RESUMO
Self-assembling peptide (SAP) RADA16-I (Ac-(RADA)4-CONH2) has been suffering from a main drawback associated with low pH, which damages cells and host tissues upon direct exposure. In this study, we presented a strategy to prepare nanofiber hydrogels from two designer SAPs at neutral pH. RADA16-I was appended with functional motifs containing cell adhesion peptide RGD and neurite outgrowth peptide IKVAV. The two SAPs were specially designed to have opposite net charges at neutral pH, the combination of which created a nanofiber hydrogel (-IKVAV/-RGD) characterized by significantly higher G' than Gâ³ in a viscoelasticity examination. Circular dichroism, Fourier transform infrared spectroscopy, and Raman measurements were performed to investigate the secondary structure of the designer SAPs, indicating that both the hydrophobic/hydrophilic properties and electrostatic interactions of the functional motifs play an important role in the self-assembling behavior of the designer SAPs. The neural progenitor cells (NPCs)/stem cells (NSCs) fully embedded in the 3D-IKVAV/-RGD nanofiber hydrogel survived, whereas those embedded within the RADA 16-I hydrogel hardly survived. Moreover, the -IKVAV/-RGD nanofiber hydrogel supported NPC/NSC neuron and astrocyte differentiation in a 3D environment without adding extra growth factors. Studies of three nerve injury models, including sciatic nerve defect, intracerebral hemorrhage, and spinal cord transection, indicated that the designer -IKVAV/-RGD nanofiber hydrogel provided a more permissive environment for nerve regeneration than the RADA 16-I hydrogel. Therefore, we reported a new mechanism that might be beneficial for the synthesis of SAPs for in vitro 3D cell culture and nerve regeneration.
Assuntos
Hidrogéis/química , Nanofibras/química , Degeneração Neural/tratamento farmacológico , Peptídeos/uso terapêutico , Sequência de Aminoácidos , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/metabolismo , Concentração de Íons de Hidrogênio , Camundongos , Microscopia de Força Atômica , Modelos Moleculares , Dados de Sequência Molecular , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Nanofibras/ultraestrutura , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Estrutura Secundária de Proteína , Ratos Sprague-Dawley , Ratos Transgênicos , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
This article reviews the recent trends, developments, and future applications of bio-based polymers produced from renewable resources. Bio-based polymers are attracting increased attention due to environmental concerns and the realization that global petroleum resources are finite. Bio-based polymers not only replace existing polymers in a number of applications but also provide new combinations of properties for new applications. A range of bio-based polymers are presented in this review, focusing on general methods of production, properties, and commercial applications. The review examines the technological and future challenges discussed in bringing these materials to a wide range of applications, together with potential solutions, as well as discusses the major industry players who are bringing these materials to the market.