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Current clinical approaches to treat articular cartilage degeneration provide only a limited ability to regenerate tissue with long-term durability and functionality. In this application, injectable bulk hydrogels and microgels containing stem cells can provide a suitable environment for tissue regeneration. However insufficient cell–cell interactions, low differentiation efficiency and poor tissue adhesion hinder the formation of high-quality hyaline type cartilage. Here, we have designed a higher order tissue-like structure using injectable cell-laden microgels as the building blocks to achieve human bone marrow-derived mesenchymal stem cell (hBMSC) long-term maintenance and chondrogenesis. We have demonstrated that a 4-arm poly(ethylene glycol)- N -hydroxysuccinimide (NHS) crosslinker induces covalent bonding between the microgel building blocks as well as the surrounding tissue mimic. The crosslinking process assembles the microgels into a 3D construct and preserves the viability and cellular functions of the encapsulated hBMSCs. This assembled microgel construct encourages upregulation of chondrogenic markers in both gene and glycosaminoglycan (GAG) expression levels. In addition, the regenerated tissue in the assembled microgels stained positively with Alcian blue and Safranin O exhibiting unique hyaline-like cartilage features. Furthermore, the immunostaining showed a favourable distribution and significantly higher content of type II collagen in the assembled microgels when compared to both the bulk hydrogel and pellet cultures. Collectively, this tissue adhesive hBMSC-laden microgel construct provides potential clinical opportunities for articular cartilage repair and other applications in regenerative medicine. Statement of Significance A reliable approach to reconstruct durable and fully functional articular cartilage tissue is required for effective clinical therapies. Here, injectable hydrogels together with cell-based therapies offer new treatment strategies in cartilage repair. For effective cartilage regeneration, the injectable hydrogel system needs to be bonded to the surrounding tissue and at the same time needs to be sufficiently stable for prolonged chondrogenesis. In this work, we utilised injectable hBMSC-laden microgels as the building blocks to create an assembled construct via N -hydroxysuccinimide-amine coupling. This crosslinking process also allows for rapid bonding between the assembled microgels and a surrounding tissue mimic. The resultant assembled microgel-construct provides both a physically stable and biologically dynamic environment for hBMSC chondrogenesis, leading to the production of a mature hyaline type cartilage structure. [ABSTRACT FROM AUTHOR]

The 2030 and 2050 targets for lifetime requirements of proton exchange membrane (PEM) fuel cell (FC) systems in heavy-duty vehicle (HDV) applications are set to 25,000 h and 30,000 h, respectively. The need to reduce PEM fuel cell system (FCS) costs is expected to be accompanied by greater uncertainty in lifetime. This will require robust and reliable approaches and algorithms for feature extraction, condition assessment and lifetime prediction to obtain the Remaining Useful Life (RUL) and to prevent premature failure, downtime and lower system availability leading to higher total cost of ownership (TCO). Current approaches to feature extraction and component-based condition assessment typically focus on in/ex situ measurement methods performed on test benches, rather than operando measurement methods that can be performed on-board commercial vehicles. Methods developed on test benches are often difficult or even impossible to transfer to commercial vehicle applications. As a result, the lifetime prediction in commercial vehicle applications often focuses on data-driven approaches to predict voltage or power decay. Since these data-driven approaches do not contain sufficient information about the component-based State of Health (SoH), a component-based lifetime prediction and subsequent optimization of operating strategy to control RUL and meet the lifetime requirements is significantly limited. Prescriptive Lifetime Management is a technique that involves developing and implementing on-board strategies and algorithms for feature extraction, condition assessment and lifetime prediction to mitigate degradation, extend the RUL and reduce the overall TCO, e.g., of the PEM fuel cell system through global optimization-based post-prognostic decision-making. With this in mind, this paper presents approaches for on-board operando feature extraction and condition assessment of the PEM integrity and the electrochemical surface area (ECSA). The calibration of macroscopic degradation models allows for lifetime prediction and RUL control to meet the lifetime requirements of PEM fuel cells. The results show that the operating parameters have a high effect on PEM fuel cell degradation. The complexity of degradation prevents the generation of reliable degradation lookup tables. Therefore, the direct implementation of calibratable macroscopic degradation models in the Prescriptive Lifetime Management framework is recommended. [Display omitted] • Feature extraction based on vehicle-based measurement equipment. • On-board condition assessment based on extracted features. • Condition-based calibration of macroscopic degradation model parameters. • Analysis of uncertainty in parameter calibration and hybrid lifetime prediction. • Investigation of the effects of operating parameter combinations on Remaining Useful Life. [ABSTRACT FROM AUTHOR]

Proton exchange membrane (PEM) fuel cells represent a promising solution for a sustainable hydrogen-based mobility. Due to remaining challenges regarding costs and durability of PEM fuel cell systems, market activation programs as a precursor to market introduction are still required to accelerate the broad commercialization of PEM fuel cell systems in transportation applications. The recent shift by some original equipment manufacturers (OEMs) from passenger car (PC) and light-duty vehicle (LDV) applications to heavy-duty vehicle (HDV) applications is accompanied by higher lifetime and system power requirements that necessitate modified design and development approaches. Design-based approaches to increase the lifetime of PEM fuel cells usually concentrate on the use of advanced materials and the design of durable fuel cell stacks. Operation-based approaches aim to mitigate degradation through the development of advanced control strategies. However, the initial design of a PEM fuel cell system as well as the calibration of its control strategy to achieve a long service life is inevitably associated with a high degree of uncertainty. In addition, often challenging time-to-market specifications result in insufficient time for extensive durability testing, necessitating the use of accelerated stress tests (AST). Results of ASTs usually deviate to a greater or lesser extent from realistic driving conditions and exacerbate the issue of uncertainty regarding durability in field operation. Therefore, the coordinated development and deployment of on-board strategies for condition assessment, lifetime prediction and degradation mitigation are of huge importance to meet the high lifetime requirements in HDV applications. With this in mind, this paper presents an on-board Prescriptive Lifetime Management system that enables optimization-based post-prognostic decision-making to extend the service life of PEM fuel cell systems while considering the need to maximize system performance and efficiency. Based on the current state of the art, the requirements of the Prescriptive Lifetime Management are defined and its conceptual design as well as modeling and simulation framework are described. [Display omitted] • Concept for Prescriptive Lifetime Management is developed. • Innovative post-prognostic decision-making based on calibratable degradation models. • Global optimization-based post-prognostic decision-making framework is presented. • Prescriptive Lifetime Management is assumed to increase Remaining Useful Life. [ABSTRACT FROM AUTHOR]