Effect of inorganic and organic bioactive signals decoration on the biological performance of chitosan scaffolds for bone tissue engineering.

The present work is focused on the design of a bioactive chitosan-based scaffold functionalized with organic and inorganic signals to provide the biochemical cues for promoting stem cell osteogenic commitment. The first approach is based on the use of a sequence of 20 amino acids corresponding to a 68-87 sequence in knuckle epitope of BMP-2 that was coupled covalently to the carboxyl group of chitosan scaffold. Meanwhile, the second approach is based on the biomimetic treatment, which allows the formation of hydroxyapatite nuclei on the scaffold surface. Both scaffolds bioactivated with organic and inorganic signals induce higher expression of an early marker of osteogenic differentiation (ALP) than the neat scaffolds after 3 days of cell culture. However, scaffolds decorated with BMP-mimicking peptide show higher values of ALP than the biomineralized one. Nevertheless, the biomineralized scaffolds showed better cellular behaviour than neat scaffolds, demonstrating the good effect of hydroxyapatite deposits on hMSC osteogenic differentiation. At long incubation time no significant difference among the biomineralized and BMP-activated scaffolds was observed. Furthermore, the highest level of Osteocalcin expression (OCN) was observed for scaffold with BMP2 mimic-peptide at day 21. The overall results showed that the presence of bioactive signals on the scaffold surface allows an osteoinductive effect on hMSC in a basal medium, making the modified chitosan scaffolds a promising candidate for bone tissue regeneration.

The accuracy of intra-oral scanners in full arch implant rehabilitation: a narrative review.

This narrative review aims to study the accuracy of different intra-oral scanner (IOS) devices already available on the market. The accuracy emerged during in vitro, in vivo and ex vivo studies made with IOS devices during the scan of a full arch implant rehabilitation that have been analysed to evaluate which device may be the most suitable in this clinical situation. The literature review was performed by searching topics and keywords using the PubMed and Medline databases, for example, 'digital workflow', 'full arch', 'full arch implant rehabilitation' and 'accuracy of IOS'. Inclusion and exclusion criteria for studies were: correct IMRAD (introduction, methods, results and discussion) structure; article with clear and detailed objectives; consistency of the articles with the purpose of the review; two-year range from the year of publication of the article; reproducible materials and methods; and correct follow-up. Most of the intra-oral scanners employed in vitro provided acceptable accuracy (below a threshold of 150 µm). The main parameters identified for their influence on precision were interim plant distance, body scan design, scanning pattern and operator experience. Even though literature is limited, significant differences emerged between the different models of intra-oral scanners evaluated in the studies considered within this review.

Recent Advances in Functionalized Electrospun Membranes for Periodontal Regeneration.

Periodontitis is a global, multifaceted, chronic inflammatory disease caused by bacterial microorganisms and an exaggerated host immune response that not only leads to the destruction of the periodontal apparatus but may also aggravate or promote the development of other systemic diseases. The periodontium is composed of four different tissues (alveolar bone, cementum, gingiva, and periodontal ligament) and various non-surgical and surgical therapies have been used to restore its normal function. However, due to the etiology of the disease and the heterogeneous nature of the periodontium components, complete regeneration is still a challenge. In this context, guided tissue/bone regeneration strategies in the field of tissue engineering and regenerative medicine have gained more and more interest, having as a goal the complete restoration of the periodontium and its functions. In particular, the use of electrospun nanofibrous scaffolds has emerged as an effective strategy to achieve this goal due to their ability to mimic the extracellular matrix and simultaneously exert antimicrobial, anti-inflammatory and regenerative activities. This review provides an overview of periodontal regeneration using electrospun membranes, highlighting the use of these nanofibrous scaffolds as delivery systems for bioactive molecules and drugs and their functionalization to promote periodontal regeneration.

Biomimetic cellulose-based superabsorbent hydrogels for treating obesity.

In the treatment of obesity, nutritional and behavioral modifications are difficult to implement and maintain. Since vegetable consumption is a fundamental part of many dietary interventions and daily nutrient requirements, we developed a novel cellulose-based superabsorbent hydrogel (CB-SAH) platform, inspired by the composition and mechanical properties of raw vegetables, as a mechanobiological therapy. The CB-SAHs properties were studied in a simulated gastrointestinal environment, while their impact on gut tissue was investigated by an ex vivo organ culture (EVOC) model. Functional fibers and raw vegetables were used as reference. CB-SAHs demonstrated orders of magnitude higher elasticity in comparison to the tested functional fibers, however performed similar to the tested raw vegetables. Notably, the biomimetic CB-SAHs with elasticity levels similar to raw vegetables showed benefits in preserving and regulating the gut tissue in the EVOC model. Non-systemic oral mechanotherapeutics based on this technology were advanced through clinical studies, with a first product cleared as an aid for weight management in the US and Europe.

Semi-interpenetrating polymer network cryogels based on poly(ethylene glycol) diacrylate and collagen as potential off-the-shelf platforms for cancer cell research.

In the present work, we investigated the potential of novel semi-interpenetrating polymer network (semi-IPN) cryogels, obtained through ultraviolet exposure of aqueous mixtures of poly(ethylene glycol) diacrylate and type I collagen, as tunable off-the-shelf platforms for 3D cancer cell research. We synthesized semi-IPN cryogels with variable collagen amounts (0.1% and 1% w/v) and assessed the effect of collagen on key cryogel properties for cell culture, for example, porosity, degradation rate and mechanical stiffness. Then, we investigated the ability of the cryogels to sustain the long-term growth of two pancreatic ductal adenocarcinoma (PDAC) cell populations, the parenchymal Panc1 cells and their derived cancer stem cells. Results revealed that both cell lines efficiently infiltrated, attached and expanded in the cryogels over a period of 14 days. However, only when grown in the cryogels with the highest collagen concentration, both cell lines reproduced their characteristic growth pattern previously observed in collagen-enriched organotypic cultures, biomimetic of the highly fibrotic PDAC stroma. Cellular preembedding in Matrigel, that is, the classical approach to develop/grow organoids, interfered with an efficient intra-scaffold migration and growth. Although preliminary, these findings highlight the potential of the proposed cryogels as reproducible and tunable cancer cell research platforms.

Marine collagen and its derivatives: Versatile and sustainable bio-resources for healthcare.

In the last two decades, marine collagen has attracted great scientific and industrial interest as a 'blue resource', with potential for use in various health-related sectors, such as food, medicine, pharmaceutics and cosmetics. In particular, the large availability of polluting by-products from the fish processing industry has been the key factor driving the research towards the conversion of these low cost by-products (e.g. fish skin and scales) into collagen-based products with high added value and low environmental impact. After addressing the extraction of collagen from aquatic sources and its physicochemical properties, this review focuses on the use of marine collagen and its derivatives (e.g. gelatin and peptides) in different healthcare sectors. Particular attention is given to the bioactive properties of marine collagen that are being explored in preclinical and clinical studies, and pave the way to an increased demand for this biomaterial in the next future. In this context, in addition to the use of native collagen for the development of tissue engineering or wound healing devices, particularly relevant is the use of gelatin and peptides for the development of dietary supplements and nutraceuticals, specifically directed to weight management and glycemic control. The marine collagen market is also briefly discussed to highlight the opportunities and the most profitable areas of interest.

An insight on type I collagen from horse tendon for the manufacture of implantable devices.

Type I collagen is the most abundant protein of the human body. Due to its favourable properties, collagen extracted from animal tissues is adopted to manufacture a wide range of devices for biomedical applications. Compared to bovine and porcine collagens, which are the most largely used, equine collagen is free from the risk of zoonosis, has no reported immune reactions, and has not religious constraints. In this work, a recently available type I collagen extracted from horse tendon was evaluated and compared with a commercially available collagen isoform derived from the same species and tissue. Detailed physical, chemical and biological investigations were performed, in agreement with the requirements of the current standard for the characterization of type I collagen to be used for the manufacture of Tissue Engineering Medical Products. To the best of our knowledge, this is the first report on the complete primary structure of the investigated collagen.

Potential of Electrospun Poly(3-hydroxybutyrate)/Collagen Blends for Tissue Engineering Applications.

In this work, tunable nonwoven mats based on poly(3-hydroxybutyrate) (PHB) and type I collagen (Coll) were successfully produced by electrospinning. The PHB/Coll weight ratio (fixed at 100/0, 70/30, and 50/50, resp.) was found to control the morphological, thermal, mechanical, and degradation properties of the mats. Increasing collagen amounts led to larger diameters of the fibers (in the approximate range 600-900 nm), while delaying their thermal decomposition (from 245°C to 262°C). Collagen also accelerated the hydrolytic degradation of the mats upon incubation in aqueous medium at 37°C for 23 days (with final weight losses of 1%, 15%, and 23% for 100/0, 70/30, and 50/50 samples, resp.), as a result of increased mat wettability and reduced PHB crystallinity. Interestingly, 70/30 meshes were the ones displaying the lowest stiffness (~116 MPa; p < 0.05 versus 100/0 and 50/50 meshes), while 50/50 samples had an elastic modulus comparable to that of 100/0 ones (~250 MPa), likely due to enhanced physical crosslinking of the collagen chains, at least at high protein amounts. All substrates were also found to allow for good viability and proliferation of murine fibroblasts, up to 6 days of culture. Collectively, the results evidenced the potential of as-spun PHB/Coll meshes for tissue engineering applications.

Development of semi- and grafted interpenetrating polymer networks based on poly(ethylene glycol) diacrylate and collagen.

PURPOSE: The objective of this work was to develop composite hydrogels based on poly(ethylene glycol) diacrylate (PEGDA) and collagen (Coll), potentially useful for biomedical applications. METHODS: Semi-interpenetrating polymer networks (semi-IPNs) were obtained by photo-stabilizing aqueous solutions of PEGDA and acrylic acid (AA), in the presence of collagen. Further grafting of the collagen macromolecules to the PEGDA/poly(AA) network was achieved by means of a carbodiimide-mediated crosslinking reaction. The resulting hydrogels were characterized in terms of swelling capability, collagen content and mechanical properties. RESULTS AND CONCLUSIONS: The grafting procedure was found to significantly improve the mechanical stability of the IPN hydrogels, due to the establishment of covalent bonding between the PEGDA/poly(AA) and the collagen networks. The suitability of the composite hydrogels to be processed by means of stereolithography (SLA) was also investigated, toward creating biomimetic constructs with complex shapes, which might be useful either as platforms for tissue engineering applications or as tissue mimicking phantoms.

Peripheral nerve morphogenesis induced by scaffold micropatterning.

Several bioengineering approaches have been proposed for peripheral nervous system repair, with limited results and still open questions about the underlying molecular mechanisms. We assessed the biological processes that occur after the implantation of collagen scaffold with a peculiar porous micro-structure of the wall in a rat sciatic nerve transection model compared to commercial collagen conduits and nerve crush injury using functional, histological and genome wide analyses. We demonstrated that within 60 days, our conduit had been completely substituted by a normal nerve. Gene expression analysis documented a precise sequential regulation of known genes involved in angiogenesis, Schwann cells/axons interactions and myelination, together with a selective modulation of key biological pathways for nerve morphogenesis induced by porous matrices. These data suggest that the scaffold's micro-structure profoundly influences cell behaviors and creates an instructive micro-environment to enhance nerve morphogenesis that can be exploited to improve recovery and understand the molecular differences between repair and regeneration.