Center for Biomedical Technology, Universidad Politécnica de Madrid, 28223 Pozuelo de Alarcón, Madrid, Spain; Departamento de Ciencia de Materiales, ETSI Caminos, Canales y Puertos, Universidad Politécnica de Madrid, 28040 Madrid, Spain.
Center for Biomedical Technology, Universidad Politécnica de Madrid, 28223 Pozuelo de Alarcón, Madrid, Spain; Departamento de Ciencia de Materiales, ETSI Caminos, Canales y Puertos, Universidad Politécnica de Madrid, 28040 Madrid, Spain; Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Calle Prof. Martín Lagos s/n, 28040 Madrid, Spain.
Biomater Adv. 2022 Feb;133:112614. doi: 10.1016/j.msec.2021.112614. Epub 2021 Dec 22.
Titanium implants are widely used in traumatology and various orthopedic fields. Titanium and other metallic-based implants have limited structural and functional integration into the body, which translates into progressive prosthesis instability and the need for new surgical interventions that have enormous social and economic impacts. To enhance the biocompatibility of titanium implants, numerous biofunctionalization strategies have been developed. However, the problem persists, as more than 70% of implant failures are due to aseptic loosening. In this study we addressed the problem of improving the physiological engraftability and acceptability of titanium-based implants by applying a robust and versatile functionalization method based on the covalent immobilization of extracellular matrix (ECM)-derived oligopeptides on Ti-6Al-4V surfaces treated by activated vapor silanization (AVS). The feasibility of this technique was evaluated with two oligopeptides of different structures and compositions. These oligopeptides were immobilized on Ti-6Al-4V substrates by a combination of AVS and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) crosslinking chemistry. The immobilization was shown to be stable and resistant to chemical denaturing upon sodium dodecyl sulfate treatment. On Ti-6Al-4V surfaces both peptides increased the attachment, spreading, rearrangement and directional growth of mesenchymal stem and progenitor cells (MSC) with chondro- and osteo-regenerative capacities. We also found that this biofunctionalization method (AVS-EDC/NHS) increased the attachment capacity of an immortalized cell line of neural origin with poor adhesive properties, highlighting the versatility and robustness of this method in terms of potential oligopeptides that may be used, and cell lineages whose anchorage to the biomaterial may be enhanced. Collectively, this novel functionalization strategy can accelerate the development of advanced peptide-functionalized metallic surfaces, which, in combination with host or exogenously implanted stem cells, have the potential to positively affect the osteoregenerative and osteointegrative abilities of metallic-based prostheses.
钛植入物广泛应用于创伤学和各种骨科领域。钛和其他基于金属的植入物与身体的结构和功能整合有限，这转化为渐进式假体不稳定和需要新的手术干预，这对社会和经济产生了巨大影响。为了提高钛植入物的生物相容性，已经开发了许多生物功能化策略。然而，问题仍然存在，超过 70%的植入物失败是由于无菌性松动。在这项研究中，我们通过应用基于细胞外基质（ECM）衍生的寡肽在经过活化蒸汽硅烷化（AVS）处理的 Ti-6Al-4V 表面上的共价固定化的强大且通用的功能化方法来解决提高基于钛的植入物的生理植入和可接受性的问题。通过使用两种具有不同结构和组成的寡肽来评估该技术的可行性。这些寡肽通过 AVS 和 N-（3-二甲基氨基丙基）-N'-乙基碳二亚胺盐酸盐/N-羟基琥珀酰亚胺（EDC/NHS）交联化学组合固定在 Ti-6Al-4V 基底上。结果表明，在十二烷基硫酸钠处理时，固定化是稳定且抗化学变性的。在 Ti-6Al-4V 表面上，两种肽均增加了具有软骨和骨再生能力的间充质干细胞和祖细胞（MSC）的附着，扩散，重排和定向生长。我们还发现，这种生物功能化方法（AVS-EDC/NHS）增加了具有不良粘附特性的神经来源的永生化细胞系的附着能力，突出了该方法在可能使用的寡肽和可能增强对生物材料附着的细胞谱系方面的多功能性和稳健性。总的来说，这种新的功能化策略可以加速先进肽功能化金属表面的开发，将宿主或外植干细胞与之结合，有可能积极影响基于金属的假体的骨再生和骨整合能力。
