Development of tuneable microgels for controlled protein delivery in tissue regeneration

控制蛋白质的输送，如生长因子，是一种非常有前途的治疗病理条件的策略，包括骨缺损和皮肤病变。有效蛋白质治疗的一个主要障碍是缺乏具有生物相容性、生物活性和可注射的载体，这些载体可以在损伤部位局部递送具有高生物活性和合适释放率的蛋白质。水凝胶是一种高度水化的交联聚合物网络，被认为是一种很有前途的蛋白质载体，可以模拟天然组织中细胞外基质的特性。将生物活性分子包封在水凝胶中，可以有针对性地持续递送到缺陷或损伤部位，为组织愈合提供足够的时间，并刺激组织生长和细胞分化。可注射的微凝胶具有高度可控的生物力学特性和蛋白质释放机制，可以在损伤部位进行微创给药。微凝胶可以通过使用微流体方法来生产，这种方法允许高通量生产球形和单分散的微颗粒，其中目标尺寸可以高精度地控制。拟议的研究项目将侧重于开发新的微凝胶平台，用于有效和受控地递送生长因子和间充质干细胞（MSCs），以促进组织修复。我们将开发生物活性微凝胶，在可降解性和粘弹性方面具有可调的物理化学特性，使用不同的天然和合成水凝胶配方，具有免疫调节特性和促进细胞增殖、迁移和分化的潜力，目的是减少GF的剂量，这将导致更安全的方法。将对微凝胶的物理化学和机械性能进行表征，并在体外评估其生物活性。最后，根据应用情况，使用相关动物模型（如软骨皮下模型和糖尿病小鼠伤口愈合模型）对最成功的微凝胶配方进行体内测试。

Controlled delivery of proteins, such as growth factors, is a highly promising strategy to treat pathological conditions, including bone defects and skin lesions. A major roadblock to effective protein therapeutics is the lack of biocompatible, bioactive, and injectable carriers that deliver proteins locally with high bioactivity and suitable release rates in the site of injury. Hydrogels, highly hydrated cross-linked polymer networks, have been studied as promising protein carriers that can mimic the properties of the extracellular matrix in native tissues. The encapsulation of bioactive molecules within the hydrogels would allow for the targeted and sustained delivery to the site of defect or injury, providing enough time for the tissue to heal and stimulating the tissue growth and cell differentiation. Injectable microgels with highly controlled biomechanical properties and protein release mechanisms can be developed, allowing a minimally invasive administration in the site of injury. Microgels can be produced by using microfluidics approaches, that allow the high-throughput production of spherical and monodisperse microparticles, where the targeted size can be controlled with high precision. The proposed research project will focus on the development of new microgels platforms for the efficient and controlled delivery of growth factors and mesenchymal stem cells (MSCs) to promote tissue repair. We will develop bioactive microgels with tuneable physicochemical properties, in terms of degradability and viscoelastic properties, using different natural- and synthetic- based hydrogel formulations with immunomodulatory properties and potential to promote cell proliferation, migration and differentiation, with the aim of reducing the GF doses, which will result in a safer approach. The physicochemical and mechanical properties of the microgels will be characterised and their bioactivity evaluated in vitro. Finally, the most successful microgel formulation will be tested in vivo using the relevant animal model according to the application (e.g., subcutaneous model for cartilage and diabetic mouse model for wound healing).