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Adenovirus vectors offer a platform technology for vaccine development. The value of the platform has been proven during the COVID-19 pandemic. Although good stability at 2–8 °C is an advantage of the platform, non-cold-chain distribution would have substantial advantages, in particular in low-income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving excellent recovery of adenovirus-vectored vaccines after storage at temperatures as high as 45 °C. This matrix is, however, prone to fragmentation and so not suitable for clinical translation. Here, we report an investigation of alternative fibrous matrices which might be suitable for clinical use. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components, finding that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to identify a potentially biocompatible matrix with encouraging performance. We discuss remaining challenges for transfer of the technology into clinical use, including reliability of process performance.

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Self-assembling peptides (SAPs) have attracted interest due to their potential value in therapeutics. The 11-residue family of peptides (P11-X), are able to self-assemble hierarchically into β-sheet tapes with higher order structures (ribbons, fibrils and fibres) being produced depending on peptide concentration. Previous studies of P11-X peptides aimed at tissue repair focused on hydrogel formats where their potential for deposition of hard tissue minerals in vivo was demonstrated due in part to their ability to mimic the physiochemical properties of natural extracellular matrix (ECM) of bone. However, SAP hydrogels are often associated with inherently weak and transient mechanical properties, which make their handling and fixation challenging in large load-bearing tissue defects. Accordingly, to engineer a more robust scaffold, the present research demonstrates the feasibility of producing electrospun webs composed of a biodegradable polymer, poly (e-caprolactone) (PCL) commixed with either P11-4 (Ac-QQRFEWEFEQQ-Am) or P11-8 (Ac QQRFOWOFEQQ-Am) self-assembling peptides. Morphological features of the electrospun webs investigated via scanning and transmission electron microscopies (SEM and TEM) revealed that PCL/P11-4 and PCL/P11-8 electrospun webs contain fibres in both nano- (10–100 nm) and submicron ranges (100–700 nm), whereas PCL fibre webs, produce a predominantly submicron fibre distribution. Homogeneous distribution of SAPs within the electrospun fibres was revealed via confocal microscopy. . Furthermore, it was discovered by spectroscopic analysis that SAPs exist entirely in their monomeric state in the electrospinning solution, and convert from monomeric form to β-sheet secondary conformation when converted into fibres. PCL/SAP fibres were shown to exhibit enhanced hydrophilicity compared to PCL-only fibres, and induce no cytotoxic response when cultured with L929 mouse fibroblasts. A study of the release kinetics of SAP from PCL fibres II in simulated conditions of biological pH (neutral pH of 7.4) after 7 days revealed at least 75% of P11-4 and 45% of P11-8 still remained, suggesting potential for long-term therapeutic delivery. Finally the ability of SAP embedded PCL fibrous scaffold to nucleate and support growth of bone minerals was investigated using two in vitro assays, specifically the simulated body fluid (SBF) method and the in vitro nucleation (IVN) tank method. PCL/SAP fibres were found to nucleate and support spheroidal growth of hydroxyapatite crystals and were capable of comparable mineral nucleation performance as SAP hydrogels.

Cell-free translational strategies are needed to accelerate the repair of mineralised tissues, particularly large bone defects, using minimally invasive approaches. Regenerative bone scaffolds should ideally mimic aspects of the tissue's ECM over multiple length scales and enable surgical handling and fixation during implantation in vivo. Leveraging the knowledge gained with bioactive self-assembling peptides (SAPs) and SAP-enriched electrospun fibres, we presented a cell free approach for promoting mineralisation via apatite deposition and crystal growth, in vitro, of SAP-enriched nonwoven scaffolds. The nonwoven scaffold was made by electrospinning poly(epsilon-caprolactone) (PCL) in the presence of either peptide P11-4 (Ac-QQRFEWEFEQQ-Am) or P11-8 (Ac-QQRFOWOFEQQ-Am), in light of the polymer's fibre forming capability and its hydrolytic degradability as well as the well-known apatite nucleating capability of SAPs. The 11-residue family of peptides (P11-X) has the ability to self-assemble into beta-sheet ordered structures at the nano-scale and to generate hydrogels at the macroscopic scale, some of which are capable of promoting biomineralisation due to their apatite-nucleating capability. Both variants of SAP-enriched nonwoven used in this study were proven to be biocompatible with murine fibroblasts and supported nucleation and growth of apatite minerals in simulated body fluid (SBF) in vitro. The fibrous nonwoven provided a structurally robust scaffold, with the capability to control SAP release behaviour. Up to 75% of P11-4 and 45% of P11-8 were retained in the fibres after 7-day incubation in aqueous solution at pH 7.4. The encapsulation of SAP in a nonwoven system with apatite-forming as well as localised and long-term SAP delivery capabilities is appealing as a potential means of achieving cost-effective bone repair therapy for critical size defects.

Self-assembling peptides (SAPs) have shown to offer great promise in therapeutics and have the ability to undergo self-assembly and form ordered nanostructures. However SAP gels are often associated with inherent weak and transient mechanical properties and incorporation of them into polymeric matrices is a route to enhance their mechanical stability. The aim of this work was to incorporate P11-8 peptide (CH3COQQRFOWOFEQQNH2) within poly(epsilon-caprolactone) (PCL) fibrous webs via one-step electrospinning, aiming to establish the underlying relationships between spinning process, molecular peptide conformation, and material internal architecture. Electrospinning of PCL solutions (6% w/w) in hexafluoro-2-propanol (HFIP) containing up to 40 mg/ml P11-8 resulted in the formation of fibres in both nano- (10-100 nm) and submicron range (100-700 nm), in contrast to PCL only webs, which displayed a predominantly submicron fibre distribution. FTIR and CD spectroscopy on both PCL/peptide solutions and resulting electrospun webs revealed monomeric and beta-sheet secondary conformation, respectively, suggesting the occurrence of peptide self-assembly during electrospinning due to solvent evaporation. The peptide concentration (0 -> 40 mg/ml) was found to primarily affect the internal structure of the fabric at the nano-scale, whilst water as well as cell culture medium contact angles were dramatically decreased. Nearly no cytotoxic response (> 90% cell viability) was observed when L929 mouse fibroblasts were cultured in contact with electrospun peptide loaded samples. This novel nanofibrous architecture may be the basis for an interesting material platform for e.g. hard tissue repair, in light of the presence of the self assembled P11-8 in the PCL fibrous structure.

Self-assembling peptides (SAPs) have the ability to spontaneously assemble into ordered nanostructures enabling the manufacture of \"designer\" nanomaterials. The reversible molecular association of SAPs has been shown to offer great promise in therapeutics via for example, the design of biomimetic assemblies for hard tissue regeneration. This could be further exploited for novel nano/micro diagnostic tools. However, self-assembled peptide gels are often associated with inherent weak and transient mechanical properties. Their incorporation into polymeric matrices has been considered as a potential strategy to enhance their mechanical stability. This study focuses on the incorporation of an 11-residue peptide, P11-8 (peptide sequence: CH3CO-Gln-Gln-Arg-Phe-Orn-Trp-Orn-Phe-Glu-Gln-Gln-NH2) within a fibrous scaffold of poly ({\\epsilon}-caprolactone) (PCL). In this study an electrospinning technique was used to fabricate a biomimetic porous scaffold out of a solution of P11-8 and PCL which resulted in a biphasic structure composed of submicron fibers (diameter of 100-700 nm) and nanofibers (diameter of 10-100 nm). The internal morphology of the fabric and its micro-structure can be easily controlled by changing the peptide concentration. The secondary conformation of P11-8 was investigated in the as-spun fibers by ATR-FTIR spectroscopy and it is shown that peptide self-assembly into \\{b}eta-sheet tapes has taken place during fiber formation and the deposition of the fibrous web.