The needs for high-resolution, well-defined and complex 3D microstructures in diverse fields call for the rapid development of novel 3D microfabrication techniques. Among those, two-photon polymerization (TPP) attracted extensive attention owing to its unique and useful characteristics. As an approach to implementing additive manufacturing, TPP has truly 3D writing ability to fabricate artificially designed constructs with arbitrary geometry. The spatial resolution of the manufactured structures via TPP can exceed the diffraction limit. The 3D structures fabricated by TPP could properly mimic the microenvironment of natural extracellular matrix, providing powerful tools for the study of cell behavior. TPP can meet the requirements of manufacturing technique for 3D scaffolds (engineering cell culture matrices) used in cytobiology, tissue engineering and regenerative medicine. In this review, we demonstrated the development in 3D microfabrication techniques and we presented an overview of the applications of TPP as an advanced manufacturing technique in complex 3D biomedical scaffolds fabrication. Given this multidisciplinary field, we discussed the perspectives of physics, materials science, chemistry, biomedicine and mechanical engineering. Additionally, we dived into the principles of tow-photon absorption (TPA) and TPP, requirements of 3D biomedical scaffolders, developed-to-date materials and chemical approaches used by TPP and manufacturing strategies based on mechanical engineering. In the end, we draw out the limitations of TPP on 3D manufacturing for now along with some prospects of its future outlook towards the fabrication of 3D biomedical scaffolds.

Objective: Two-photon polymerization (TPP) utilizes an optical nonlinear absorption process to initiate the polymerization of photopolymerizable materials. To date, it is the only technique capable of fabricating complex 3D microstructures with finely adjusted geometry on the cell and sub-cell scales. TPP shows a very promising potential in biomedical applications related to high-resolution features, including drug delivery, tissue engineering, microfluidic devices, and so forth. Therefore, it is of high significance to grasp the global scientific achievements in this field. An analysis of publications concerning the applications of TPP in the biomedical field was performed, and the knowledge domain, research hotspots, frontiers, and research directions in this topic were identified according to the research results.Methods: The publications concerning TPP applications in biomedical field were retrieved from WoSCC between 2003 and 2022, Bibliometrics and visual analysis employing CiteSpace software and R-language package Bibliometrix were performed in this study.Results: A total of 415 publications regarding the TPP applications in the biomedical field were retrieved from WoSCC, including 377 articles, and 38 review articles. The studies pertaining to the biomedical applications of TPP began back in 2003 and showed an upward trend constantly. Especially in the recent 5 years, studies of TPP in biomedical field have increased rapidly, with the number of publications from 2017 to 2021 accounting for 52.29% of the total. In terms of output, China was the leading country and Chinese Acad Sci, Tech Inst Phys and Chem was the leading institution. The United States showed the closest cooperation with other countries. ACS applied materials and interfaces was the most prolific journal (n = 13), followed by Biofabrication (n = 11) and Optics express (n = 10). The journals having the top cited papers were Biomaterials, Advanced materials, and Applied physic letters. The most productive author was Aleksandr Ovsianikov (27 articles). Meanwhile, researchers who had close cooperation with other researchers were also prolific authors. “cell behavior”, " (tissue engineering) scaffolds”, “biomaterials,” and “hydrogel” were the main co-occurrence keywords and “additional manufacturing”, “3D printing,” and “microstructures” were the recent burst keywords. The Keyword clusters, “stem cells,” and “mucosal delivery”, appeared recently. A paper reporting unprecedented high-resolution bull models fabricated by TPP was the most locally cited reference (cited 60 times). “Magnetic actuation” and “additive manufacturing” were recently co-cited reference clusters and an article concerning ultracompact compound lens systems manufactured by TPP was the latest burst reference.Conclusion: The applications of TPP in biomedical field is an interdisciplinary research topic and the development of this field requires the active collaboration of researchers and experts from all relevant disciplines. Bringing up a better utilization of TPP as an additive manufacturing technology to better serve the biomedical development has always been the research focus in this field. Research on stem cells behaviors and mucosal delivery based on microstructures fabricated using TPP were becoming new hotspots. And it can be predicted that using TPP as a sourcing technique to fabricate biomedical-related structures and devices is a new research direction. In addition, the research of functional polymers, such as magnetic-driven polymers, was the frontier topic of TPP biomedical applications.

Background: Nanocomposite Hydrogels (NHs) are 3D molecular networks formed by physically or covalently crosslinking polymer with nanoparticles or nanostructures, which are particularly suitable for serving as carriers for drug delivery systems. Many articles pertaining to the applications of Nanocomposite Hydrogels for drug delivery have been published, however, the use of bibliometric and visualized analysis in this area remains unstudied. The purpose of this bibliometric study intended to comprehensively analyze the knowledge domain, research hotspots and frontiers associated with the applications of Nanocomposite Hydrogels for drug delivery.Methods: We identified and retrieved the publications concerning the applications of NHs for drug delivery between 2003 and 2022 from Web of Science Core Collection Bibliometric and visualized analysis was utilized in this investigative study.Results: 631 articles meeting the inclusion criteria were identified and retrieved from WoSCC. Among those, 2,233 authors worldwide contributed in the studies, accompanied by an average annual article increase of 24.67%. The articles were co-authored by 764 institutions from 52 countries/regions, and China published the most, followed by Iran and the United States. Five institutions published more than 40 papers, namely Univ Tabriz (n = 79), Tabriz Univ Med Sci (n = 70), Islamic Azad Univ (n = 49), Payame Noor Univ (n = 42) and Texas A&M Univ (n = 41). The articles were published in 198 journals, among which the International Journal of Biological Macromolecules (n = 53) published the most articles, followed by Carbohydrate Polymers (n = 24) and ACS Applied Materials and Interfaces (n = 22). The top three journals most locally cited were Carbohydrate Polymers, Biomaterials and Advanced materials. The most productive author was Namazi H (29 articles), followed by Bardajee G (15 articles) and Zhang J (11 articles) and the researchers who worked closely with other ones usually published more papers. “Doxorubicin,” “antibacterial” and “responsive hydrogels” represent the current research hotspots in this field and “cancer therapy” was a rising research topic in recent years. “(cancer) therapeutics” and “bioadhesive” represent the current research frontiers.Conclusion: This bibliometric and visualized analysis offered an investigative study and comprehensive understanding of publications regarding the applications of Nanocomposite Hydrogels for drug delivery from 2003 to 2022. The outcome of this study would provide insights for researchers in the field of Nanocomposite Hydrogels applications for drug delivery.

Objective: The aim of tissue engineering (TE) is to replace the damaged tissues or failed organs, or restore their missing functions. The important means to achieve this aim is to integrate biomaterials and life elements. Hydrogels are very attractive biomaterials in the field of TE. In particular, engineering extracellular matrices (ECMs) formed by photosensitive hydrogels have captivated much attention, because photopolymerization has many advantages over traditional polymerization approaches, such as rapidity of reaction, spatiotemporal controllability of polymerization process, and operability at physiological temperature, especially it can realize the fabrications of engineering ECMs in the presence of living cells. There have been many excellent reviews on the applications of photosensitive hydrogels in TE in recent years, however, it is inevitable that researchers may have left out many important facts due to exploring the literature from one or a few aspects. It is also a great challenge for researchers to explore the internal relationships among countries, institutions, authors, and references from a large number of literatures in related fields. Therefore, bibliometrics may be a powerful tool to solve the above problems. A bibliometric and visualized analysis of publications concerning the photosensitive hydrogels for TE applications was performed, and the knowledge domain, research hotspots and frontiers in this topic were identified according to the analysis results.Methods: We identified and retrieved the publications regarding the photosensitive hydrogels for TE applications between 1996 and 2022 from Web of Science Core Collection (WoSCC). Bibliometric and visualized analysis employing CiteSpace software and R-language package Bibliometrix were performed in this study.Results: 778 publications meeting the eligibility criteria were identified and retrieved from WoSCC. Among those, 2844 authors worldwide participated in the studies in this field, accompanied by an average annual article growth rate of 15.35%. The articles were co-authored by 800 institutions from 46 countries/regions, and the United States published the most, followed by China and South Korea. As the two countries that published the most papers, the United States and China could further strengthen cooperation in this field. Univ Colorado published the most articles (n = 150), accounting for 19.28% of the total. The articles were distributed in 112 journals, among which Biomaterials (n = 66) published the most articles, followed by Acta Biomaterialia (n = 54) and Journal of Biomedical Materials Research Part A (n = 42). The top 10 journals published 47.8% of the 778 articles. The most prolific author was Anseth K (n = 33), followed by Khademhosseini A (n = 29) and Bryant S (n = 22). A total of 1443 keywords were extracted from the 778 articles and the keyword with the highest centrality was “extracellular matrix” (centrality: 0.12). The keywords appeared recently with strong citation bursts were “gelatin”, “3d printing” and “3d bioprinting”, representing the current research hotspots in this field. “Gelma”, “3d printing” and “thiol-ene” were the research frontiers in recent years.Conclusion: This bibliometric and visualized study offered a comprehensive understanding of publications regarding the photosensitive hydrogels for TE applications from 1996 to 2022, including the knowledge domain, research hotspots and frontiers in this filed. The outcome of this study would provide insights for scholars in the related research filed.