An appropriate cellular response to implanted surfaces is essential for tissue regeneration and integration. It is well described that implanted materials are immediately coated with proteins from blood and interstitial fluids, and it is through this adsorbed layer that cells sense foreign surfaces. Hence, it is the adsorbed proteins, rather than the surface itself, to which cells initially respond. Diverse studies using a range of materials have demonstrated the pivotal role of extracellular adhesion proteins—fibronectin and vitronectin in particular—in cell adhesion, morphology, and migration. These events underlie the subsequent responses required for tissue repair, with the nature of cell surface interactions contributing to survival, growth, and differentiation. The pattern in which adhesion proteins and other bioactive molecules adsorb thus elicits cellular reactions specific to the underlying physicochemical properties of the material. Accordingly, in vitro studies generally demonstrate favorable cell responses to charged, hydrophilic surfaces, corresponding to superior adsorption and bioactivity of adhesion proteins. This review illustrates the mediation of cell responses to biomaterials by adsorbed proteins, in the context of osteoblasts and selected materials used in orthopedic implants and bone tissue engineering. It is recognized, however, that the periimplant environment in vivo will differ substantially from the cell–biomaterial interface in vitro. Hence, one of the key issues yet to be resolved is that of the interface composition actually encountered by osteoblasts within the sequence of inflammation and bone regeneration.

Mediation of biomaterial-cell interactions by adsorbed proteins: A review

Hemocompatibility of blood-contacting biomaterials is one of the most important criteria for their successful in vivo applicability. Thus, extensive in vitro analyses according to ISO 10993-4 are required prior to clinical applications. In this review, we summarize essential aspects regarding the evaluation of the hemocompatibility of biomaterials and the required in vitro analyses for determining the blood compatibility. Static, agitated, or shear flow models are used to perform hemocompatibility studies. Before and after the incubation of the test material with fresh human blood, hemolysis, cell counts, and the activation of platelets, leukocytes, coagulation and complement system are analyzed. Furthermore, the surface of biomaterials are evaluated concerning attachment of blood cells, adsorption of proteins, and generation of thrombus and fibrin networks.

/pdf/blood-contacting-biomaterials-in-vitro-evaluation-of-the-5g9tmbtie0.pdf

Blood-Contacting Biomaterials : In Vitro Evaluation of the Hemocompatibility

Overview of Silk Fibroin Use in Wound Dressings.

Bioprinting allows the fabrication of living constructs with custom-made architectures by spatially controlled deposition of multiple bioinks. This is important for the generation of tissue, such as osteochondral tissue, which displays a zonal composition in the cartilage domain supported by the underlying subchondral bone. Challenges in fabricating functional grafts of clinically relevant size include the incorporation of cues to guide specific cell differentiation and the generation of sufficient cells, which is hard to obtain with conventional cell culture techniques. A novel strategy to address these demands is to combine bioprinting with microcarrier technology. This technology allows for the extensive expansion of cells, while they form multi-cellular aggregates, and their phenotype can be controlled. In this work, living constructs were fabricated via bioprinting of cell-laden microcarriers. Mesenchymal stromal cell (MSC)-laden polylactic acid microcarriers, obtained via static culture or spinner flask expansion, were encapsulated in gelatin methacrylamide-gellan gum bioinks, and the printability of the composite material was studied. This bioprinting approach allowed for the fabrication of constructs with high cell concentration and viability. Microcarrier encapsulation improved the compressive modulus of the hydrogel constructs, facilitated cell adhesion, and supported osteogenic differentiation and bone matrix deposition by MSCs. Bilayered osteochondral models were fabricated using microcarrier-laden bioink for the bone compartment. These findings underscore the potential of this new microcarrier-based biofabrication approach for bone and osteochondral constructs.

https://iopscience.iop.org/article/10.1088/1758-5082/6/3/035020/pdf

Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers.

In this study, we report the design and fabrication of a novel biocompatible sponge with excellent antibacterial property, making it a promising material for wound dressings. The sponge is formed by grafting amoxicillin onto regenerated bacterial cellulose (RBC). It was observed that the grafted RBC could enhance the antibacterial activity against fungus, Gram-negative, and Gram-positive bacteria. The morphology of strains treated with the grafted RBC and fluorescent stain results further demonstrated the antibacterial ability of the fabricated sponge. Moreover, a cytocompatibility test evaluated in vitro and in vivo illustrates the nontoxicity of the prepared sponge. More importantly, the wound infection model reveals that this sponge can accelerate the wound healing in vivo. This work indicates the novel sponge has the huge potential in wound dressing application for clinical use.

Flexible Amoxicillin-Grafted Bacterial Cellulose Sponges for Wound Dressing: In Vitro and in Vivo Evaluation

Enhanced Cell-Material Interactions through the Biofunctionalization of Polymeric Surfaces with Engineered Peptides

Polylactic acid organogel as versatile scaffolding technique

Most of the synthetic polymeric biomaterials used for biomedical applications lack of functional groups able to specifically instruct cells to unlock their potential for tissue regeneration. Surface modification strategies are able to overcome this limitation by introducing bioactive cues. In this study, several functionalization approaches are analyzed. Wet chemical methods such as controlled hydrolysis of polyesters followed by biomolecules grafting by carbodiimide chemistry are simple and versatile approaches, able to succesfully improve the bioactivity of devices with virtually any architecture. Grafting of short peptides, extracellular matrix proteins (ECM) or engineered protein-like recombinamers are promising techniques to improve cell adhesion to biomaterials, including polylactic acid (PLA) and its derivatives. ECM molecules and recombinamers can present more effectively bioactive signals, even in presence of competing, nonadhesive serum proteins. Besides adhesion, surface modifications intended to improve cell attachment, play a role on other cell responses, such as migratory potential. Collagen coating were shown to enhance the expression of the migratory receptor CXCR4 in mesenchymal stromal cells, when compared to short RGD peptides, while the modality of functionalization (covalent vs. physisorbed) tuned the rate of cell migration from PLA-based microcarriers. This multiple effects have to be taken into account when designing biomaterials for cell delivery and tissue engineering. Furthermore, as we aim to recapitulate in vitro the complexity of native tissues, alternative strategies based on the generation of decellularized polymer scaffold rich in cell-deposited ECM are proposed.

Biofunctionalization of polymeric surfaces

The integration of implants or medical devices into the body tissues requires of good cell–material interactions. However, most polymeric materials used for these applications lack on biological cues, which enhanced mid- and long-term implant failure due to weak integration with the surrounding tissue. Commonly used strategies for tissue–material integration focus on functionalization of the material surface by means of natural proteins or short peptides. However, the use of these biomolecules involves major drawbacks such as immunogenic problems and oversimplification of the constructs. Here, designed elastin-like recombinamers (ELRs) are used to enhance poly(methyl methacrylate) surface properties and compared against the use of short peptides. In this study, cell response has been analysed for different functionalization conditions in the presence and absence of a competing protein, which interferes on surface–cell interaction by unspecific adsorption on the interface. The study has shown that ELRs can induce higher rates of cell attachment and stronger cell anchorages than short peptides, being a better choice for surface functionalization.

/pdf/biomolecular-functionalization-for-enhanced-cell-material-1oqsldkwyc.pdf

Biomolecular functionalization for enhanced cell-material interactions of poly(methyl methacrylate) surfaces.

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Enhanced Cell-Material Interactions through the Biofunctionalization of Polymeric Surfaces with Engineered Peptides

Polylactic acid organogel as versatile scaffolding technique

Biofunctionalization of polymeric surfaces

Biomolecular functionalization for enhanced cell-material interactions of poly(methyl methacrylate) surfaces.