The intestine is a key component of the barrier, absorption, and immune systems, contributing significantly to maintaining internal homeostasis and influencing disease progression. Its distinctive physiological functions arise from a complex interplay between its structure and microenvironment. Recent advancements in bioengineering technologies now enable the construction of in vitro intestinal models that faithfully recapitulate the organizational and functional characteristics of native tissue. This review examines the interface between in vitro models and native intestinal biology, offering insights into the replication of organ functions from a manufacturing perspective. We explore bioengineering strategies that enable the mapping of cross-scale structures and the creation of biomimetic environments essential for physiological performance. Furthermore, we discuss pragmatic optimization strategies for applying these models to both physiological and pathological studies, thereby enhancing their translational potential for drug development, disease modeling, and personalized medicine. In contrast to previous reviews, this work proposes an engineering-centered framework for linking structural fabrication strategies to functional performance across intestinal model types.(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).

Oral administration is the most simple, noninvasive, convenient treatment. With the increasing demands on the targeted drug delivery, the traditional oral treatment now is facing some challenges: 1) biologics how to implement the oral treatment and ensure the bioavailability is not lower than the subcutaneous injections; 2) How to achieve targeted therapy of some drugs in the gastrointestinal tract? Based on these two issues, drug delivery microrobots have shown great application prospect in oral drug delivery due to their characteristics of flexible locomotion or driven ability. Therefore, this paper summarizes various drug delivery microrobots developed in recent years and divides them into four categories according to different driving modes: magneticcontrolled drug delivery microrobots, anchored drug delivery microrobots, self-propelled drug delivery microrobots and biohybrid drug delivery microrobots. As oral drug delivery microrobots involve disciplines such as materials science, mechanical engineering, medicine, and control systems, this paper begins by introducing the gastrointestinal barriers that oral drug delivery must overcome. Subsequently, it provides an overview of typical materials involved in the design process of oral drug delivery microrobots. To enhance readers' understanding of the working principles and design process of oral drug delivery microrobots, we present a guideline for designing such microrobots. Furthermore, the current development status of various types of oral drug delivery microrobots is reviewed, summarizing their respective advantages and limitations. Finally, considering the significant concerns regarding safety and clinical translation, we discuss the challenges and prospections of clinical translation for various oral drug delivery microrobots presented in this paper, providing corresponding suggestions for addressing some existing challenges.

A vast amount of knowledge has been acquired through human activities such as farming, hunting, and fishing. Throughout history, humans have utilized living creatures for disease treatment, relying on the natural world's healing powers. The special "healers" may be able to treat patients via the power of nature. However, there was no systematic introduction or summary of these treatments. Therefore, we conducted a literature review based on PubMed, Google Scholar, Web of Science, Scopus, CNKI and WanFang DATA. Here, we defined this unique method as "animal healer" and six common kinds of animal healers were reviewed. These are fish therapy, pet therapy, worm therapy, leech therapy, maggot therapy, and bee therapy. According to the different characteristics of healers, treatment methods mainly included bite, parasitism, contact and communication. With the advantages of green and effectiveness, animal healers have great therapy potential against a variety of refractory diseases. The main purpose of this review is to draw people's attention to animal healer, promote it to become a possible clinical treatment strategy, and make further exploration in species cultivation, mechanism research, animal welfare, standard setting, safety evaluation and other aspects. In the future, animal healers will play an increasingly important role in medicine and hopefully solve more medical problems and dilemmas.

Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult, greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.Module assembly approaches for 3D vascularized organotypic tissues are summarized.Key issues for engineering organotypic tissue through various techniques are addressed.Module assembly offers advantages such as high cell density and advanced function.

In the human body, almost all cells interact with extracellular matrices (ECMs), which have tissue and organspecific 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 ECMmimics in the context of tissue engineering and organ-on-a-chip applications, offering potential advancements in therapeutic approaches and improved patient outcomes.

Recent advances in tumor microenvironment (TME) modeling as well as its applications to cancer therapy has brought various dramatical changes in multiple malignancies management. Understanding the mechanisms of response and resistance to cancer therapy requires a clear elucidation of the intricate interactions between TME cells, the surrounding stroma, and distant affected tissues or organs. To address this demand, various three-dimensional (3D) cell culture techniques have been developed in order to recapitulate and understand cancer biology over the past decade. This review summarizes some saliant progresses in in vitro 3D TME modeling, including the cell-based, matrix-based, and vessel-based dynamic 3D modeling techniques and their applications in investigating tumor-stroma interactions and responses to cancer therapies. The review also discusses the limitations of current TME modeling approaches and proposes some new thoughts on the construction of more clinically relevant models.

This Review describes recent advances in the field of 3D in vitro modelling technologies that enable a better understanding of immune cell and tumour cell interactions in the tumour microenvironment. The authors explain how such systems can be used to assess the efficacy of novel immunotherapies, including personalized immunotherapies, for patients with cancer.In vitro 3D models are advanced biological tools that have been established to overcome the shortcomings of oversimplified 2D cultures and mouse models. Various in vitro 3D immuno-oncology models have been developed to mimic and recapitulate the cancer-immunity cycle, evaluate immunotherapy regimens, and explore options for optimizing current immunotherapies, including for individual patient tumours. Here, we review recent developments in this field. We focus, first, on the limitations of existing immunotherapies for solid tumours, secondly, on how in vitro 3D immuno-oncology models are established using various technologies - including scaffolds, organoids, microfluidics and 3D bioprinting - and thirdly, on the applications of these 3D models for comprehending the cancer-immunity cycle as well as for assessing and improving immunotherapies for solid tumours.

Autograft replaced by a nerve guidance conduit (NGC) is challenging in peripheral nerve injury because current NGC is still limited by precise conductivity and excellent biocompatibility in vivo, which influences the peripheral nerve repair even for a long lesion gap repair. Several particular elements have the potential function for nerve conductivity acceleration based on the traditional three factors of neural tissue engineering. The review aims to address three questions: 1) What is the superior factor for nerve conduction in the application? 2) How can a more conductive regenerative scaffold be constructed in vivo? 3) What is the next step in nerve regeneration for NGC? The bibliometrics analysis of NGC-related references is adopted to acquire that the conductive material, manufacturing technology of neural scaffold, and electrical stimulation (ES) play essential roles in the acceleration of nerve conduction. This review visually analyses the research status and summarizes the main types of conductive materials, the manufacturing technologies of neural scaffolds, and the characteristics of ES. The viewpoints and outlook of developing NGC are also discussed in this review. The proposed three elements are expected to improve the nerve conduction of NGC in vivo and even address the dilemma of long-distance peripheral nerve injury.