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Controlling biomolecular-cell interactions is crucial for the design of scaffolds for tissue engineering (TE). Regenerated silk fibroin (RSF) has been extensively used as TE scaffolds, however, RSF showed poor attachment of neuronal cells, such as rat pheochromocytoma (PC12) cells. In this work, amphiphilic peptides containing a hydrophobic isoleucine tail (I 3 ) and laminin or fibronectin derived peptides (IKVAV, PDSGR, YIGSR, RGDS and PHSRN) were designed for promoting scaffold-cell interaction. Three of them (I 3 KVAV, I 3 RGDS and I 3 YIGSR) can self-assemble into nanofibers, therefore, were used to enhance the application of RSF in neuron TE. Live / dead assays revealed that the peptides exhibited negligible cytotoxicity against PC12 cells. The specific interaction between PC12 cells and the peptides were investigate using atomic force microscopy (AFM). The results indicated a synergistic effect in the designed peptides, promoting cellular attachment, proliferation and morphology changes. In addition, AFM results showed that co-assembling peptides I 3 KVAV and I 3 YIGSR possesses the best regulation of proliferation and attachment of PC12 cells, consistent with immunofluorescence staining results. Moreover, cell culture with hydrogels revealed that a mixture of peptides I 3 KVAV and I 3 YIGSR can also promote 3D neurites outgrowth. The approach of combining two different self-assembling peptides shows great potential for nerve regeneration applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tissue-engineered bone material is one of the effective methods to repair bone defects, but the application is restricted in clinical because of the lack of excellent scaffolds that can induce bone regeneration as well as the difficulty in making scaffolds with personalized structures. 3D printing is an emerging technology that can fabricate bespoke 3D scaffolds with precise structure. However, it is challenging to develop the scaffold materials with excellent printability, osteogenesis ability, and mechanical strength. In this study, graphene oxide (GO), attapulgite (ATP), type I collagen (Col I) and polyvinyl alcohol were used as raw materials to prepare composite scaffolds via 3D bioprinting. The composite materials showed excellent printability. The microcosmic architecture and properties was characterized by scanning electron microscopy, Fourier transform infrared and thermal gravimetric analyzer, respectively. To verify the biocompatibility of the scaffolds, the viability, proliferation and osteogenic differentiation of Bone Marrow Stromal Cells (BMSCs) on the scaffolds were assessed by CCK-8, Live/Dead staining and Real-time PCR in vitro . The composited scaffolds were then implanted into the skull defects on rat for bone regeneration. Hematoxylin-eosin staining, Masson staining and immunohistochemistry staining were carried out in vivo to evaluate the regeneration of bone tissue.The results showed that GO/ATP/COL scaffolds have been demonstrated to possess controlled porosity, water absorption, biodegradability and good apatite-mineralization ability. The scaffold consisting of 0.5% GO/ATP/COL have excellent biocompatibility and was able to promote the growth, proliferation and osteogenic differentiation of mouse BMSCs in vitro . Furthermore, the 0.5% GO/ATP/COL scaffolds were also able to promote bone regeneration of in rat skull defects. Our results illustrated that the 3D printed GO/ATP/COL composite scaffolds have good mechanical properties, excellent cytocompatibility for enhanced mouse BMSCs adhesion, proliferation, and osteogenic differentiation. All these advantages made it potential as a promising biomaterial for osteogenic reconstruction.

Biomaterial-immune system interactions play an important role in postimplantation osseointegration to retain the functionality of healthy and intact bones. Therefore, appropriate osteoimmunomodulation of implants has been considered and validated as an efficient strategy to alleviate inflammation and enhance new bone formation. Here, we fabricated a nanostructured PCL/PVP (polycaprolactone/polyvinylpyrrolidone) electrospinning scaffold for cell adhesion, tissue ingrowth, and bone defect padding. In addition, telmisartan, an angiotensin 2 receptor blocker with distinct immune bioactivity, was doped into PCL-/PVP-electrospun scaffolds at different proportions [1% (TPP-1), 5% (TPP-5), and 10% (TPP-10)] to investigate its immunomodulatory effects and osteoinductivity/conductivity. Telmisartan-loaded scaffolds displayed in vitro anti-inflammatory bioactivity on lipopolysaccharide-induced M1 macrophages by polarizing them to an M2-like phenotype and exhibited pro-osteogenic properties on bone marrow-derived mesenchymal stem cells (BMSCs). Histological analysis and micro-CT results of a rat skull defect model also showed that the telmisartan-loaded scaffolds induced a higher M2/M1 ratio, less inflammatory infiltration, and better bone regenerative patterns. Furthermore, activation of the BMP2 (bone morphogenetic protein-2)-Smad signaling pathway was found to be dominant in telmisartan-loaded scaffold-mediated macrophage-BMSC interactions. These findings indicate that telmisartan incorporation with PCL/PVP nanofibrous scaffolds is a potential therapeutic strategy for promoting bone healing by modulating M1 macrophages to a more M2 phenotype at early stages of postimplantation.

Electrospun PCL scaffolds have been widely used for tissue engineering as they have shown great potential to mimic the structure of the natural extracellular matrix (ECM). However, the small pore size and low bioactivity of the scaffolds limit cell migration and tissue formation. In this study, PCL (polycaprolactone), PCL/PEG (polyethylene glycol), and PCL/PEG/ATP (nano-attapulgite) scaffolds were fabricated via electrospinning. To increase the porosity of the scaffolds, they were washed to remove water-soluble PEG fibers. Then the porous structure was measured using scanning electron microscopy (SEM) and atomic force microscopy (AFM), which showed an increased porosity when PEG fibers were removed in PCL/PEG and PCL/PEG/ATP scaffolds. Moreover, the mechanical properties were also analyzed in dry and wet conditions. In vitro mouse multipotent mesenchymal precursor cells were used to assess the biocompatibility of the scaffolds, and osteogenesis was analyzed using CCK-8 and real-time PCR (RT-PCR) methods. Moreover, in vivo μCT, histological and immunohistochemical analyses were conducted to evaluate new bone formation in rat cranium defect models. Washed PCL/PEG/ATP scaffolds were implanted into the cranium defects in rats for 4 or 8 weeks, better cell infiltration was observed in these scaffolds than in unwashed ones. The result demonstrated that washed PCL/PEG/ATP scaffold facilitated the differentiation of MSCs into osteoblasts compared with PCL scaffold, as proved by the increased expression of osteogenic key genes as well as Smad1, Smad4, and Smad5. Furthermore, in vivo studies demonstrated that using the ATP-doped electrospun PCL scaffold can improve the bone regeneration of rat cranium defects. Particularly, the PCL/ATP-30% scaffold has the best effect compared to the other scaffolds. The enhanced osteogenesis and bone repair were related to the PCL/ATP activated BMP/Smad signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no competing financial interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Electrospinning is a widely used technology that can produce scaffolds with high porosity and surface area for bone regeneration. However, the small pore sizes in electrospun scaffolds constrain cell growth and tissue-ingrowth. In this study, novel drug-loading core-shell scaffolds were fabricated via electrospinning and freeze drying to facilitate the repair of tibia bone defects in rabbit models., Materials and Methods: The collagen core scaffolds were freeze-dried containing icariin (ICA)-loaded chitosan microspheres. The shell scaffolds were electrospun using collagen, polycaprolactone and hydroxyapatite materials to form CPH composite scaffolds with the ones containing ICA microspheres named CPHI. The core-shell scaffolds were then cross-linked by genipin. The morphology, microstructure, physical and mechanical properties of the scaffolds were assessed. Rat marrow mesenchymal stem cells from the wistar rat were cultured with the scaffolds. The cell adhesion and proliferation were analysed. Adult rabbit models with tibial plateau defects were used to evaluate the performance of these scaffolds in repairing the bone defects over 4 to 12 weeks., Results: The results reveal that the novel drug-loading core-shell scaffolds were successfully fabricated, which showed good physical and chemical properties and appropriate mechanical properties. Furthermore, excellent cells attachment was observed on the CPHI scaffolds. The results from radiography, micro-computed tomography, histological and immunohistochemical analysis demonstrated that abundant new bones were formed on the CPHI scaffolds., Conclusion: These new core-shell composite scaffolds have great potential for bone tissue engineering applications and may lead to effective bone regeneration and repair., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Zhao et al.)

Tissue engineering (TE) is the approach to combine cells with scaffold materials and appropriate growth factors to regenerate or replace damaged or degenerated tissue or organs. The scaffold material as a template for tissue formation plays the most important role in TE. Among scaffold materials, silk fibroin (SF), a natural protein with outstanding mechanical properties, biodegradability, biocompatibility, and bioresorbability has attracted significant attention for TE applications. SF is commonly dissolved into an aqueous solution and can be easily reconstructed into different material formats, including films, mats, hydrogels, and sponges via various fabrication techniques. These include spin coating, electrospinning, freeze drying, physical, and chemical crosslinking techniques. Furthermore, to facilitate fabrication of more complex SF-based scaffolds with high precision techniques including micro-patterning and bio-printing have recently been explored. This review introduces the physicochemical and mechanical properties of SF and looks into a range of SF-based scaffolds that have been recently developed. The typical TE applications of SF-based scaffolds including bone, cartilage, ligament, tendon, skin, wound healing, and tympanic membrane, will be highlighted and discussed, followed by future prospects and challenges needing to be addressed. [ABSTRACT FROM AUTHOR]

Peptide amphiphiles (PAs) are peptide-based molecules that contain a peptide sequence as a head group covalently conjugated to a hydrophobic segment, such as lipid tails. They can self-assemble into well-ordered supramolecular nanostructures such as micelles, vesicles, twisted ribbons and nanofibers. In addition, the diversity of natural amino acids gives the possibility to produce PAs with different sequences. These properties along with their biocompatibility, biodegradability and a high resemblance to native extracellular matrix (ECM) have resulted in PAs being considered as ideal scaffold materials for tissue engineering (TE) applications. This review introduces the 20 natural canonical amino acids as building blocks followed by highlighting the three categories of PAs: amphiphilic peptides, lipidated peptide amphiphiles and supramolecular peptide amphiphile conjugates, as well as their design rules that dictate the peptide self-assembly process. Furthermore, 3D bio-fabrication strategies of PAs hydrogels are discussed and the recent advances of PA-based scaffolds in TE with the emphasis on bone, cartilage and neural tissue regeneration both in vitro and in vivo are considered. Finally, future prospects and challenges are discussed. [Display omitted] • The classification and design rules of the peptide amphiphiles have been introduced. • The technologies for the fabrication of 3D peptide amphiphilic scaffolds have been discussed. • The applications of peptide amphiphile scaffolds in tissue engineering have been reviewed. [ABSTRACT FROM AUTHOR]

[Display omitted] Guiding neuronal cell growth is desirable for neural tissue engineering but is very challenging. In this work, a self-assembling ultra-short surfactant-like peptide I 3 K which possesses positively charged lysine head groups, and hydrophobic isoleucine tails, was chosen to investigate its potential for guiding neuronal cell growth. The peptides were able to self-assemble into nanofibrous structures and interact strongly with silk fibroin (SF) scaffolds, providing a niche for neural cell attachment and proliferation. SF is an excellent biomaterial for tissue engineering. However neuronal cells, such as rat PC12 cells, showed poor attachment on pure regenerated SF (RSF) scaffold surfaces. Patterning of I 3 K peptide nanofibers on RSF surfaces significantly improved cellular attachment, cellular density, as well as morphology of PC12 cells. The live / dead assay confirmed that RSF and I 3 K have negligible cytotoxicity against PC12 cells. Atomic force microscopy (AFM) was used to image the topography and neurite formation of PC12 cells, where results revealed that self-assembled I 3 K nanofibers can support the formation of PC12 cell neurites. Immunolabelling also demonstrated that coating of I 3 K nanofibers onto the RSF surfaces not only increased the percentage of cells bearing neurites but also increased the average maximum neurite length. Therefore, the peptide I 3 K could be used as an alternative to poly- l -lysine for cell culture and tissue engineering applications. As micro-patterning of neural cells to guide neurite growth is important for developing nerve tissue engineering scaffolds, inkjet printing was used to pattern self-assembled I 3 K peptide nanofibers on RSF surfaces for directional control of PC12 cell growth. The results demonstrated that inkjet-printed peptide micro-patterns can effectively guide the cell alignment and organization on RSF scaffold surfaces, providing great potential for nerve regeneration applications. [ABSTRACT FROM AUTHOR]