The lack of a functional vascular supply has, to a large extent, hampered the whole range of clinical applications of ‘successful’ laboratory‐based bone tissue engineering strategies. To the present, ...grafts have been dependent on post‐implant vascularization, which jeopardizes graft integration and often leads to its failure. For this reason, the development of strategies that could effectively induce the establishment of a microcirculation in the engineered constructs has become a major goal for the tissue engineering research community. This review addresses the role and importance of the development of a vascular network in bone tissue engineering and provides an overview of the most up to date research efforts to develop such a network.
The lack of a functional vasculature is recognized by the tissue engineering scientific community as the major hurdle for the clinical success of the field. Although this problem is common to most the engineered tissues there are differences inherent to the different physiologies and regenerative strategies. Therefore, this paper addresses the vascularization problem but specifically focuses on the context of bone tissue engineering.
Injectable hyaluronic acid (HA)-based hydrogels compose a promising class of materials for tissue engineering and regenerative medicine applications. However, their limited mechanical properties ...restrict the potential range of application. In this study, cellulose nanocrystals (CNCs) were employed as nanofillers in a fully biobased strategy for the production of reinforced HA nanocomposite hydrogels. Herein we report the development of a new class of injectable hydrogels composed of adipic acid dihydrazide-modified HA (ADH-HA) and aldehyde-modified HA (a-HA) reinforced with varying contents of aldehyde-modified CNCs (a-CNCs). The obtained hydrogels were characterized in terms of internal morphology, mechanical properties, swelling, and degradation behavior in the presence of hyaluronidase. Our findings suggest that the incorporation of a-CNCs in the hydrogel resulted in a more organized and compact network structure and led to stiffer hydrogels (maximum storage modulus, E', of 152.4 kPa for 0.25 wt % a-CNCs content) with improvements of E' up to 135% in comparison to unfilled hydrogels. In general, increased amounts of a-CNCs led to lower equilibrium swelling ratios and higher resistance to degradation. The biological performance of the developed nanocomposites was assessed toward human adipose derived stem cells (hASCs). HA-CNCs nanocomposite hydrogels exhibited preferential cell supportive properties in in vitro culture conditions due to higher structural integrity and potential interaction of microenvironmental cues with CNC's sulfate groups. hASCs encapsulated in HA-CNCs hydrogels demonstrated the ability to spread within the volume of gels and exhibited pronounced proliferative activity. Together, these results demonstrate that the proposed strategy is a valuable toolbox for fine-tuning the structural, biomechanical, and biochemical properties of injectable HA hydrogels, expanding their potential range of application in the biomedical field.
Researchers have many times turned their attention to nature and biological processes to develop novel technologies and materials. In a medical perspective, nature-based products are believed to be a ...strategic alternative approach to the use of fully synthetic materials, particularly in the design of medical devices. In the past decades, marine organisms have become the focus of considerable attention as potential sources of valuable materials. The sustainable exploitation and valorisation of natural marine resources constitutes a highly attractive and strategic platform for the development of novel biomaterials, with both economic and environmental benefits. In this context, algae are known to synthesise large quantities of polysaccharides and are well established sources of these particularly interesting molecules, many of which are known for their applicability in the design of biomaterials. Agar, carrageenan and alginates are some of the most known examples, and their uses can range from food to biomedical applications. However, few of the world’s available seaweed species are used commercially. Among the three main divisions of macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), the green algae remain largely unexploited in this biomedical arena. While the demand for novel materials and technologies increases, so does the research of unexploited marine green algae including its unique polysaccharide ulvan.
Polyacrylic acid (PAA) and its derivatives are commonly used as essential matrices in wound dressings, but their weak wet adhesion restricts the clinical application. To address this issue, a ...PAA‐based coacervate hydrogel with strong wet adhesion capability is fabricated through a facile mixture of PAA copolymers with isoprenyl oxy poly(ethylene glycol) ether and tannic acid (TA). The poly(ethylene glycol) segments on PAA prevent the electrostatic repulsion among the ionized carboxyl groups and absorbed TA to form coacervates. The absorbed TA provides solid adhesion to dry and wet substrates via multifarious interactions, which endows the coacervate with an adhesive strength to skin of 23.4 kPa and 70% adhesion underwater. This coacervate achieves desirable self‐healing and extensible properties suitable for frequently moving joints. These investigations prove that the coacervate has strong antibacterial activity, facilitates fibroblast migration, and modulates M1/M2 polarization of macrophages. In vivo hemorrhage experiments further confirm that the coacervate dramatically shortens the hemostatic time from hundreds to tens of seconds. In addition, full‐thickness skin defect experiments demonstrate that the coacervate achieves the best therapeutic effect by significantly promoting collagen deposition, angiogenesis, and epithelialization. These results demonstrate that a PAA‐based coacervate hydrogel is a promising wound dressing for medical translation.
A polyacrylic acid (PAA)‐based coacervate hydrogel with robust wet adhesion and self‐healing capabilities is obtained through a mixture of PAA copolymers and tannic acid. This coacervate hydrogel promotes fibroblast migration, regulates macrophage polarization, kills bacteria, and facilitates wound healing via improving collagen deposition, angiogenesis, and re‐epithelialization, suggesting its considerable potential as a wound dressing.
Collagens are the most abundant high molecular weight proteins in both invertebrate and vertebrate organisms, including mammals, and possess mainly a structural role, existing different types ...according with their specific organization in distinct tissues. From this, they have been elected as one of the key biological materials in tissue regeneration approaches. Also, industry is constantly searching for new natural sources of collagen and upgraded methodologies for their production. The most common sources are from bovine and porcine origin, but other ways are making their route, such as recombinant production, but also extraction from marine organisms like fish. Different organisms have been proposed and explored for collagen extraction, allowing the sustainable production of different types of collagens, with properties depending on the kind of organism (and their natural environment) and extraction methodology. Such variety of collagen properties has been further investigated in different ways to render a wide range of applications. The present review aims to shed some light on the contribution of marine collagens for the scientific and technological development of this sector, stressing the opportunities and challenges that they are and most probably will be facing to assume a role as an alternative source for industrial exploitation.
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Bioengineered soft tissues on any meaningful scale or complexity must incorporate aspects of the functional tissue, namely a vasculature, providing cells oxygen and nutrients critical ...for their survival. However, the ability of tissue engineering strategies to promote a fast revascularization is critically limited. Particularly in endodontic regenerative therapies, the complicated anatomy of the root canal system, and the narrow apical access limit the supply of new blood vessels and pulp tissue ingrowth.
Here we characterize the viscoelastic and microstructural properties of a class of injectable hyaluronic acid (HA) hydrogels formed in situ, reinforced with cellulose nanocrystals (CNCs) and enriched with platelet lysate (PL), and test its ability to promote cells recruitment and proangiogenic activity in vitro. The incorporation of CNCs enhanced the stability of the materials against hydrolytic and enzymatic degradation. Moreover, the release of the chemotactic and pro-angiogenic growth factors (GFs) (PDGF and VEGF) from the PL-laden hydrogels showed an improved sustained profile proportional to the amount of incorporated CNCs. The PL-laden hydrogels exhibited preferential supportive properties of encapsulated human dental pulp cells (hDPCs) in in vitro culture conditions.
Finally, PL-laden hydrogels stimulated chemotactic and pro-angiogenic activity by promoting hDPCs recruitment and cell sprouting in hDPCs/human umbilical vein endothelial cell co-cultures in vitro, and in an ex vivo model. These results support the use of the combined system as a scaffold for GFs delivery and cells recruitment, thereby exhibiting great clinical potential in treating injuries in vascularized tissues.
Innovative strategies for improved chemotactic and pro-angiogenic features of TE constructs are needed. In this study, we developed an injectable HA/CNC/PL hydrogel with improved structural and biologic properties, that not only provide a sustained release of chemotactic and proangiogenic GFs from PL but also enhance the cells’ viability and angiogenic activity. As a result of their unique traits, the developed hydrogels are ideally suited to simultaneously act as a GFs controlled delivery system and as a supportive matrix for cell culture, recruitment, and revascularization induction, holding great potential for the regeneration of vascularized soft tissues, such as the dentin-pulp complex.
In this study, we present a novel chitosan-intercalated montmorillonite/poly(vinyl alcohol) (OMMT/PVA) nanofibrous mesh as a microenvironment for guiding differentiation of human dental pulp stem ...cells (hDPSCs) toward neuronlike cells. The OMMT was prepared through ion exchange reaction between the montmorillonite (MMT) and chitosan. The PVA solutions containing various concentrations of OMMT were electrospun to form 3D OMMT-PVA nanofibrous meshes. The biomechanical and biological characteristics of the nanofibrous meshes were evaluated by ATR-FTIR, XRD, SEM, MTT, and LDH specific activity, contact angle, and DAPI staining. They were carried out for mechanical properties, overall viability, and toxicity of the cells. The hDPSCs were seeded on the prepared scaffolds and induced with neuronal specific differentiation media at two differentiation stages (2 days at preinduction stage and 6 days at induction stage). The neural differentiation of the cells cultured on the meshes was evaluated by determining the expression of Oct-4, Nestin, NF-M, NF-H, MAP2, and βIII-tubulin in the cells after preinduction, at induction stages by real-time PCR (RT-PCR) and immunostaining. All the synthesized nanofibers exhibited a homogeneous morphology with a favorable mechanical behavior. The population of the cells differentiated into neuronlike cells in all the experimental groups was significantly higher than that in control group. The expression level of the neuronal specific markers in the cells cultured on 5% OMMT/PVA meshes was significantly higher than the other groups. This study demonstrates the feasibility of the OMMT/PVA artificial nerve graft cultured with hDPSCs for regeneration of damaged neural tissues. These fabricated matrices may have a potential in neural tissue engineering applications.
Novel silicate nanoplatelets that induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) in the absence of any osteoinductive factor are reported. The presence of the silicate ...triggers a set of events that follows the temporal pattern of osteogenic differentiation. These findings underscore the potential applications of these silicate nanoplatelets in designing bioactive scaffolds for musculoskeletal tissue engineering.
Chronic skin wounds are the leading cause of nontraumatic foot amputations worldwide and present a significant risk of morbidity and mortality due to the lack of efficient therapies. The intrinsic ...characteristics of hydrogels allow them to benefit cutaneous healing essentially by supporting a moist environment. This property has long been explored in wound management to aid in autolytic debridement. However, chronic wounds require additional therapeutic features that can be provided by a combination of hydrogels with biochemical mediators or cells, promoting faster and better healing. We survey hydrogel-based approaches with potential to improve the healing of chronic wounds by reviewing their effects as observed in preclinical models. Topics covered include strategies to ablate infection and resolve inflammation, the delivery of bioactive agents to accelerate healing, and tissue engineering approaches for skin regeneration. The article concludes by considering the relevance of treating chronic skin wounds using hydrogel-based strategies.
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