Electrospinning with polymer melts - state of the art and future perspectives

It is broadly valued by the biomaterials community that electrospinning from both the solution and melt is a technologically attractive method to process polymeric and composite materials; yet the number of publications reported in the current scientific literature regards the two methods has an estimated ratio of 1 to 400. Among the many reasons for the currently limited research output in melt electrospinning (MES) is that the fabrication of a well-designed melt-based electrospinning devices is technologically and scientifically more challenging than assembling a laboratory-scaled bench top solution electrospinning (SES) machine. Interestingly, the traditional polymer science-rooted MES community has for the most part published studies using micron-diameter fibers; however, the biomaterials community prefers scaffold-processing technologies that allow the fabrication of submicron architectures. From a manufacturing point of view and compared to other fiber forming processes, less operational volatility is induced, as MES is a solvent-free process. Additionally to this key aspect and from a users’ safety perspective, no further concerns exist in regards to toxicity. If controlled appropriately, the charged polymer jet, which is formed during MES can be accurately directed to the collector without instabilities. Through the application of MES in a direct writing mode, i.e., the implementation of moving stages in two dimensions (X and Y), the resulting process can be considered as a new class of three-dimensional (3D) printing. This article reviews MES research from a polymer processing and machine design point of view. It concludes postulating that the emergence of the progressive, innovative, and creative MES technology will increasingly supersede the conventionally used SES until it becomes successfully established within the biomaterials community

Melt electrospinning writing of three-dimensional poly(epsilon-caprolactone) scaffolds with controllable morphologies for tissue engineering applications

This tutorial reflects on the fundamental principles and guidelines for electrospinning writing with polymer melts, an additive manufacturing technology with great potential for biomedical applications. The technique facilitates the direct deposition of biocompatible polymer fibers to fabricate well-ordered scaffolds in the sub-micron to micro scale range. The establishment of a stable, viscoelastic, polymer jet between a spinneret and a collector is achieved using an applied voltage and can be direct-written. A significant benefit of a typical porous scaffold is a high surface-to-volume ratio which provides increased effective adhesion sites for cell attachment and growth. Controlling the printing process by fine-tuning the system parameters enables high reproducibility in the quality of the printed scaffolds. It also provides a flexible manufacturing platform for users to tailor the morphological structures of the scaffolds to their specific requirements. For this purpose, we present a protocol to obtain different fiber diameters using melt electrospinning writing (MEW) with a guided amendment of the parameters, including flow rate, voltage and collection speed. Furthermore, we demonstrate how to optimize the jet, discuss often experienced technical challenges, explain troubleshooting techniques and showcase a wide range of printable scaffold architectures

Complications associated using the reamer–irrigator –aspirator (RIA) system : a systematic review and meta-analysis

Introduction: Complications associated with the application of the Reamer–irrigator–Aspirator (RIA) system are described in the literature. However, to date a systematic review and meta-analysis to assess prevalence of complications associated with the use of the RIA system have not been conducted. Materials and methods: The review is registered with PROSPERO (CRD42021269982). MEDLINE, the Web of Science Core Collection, and Embase were searched from the inception to 10 August 2021. The primary objective was to assess complications and blood loss associated with the use of the RIA system. Results: Forty-seven studies involving 1834 procedures performed with the RIA system were finally included. A total of 105 complications were reported, with a pooled estimated overall prevalence of 1.7% with a 95% confidence interval (CI) of 0.40 to 3.60, with cortex perforation being the largest reported complication with a total of 34 incidences. A significant subgroup difference was observed (p = 0.02). In subgroup 1 (bone graft harvesting), complication prevalence was 1.4% (95% CI 0.2–3.4); in subgroup 2 (clearance intramedullary canal) it was 0.7% (95% CI 0.00–6.30) and in subgroup 3 (reaming with RIA system prior to nail fixation) 11.9% (95% CI 1.80–26.40). No statistically significant difference for tibia and femur as RIA system application site was observed (CI 0.69–4.19). In studies reporting blood loss, a mean volume of 803.29 ml, a mean drop of hemoglobin of 3.74 g/dl and a necessity of blood transfusion in 9.72% of the patients were observed. Conclusions: The systematic review and meta-analysis demonstrate a low overall prevalence rate of complications associated with the RIA system. However, especially the risk of cortical perforation and the frequently reported relevant intraoperative blood loss are complications that should be anticipated in perioperative management and ultimately considered when using the RIA system.</p

Design and development of a three-dimensional printing high-throughput melt electrowriting technology platform

Three-dimensionally (3D) printed scaffolds and cell culture lattices with microscale features are increasingly being used in tissue engineering and regenerative medicine. One additive manufacturing technology used to design and fabricate such structures is melt electrowriting (MEW), a process which needs to be scaled in production to effectively translate to industrial applications. In this study, a scale-up printer, designed with eight simultaneously extruding heads, is constructed and validated. Importantly, identical structures could be fabricated using parameters developed from a single-head system, therefore establishing a MEW printer ecosystem that allows for direct upscaling from laboratory research. The successful transfer to vertically mounted collectors produced homogeneous reproducible scaffolds with identical morphologies and fiber diameters. These proof-of-concept experiments also show that MEW is capable of large-scale fabrication, successfully demonstrated by manufacturing 780 × 780-mm sheets of scaffolds/lattices. This study demonstrates that upscaling MEW can be realized by multiplying the number of print heads, while vertical mounting of the collector significantly reduces the MEW footprint. Additionally, economic aspects were considered during the development and costly components, such as the x, y, and z linear axes, were minimized. Herein, a systems engineering approach for the development of a high-throughput MEW technology platform is presented for the first time

Challenges and opportunities in the manufacture and expansion of cells for therapy

Introduction: Laboratory-based ex vivo cell culture methods are largely manual in their manufacturing processes. This makes it extremely difficult to meet regulatory requirements for process validation, quality control and reproducibility. Cell culture concepts with a translational focus need to embrace a more automated approach where cell yields are able to meet the quantitative production demands, the correct cell lineage and phenotype is readily confirmed and reagent usage has been optimized. Areas covered: This article discusses the obstacles inherent in classical laboratory-based methods, their concomitant impact on cost-of-goods and that a technology step change is required to facilitate translation from bed-to-bedside. Expert opinion: While traditional bioreactors have demonstrated limited success where adherent cells are used in combination with microcarriers, further process optimization will be required to find solutions for commercial-scale therapies. New cell culture technologies based on 3D-printed cell culture lattices with favourable surface to volume ratios have the potential to change the paradigm in industry. An integrated Quality-by-Design /System engineering approach will be essential to facilitate the scaled-up translation from proof-of-principle to clinical validation

Melt electrospinning writing of highly ordered large volume scaffold architectures

The additive manufacturing of highly ordered, micrometer‐scale scaffolds is at the forefront of tissue engineering and regenerative medicine research. The fabrication of scaffolds for the regeneration of larger tissue volumes, in particular, remains a major challenge. A technology at the convergence of additive manufacturing and electrospinning–melt electrospinning writing (MEW)–is also limited in thickness/volume due to the accumulation of excess charge from the deposited material repelling and hence, distorting scaffold architectures. The underlying physical principles are studied that constrain MEW of thick, large volume scaffolds. Through computational modeling, numerical values variable working distances are established respectively, which maintain the electrostatic force at a constant level during the printing process. Based on the computational simulations, three voltage profiles are applied to determine the maximum height (exceeding 7 mm) of a highly ordered large volume scaffold. These thick MEW scaffolds have fully interconnected pores and allow cells to migrate and proliferate. To the best of the authors knowledge, this is the first study to report that z‐axis adjustment and increasing the voltage during the MEW process allows for the fabrication of high‐volume scaffolds with uniform morphologies and fiber diameters

Melt Electrospinning Writing of Highly Ordered Large Volume Scaffold Architectures

The additive manufacturing of highly ordered, micrometer‐scale scaffolds is at the forefront of tissue engineering and regenerative medicine research. The fabrication of scaffolds for the regeneration of larger tissue volumes, in particular, remains a major challenge. A technology at the convergence of additive manufacturing and electrospinning–melt electrospinning writing (MEW)–is also limited in thickness/volume due to the accumulation of excess charge from the deposited material repelling and hence, distorting scaffold architectures. The underlying physical principles are studied that constrain MEW of thick, large volume scaffolds. Through computational modeling, numerical values variable working distances are established respectively, which maintain the electrostatic force at a constant level during the printing process. Based on the computational simulations, three voltage profiles are applied to determine the maximum height (exceeding 7 mm) of a highly ordered large volume scaffold. These thick MEW scaffolds have fully interconnected pores and allow cells to migrate and proliferate. To the best of the authors knowledge, this is the first study to report that z‐axis adjustment and increasing the voltage during the MEW process allows for the fabrication of high‐volume scaffolds with uniform morphologies and fiber diameters