bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–12–08
eleven papers selected by
Seerat Maqsood, University of Teramo



  1. J Maxillofac Oral Surg. 2024 Dec;23(6): 1601-1607
      Oral and maxillofacial surgery has seen various advancements throughout years. From dental implants to 3D printing, every advancement this field has witnessed has taken it one step ahead into the future. Reconstructive surgeries in oral and maxillofacial surgery have evolved drastically over the years. Till now, autografts are considered the best possible alternative to soft tissue or hard tissue defects. The advent of 3D bioprinting has not only broadened the vision of surgeons, physicians, and bioengineers but also enkindled the hope for a better future in reconstructive surgeries. All in all, the facial structures are full of complexities and loss of tissues in maxillofacial area is much common. 3D bioprinting with the ability to print a tissue with pre-defined arrangement of cells having its own vascularization can prove to be a valuable tool in the field of maxillofacial surgeries. Although still it has a long way to go to make it accessible for all, 3D bioprinting can be considered an asset for the field of oral and maxillofacial surgery. This article throws some light on the applications of 3D bioprinting in the field of oral and maxillofacial surgery and the promising future it holds in reconstructive surgeries.Structured abstract is required. Please provide.Respected sir/madam, This is a mini review article and as per the submission guidelines for abstract in the Journal of Maxillofacial and Oral Surgery, no instructions were given about the structured abstract for mini review. But, with due respect, if we are mistaken, then kindly guide us regarding the same and give us couple of days more to rectify this mistake. Regards.Kindly check and confirm whether the corresponding author and mail gigiid is correctly identified.Yes, the corresponding author and mail id is correctly identified.Journal standard instruction requires a structured abstract; however, none was provided. Please supply an Abstract with subsections "supply required Abstract sections separated by ;".Respected sir/madam, This is a mini review article and as per the submission guidelines for abstract in the journal of maxillofacial and oral surgery, no instructions were given about the structured abstract for mini review. But, with due respect if we are mistaken kindly guide us regarding the same and give us couple of days more to rectify this mistake. Regards.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 3 Given name: [Gurinder Bir Singh] Last name [Thind]. Also, kindly confirm the details in the metadata are correct.Yes, Author 3 given name is in correct order. Given name : Gurinder Middle Name : Bir Singh Last Name: Thind Yes, details are correct.As per the instruction, other language titles like ……….. are required, but are not provided. Could you please provide the missing titles?There are no other language titles in this mini review article.As per the instruction, other language abstracts like ……….. are required, but are not provided. Could you please provide the other language abstracts?There are no other language abstract in this article.
    Keywords:  3D bioprinting; 3D reconstruction; 3D scaffolds; Additive manufacturing; Oral and maxillofacial surgeries
    DOI:  https://doi.org/10.1007/s12663-023-02063-7
  2. Biomacromolecules. 2024 Dec 03.
      Since its invention in the 1980s, photopolymerization-based 3D printing has attracted significant attention for its capability to fabricate complex microstructures with high precision, by leveraging light patterning to initiate polymerization and cross-linking in liquid resin materials. Such precision makes it particularly suitable for biomedical applications, in particular, advanced and customized drug delivery systems. This review summarizes the latest advancements in photopolymerization 3D printing technology and the development of biocompatible and/or biodegradable materials that have been used or shown potential in the field of drug delivery. The drug loading methods and release characteristics of the 3D printing drug delivery systems are summarized. Importantly, recent trends in the drug delivery applications based on photopolymerization 3D printing, including oral formulations, microneedles, implantable devices, microrobots and recently emerging systems, are analyzed. In the end, the challenges and opportunities in photopolymerization 3D printing for customized drug delivery are discussed.
    DOI:  https://doi.org/10.1021/acs.biomac.4c01004
  3. Adv Funct Mater. 2024 Oct 29. pii: 2404860. [Epub ahead of print]34(44):
      3D printed biomaterial implants are revolutionizing personalized medicine for tissue repair, especially in orthopedics. In this study, a radiopaque bismuth oxide (Bi2O3) doped polycaprolactone (PCL) composite is developed and implemented to enable the use of diagnostic X-ray technologies, especially spectral photon counting X-ray computed tomography (SPCCT), for comprehensive tissue engineering scaffold (TES) monitoring. PCL filament with homogeneous Bi2O3 nanoparticle (NP) dispersion (0.8 to 11.7 wt%) are first fabricated. TES are then 3D printed with the composite filament, optimizing printing parameters for small features and severely overhung geometries. These composite TES are characterized via micro-computed tomography (μCT), tensile testing, and a cytocompatibility study, with 2 wt% Bi2O3 NPs providing improved tensile properties, equivalent cytocompatibility to neat PCL, and excellent radiographic distinguishability. Radiographic performance is validated in situ by imaging 4 and 7 wt% Bi2O3 doped PCL 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 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 SPCCT unambiguously distinguishes the implanted meniscus in situ via means of color K-edge imaging.
    Keywords:  3D printing; biomaterials; bismuth oxide; computed tomography; meniscus; organic-inorganic hybrid composites; scaffold
    DOI:  https://doi.org/10.1002/adfm.202404860
  4. J Contemp Brachytherapy. 2024 Jun;16(3): 173-183
       Purpose: This study outlined the prevalent use of brachytherapy in skin cancers, such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The importance of customized applicator fabrication for optimal treatment delivery was highlighted, focusing on adaptable devices tailored to individual patient anatomy, often facilitated by 3D printing technology. The purpose of this work was to investigate the association of medical science and 3D printing in customized applicator fabrication for brachytherapy, leveraging the advancements in fabrication techniques to enhance treatment precision and patient outcomes.
    Material and methods: The study enrolled five patients with tumor lesions unsuitable for surgical intervention, situated across various anatomical locations, such as earlobe, temple, hand, and cheek. Customized applicators were fabricated via 3D printing (fused deposition modeling) for each patient, followed by radiotherapy protocol delivering a total dose of 51 Gy in 17 fractions. Patient assessments during and post-radiotherapy were done by radiation oncologist using RTOG scale as well as dermatological evaluations with dermatoscopy and reflectance confocal microscopy. Methodologically, applicators were 3D-printed using fused deposition modeling technology. Printing parameters were optimized in Prusa Slicer software, ensuring precise control in printout shape correlated with treatment efficacy.
    Results: This study examined the therapeutic outcomes of brachytherapy in five patients with inoperable skin cancer lesions. Utilizing customized 3D-printed applicators, the patients underwent brachytherapy regimen delivering a cumulative dose of 51 Gy in 17 fractions. The evaluation with RTOG scale revealed varied treatment responses, with complete remission achieved in all cases. Reflectance confocal microscopy showed post-treatment normalization of epidermal morphology and notable scar formation. Optical profilometry demonstrated consistent micro-structures on the applicator surfaces, without compromising treatment efficacy. These findings indicated the potential of 3D-printed applicators in optimizing brachytherapy outcomes in skin cancer management.
    Conclusions: Our study demonstrates the effectiveness of 3D-printed applicators in treating inoperable skin cancer lesions with high precision. In personalized fabrication, optimal conformity with anatomical features was achieved, resulting in complete remission in all patients. This approach minimizes treatment-related side effects and enhances overall patient outcomes, suggesting a promising future for 3D printing technology in skin cancer treatment applications. Further research and clinical validation are needed to establish 3D printing as a standard practice in skin cancer treatment.
    Keywords:  3D printing; fused deposition modeling; individual applicator; skin cancer; superficial brachytherapy
    DOI:  https://doi.org/10.5114/jcb.2024.141420
  5. Chirurgie (Heidelb). 2024 Dec 04.
      Biological 3D printing (bioprinting) is an extension of what is defined as additive manufacturing in the American Society for Testing and Materials (ASTM) and International Organization for Standardization (ISO) standards and is based on the automated printing of living cells and biomaterials. Researchers and experts in the field of biomaterial science, tissue engineering and regenerative medicine (TE&RM) are constantly pointing to the potential of biological 3D printing and scientific articles regularly announce the imminent clinical application. We argue in this article that these announcements are often premature and counterproductive as they focus heavily on technological progress but regularly ignore the critical stages that need to be completed in order to successfully translate a technology into the healthcare market. The technology readiness level (TRL) scale is a potentially useful tool for measuring the relative maturity of a technology in terms of overcoming a series of critical milestones. We propose an adaptation of the TRL scale and use it to discuss the current state of research on biological 3D printing. Finally, we provide specific recommendations for optimizing future research projects to pave the way for clinical applications of biological 3D printing and thus achieve a direct positive impact on surgical patient care.
    Keywords:  3D printing; Bioprinting; Clinical translation; Innovation assessment; Technology readiness level
    DOI:  https://doi.org/10.1007/s00104-024-02197-5
  6. Biofabrication. 2024 Dec 03.
      Bioprinting has enabled the creation of intricate scaffolds that replicate the physical, chemical, and structural characteristics of natural tissues. Recently, hydrogels have been used to fabricate such scaffolds for several biomedical applications and tissue engineering. However, the small pore size of conventional hydrogels impedes cellular migration into and remodeling of scaffolds, diminishing their regenerative potential. Porous scaffolds have been utilized for their improved diffusion of nutrients, dissolved oxygen, and waste products. However, traditional methods of generating porous structures require multiple processing steps, making them incompatible with bioprinting. Recently, we developed a method to generate multi-scale porous structures by foaming hydrogel precursors prior to printing to form colloidal bioinks. Here, to further improve the biological, mechanical, and physical properties, we functionalize colloidal bioinks with nanoliposomes (NL), one of the most promising methods for bioactive delivery. We assess the impact of the concentration of NL on the characteristics of bioinks made from gelatin methacryloyl (GelMA) and their resulting scaffolds. Anionic liposomes made from rapeseed lecithin of 110 nm were synthesized and found to be stable over several weeks. Increasing concentrations of NL decreased the zeta potential and increased the viscosity of foamed bioinks, improving their rheological properties for printing. Furthermore, the incorporation of NL allowed for precise adjustment of the macropore size and bulk mechanical properties without any chemical interaction or impact on photocrosslinking. The nanofunctionalized foam bioinks, composed exclusively of natural components, demonstrated significant antioxidant activity and were printed into multilayered scaffolds with high printability. The foam-embedded NL showed remarkable biocompatibility with myoblasts, and cell-laden bioinks were able to be successfully bioprinted. Due to their high biocompatibility, tunable mechanical properties, printability, and antioxidant behavior, the nanofunctionalized porous scaffolds have promise for a variety of biomedical applications, including those that require precise delivery of therapeutic substances and tissue engineering.
    Keywords:  3D printing; GelMA; Nanoliposome; colloidal; functionalized; inks
    DOI:  https://doi.org/10.1088/1758-5090/ad9a01
  7. J Maxillofac Oral Surg. 2024 Dec;23(6): 1440-1441
      Intra-oral flaps serve as a valuable solution for small to medium-sized oral cavity defects, yet complications such as flap sagging, tension at suture lines, mastication-related injuries, and patient discomfort remain challenges. The use of intraoral splint to support the flap diminishes these risks and complications. Conventional intraoral impression techniques are fraught with risks, including impression material infiltration and muco-compression, compromising blood supply. To overcome these challenges, the integration of digital impressions and 3D printing offers a novel solution for fabrication of intraoral splint.
    Keywords:  3D printing; Digital impression of flap; Intraoral splint
    DOI:  https://doi.org/10.1007/s12663-023-02081-5
  8. J Ultrasound Med. 2024 Dec 03.
      This systematic review aimed to identify studies that have created ultrasound-able models for resident procedural training by means of 3D-printing techniques and examine their tissue specific properties. There were 456 articles identified from 3 databases, of which, 35 studies were assessed for eligibility, and 11 total studies were included. All qualitative studies showed improvements in procedural skills and 89% of the quantitative studies showed significant results. Studies that documented modeling price showed a 90% reduction in fabrication cost compared to commercial models. Three-dimensional-printed, ultrasound-able models have the potential to provide trainees with low-cost, high-fidelity training opportunities.
    Keywords:  3D printing; anthropomorphic phantom; graduate medical education; simulation‐based medical education; ultrasound
    DOI:  https://doi.org/10.1002/jum.16624
  9. Biomater Sci. 2024 Dec 06.
      Adhesive tissue engineering scaffold (ATES) devices can be secured on tissues by relying on their intrinsic adhesive properties, hence, avoiding the complications such as host tissue/scaffold damage that are associated with conventional scaffold fixation methods like suturing or bioglue. This study introduces a new generation of three-dimensional (3D) bioprinted ATES systems for use as cardiac patches to regenerate the adult human heart. Tyramine-modified methacrylated hyaluronic acid (HAMA-tyr), gelatin methacrylate (GelMA), and gelatin were used to create the hybrid bioink formulation with self-adhesive properties. ATESs were bioprinted and further modified to improve the adhesion properties. In-depth characterization of printing fidelity, pore size, mechanical properties, swelling behavior, as well as biocompatibility was used to create ATESs with optimal biological function. Following in vitro testing, the ATESs were tested in a mouse model of myocardial infarction to study the scaffold adhesive strength in biological milieu. The method developed in this study can be used to manufacture off-the-shelf ATESs with complex cellular and extracellular architecture, with robust potential for clinical translation into a variety of personalized tissue engineering and regenerative medicine applications.
    DOI:  https://doi.org/10.1039/d4bm00988f
  10. Adv Healthc Mater. 2024 Dec 06. e2403583
      Microporous hydrogels have been utilized in an unprecedented manner in the last few decades, combining materials science, biology, and medicine. Their microporous structure makes them suitable for wide applications, especially as cell carriers in tissue engineering and regenerative medicine. Microporous hydrogel scaffolds provide spatial and platform support for cell growth and proliferation, which can promote cell growth, migration, and differentiation, influencing tissue repair and regeneration. This review gives an overview of recent developments in the fabrication techniques and applications of microporous hydrogels. The fabrication of microporous hydrogels can be classified into two distinct categories: fabrication of non-injectable microporous hydrogels including freeze-drying microporous method, two-phase sacrificial strategy, 3D biofabrication technology, etc., and fabrication of injectable microporous hydrogels mainly including microgel assembly. Then, the biomedical applications of microporous hydrogels in cell carriers for tissue engineering, including but not limited to bone regeneration, nerve regeneration, vascular regeneration, and muscle regeneration are emphasized. Additionally, the ongoing and foreseeable applications and current limitations of microporous hydrogels in biomedical engineering are illustrated. Through stimulating innovative ideas, the present review paves new avenues for expanding the application of microporous hydrogels in tissue engineering.
    Keywords:  cell‐loaded scaffolds; microporous hydrogels; tissue engineering and regenerative medicine
    DOI:  https://doi.org/10.1002/adhm.202403583
  11. J Biomater Appl. 2024 Dec 04. 8853282241297767
      Fabricating scaffolds using three-dimensional (3D) printing is an emerging approach in tissue engineering (TE), where filaments with a controlled arrangement are printed. Using fused deposition modeling in bone replacement enables the simulation of bone structure. However, the microenvironment created by the scaffold must meet specific requirements. These requirements aim to create an environment that promotes adhesion, proliferation, differentiation, and cell migration. One of the challenges in creating polylactic acid scaffolds is controlling the degradation rate to match the target tissue. This study investigates the degradation of scaffolds with different geometries and the relationship between scaffolds' geometry and degradation rate. These scaffolds are made of polylactic acid and prepared using 3D printing. The lattice geometry was exposed to acidic media with varying pH levels for 1 month, and pH2 was selected for all geometries for further investigation. The five selected geometries were then immersed in the desired acid for 2 months, and measurements were taken for wet weight, dry weight, morphology, molecular weight, and crystallinity during degradation. The results showed that the hexagonal sample had a 1.5% increase in wet weight, and the gyroid sample had a 1.2% increase, indicating that the wavy shapes had a higher fluid-holding capacity. The degradation analysis indicated that the hexagonal geometry had accelerated degradation compared to the other geometries. Based on these findings, it can be concluded that filament separation not only results in rapid cooling and prevents the recovery of the crystalline arrangement but also increases the surface area to volume ratio, allowing for more acid penetration and faster degradation. Finally, mechanical properties and in vitro evaluation were assessed for three selected geometries. On the 60th day, the hexagonal scaffold had the highest elastic modulus value of 105 ± 0.45 MPa, while the gyroid scaffold had the lowest value of 58.8 ± 0.40 MPa. The lattice scaffold had the highest amount of cell attachment, with 210.88 ± 0.35 cells surviving after 24 hours and 94.01 ± 0.18 cells surviving after 72 hours. These high viability rates indicate that the three scaffolds with the selected geometries are suitable for promoting cell growth.
    Keywords:  Bone scaffold geometry; degradation; fused deposition modeling; polylactic acid
    DOI:  https://doi.org/10.1177/08853282241297767