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Biopolymers, such as collagens, elastin, silk fibroin, spider silk, fibrin, keratin, and resilin have gained significant interest for their potential biomedical applications due to their biocompatibility, biodegradability, and mechanical properties. This review focuses on the design and integration of biomimetic peptides into these biopolymer platforms to control the release of bioactive molecules, thereby enhancing their functionality for drug delivery, tissue engineering, and regenerative medicine. Elastin-like polypeptides (ELPs) and silk fibroin repeats, for example, demonstrate how engineered peptides can mimic natural protein domains to modulate material properties and drug release profiles. Recombinant spider silk proteins, fibrin-binding peptides, collagen-mimetic peptides, and keratin-derived structures similarly illustrate the ability to engineer precise interactions and to design controlled release systems. Additionally, the use of resilin-like peptides showcases the potential for creating highly elastic and resilient biomaterials. This review highlights current achievements and future perspectives in the field, emphasizing the potential of biomimetic peptides to transform biopolymer-based biomedical applications.

In recent years, combination chemotherapy with therapeutic nucleic acids has emerged as a promising strategy to enhance the effectiveness of cancer therapy. However, developing an effective co-delivery system to simultaneously transport both chemotherapeutic drugs and nucleic acids remains challenging. Herein, we fabricated cholesterol-conjugated polyion complex nanoparticles (PCNs) for combination delivery of hydrophobic paclitaxel (PTX) and hydrophilic miR-34a. Cholesterol was conjugated to polyethylenimine (PEI) and hyaluronic acid (HA), producing C–PEI and C–HA, respectively. PTX was initially encapsulated within the hydrophobic core formed by the self-assembly of C–HA and C–PEI, yielding polyion complex nanoparticles (PTX@C–HA/C–PEI PCNs). Subsequently, the negatively charged miR-34a was electrostatically complexed with the cationic C–PEI moieties to generate miR-34a/PTX@C–HA/C–PEI PCNs. These PCNs exhibited a nanoscale structure with a uniform size distribution and demonstrated low cytotoxicity in colon cancer cells. Fluorescence microscopy confirmed efficient cytosolic delivery of C–HA/C–PEI PCNs in colon carcinoma cells. Furthermore, combination delivery of PTX and miR-34a using C–HA/C–PEI PCNs exhibited significantly enhanced transfection efficiency and cellular uptake for human colon cancer cells. Notably, PTX/miR-34a@C–HA/C–PEI PCNs effectively downregulated critical oncogenic targets, including Notch1, Snail1, and BCL-2, resulting in reduced cancer cell migration and proliferation. These findings indicate that PTX/miR-34a@C–HA/C–PEI PCNs hold significant potential as an innovative combination delivery platform, offering improved therapeutic efficacy for colon cancer therapy.

3D porous scaffolds fabricated from binary and ternary blends of silk fibroin (SF), gelatin (G), and hyaluronan (HA) and crosslinked by the carbodiimide coupling reaction were developed. Water-stable scaffolds can be obtained after crosslinking, and the SFG and SFGHA samples were stable in cell culture medium up to 10 days. The presence of HA in the scaffolds with appropriate crosslinking conditions greatly enhanced the swellability. The microarchitecture of the freeze-dried scaffolds showed high porosity and interconnectivity. In particular, the pore size was significantly larger with an addition of HA. Biological activities of NIH/3T3 fibroblasts seeded on SFG and SFGHA scaffolds revealed that both scaffolds were able to support cell adhesion and proliferation of a 7-day culture. Furthermore, cell penetration into the scaffolds can be observed due to the interconnected porous structure of the scaffolds and the presence of bioactive materials which could attract the cells and support cell functions. The higher cell number was noticed in the SFGHA samples, possibly due to the HA component and the larger pore size which could improve the microenvironment for fibroblast adhesion, proliferation, and motility. The developed scaffolds from ternary blends showed potential in their application as 3D cell culture substrates in fibroblast-based tissue engineering.

Large critical-size bone defects in the oral and craniofacial region are difficult to regenerate. We evaluated the effectiveness of mRNA encoding bone morphogenic protein-2 (BMP-2) in enhancing bone regeneration using a rat calvarial defect model. Two delivery approaches were investigated: (1) in vivo application of BMP-2 mRNA encapsulated in lipid nanoparticles incorporated in a scaffold, and (2) application of ex vivo BMP-2 mRNA-transfected rat bone marrow mesenchymal stem cells (rBMSCs), loaded on a scaffold and implanted into calvarial defects. The direct application of BMP-2 mRNA encapsulated in lipid nanoparticles improved bone regeneration as indicated by micro-computed tomography analysis. The enhancement was even more pronounced with ex vivo transfected rBMSCs. rBMSCs transfected with FGF-2 mRNA did not improve bone regeneration, either alone or combined with BMP-2 mRNA-transfected rBMSCs. Similarly, PDGF-BB mRNA-transfected rBMSCs failed to enhance bone regeneration alone and notably suppressed BMP-2 mRNA-transfected rBMSCs’ effects. Interestingly, BMP-2 mRNA-transfected rat fibroblasts showed comparable bone regeneration to transfected rBMSCs. Osteogenic differentiation was absent in BMP-2 mRNA-transfected rBMSCs, implying that they may primarily serve as a source of translated BMP-2 for bone regeneration rather than undergoing osteogenic differentiation. These findings highlight the translational potential of BMP-2 mRNA for bone regeneration, particularly in oral and craniofacial applications.

Controlled release of proteins, such as growth factors, from biocompatible silk fibroin (SF) hydrogel is valuable for its use in tissue engineering, drug delivery, and other biological systems. To achieve this, we introduced silk fibroin-mimetic peptides (SFMPs) with the repeating unit (GAGAGS) n . Using green fluorescent protein (GFP) as a model protein, our results showed that SFMPs did not affect the GFP function when conjugated to it. The SFMP-GFP conjugates incorporated into SF hydrogel did not change the gelation time and allowed for controlled release of the GFP. By varying the length of SFMPs, we were able to modulate the release rate, with longer SFMPs resulting in a slower release, both in water at room temperature and PBS at 37 °C. Furthermore, the SF hydrogel with the SFMPs showed greater strength and stiffness. The increased β-sheet fraction of the SF hydrogel, as revealed by FTIR analysis, explained the gel properties and protein release behavior. Our results suggest that the SFMPs effectively control protein release from SF hydrogel, with the potential to enhance its mechanical stability. The ability to modulate release rates by varying the SFMP length will benefit personalized and controlled protein delivery in various systems.

Bioactive glass (70 mol% Si and 30% Ca; 70S30C) has been used as tissue engineering scaffolds in various research despite its brittleness due to its easy-to-replicate formula, extensive interconnected pores and natural bone bonding property of bioactive glass (BG). Thai silk fibroin (SF) is natural polymer with many desirable properties; biocompatibility, mechanical strength, biodegradability. Using BG-SF hybrid scaffolds could employ the positive effects of both bioactive glass and silk fibroin. Serving as bone scaffolds, BG-SF scaffolds must resist compression and other types of mechanical load depending on the application. This study fabricates scaffolds with various ratios of BG:SF (BG:SF; 90:10, 80:20 with 100:0 as control), and their stress-strain profiles were investigated. As expected, the scaffolds with highest BG content exhibited the curve resembling that of porous foam while the elastomeric stress-strain profile was becoming more evident when the SF content was increased. This study hence demonstrated fine-tuning mechanical properties of the BG using locally enriched SF.

Gamma irradiation, which is one of the more conventional sterilization methods, was used to induce the hydrogelation of silk fibroin in this study. The physical and chemical characteristics of the irradiation-induced silk fibroin hydrogels were investigated. Silk fibroin solution with a concentration greater than 1 wt% formed hydrogel when irradiated by gamma rays at a dose of 25 or 50 kGy. The hydrogel induced by 50 kGy of radiation was more thermally stable at 80 °C than those induced by 25 kGy of radiation. When compared to the spontaneously formed hydrogels, the irradiated hydrogels contained a greater fraction of random coils and a lower fraction of β-sheets. This finding implies that gelation via gamma irradiation occurs via other processes, in addition to crystalline β–sheet formation, which is a well-established mechanism. Our observation suggests that crosslinking and chain scission via gamma irradiation could occur in parallel with the β–sheet formation. The irradiation-induced hydrogels were obtained when the solution concentration was adequate to support the radiation crosslinking of the silk fibroin chains. This work has, therefore, demonstrated that gamma irradiation can be employed as an alternative method to produce chemical-free, random coil-rich, and sterilized silk fibroin hydrogels for biomedical applications.