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      From Dermal Patch to Implants—Applications of Biocomposites in Living Tissues

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          Abstract

          Composites are composed of two or more materials, displaying enhanced performance and superior mechanical properties when compared to their individual components. The use of biocompatible materials has created a new category of biocomposites. Biocomposites can be applied to living tissues due to low toxicity, biodegradability and high biocompatibility. This review summarizes recent applications of biocomposite materials in the field of biomedical engineering, focusing on four areas—bone regeneration, orthopedic/dental implants, wound healing and tissue engineering.

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          Tensional homeostasis and the malignant phenotype.

          Matthew J. Paszek, Nastaran Zahir, Kandice R. Johnson … (2005)
          Tumors are stiffer than normal tissue, and tumors have altered integrins. Because integrins are mechanotransducers that regulate cell fate, we asked whether tissue stiffness could promote malignant behavior by modulating integrins. We found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation. Matrix stiffness perturbs epithelial morphogenesis by clustering integrins to enhance ERK activation and increase ROCK-generated contractility and focal adhesions. Contractile, EGF-transformed epithelia with elevated ERK and Rho activity could be phenotypically reverted to tissues lacking focal adhesions if Rho-generated contractility or ERK activity was decreased. Thus, ERK and Rho constitute part of an integrated mechanoregulatory circuit linking matrix stiffness to cytoskeletal tension through integrins to regulate tissue phenotype.
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            Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

            I Acerbi, L Cassereau, I Dean … (2015)
            Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta.
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              Fabrication methods of porous metals for use in orthopaedic applications.

              Garrett Ryan, Abhay Pandit, Dimitrios Apatsidis (2006)
              Implant stability is not only a function of strength but also depends on the fixation established with surrounding tissues [Robertson DM, Pierre L, Chahal R. Preliminary observations of bone ingrowth into porous materials. J Biomed Mater Res 1976;10:335-44]. In the past, such stability was primarily achieved using screws and bone cements. However, more recently, improved fixation can be achieved by bone tissue growing into and through a porous matrix of metal, bonding in this way the implant to the bone host. Another potentially valuable property of porous materials is their low elastic modulus. Depending on the porosity, moduli can even be tailored to match the modulus of bone closer than solid metals can, thus reducing the problems associated with stress shielding. Finally, extensive body fluid transport through the porous scaffold matrix is possible, which can trigger bone ingrowth, if substantial pore interconnectivity is established [Cameron HU, Macnab I, Pilliar RM. A porous metal system for joint replacement surgery. Int J Artif Organs 1978;1:104-9; Head WC, Bauk DJ, Emerson Jr RH. Titanium as the material of choice for cementless femoral components in total hip arthroplasty. Clin Orthop 1995;85-90]. Over the years, a variety of fabrication processes have been developed, resulting in porous implant substrates that can address unresolved clinical problems. The advantages of metals exhibiting surface or bulk porosity have led researchers to conduct systematic research aimed at clarifying the fundamental aspects of interactions between porous metals and hard tissue. This review summarises all known methods for fabricating such porous metallic scaffolds.
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                Author and article information

                Contributors
                Frank Ko: Role: Academic Editor
                Abbas Milani: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 24 January 2020
                Publication date Collection: February 2020
                Volume: 25
                Issue: 3
                Electronic Location Identifier: 507
                Affiliations
                [1 ]Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada; kvalente@ 123456uvic.ca
                [2 ]Department of Chemistry, University of Victoria, Victoria, BC V8P 5C2, Canada; agbrolo@ 123456uvic.ca
                Author notes
                [* ]Correspondence: suleman@ 123456uvic.ca ; Tel.: +1-250-721-6039
                Article
                Publisher ID: molecules-25-00507
                DOI: 10.3390/molecules25030507
                PMC ID: 7037691
                PubMed ID: 31991641
                SO-VID: d913f146-4661-4645-95ae-34712662b688
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 23 November 2019
                Date accepted : 20 January 2020
                Categories
                Subject: Review

                Keywords: biocomposites,scaffolds,biocompatibility,bone regeneration,orthopedic implants,wound healing,tissue engineering
                Data availability:
                Keywords: biocomposites, scaffolds, biocompatibility, bone regeneration, orthopedic implants, wound healing, tissue engineering

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