Microfluidics development of polymeric hydrogel microspheres for drug delivery applications.

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ICE Krakow

ICE Krakow

ul. Marii Konopnickiej 17 30-302 Kraków


Pareja Tello, Rubén (University of Helsinki)


"Introduction: Musculoskeletal diseases include more than 150 pathologies and have been reported to affect 1.71 billion people worldwide (1). Among the different conditions described, the number of cases of chronic tendinopathy and tendon/ligament injuries has reportedly increased, mainly due to the rise of life expectancy in many countries (2). The currently used therapeutic tools mainly focus on the treatment of the associated symptomatology and, in the case of major injuries, surgery remains a common alternative, even though the complete recovery of the patient is highly difficult due to the risk of scar development, tendon adhesion, reduced joint movement, limited mechanical properties (1). Regarding chronic tendinopathy, tendon regeneration can be enhanced thanks to the administration of specific drugs such as different growth factors (3). Bearing this in mind, new therapeutical alternatives for the treatment of tendon injuries should be studied. This project focuses on studying polymeric hydrogel microspheres for the delivery of biological agents with tendon regenerative properties.
Methodology: Polymeric hydrogel microspheres are prepared using glass microfluidic technology (4). The formulation is prepared using two different precursor polymers: Norbornene functionalized 8-arm Polyethylene glycol (PEG) and Tetrazine functionalized 4-arm PEG. The obtained polymeric hydrogel microspheres are studied in terms of their size and variation coefficient. Subsequently, the formulation is morphologically studied using scanning electron microscope (SEM) and the rheological properties are studied. Moreover, the degradation behavior of the formulation is also assessed. The formulation is loaded with a model protein, such as bovine serum albumin (BSA) to study the entrapment efficiency and the release rate. Afterwards, the microspheres are loaded with different growth factors and, subsequently, in vitro cell viability and efficacy studies is performed in tenocytes.
Results: Monodisperse polymeric hydrogel microspheres with a lower size than 50 µm and a low variation coefficient are obtained. The microspheres have a high entrapment efficiency of biological compounds and a slow-release rate. The selected precursor polymers do not show any toxic effects.
Conclusion: In this study, we have developed a co-flow focusing microfluidic technique for the preparation of polymeric hydrogel microspheres via an emulsion method in mineral oil. The microspheres were used to encapsulate different drugs and release them following a slow process. This system is expected to release bioactive molecules and be loaded in an external hydrogel with other bioactive molecules and even stem cells in the future.
1. Lei T, Zhang T, Ju W, Chen X, Heng BC, Shen W, et al. Biomimetic strategies for tendon/ligament-to-bone interface regeneration. Bioact Mater [Internet]. 2021;6(8):2491–510.
2. Kaizawa Y, Leyden J, Behn AW, Tulu US, Franklin A, Wang Z, et al. Human Tendon–Derived Collagen Hydrogel Significantly Improves Biomechanical Properties of the Tendon-Bone Interface in a Chronic Rotator Cuff Injury Model. J Hand Surg Am [Internet]. 2019;44(10):899.e1-899.e11.
3. Liu R, Zhang S, Chen X. Injectable hydrogels for tendon and ligament tissue engineering. J Tissue Eng Regen Med [Internet]. 2020;14(9):1333–48.
4. Liu D, Zhang H, Fontana F, Hirvonen JT, Santos HA. Microfluidic-assisted fabrication of carriers for controlled drug delivery. Lab Chip [Internet]. 2017 May 31; 17(11):1856–83."

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