Biomimetic peptide enriched nonwoven scaffolds promote calcium phosphate mineralisation

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(ε-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 β-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

Poly(amino acid)-polyester graft copolymer nanoparticles for the acid-mediated release of doxorubicin

Biodegradable polymers have emerged as highly effective drug delivery vehicles. We combine N-carboxyanhydride and O-carboxyanhydride ring opening polymerisations to synthesise a poly(amino acid)-polyester graft copolymer capable of encapsulating, and subsequently releasing doxorubicin via acid-mediated hydrolysis. Consequently, the nanoparticles detailed are extremely promising vehicles for the controlled delivery of chemotherapeutic agents

An In-vivo Intraoral Defect Model for Assessing the Use of P11-4 Self-Assembling Peptide in Periodontal Regeneration

Periodontal disease is one of the most common diseases worldwide. It has a significant impact on oral health and subsequently the individual’s quality of life. However, optimal regeneration of periodontal tissues, using current treatments, has yet to be achieved. Peptide self-assembly has provided a step-change in nanobiotechnology and regenerative medicine fields. Our aim was to investigate the effects of a self-assembling peptide (SAP; P11-4) on periodontal regeneration in a preclinical model. Twenty-six bilateral maxillary critical-sized periodontal defects were created surgically in 13 rats. Defects on one side of the mouth were filled with P11-4 hydrogel; the contra-lateral defect was untreated (control). Rats were sacrificed immediately post-surgery (time 0) and after 2 and 4 weeks. Retrieved maxillae were processed for histological, immunohistochemical, and histomorphometric assessments. The results of histological analysis showed greater organization of periodontal fibers in defects treated with P11-4, at both time points, when compared to untreated defects. Histomorphometry showed that treated defects had both a significant increase in functional periodontal ligament length and a reduction in epithelial down growth after 4 weeks. At 2 weeks, treated defects showed a significant increase in expression of osteocalcin and osteoprotegerin as judged by immunohistochemistry. Also, a significantly higher osteoprotegerin/RANKL ratio was shown in treated defects. In conclusion, the results demonstrated enhanced regeneration of periodontal tissues when SAP P11-4 was used to fill periodontal defects in rats. The findings of this study suggest that SAP P11-4 is a promising novel candidate for periodontal regenerative therapy. Further investigations are required for optimization before clinical use

A biomimetic self-assembling peptide promotes bone regeneration in vivo: A rat cranial defect study

Rationally designed, pH sensitive self-assembling β-peptides (SAPs) which are capable of reversibly switching between fluid and gel phases in response to environmental triggers are potentially useful injectable scaffolds for skeletal tissue engineering applications. SAP P11-4 (CH3COQQRFEWEFEQQNH2) has been shown to nucleate hydroxyapatite mineral de novo and has been used in dental enamel regeneration. We hypothesised that addition of mesenchymal stromal cells (MSCs) would enhance the in vivo effects of P11-4 in promoting skeletal tissue repair. Cranial defects were created in athymic rats and filled with either Bio-Oss® (anorganic bone chips) or P11-4 ± human dental pulp stromal cells (HDPSCs). Unfilled defects served as controls. After 4 weeks, only those defects filled with P11-4 alone showed significantly increased bone regeneration (almost complete healing), compared to unfilled control defects, as judged using quantitative micro-CT, histology and immunohistochemistry. In silico modelling indicated that fibril formation may be essential for any mineral nucleation activity. Taken together, these data suggest that self-assembling peptides are a suitable scaffold for regeneration of bone tissue in a one step, cell-free therapeutic approach

Embodied Artificial Evolution - Artificial Evolutionary Systems in the 21st Century

Evolution is one of the major omnipresent powers in the universe that has been studied for about two centuries. Recent scientific and technical developments make it possible to make the transition from passively understanding to actively using evolutionary processes. Today this is possible in Evolutionary Computing, where human experimenters can design and manipulate all components of evolutionary processes in digital spaces. We argue that in the near future it will be possible to implement artificial evolutionary processes outside such imaginary spaces and make them physically embodied. In other words, we envision the “Evolution of Things”, rather than just the evolution of digital objects, leading to a new field of Embodied Artificial Evolution (EAE). The main objective of this paper is to present a unifying vision in order to aid the development of this high potential research area. To this end, we introduce the notion of EAE, discuss a few examples and applications, and elaborate on the expected benefits as well as the grand challenges this developing field will have to address