Department of Developmental BioEngineering, TechMed Institute, University of Twente, The Netherlands. Drienerlolaan 5, 7522 NB, Enschede, the Netherlands.
Department of Developmental BioEngineering, TechMed Institute, University of Twente, The Netherlands. Drienerlolaan 5, 7522 NB, Enschede, the Netherlands.
Acta Biomater. 2023 Oct 15;170:1-14. doi: 10.1016/j.actbio.2023.07.045. Epub 2023 Jul 29.
Over the years, much research has been focused on the use of small molecules such as peptides or aptamers or more recently on the use of variable antigen-binding domain of heavy chain only antibodies in the field of tissue engineering and regenerative medicine. The use of these molecules originated as an alternative for the larger conventional antibodies, of which most drawbacks are derived from their size and complex structure. In the field of tissue engineering and regenerative medicine, biological functionalities are often conjugated to biomaterials in order to (re-)create an in vivo like situation, especially when bioinert biomaterials are used. Those biomaterials are functionalized with these functionalities for instance for the purpose of cell attachment or cell targeting for targeted drug delivery but also for local enrichment or blocking of ligands such as growth factors or cytokines on the biomaterial surface. In this review, we further refer to peptides, aptamers, and variable antigen-binding domain of heavy chain only antibodies as biological functionalities. Here, we compare these biological functionalities within the field of tissue engineering and regenerative medicine and give an overview of recent work in which these biological functionalities have been explored. We focus on the previously mentioned purposes of the biological functionalities. We will compare structural differences, possible modifications and (chemical) conjugation strategies. In addition, we will provide an overview of biologicals that are, or have been, involved in clinical trials. Finally, we will highlight the challenges of each of these biologicals. STATEMENT OF SIGNIFICANCE: In the field of tissue engineering there is broad application of functionalized biomaterials for cell attachment, targeted drug delivery and local enrichment or blocking of growth factors. This was previously mostly done via conventional antibodies, but their large size and complex structure impose various challenges with respect of retaining biological functionality. Peptides, aptamers and VHHs may provide an alternative solution for the use of conventional antibodies. This review discusses the use of these molecules for biological functionalization of biomaterials. For each of the molecules, their characteristics, conjugation possibilities and current use in research and clinical trials is described. Furthermore, this review sets out the benefits and challenges of using these types of molecules for different fields of application.
多年来，人们一直致力于研究小分子（如肽或适体），或者最近研究仅重链可变抗原结合域抗体在组织工程和再生医学领域的应用。这些分子的使用源于对更大的传统抗体的替代，而传统抗体的大多数缺点来自于其尺寸和复杂结构。在组织工程和再生医学领域，生物功能通常与生物材料结合使用，以便（重新）创造出类似于体内的环境，尤其是在使用生物惰性生物材料时。这些生物材料被赋予这些功能，例如用于细胞附着或靶向细胞以实现靶向药物输送，但也用于在生物材料表面局部富集或阻断配体（如生长因子或细胞因子）。在这篇综述中，我们进一步将肽、适体和仅重链可变抗原结合域抗体称为生物功能。在这里，我们比较了这些生物功能在组织工程和再生医学领域的应用，并概述了最近探索这些生物功能的工作。我们重点介绍了生物功能的上述目的。我们将比较结构差异、可能的修饰和（化学）偶联策略。此外，我们将概述涉及临床试验的生物制品。最后，我们将强调这些生物制品的挑战。
在组织工程领域，功能化生物材料广泛应用于细胞附着、靶向药物输送以及生长因子的局部富集或阻断。这以前主要是通过传统抗体来完成的，但它们的尺寸大和复杂结构在保留生物功能方面带来了各种挑战。肽、适体和 VHH 可能为使用传统抗体提供替代解决方案。本综述讨论了这些分子在生物材料的生物功能化中的应用。对于每种分子，描述了它们的特性、偶联可能性以及在研究和临床试验中的当前用途。此外，本综述阐述了在不同应用领域使用这些类型分子的好处和挑战。
