Additive manufacturing, in particular powder bed-based fabrication processes hold promise to revolutionize biomedical engineering for the ability to provide customized, functional implants, for example as bone replacement materials. However, providing functional powder particles that unify material requirements for biodegradable and bioactive biomaterials and process requirements to enable successful powder bed fusion remains an unmet challenge. Here, a supraparticle-based approach to create biodegradable poly(lactic acid) and composite powders for the additive manufacturing of bone replacement materials is introduced. Colloidal binary Ca-SiO 2 glasses and hydroxyapatite are incorporated as bioactive functional additives to support the formation of bone-like calcium phosphate. The supraparticle powders are prepared by a scalable spraydrying process, which offers control of particle size, shape, and composition. All process-relevant powder characteristics are analyzed as a function of composition and structure, including flowability, thermal, and melt rheological properties. The optimized supraparticle powders are successfully used in the process of laser powder bed fusion of polymers to prepare macroscopic specimens via additive manufacturing. It is demonstrated that the material combination of the composites provides relevant functional properties, including biodegradation and bioactivity. The process provides a flexible and adjustable toolbox for the design of functional powders toward biomedical additive manufacturing.
Translating innovative nanomaterials to medical products requires efficient manufacturing techniques that enable large‐scale high‐throughput synthesis with high reproducibility. Drug carriers in medicine embrace a complex subset of tasks calling for multifunctionality. Here, the synthesisof pro‐drug‐loaded core cross‐linked polymeric micelles (CCPMs) in a continuous flow processis reported, which combines the commonly separated steps of micelle formation, core cross‐linking, functionalization, and purification into a single process. Redox‐responsive CCPMs are formed from thiol‐reactive polypept(o)ides of polysarcosine‐block‐poly(S‐ethylsulfonyl‐l‐cysteine) and functional cross‐linkers based on dihydrolipoic acid hydrazide for pH‐dependent release of paclitaxel. The precisely controlled microfluidic process allows the production of spherical micelles (Dh = 35 nm) with low polydispersity values (PDI < 0.1) while avoiding toxic organic solvents and additives with unfavorable safety profiles. Self‐assembly and cross‐linking via slit interdigital micromixers produces 350–700 mg of CCPMs/h per single system, while purification by online tangential flow filtration successfully removes impurities (unimer ≤ 0.5%). The formed paclitaxel‐loaded CCPMs possess the desired pH‐responsive release profile, display stable drug encapsulation, an improved toxicity profile compared to Abraxane (a trademark of Bristol‐Myers Squibb), and therapeutic efficiency in the B16F1‐xenotransplanted zebrafish model. The combination of reactive polymers, functional cross‐linkers, and microfluidics enables the continuous‐flow synthesis of therapeutically active CCPMs in a single process.
Nanoparticular materials have a great potential in various fields including technical and biomedical applications; to meet the specific requirements, a good control over the particle characteristics is mandatory. Addressing this, a modular system for the automated and continuous synthesis, workup, and analysis of a broad range of nanoparticles was developed. Application examples of inorganic (silica) and organic (polymersomes, niosomes) nanoparticles demonstrate the versatility of the production platform. Modules for downstream processing via a falling‐film microreactor or tangential flow filtration are presented. The hydrodynamic size as a key parameter is acquired in real time, with an inline dynamic light scattering device. All modules are controlled and operated by a process control system.
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