3D bioprinted hyaluronic acid‑based cell‑laden scaffold for brain microenvironment simulation

Treatments for lesions in central nervous system(CNS)are always faced with challenges due to the anatomical and physiological particularity of the CNS despite the fact that several achievements have been made in early diagnosis and precision medicine to improve the survival and quality of life of patients with brain tumors in recent years.Understanding the complexity as well as role of the microenvironment of brain tumors may suggest a better revealing of the molecular mechanism of brain tumors and new therapeutic directions,which requires an accurate recapitulation of the complex microenvironment of human brain in vitro.Here,a 3D bioprinted in vitro brain matrix-mimetic microenvironment model with hyaluronic acid(HA)and normal glial cells(HEBs)is developed which simulates both mechanical and biological properties of human brain microenvironment in vivo through the investigation of the formulation of bioinks and optimization of printing process and parameters to study the effects of different concentration of gelatin(GA)within the bioink and different printing structures of the scaffold on the performance of the brain matrix-mimetic microenvironment models.The study provides experimental models for the exploration of the multiple factors in the brain microenvironment and scaffolds for GBM invasion study.

The construction of in vitro tumormodels based on 3D bioprinting

Cancer is characterized by a high fatality rate,complex molecular mechanism,and costly therapies.The microenvironment of a tumor consists of multiple biochemical cues and the interaction between tumor cells,stromal cells,and extracellular matrix plays a key role in tumor initiation,development,angiogenesis,invasion and metastasis.To better understand the biological features of tumor and reveal the critical factors of therapeutic treatments against cancer,it is of great significance to build in vitro tumor models that could recapitulate the stages of tumor progression and mimic tumor behaviors in vivo for efficient and patient-specific drug screening and biological studies.Since conventional tissue engineering methods of constructing tumor models always fail to simulate the later stages of tumor development due to the lack of ability to build complex structures and angiogenesis potential,three-dimensional(3D)bioprinting techniques have gradually found its applications in tumor microenvironment modeling with accurate composition and well-organized spatial distribution of tumor-related cells and extracellular components in the past decades.The capabilities of building tumor models with a large range of scale,complex structures,multiple biomaterials and vascular network with high resolution and throughput make 3D bioprinting become a versatile platform in bio-manufacturing aswell as inmedical research.In this review,wewill focus on 3D bioprinting strategies,design of bioinks,current 3D bioprinted tumor models in vitro classified with their structures and propose future perspectives.

Engineered Vasculature for Organ-on-a-Chip Systems

Organ-on-a-chip technology,a promising three-dimensional(3D)dynamic culture method,ensures accu-rate and efficient cell culture and has great potential for replacing animal models in preclinical testing.The circulatory system,the most abundant organ in the human body,plays a crucial role in oxygen exchange and mass transfer,which is the determining factor for the survival of tissues and organs.Thus,it is essential to integrate the circulatory system into an organ-on-a-chip to recreate tissue and organ microenvironments and physiological functions.This review discusses the synergy between the vasculature and the emerging organ-on-a-chip technology,which offers even better possibilities of dupli-cating physiology and disease characteristics.In addition,we review the different steps of a vascularized organ-on-a-chip fabrication process,including structure fabrication and tissue construction using differ-ent biofabrication strategies.Finally,we outline the applicability of this technology in the fascinating and fast-developing field of organ and tumor culture.

Biofabrication methods for reconstructing extracellular matrix mimetics

In the human body,almost all cells interact with extracellular matrices(ECMs),which have tissue and organ-specific compositions and architectures.These ECMs not only function as cellular scaffolds,providing structural support,but also play a crucial role in dynamically regulating various cellular functions.This comprehensive review delves into the examination of biofabrication strategies used to develop bioactive materials that accurately mimic one or more biophysical and biochemical properties of ECMs.We discuss the potential integration of these ECM-mimics into a range of physiological and pathological in vitro models,enhancing our understanding of cellular behavior and tissue organization.Lastly,we propose future research directions for ECM-mimics in the context of tissue engineering and organ-on-a-chip applications,offering potential advancements in therapeutic approaches and improved patient outcomes.

Enhanced mixing efficiency for a novel 3D Tesla micromixer for Newtonian and non-Newtonian fluids

The fabrication of constructs with gradients for chemical,mechanical,or electrical composition is becoming critical to achieving more complex structures,particularly in 3D printing and biofabrication.This need is underscored by the complexity of in vivo tissues,which exhibit heterogeneous structures comprised of diverse cells and matrices.Drawing inspiration from the classical Tesla valve,our study introduces a new concept of micromixers to address this complexity.The innovative micromixer design is tailored to enhance the re-creation of in vivo tissue structures and demonstrates an advanced capability to efficiently mix both Newtonian and non-Newtonian fluids.Notably,our 3D Tesla valve micromixer achieves higher mixing efficiency with fewer cycles,which represents a significant improvement over the traditional mixing method.This advance is pivotal for the field of 3D printing and bioprinting,and offers a robust tool that could facilitate the development of gradient hydrogel-based constructs that could also accurately mimic the intricate heterogeneity of natural tissues.

Constructing biomimetic liver models through biomaterials and vasculature engineering

The occurrence of various liver diseases can lead to organ failure of the liver,which is one of the leading causes of mortality worldwide.Liver tissue engineering see the potential for replacing liver transplantation and drug toxicity studies facing donor shortages.The basic elements in liver tissue engineering are cells and biomaterials.Both mature hepatocytes and differentiated stem cells can be used as themain source of cells to construct spheroids and organoids,achieving improved cell function.To mimic the extracellular matrix(ECM)environment,biomaterials need to be biocompatible and bioactive,which also help support cell proliferation and differentiation and allow ECM deposition and vascularized structures formation.In addition,advancedmanufacturing approaches are required to construct the extracellular microenvironment,and it has been proved that the structured three-dimensional culture system can help to improve the activity of hepatocytes and the characterization of specific proteins.In summary,we review biomaterials for liver tissue engineering,including natural hydrogels and synthetic polymers,and advanced processing techniques for building vascularized microenvironments,including bioassembly,bioprinting and microfluidic methods.We then summarize the application fields including transplant and regeneration,disease models and drug cytotoxicity analysis.In the end,we put the challenges and prospects of vascularized liver tissue engineering.