Bioactive polysaccharide-based hydrogels for growth factors delivery during tissue repair.

由于人口老龄化，癌症发展过程中的病理状况，包括骨不连、皮肤病变、神经系统疾病和炎症过程的发生率正在增加。这些问题使人衰弱，代价高昂，目前的办法在减轻痛苦方面成效有限。生物分子的受控递送，例如生长因子（GF）-协调我们的发育并具有刺激细胞生长和分化的能力的蛋白质，从而可以驱动再生-可以提供有效的组织工程策略来促进组织发育和修复。然而，这些蛋白质的可溶性给药通常意味着它们以高剂量递送，这产生不期望的、潜在严重/致命的全身作用，限制了它们的临床应用。在这项提案中，我们将开发一种新的水凝胶，基于醋甘露聚糖多糖-芦荟内叶的主要生物活性成分-将作为组织工程应用中高效和局部递送GF的生物活性载体。作为水凝胶，这种天然载体将增加GF在愈合部位内的保留足够长的时间，以允许细胞迁移、增殖和分化。此外，载体的固有生物活性（例如抗炎性质、防腐功能和促进血管形成、刺激成骨分化的潜力）与释放的GF一起将提供协同效应，其将允许超低剂量GF递送，比当前临床技术中使用的低几个数量级。因此，这种策略将通过增加再生潜力，同时减少与使用高GF剂量相关的危及生命的问题和高成本，显着改善社会健康。此外，微载体将通过微创手术容易地注射到体内。为此，一种新型的微流体技术将被用作一种有效的工具，以比传统技术更高的通量生成微载体，这将使我们能够轻松地扩展该技术，以满足临床实践中的高需求水平。虽然这项建议将集中在骨再生过程中的GF输送，这种新的生物活性载体将提供一个通用的平台，GFs交付的潜力，被广泛用于不同的生物医学应用。

Pathological conditions, including non-union bone defects, skin lesions, neurological disorders and inflammatory processes during cancer development are growing in occurrence due to an aging population. These problems are debilitating, costly and current approaches have limited success in alleviating suffering. The controlled delivery of biological molecules, such as growth factors (GFs) - proteins that orchestrate our development and hold the capacity to stimulate cellular growth and differentiation and that could thus drive regeneration - could provide potent tissue engineering strategies to promote tissue development and repair. However, the soluble administration of these proteins usually implies their delivery at high doses, which produces undesired, potentially serious/fatal systemic effects limiting their clinical use. In this proposal we will develop a new hydrogel, based on the acemannan polysaccharide - main bioactive component from the inner leaves of Aloe Vera - that will act as a bioactive carrier for the efficient and local delivery of GFs for tissue engineering applications. As a hydrogel, this natural carrier will increase the retention of the GFs within the healing site for a sufficient period to allow cells to migrate, proliferate and differentiate. Moreover, the inherent biological activity of the carrier (e.g. anti-inflammatory properties, antiseptic functions and potential to promote vascularisation, stimulate osteogenic differentiation), together with the released GFs, will provide a synergistic effect that will allow ultra-low dose GF delivery, several orders of magnitude lower than the ones used in current clinical technologies. Thus, this strategy will significantly improve societal health by increasing regenerative potential while reducing the life-threatening issues and high cost associated with the use of high GF doses. Also, microcarriers will be generated for their easy injection into the body through minimally invasive surgery. To do so, a novel microfluidics technology will be used as an efficient tool to generate microcarriers at higher throughput than conventional technologies, which will allow us to easily scale the technology to meet high demand levels in clinical practice. Although this proposal will focus on GF delivery during processes of bone regeneration, this new bioactive carrier will provide a versatile platform of GFs delivery with the potential to be widely used for different biomedical applications.