Regenerative Engineering and Translational Medicine最新文献

Purpose: Mesenchymal stem cells (MSCs) represent a promising source for stem cell therapies in numerous diseases, including pediatric respiratory system diseases. Characterized by low immunogenicity, high anti-inflammatory, and immunoregulatory features, MSCs demonstrated an excellent therapeutic profile in numerous in vitro and preclinical models. MSCs reside in a specialized physiologic microenvironment, characterized by a unique combination of biophysical, biochemical, and cellular properties. The exploitation of the 3D micro-scaffold Nichoid, which simulates the native niche, enhanced the anti-inflammatory potential of stem cells through mechanical stimulation only, overcoming the limitation of biochemical and xenogenic growth factors application.

Materials and methods: In this work, we expanded pediatric bone marrow MSCs (BM-MSCs) inside the Nichoid and performed a complete cellular characterization with different approaches including viability assays, immunofluorescence analyses, RNA sequencing, and gene expression analysis.

Results: We demonstrated that BM-MSCs inside the scaffold remain in a stem cell quiescent state mimicking the condition of the in vivo environment. Moreover, the gene expression profile of these cells shows a significant up-regulation of genes involved in immune response when compared with the flat control.

Conclusion: The significant changes in the expression profile of anti-inflammatory genes could potentiate the therapeutic effect of BM-MSCs, encouraging the possible clinical translation for the treatment of pediatric congenital and acquired pulmonary disorders, including post-COVID lung manifestations.

Lay summary: Regenerative medicine is the research field integrating medicine, biology, and biomedical engineering. In this context, stem cells, which are a fundamental cell source able to regenerate tissues and restore damage in the body, are the key component for a regenerative therapeutic approach. When expanded outside the body, stem cells tend to differentiate spontaneously and lose regenerative potential due to external stimuli. For this reason, we exploit the scaffold named Nichoid, which mimics the in vivo cell niche architecture. In this scaffold, mesenchymal stem cells "feel at home" due to the three-dimensional mechanical stimuli, and our findings could be considered as an innovative culture system for the in vitro expansion of stem cells for clinical translation.

Future perspective: The increasing demand of safe and effective cell therapies projects our findings toward the possibility of improving cell therapies based on the use of BM-MSCs, particularly for their clinical translation in lung diseases.

Graphical abstract:

Purpose: Key natural polymers, known as hydrogels, are an important group of materials in design of tissue-engineered constructs that can provide suitable habitat for cell attachment and proliferation. However, in comparison to tissues within the body, these hydrogels display poor mechanical properties. Such properties cause challenges in 3D printing of hydrogel scaffolds as well as their surgical handling after fabrication. For this reason, the purpose of this study is to critically review the 3D printing processes of hydrogels and their characteristics for tissue engineering application.

Methods: A search of Google Scholar and PubMed has been performed from 2003 to February 2022 using a combination of keywords. A review of the types of 3D printing is presented. Additionally, different types of hydrogels and nano-biocomposite materials for 3D printing application are critically reviewed. The rheological properties and crosslinking mechanisms for the hydrogels are assessed.

Results: Extrusion-based 3D printing is the most common practice for constructing hydrogel-based scaffolds, and it allows for the use of varying types of polymers to enhance the properties and printability of the hydrogel-based scaffolds. Rheology has been found to be exceedingly important in the 3D printing process; however, shear-thinning and thixotropic characteristics should also be present in the hydrogel. Despite these features of extrusion-based 3D printing, there are limitations to its printing resolution and scale.

Conclusion: Combining natural and synthetic polymers and a variety of nanomaterials, such as metal, metal oxide, non-metal, and polymeric, can enhance the properties of hydrogel and provide additional functionality to their 3D-printed constructs.

Purpose: Organoids are three-dimensional cultures of stem cells in an environment similar to the body's extracellular matrix. This is also a novel development in the realm of regenerative medicine. Stem cells can begin to develop into 3D structures by modifying signaling pathways. To form organoids, stem cells are transplanted into the extracellular matrix. Organoids have provided the required technologies to reproduce human tissues. As a result, it might be used in place of animal models in scientific study. The key goals of these investigations are research into viral and genetic illnesses, malignancies, and extracellular vesicles, pharmaceutical discovery, and organ transplantation. Organoids can help pave the road for precision medicine through genetic editing, pharmaceutical development, and cell therapy.

Methods: PubMed, Google Scholar, and Scopus were used to search for all relevant papers written in English (1907-2021). The study abstracts were scrutinized. Studies on the use of stem-cell-derived organoids in regenerative medicine, organoids as 3D culture models for EVs analysis, and organoids for precision medicine were included. Articles with other irrelevant aims, meetings, letters, commentaries, congress and conference abstracts, and articles with no available full texts were excluded.

Results: According to the included studies, organoids have various origins, types, and applications in regenerative and precision medicine, as well as an important role in studying extracellular vesicles.

Conclusion: Organoids are considered a bridge that connects preclinical studies to clinical ones. However, the lack of a standardized protocol and other barriers addressed in this review, hinder the vast use of this technology.

Lay summary: Organoids are 3D stem cell propagations in biological or synthetic scaffolds that mimic ECM to allow intercellular or matrix-cellular crosstalk. Because these structures are similar to organs in the body, they can be used as research models. Organoids are medicine's future hope for organ transplantation, tumor biobank formation, and the development of precision medicine. Organoid models can be used to study cell-to-cell interactions as well as effective factors like inflammation and aging. Bioengineering technologies are also used to define the size, shape, and composition of organoids before transforming them into precise structures. Finally, the importance of organoid applications in regenerative medicine has opened a new window for a better understanding of biological research, as discussed in this study.

Abstract: The immune system plays a crucial role during tissue repair and wound healing processes. Biomaterials have been leveraged to assist in this in situ tissue regeneration process to dampen the foreign body response by evading or suppressing the immune system. An emerging paradigm within regenerative medicine is to use biomaterials to influence the immune system and create a pro-reparative microenvironment to instigate endogenously driven tissue repair. In this review, we discuss recent studies that focus on immunomodulation of innate and adaptive immune cells for tissue engineering applications through four biomaterial-based mechanisms of action: biophysical cues, chemical modifications, drug delivery, and sequestration. These materials enable augmented regeneration in various contexts, including vascularization, bone repair, wound healing, and autoimmune regulation. While further understanding of immune-material interactions is needed to design the next generation of immunomodulatory biomaterials, these materials have already demonstrated great promise for regenerative medicine.

Lay summary: The immune system plays an important role in tissue repair. Many biomaterial strategies have been used to promote tissue repair, and recent work in this area has looked into the possibility of doing repair by tuning. Thus, we examined the literature for recent works showcasing the efficacy of these approaches in animal models of injuries. In these studies, we found that biomaterials successfully tuned the immune response and improved the repair of various tissues. This highlights the promise of immune-modulating material strategies to improve tissue repair.