons and their CNS targets are thus urgently need. Previous research has shown that sensory axons from peripherally grafted human sensory neurons are able to enter the spinal cord by growing along BVs which penetrate the CNS from the spinal cord surface. In this study we analysed the distribution of BVs after avulsion injury and how their pattern is affected by implantation at the injury site of boundary cap neural crest stem cells (bNCSCs), a transient cluster of cells, which are located at the boundary between the spinal cord and peripheral system and assist the growth of sensory axons from periphery into the spinal cord during development. The superficial dorsal spinal cord vasculature was examined using intravital microscopy and intravascular BV labelling. bNCSC transplantation increased vascular volume in a non-dose responsive manner, whereas dorsal root avulsion alone did not decrease the vascular volume. To determine whether bNCSC are endowed with angiogenic properties we prepared 3D printed scaffolds, containing bNCSCs together with rings prepared from mouse aorta. We show that bNCSC do induce migration and assembly of endothelial cells in this system. These findings suggest that bNCSC transplant can promote vascularization in vivo and contribute to BV formation in 3D printed scaffolds.
    Keywords:  3D printing; Angiogenesis; Dorsal root; Neural stem cell; Spinal cord injury; Transplantation
    DOI:  https://doi.org/10.1016/j.neulet.2024.137724
  6. Clin Shoulder Elb. 2024 Mar;27(1): 72-78
       BACKGROUND: Clinical outcomes after fixation of distal humerus intraarticular fractures are directly related to the quality of reduction. The use of three-dimensional (3D)-printed fracture models can benefit preoperative planning to ensure good reduction. This review aims to determine if surgery performed with 3D printing assistance are faster and result in fewer complications and improved clinical outcomes than conventional methods. We also outline the benefits and drawbacks of this novel technique in surgical management of distal humerus fractures.
    METHODS: A systematic literature search was carried out in various electronic databases. Search results were screened based on title and abstract. Data from eligible studies were extracted into spreadsheets. Meta-analysis was performed using appropriate computer software.
    RESULTS: Three randomized controlled trials with 144 cases were included in the final analysis. The 3D-printed group had significantly shorter mean operating time (mean difference, 16.25 minutes; 95% confidence interval [CI], 12.74-19.76 minutes; P<0.001) and mean intraoperative blood loss (30.40 mL; 95% CI, 10.45-60.36 mL; P=0.005) compared with the conventional group. The 3D-printed group also tended to have fewer complications and a better likelihood of good or excellent outcomes as per the Mayo elbow performance score, but this did not reach statistical significance.
    CONCLUSIONS: Three-dimensional-printing-assisted surgery in distal humerus fractures has several benefits in reduced operating time and lower blood loss, indirectly decreasing other complications such as infection and anemia-related issues. Future good-quality studies are required to conclusively demonstrate the benefits of 3D printing in improving clinical outcomes. Level of evidence: I.
    Keywords:   Distal humerus fractures; Intercondylar humerus fractures; Meta-analysis ; Systematic review; Three-dimensional printing
    DOI:  https://doi.org/10.5397/cise.2023.00591
  7. Z Med Phys. 2024 Mar 12. pii: S0939-3889(24)00026-6. [Epub ahead of print]
      In recent years, access to 3D printers has become increasingly affordable. Alongside industrial and private applications, the significance of 3D printing in the clinical context is also growing. For instance, 3D printing processes enable the production of individual anatomical models that can be used to support patient communication or aid in surgical planning. While filament 3D printing is common, stereolithography (SLA) and selective laser sintering (SLS) printing processes offer higher precision. For the use of 3D printing materials in radiology, understanding their attenuation properties concerning ionizing radiation is crucial. Polymethyl methacrylate (PMMA) serves as an important reference material for radiological applications in this regard. In this research, linear- and mass attenuation coefficients of 38 SLA-/SLS-materials from Formlabs (Somerville, Massachusetts, USA) and PMMA will be determined through intensity measurements in nuclear medicine for the radionuclides technetium-99 m and iodine-131, as well as for X-ray imaging in the range of 60 kVp - 110 kVp tube voltage. Based on the mass attenuation coefficients, correction factors in respect to PMMA will be calculated for each material. A significant number of materials exhibit a deviance within approximately ±5% in respect to PMMA regardless of radiation energy. However, certain materials from the dental and industrial application show deviances up to +500% at the lower end of radiation energy spectrum. In conclusion, most materials can be considered equivalent to PMMA with only minor adjustments required. Materials with high deviances can be utilized as high-contrast materials in custom X-ray phantoms.
    Keywords:  3D-Printing; Correction factors; Formlabs; Mass-attenuation; Nuclear medicine; X-ray
    DOI:  https://doi.org/10.1016/j.zemedi.2024.02.003
  8. Int J Biol Macromol. 2024 Mar 11. pii: S0141-8130(24)01536-8. [Epub ahead of print]264(Pt 2): 130732
      Nanocellulose-based tissue adhesives show promise for achieving rapid hemostasis and effective wound healing. Conventional methods, such as sutures and staples, have limitations, prompting the exploration of bioadhesives for direct wound adhesion and minimal tissue damage. Nanocellulose, a hydrolysis product of cellulose, exhibits superior biocompatibility and multifunctional properties, gaining interest as a base material for bioadhesive development. This study explores the potential of nanocellulose-based adhesives for hemostasis and wound healing using 3D printing techniques. Nanocellulose enables the creation of biodegradable adhesives with minimal adverse effects and opens avenues for advanced wound healing and complex tissue regeneration, such as skin, blood vessels, lungs, cartilage, and muscle. This study reviews recent trends in various nanocellulose-based 3D printed hydrogel patches for tissue engineering applications. The review also introduces various types of nanocellulose and their synthesis, surface modification, and bioadhesive fabrication techniques via 3D printing for smart wound healing.
    Keywords:  3D printing; Bioadhesives; Hemostasis; Nanocellulose; Wound healing
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.130732
  9. Curr Med Chem. 2024 Mar 08.
      The burden of increasing cancer incidence among the population, and, in particular, of prostate cancer in men living in highly developed countries, brings with it, on one hand, the need for new devices that allow a faster and earlier diagnosis, ideally in a non-invasive way and with low consumption of expensive reagents, and on the other the need for the assessment of new in vitro models that allow a more reliable assessment of cancer features, including its microenvironment and sensibility to different drugs. At the crossroads of these features, microfluidic devices are found. These, taking advantage of the chemical-physical properties of cells and human samples, have demonstrated great sensitivity and sensibility at an on-chip scale. Many fields of biomedical sciences have tried to exploit all their potentialities: from the detection of antigens in the early phases of the disease (when they are very low concentrated, but the treatment is more effective) to isolation and characterization of circulating tumor cells. However, the development of in vitro 3D models to better assess and comprehend the fundamental dynamics of tumor microenvironment and metastasis using 3D bioprinting techniques. The aim of the present review is to describe the potential of these two different cutting-edge technologies for the detection and treatment of prostate cancer, in the perspective of a possible future combination of them that allows scientists to fill the gaps present in the field to improve patient care and treatment.
    Keywords:  3D bioprinting; Prostate cancer; antigen detection; cancer treatment; circulating tumor cells; in vitro models.; microfluidics
    DOI:  https://doi.org/10.2174/0109298673298382240307040239