The extracellular matrix (ECM) of soft tissues in vivo has remarkable biological and structural properties. Thereby, the ECM provides mechanical stability while it still can be rearranged via cellular remodeling during tissue maturation or healing processes. However, modern synthetic alternatives fail to provide these key features among basic properties. Synthetic matrices are usually completely degraded or are inert regarding cellular remodeling. Based on a refined electrospinning process, a method is developed to generate synthetic scaffolds with highly porous fibrous structures and enhanced fiber‐to‐fiber distances. Since this approach allows for cell migration, matrix remodeling, and ECM synthesis, the scaffold provides an ideal platform for the generation of soft tissue equivalents. Using this matrix, an electrospun‐based multilayered skin equivalent composed of a stratified epidermis, a dermal compartment, and a subcutis is able to be generated without the use of animal matrix components. The extension of classical dense electrospun scaffolds with high porosities and motile fibers generates a fully synthetic and defined alternative to collagen‐gel‐based tissue models and is a promising system for the construction of tissue equivalents as in vitro models or in vivo implants.

The aim of the review was to map the current landscape of dental stem cell manufacturing practice and biobanking for clinical use and to identify variable factors that may hinder clinical translation and standardization of dental stem cell-based therapy. An electronic search was performed using Medline/PubMed, Web of Science, and Scopus, using "Dental stem cells" and "Dental pulp stem cells" as keywords. In addition, ClinicalTrials.gov was used to identify clinical trials of dental stem cells for therapeutic purposes. Relevant articles and bibliographic references from the reviewed studies were used to develop the narrative review. The initial search yielded 48 records from PubMed, 66 from Scopus, 33 from Web of Science, and 23 registered trials from ClinicalTrials.gov. In total, 23 registered trials were identified, of which 14 involved the therapeutic use of dental stem cells in clinical settings. For reviewing the current practices of dental stem cell manufacturing for clinical use, 20 studies were selected for an in-depth full-text analysis, among which fifteen and five articles addressed the ex-vivo expanding cells and chair-side preparation of micrograft containing dental stem cells, respectively. Although dental stem cells have been applied in clinical settings for regenerative therapies, cell manufacturing practices have varied widely across reported cases, reflecting a lack of standardization. Furthermore, dental-specific challenges-such as logistical constraints and the complex involvement of multiple stakeholders-hinder compliance with stringent regulatory requirements, contributing to slower clinical translation compared to somatic-cell therapy medicine in other fields. This highlights a need for global collaboration among academia, industry, clinicians, and regulators to establish standardized practice, enhance predictability, and ensure long-term traceability. Dental stem cells have been used in clinical settings, with private practitioners playing a leading role in translating them into regenerative therapies in dentistry. This trend is expected to accelerate, driven by the growing number of enterprises entering the global dental stem cell biobanking market. Currently, cell manufacturing protocols vary widely across organizations with intricated regulatory framework applied. Furthermore, uncertainties remain regarding the use of long-term cryopreserved dental stem cells and the regulatory interpretation of such products.

Bioprinting provides a powerful tool for regenerative medicine, as it allows tissue construction with a patient’s specific geometry. However, tissue culture and maturation, commonly supported by dynamic bioreactors, are needed. We designed a workflow that creates an implant-specific bioreactor system, which is easily producible and customizable and supports cell cultivation and tissue maturation. First, a bioreactor was designed and different tissue geometries were simulated regarding shear stress and nutrient distribution to match cell culture requirements. These tissues were then directly bioprinted into the 3D-printed bioreactor. To prove the ability of cell maintenance, C2C12 cells in two bioinks were printed into the system and successfully cultured for two weeks. Next, human mesenchymal stem cells (hMSCs) were successfully differentiated toward an adipocyte lineage. As the last step of the presented strategy, we developed a prototype of an automated mobile docking station for the bioreactor. Overall, we present an open-source bioreactor system that is adaptable to a wound-specific geometry and allows cell culture and differentiation. This interdisciplinary roadmap is intended to close the gap between the lab and clinic and to integrate novel 3D-printing technologies for regenerative medicine.

The Food and Drug Administration's recent decision to eliminate mandatory animal testing for drug approval marks a significant shift to alternative methods. Similarly, the European Parliament is advocating for a faster transition, reflecting public preference for animal‐free research practices. In vitro tissue models are increasingly recognized as valuable tools for regulatory assessments before clinical trials, in line with the 3R principles (Replace, Reduce, Refine). Despite their potential, barriers such as the need for standardization, availability, and cost hinder their widespread adoption. To address these challenges, the Robotic Enabled Biological Automation (ReBiA) system is developed. This system uses a dual‐arm robot capable of standardizing laboratory processes within a closed automated environment, translating manual processes into automated ones. This reduces the need for process‐specific developments, making in vitro tissue models more consistent and cost‐effective. ReBiA's performance is demonstrated through producing human reconstructed epidermis, human airway epithelial models, and human intestinal organoids. Analyses confirm that these models match the morphology and protein expression of manually prepared and native tissues, with similar cell viability. These successes highlight ReBiA's potential to lower barriers to broader adoption of in vitro tissue models, supporting a shift toward more ethical and advanced research methods.

Onchocerciasis also known as river blindness is a neglected tropical disease and the world's second-leading infectious cause of blindness in humans; it is caused by Onchocerca volvulus. Current treatment with ivermectin targets microfilariae and transmission and does not kill the adult parasites, which reside within subcutaneous nodules. To support the development of macrofilaricidal drugs that target the adult worm to further support the elimination of onchocerciasis, an in-depth understanding of O. volvulus biology especially the factors that support the longevity of these worms in the human host (>10 years) is required. However, research is hampered by a lack of access to adult worms. O. volvulus is an obligatory human parasite and no small animal models that can propagate this parasite were successfully developed. The current optimized 2-dimensional (2-D) in vitro culturing method starting with O. volvulus infective larvae does not yet support the development of mature adult worms. To overcome these limitations, we have developed and applied 3-dimensional (3-D) culture systems with O. volvulus larvae that simulate the human in vivo niche using in vitro engineered skin and adipose tissue. Our proof of concept studies have shown that an optimized indirect co-culture of in vitro skin tissue supported a significant increase in growth of the fourth-stage larvae to the pre-adult stage with a median length of 816–831 μm as compared to 767 μm of 2-D cultured larvae. Notably, when larvae were co-cultured directly with adipose tissue models, a significant improvement for larval motility and thus fitness was observed; 95% compared to 26% in the 2-D system. These promising co-culture concepts are a first step to further optimize the culturing conditions and improve the long-term development of adult worms in vitro. Ultimately, it could provide the filarial research community with a valuable source of O. volvulus worms at various developmental stages, which may accelerate innovative unsolved biomedical inquiries into the parasite’s biology.