Engineering growth factor microenvironments - a new therapeutic paradigm for regenerative medicine

工程生长因子微环境——再生医学的新治疗范例

• 批准号: EP/P001114/1
• 负责人: Manuel Salmeron-Sanchez
• 金额: $ 466.89万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FP001114%2F1
• 关键词: Engineering; growth; factor; microenvironments; new

Growth factors are molecules within our body that participate in many physiological process that are key during development as they control stem cell function. These molecules thus have the potential to drive the regeneration of tissues in a broad range of medical conditions, including in musculoskeletal (bone repair), haematological (bone marrow transplantation) and cardiovascular (infarction, heart attack) diseases. Growth factors are currently produced commercially and are used regularly in clinical applications. However, they are very power cell signalling molecules and dose is critical as balance between effect and safety has to be considered. To date the use of growth factors in regenerative medicine has been only partially successful and even controversial. The growth factors are rapidly broken down and cleared by the body. This makes prolonged delivery (as is required to effect repair) a problem and typically higher than wanted doses are administered to get around this. While their help in regeneration is undoubted, collateral side effects can be catastrophic e.g. tumour formation. We have developed new technology that directly addresses these concerns as it uses materials (that can be topically implanted) to deliver low, but effective, growth factor doses; this programme is about the safe use of growth factors in clinical applications. This will not only reduce risks for patients who currently receive growth factor treatments, but will open up therapies that can include co-transplantation with stem cells to a wider range of patients as doctors would not have to keep these therapies back for cases of most pressing need. This increased use would minimise costs as growth factors are very expensive and reduced dose would save money per treatment. Our approach is unique and this programme grant will allow us to enhance the UK's world leading position through innovative bioengineering. We know that stem cells have huge regenerative potential and that growth factors provide exquisite stem cell control - both are currently untapped. We will engineer new materials to enable growth factor technology, and critically stem cell technologies, where traditional approaches are falling very short of the mark.

生长因子是我们体内的分子，参与许多生理过程，这些过程在发育过程中是关键的，因为它们控制干细胞功能。因此，这些分子有可能在广泛的医疗条件下驱动组织再生，包括肌肉骨骼（骨修复），血液学（骨髓移植）和心血管（梗死，心脏病发作）疾病。生长因子目前已商业化生产，并经常用于临床应用。然而，它们是非常强大的细胞信号分子，剂量至关重要，因为必须考虑效果和安全性之间的平衡。到目前为止，生长因子在再生医学中的应用只取得了部分成功，甚至存在争议。生长因子被身体迅速分解和清除。这使得延长递送（如实现修复所需的）成为问题，并且通常施用高于所需剂量的剂量来解决这个问题。虽然它们对再生的帮助被忽视，但附带的副作用可能是灾难性的，例如肿瘤形成。我们已经开发了直接解决这些问题的新技术，因为它使用材料（可以局部植入）提供低，但有效的生长因子剂量;该计划是关于在临床应用中安全使用生长因子。这不仅会降低目前接受生长因子治疗的患者的风险，而且会为更广泛的患者提供包括与干细胞共同移植在内的治疗方法，因为医生不必为最迫切需要的病例保留这些治疗方法。这种增加的使用将使成本最小化，因为生长因子非常昂贵，减少剂量将节省每次治疗的费用。 我们的方法是独特的，这项计划拨款将使我们能够通过创新的生物工程提高英国的世界领先地位。我们知道，干细胞具有巨大的再生潜力，生长因子提供了精致的干细胞控制-这两个目前尚未开发。我们将设计新材料，使生长因子技术和关键的干细胞技术成为可能，而传统方法远远达不到这一目标。

项目成果

Confined Sandwichlike Microenvironments Tune Myogenic Differentiation.

• DOI: 10.1021/acsbiomaterials.7b00109
• 发表时间: 2017-08-14
• 期刊: ACS biomaterials science & engineering
• 影响因子: 5.8
• 作者: Ballester-Beltrán J;Trujillo S;Alakpa EV;Compañ V;Gavara R;Meek D;West CC;Péault B;Dalby MJ;Salmerón-Sánchez M
• 通讯作者: Salmerón-Sánchez M

Molecular clutch drives cell response to surface viscosity.

• DOI: 10.1073/pnas.1710653115
• 发表时间: 2018-02-06
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Bennett M;Cantini M;Reboud J;Cooper JM;Roca-Cusachs P;Salmeron-Sanchez M
• 通讯作者: Salmeron-Sanchez M

Alignment-free construction of double emulsion droplet generation devices incorporating surface wettability contrast.

结合表面润湿性对比的双乳液液滴生成装置的免对准结构。

• DOI: 10.1039/d3lc00584d
• 发表时间: 2023
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Aslan Y

Minor Chemistry Changes Alter Surface Hydration to Control Fibronectin Adsorption and Assembly into Nanofibrils

• DOI: 10.1002/adts.201900169
• 发表时间: 2019-10-28
• 期刊: ADVANCED THEORY AND SIMULATIONS
• 影响因子: 3.3
• 作者: Bieniek, Mateusz K.;Llopis-Hernandez, Virginia;Lorenz, Christian D.
• 通讯作者: Lorenz, Christian D.