bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023‒12‒10
ten papers selected by
Seerat Maqsood, University of Teramo

  1. Adv Mater Technol. 2022 Nov;pii: 2101636. [Epub ahead of print]7(11):
      Cardiovascular diseases (CVDs) are known as the major cause of death worldwide. In spite of tremendous advancements in medical therapy, the gold standard for CVD treatment is still transplantation. Tissue engineering, on the other hand, has emerged as a pioneering field of study with promising results in tissue regeneration using cells, biological cues, and scaffolds. Three-dimensional (3D) bioprinting is a rapidly growing technique in tissue engineering because of its ability to create complex scaffold structures, encapsulate cells, and perform these tasks with precision. More recently, 3D bioprinting has made its debut in cardiac tissue engineering, and scientists are investigating this technique for development of new strategies for cardiac tissue regeneration. In this review, the fundamentals of cardiac tissue biology, available 3D bioprinting techniques and bioinks, and cells implemented for cardiac regeneration are briefly summarized and presented. Afterwards, the pioneering and state-of-the-art works that have utilized 3D bioprinting for cardiac tissue engineering are thoroughly reviewed. Finally, regulatory pathways and their contemporary limitations and challenges for clinical translation are discussed.
    Keywords:  3D bioprinting; bioinks; bioreactor; cardiovascular system; clinical translation; tissue engineering
  2. Trends Biotechnol. 2023 Dec 05. pii: S0167-7799(23)00300-1. [Epub ahead of print]
      Urethral conditions affect children and adults, increasing the risk of urinary tract infections, voiding and sexual dysfunction, and renal failure. Current tissue replacements differ from healthy urethral tissues in structural and mechanical characteristics, causing high risk of postoperative complications. 3D bioprinting can overcome these limitations through the creation of complex, layered architectures using materials with location-specific biomechanical properties. This review highlights prior research and describes the potential for these emerging technologies to address ongoing challenges in urethral tissue engineering, including biomechanical and structural mismatch, lack of individualized repair solutions, and inadequate wound healing and vascularization. In the future, the integration of 3D bioprinting technology with advanced biomaterials, computational modeling, and 3D imaging could transform personalized urethral surgical procedures.
    Keywords:  3D bioprinting; biomaterials; tissue engineering; urethra; urological disease
  3. Front Bioeng Biotechnol. 2023 ;11 1254739
      Myocardial infarction is one of the major causes of mortality as well as morbidity around the world. Currently available treatment options face a number of drawbacks, hence cardiac tissue engineering, which aims to bioengineer functional cardiac tissue, for application in tissue repair, patient specific drug screening and disease modeling, is being explored as a viable alternative. To achieve this, an appropriate combination of cells, biomimetic scaffolds mimicking the structure and function of the native tissue, and signals, is necessary. Among scaffold fabrication techniques, three-dimensional printing, which is an additive manufacturing technique that enables to translate computer-aided designs into 3D objects, has emerged as a promising technique to develop cardiac patches with a highly defined architecture. As a further step toward the replication of complex tissues, such as cardiac tissue, more recently 3D bioprinting has emerged as a cutting-edge technology to print not only biomaterials, but also multiple cell types simultaneously. In terms of bioinks, biomaterials isolated from natural sources are advantageous, as they can provide exceptional biocompatibility and bioactivity, thus promoting desired cell responses. An ideal biomimetic cardiac patch should incorporate additional functional properties, which can be achieved by means of appropriate functionalization strategies. These are essential to replicate the native tissue, such as the release of biochemical signals, immunomodulatory properties, conductivity, enhanced vascularization and shape memory effects. The aim of the review is to present an overview of the current state of the art regarding the development of biomimetic 3D printed natural biomaterial-based cardiac patches, describing the 3D printing fabrication methods, the natural-biomaterial based bioinks, the functionalization strategies, as well as the in vitro and in vivo applications.
    Keywords:  3D bioprinting; 3D printing; bioink; biomimicry; cardiac tissue engineering; functionalization; natural biomaterials
  4. Biomaterials. 2023 Nov 27. pii: S0142-9612(23)00416-7. [Epub ahead of print]304 122408
      The limitations of traditional two-dimensional (2D) cultures and animal testing, when it comes to precisely foreseeing the toxicity and clinical effectiveness of potential drug candidates, have resulted in a notable increase in the rate of failure during the process of drug discovery and development. Three-dimensional (3D) in-vitro models have arisen as substitute platforms with the capacity to accurately depict in-vivo conditions and increasing the predictivity of clinical effects and toxicity of drug candidates. It has been found that 3D models can accurately represent complex tissue structure of human body and can be used for a wide range of disease modeling purposes. Recently, substantial progress in biomedicine, materials and engineering have been made to fabricate various 3D in-vitro models, which have been exhibited better disease progression predictivity and drug effects than convention models, suggesting a promising direction in pharmaceutics. This comprehensive review highlights the recent developments in 3D in-vitro tissue models for preclinical applications including drug screening and disease modeling targeting multiple organs and tissues, like liver, bone, gastrointestinal tract, kidney, heart, brain, and cartilage. We discuss current strategies for fabricating 3D models for specific organs with their strengths and pitfalls. We expand future considerations for establishing a physiologically-relevant microenvironment for growing 3D models and also provide readers with a perspective on intellectual property, industry, and regulatory landscape.
    Keywords:  3D tissue models; Biofabrication; Bioprinting; Disease modeling; Drug screening; Microfluidics
  5. APL Bioeng. 2023 Dec;7(4): 046113
      There is critical need for a predictive model of human cardiac physiology in drug development to assess compound effects on human tissues. In vitro two-dimensional monolayer cultures of cardiomyocytes provide biochemical and cellular readouts, and in vivo animal models provide information on systemic cardiovascular response. However, there remains a significant gap in these models due to their incomplete recapitulation of adult human cardiovascular physiology. Recent efforts in developing in vitro models from engineered heart tissues have demonstrated potential for bridging this gap using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in three-dimensional tissue structure. Here, we advance this paradigm by implementing FRESH™ 3D bioprinting to build human cardiac tissues in a medium throughput, well-plate format with controlled tissue architecture, tailored cellular composition, and native-like physiological function, specifically in its drug response. We combined hiPSC-CMs, endothelial cells, and fibroblasts in a cellular bioink and FRESH™ 3D bioprinted this mixture in the format of a thin tissue strip stabilized on a tissue fixture. We show that cardiac tissues could be fabricated directly in a 24-well plate format were composed of dense and highly aligned hiPSC-CMs at >600 million cells/mL and, within 14 days, demonstrated reproducible calcium transients and a fast conduction velocity of ∼16 cm/s. Interrogation of these cardiac tissues with the β-adrenergic receptor agonist isoproterenol showed responses consistent with positive chronotropy and inotropy. Treatment with calcium channel blocker verapamil demonstrated responses expected of hiPSC-CM derived cardiac tissues. These results confirm that FRESH™ 3D bioprinted cardiac tissues represent an in vitro platform that provides data on human physiological response.
  6. ACS Appl Bio Mater. 2023 Dec 05.
      Hybrid collagen (Coll) bioscaffolds have emerged as a promising solution for tissue engineering (TE) and regenerative medicine. These innovative bioscaffolds combine the beneficial properties of Coll, an important structural protein of the extracellular matrix, with various other biomaterials to create platforms for long-term cell growth and tissue formation. The integration or cross-linking of Coll with other biomaterials increases mechanical strength and stability and introduces tailored biochemical and physical factors that mimic the natural tissue microenvironment. This work reports on the fabrication of chemically cross-linked hybrid bioscaffolds with enhanced properties from the combination of Coll, nanofibrillated cellulose (NFC), carboxymethylcellulose (CMC), and citric acid (CA). The bioscaffolds were prepared by 3D printing ink containing Coll-NFC-CMC-CA followed by freeze-drying, dehydrothermal treatment, and neutralization. Cross-linking through the formation of ester bonds between the polymers and CA in the bioscaffolds was achieved by exposing the bioscaffolds to elevated temperatures in the dry state. The morphology, pores/porosity, chemical composition, structure, thermal behavior, swelling, degradation, and mechanical properties of the bioscaffolds in the dry and wet states were investigated as a function of Coll concentration. The bioscaffolds showed no cytotoxicity to MG-63 human bone osteosarcoma cells as tested by different assays measuring different end points. Overall, the presented hybrid Coll bioscaffolds offer a unique combination of biocompatibility, stability, and structural support, making them valuable tools for TE.
    Keywords:  3D printing; carboxymethyl cellulose; citric acid; collagen; cross-linking; hybrid scaffolds; nanofibrillated cellulose
  7. Cureus. 2023 Nov;15(11): e48242
      Maxillofacial reconstructive implants are typically created in standard shapes and have a widespread application in head and neck surgery. During surgical procedures, the implant must be correctly bent according to the architecture of the particular bones. Bending takes practice, especially for untrained surgeons. Furthermore, repeated bending may increase internal stress, resulting in fatigue in vivo under masticatory loading and an array of consequences, including implant failure. There is a risk of fracture, screw loosening, and bone resorption. Resorption, infection, and displacement are usually associated with the use of premade alloplastic implants and autogenous grafts. Recent technological breakthroughs have led to the use of patient-specific implants (PSIs) developed by computer-designed additive manufacturing in reconstructive surgery. The use of computer-designed three-dimensional (3D)-printed PSI allows for more precise restoration of maxillofacial deformities, avoiding the common difficulties associated with premade implants and increasing patient satisfaction. Additive manufacturing is something that refers to a group of additive manufacturing methods. This technique has been quickly used in a variety of surgical procedures. The exponential expansion of this technology can be attributed to its enormous surgical value. Adding 3D printing to a medical practice can be a rewarding experience with stunning results.
    Keywords:  3d printing; additive manufacturing; maxillofacial reconstructive surgery; patient-specific implant design; rapid prototyping
  8. Macromol Rapid Commun. 2023 Dec 04. e2300508
      Interface tissue repair requires the construction of biomaterials with integrated structures of multiple protein types. Hydrogels that modulate internal porous structures provide a three-dimensional microenvironment for encapsulated cells, making them promise for interface tissue repair. Currently, reduction of intrinsic immunogenicity and increase of bioactive extracellular matrix secretion are issues to be considered in these materials. In this study, we used gelatin methacrylate (GelMA) hydrogel to encapsulate chondrocytes and construct a phase transition three-dimensional cell culture system (GelMA PTCC) by utilizing the thermosensitivity of gelatin microspheres to create micropores within the hydrogel. The types of bioactive extracellular matrix protein formation by chondrocytes encapsulated in hydrogels was investigated in vitro. After 28 days of culture, GelMA PTCC formed an extracellular matrix predominantly composed of collagen type II, collagen type I, and fibronectin. After decellularization, the protein types and mechanical properties were well preserved, fabricating a decellularized tissue engineered extracellular matrix interpenetrating network hydrogel (dECM-GelMA IPN) consisting of GelMA hydrogel as the first-level network and the extracellular matrix secreted by chondrocytes as the second-level network. This material has the potential to mediate the repair and regeneration of tendon-bone interface tissues with multiple protein types. This article is protected by copyright. All rights reserved.
    Keywords:  3D cell culture; Extracellular matrix; Hydrogel; Interface defect repair; Interpenetrating network
  9. Mater Today Bio. 2023 Dec;23 100865
      Hydrogels play an important role in tissue engineering due to their native extracellular matrix-like characteristics, but they are insufficient in providing the necessary stimuli to support tissue formation. Efforts to integrate bioactive cues directly into hydrogels are hindered by incompatibility with hydrophobic drugs, issues of burst/uncontrolled release, and rapid degradation of the bioactive molecules. Skeletal muscle tissue repair requires internal stimuli and communication between cells for regeneration, and nanocomposite systems offer to improve the therapeutic effects in tissue regeneration. Here, the versatility of mesoporous silica nanoparticles (MSN) was leveraged to formulate a nanoparticle-hydrogel composite and to combine the benefits of controlled delivery of bioactive cues and cellular support. The tunable surface characteristics of MSNs were exploited to optimize homogeneity and intracellular drug delivery in a 3D matrix. Nanocomposite hydrogels formulated with acetylated or succinylated MSNs achieved high homogeneity in 3D distribution, with succinylated MSNs being rapidly internalized and acetylated MSNs exhibiting slower cellular uptake. MSN-hydrogel nanocomposites simultaneously allowed efficient local intracellular delivery of a hydrophobic model drug. To further study the efficiency of directing cell response, a Notch signaling inhibitor (DAPT) was incorporated into succinylated MSNs and incorporated into the hydrogel. MSN-hydrogel nanocomposites effectively downregulated the Notch signaling target genes, and accelerated and maintained the expression of myogenic markers. The current findings demonstrate a proof-of-concept in effective surface engineering strategies for MSN-based nanocomposites, suited for hydrophobic drug delivery in tissue regeneration with guided cues.
    Keywords:  3D cell culture; Hydrophobic drug delivery; Mesoporous silica nanoparticles; Nanocomposite hydrogel; Surface modification; Tissue engineering
  10. Reprod Toxicol. 2023 Dec 01. pii: S0890-6238(23)00193-4. [Epub ahead of print] 108519
      The placenta is a unique organ with an active metabolism and dynamically changing physiology throughout pregnancy. It is difficult to elucidate the structure of cell-cell and cell-extracellular matrix interactions of the placenta in in vivo studies due to interspecies differences and ethical constraints. In this study, human umbilical cord vein cells (HUVEC) and human placental choriocarcinoma cells (BeWo) were co-cultured for the first time to form spheroids (microtissues) on a three-dimensional (3D) Petri Dish® mold and compared with a traditional two-dimensional (2D) system. Vortioxetine is an antidepressant with a lack of literature on its use in pregnancy in established cultures, the toxicity of vortioxetine was studied to investigate the response of spheroids representing placental tissue. Spheroids were characterised by morphology and exposed to vortioxetine. Cell viability and barrier integrity were then measured. Intercellular junctions and the localisation of serotonin transporter (SERT) proteins were demonstrated by immunofluorescence (IF) staining in BeWo cells. Human chorionic gonadotropin (beta-hCG) hormone levels were also measured. In the 3D system, cell viability and hormone production were higher than in the 2D system. It was observed that the barrier structure was impaired, the structure of intracellular skeletal elements was altered and SERT expression decreased depending on vortioxetine exposure. These results demonstrate that the multicellular microtissue placenta model can be used to obtain results that more closely resemble in vivo toxicity studies of various xenobiotics than other 2D and mono-culture spheroid models in the literature. It also describes the use of 3D models for soft tissues other than the placenta.
    Keywords:  3D placental model; BeWo cells; HUVEC; spheroid; vortioxetine