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Biomaterials and Antimicrobial Materials for Orthopaedic Application

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 24042

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Dr. Seung Hun Lee

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Guest Editor

Institute for Biomechanics, ETH Zurich, 8093 Zurich, Switzerland
Interests: bone tissue engineering; biomaterials; scaffold; stem cell; hydrogel

Prof. Dr. Irena Maliszewska

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Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland
Interests: synthesis of metallic nanoparticles; nanofibers; antimicrobial activity; photodynamic therapy
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Dear Colleagues,

Bone is a complex tissue that continuously undergoes dynamic biological remodelling to maintain homeostasis. However, healing in large and critical defect areas is often impaired, leading to inferior bone regeneration and extended hospitalization periods. Along with this, the increasing number of bone fractures and orthopaedic-related injuries due to an exponential growth of the elderly population has prompted researchers to explore biomaterials to address these issues. To promote bone regeneration, many therapeutic strategies have been suggested, including scaffolds, stem cells and growth factors. Moreover, antimicrobial effect has been another important factor to consider after quality due to its protection against infection. Hence, the choice of appropriate biomaterials has become one of the key success paths for orthopaedic applications.

This issue focuses on studies and applications of biomaterials and/or antimicrobial materials which are essential for orthopaedic applications. The main aim of this Special Issue is to publish original research articles that show the advanced development of biomaterials for orthopaedic application, antimicrobial scaffolding for bone tissue engineering or a comprehensive analysis of antimicrobial materials. Review articles discussing the current trends in the field of antimicrobial biomaterials in orthopaedic applications will also be considered for inclusion in this Special Issue.

Research areas may include (but are not limited to) the following:

Biomaterials for orthopaedic application;
The role of antibacterial biomaterial in regenerative medicine;
Bone tissue engineering scaffolds with antibacterial activity;
Mechanisms of action of antimicrobial nanomaterials;
Future perspectives for antimicrobial nanomaterials.

I look forward to receiving your contributions.

Dr. Seung Hun Lee
Prof. Dr. Irena Maliszewska
Guest Editors

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Keywords

biomaterials
antimicrobial materials
orthopaedic application
regenerative medicine
biocompatible polymers
scaffold
tissue engineering
bone regeneration
spine
hydrogel
cryogel
stem cell

Related Special Issue

Biomaterials and Antimicrobial Materials for Orthopaedic Application 2.0 in International Journal of Molecular Sciences

Published Papers (10 papers)

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Research

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17 pages, 2704 KiB

Open AccessArticle

Porous Zirconia Scaffolds Functionalized with Calcium Phosphate Layers and PLGA Nanoparticles Loaded with Hydrophobic Gentamicin

by Iwona Pudełko, Anna Moskwik, Konrad Kwiecień, Sven Kriegseis, Małgorzata Krok-Borkowicz, Karolina Schickle, Dorota Ochońska, Piotr Dobrzyński, Monika Brzychczy-Włoch, Jesus Gonzalez-Julian and Elżbieta Pamuła

Int. J. Mol. Sci. 2023, 24(9), 8400; https://doi.org/10.3390/ijms24098400 - 07 May 2023

Cited by 3 | Viewed by 1982

Abstract

Implant-related infections are a worldwide issue that is considered very challenging. Conventional therapies commonly end up failing; thus, new solutions are being investigated to overcome this problem. The in situ delivery of the drug at the implant site appears to be more sufficient compared to systemic antibiotic therapy. In this study, we manufactured porous zirconia scaffolds using the foam replication method. To improve their overall bioactivity, they were coated with a calcium phosphate (CaP) layer containing antibiotic-loaded degradable polymer nanoparticles (NPs) obtained by the double emulsion method to achieve the antibacterial effect additionally. Encapsulation efficiency (EE) and drug loading (DL) were superior and were equal to 99.9 ± 0.1% and 9.1 ± 0.1%, respectively. Scaffolds were analyzed with scanning electron microscopy, and their porosity was evaluated. The porosity of investigated samples was over 90% and resembled the microstructure of spongy bone. Furthermore, we investigated the cytocompatibility with osteoblast-like MG-63 cells and antimicrobial properties with Staphylococcus aureus. Scaffolds coated with a CaP layer were found non-toxic for MG-63 cells. Moreover, the presence of antibiotic-loaded nanoparticles had no significant influence on cell viability, and the obtained scaffolds inhibited bacteria growth. Provided processes of fabrication of highly porous zirconia scaffolds and surface functionalization allow minimizing the risk of implant-related infection. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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12 pages, 3279 KiB

Open AccessArticle

Effect of Fibrillization pH on Gelation Viscoelasticity and Properties of Biofabricated Dense Collagen Matrices via Gel Aspiration-Ejection

by Ehsan Rezabeigi, Gabriele Griffanti and Showan N. Nazhat

Int. J. Mol. Sci. 2023, 24(4), 3889; https://doi.org/10.3390/ijms24043889 - 15 Feb 2023

Cited by 2 | Viewed by 1882

Abstract

Reconstituted hydrogels based on the self-assembly of acid-solubilized collagen molecules have been extensively used as in vitro models and precursors in biofabrication processes. This study investigated the effect of fibrillization pH—ranging from 4 to 11—on real-time rheological property changes during the gelation of collagen hydrogels and its interplay with the properties of subsequently biofabricated dense collagen matrices generated via automated gel aspiration-ejection (GAE). A contactless, nondestructive technique was used to characterize the temporal progression in shear storage modulus (G’, or stiffness) during collagen gelation. There was a relative increase in G′ of the hydrogels from 36 to 900 Pa with an increase in gelation pH. Automated GAE, which simultaneously imparts collagen fibrillar compaction and alignment, was then applied to these precursor collagen hydrogels to biofabricate native extracellular matrix-like densified gels. In line with viscoelastic properties, only hydrogels fibrillized in the 6.5 < pH ≤ 10 range could be densified via GAE. There was an increase in both fibrillar density and alignment in the GAE-derived matrices with an increase in gelation pH. These factors, combined with a higher G′ in the alkaline precursor hydrogels, led to a significant increase in the micro-compressive modulus of GAE-densified gels of pH 9 and 10. Furthermore, NIH/3T3 fibroblast-seeded GAE-derived matrices densified from gels fibrillized in the pH range of 7 to 10 exhibited low cell mortality with >80% viability. It is anticipated that the results of this study can be potentially applicable to other hydrogel systems, as well as biofabrication techniques involving needles or nozzles, such as injection and bioprinting. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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23 pages, 4804 KiB

Open AccessArticle

Preparation and In Vitro Characterization of Magnetic CS/PVA/HA/pSPIONs Scaffolds for Magnetic Hyperthermia and Bone Regeneration

by Francisco J. T. M. Tavares, Paula I. P. Soares, Jorge Carvalho Silva and João Paulo Borges

Int. J. Mol. Sci. 2023, 24(2), 1128; https://doi.org/10.3390/ijms24021128 - 06 Jan 2023

Cited by 8 | Viewed by 1955

Abstract

Conventional bone cancer treatment often results in unwanted side effects, critical-sized bone defects, and inefficient cancer-cell targeting. Therefore, new approaches are necessary to better address bone cancer treatment and patient’s recovery. One solution may reside in the combination of bone regeneration scaffolds with magnetic hyperthermia. By incorporating pristine superparamagnetic iron oxide nanoparticles (pSPIONs) into additively manufactured scaffolds we created magnetic structures for magnetic hyperthermia and bone regeneration. For this, hydroxyapatite (HA) particles were integrated in a polymeric matrix composed of chitosan (CS) and poly (vinyl alcohol) (PVA). Once optimized, pSPIONs were added to the CS/PVA/HA paste at three different concentrations (1.92, 3.77, and 5.54 wt.%), and subsequently additively manufactured to form a scaffold. Results indicate that scaffolds containing 3.77 and 5.54 wt.% of pSPIONs, attained temperature increases of 6.6 and 7.5 °C in magnetic hyperthermia testing, respectively. In vitro studies using human osteosarcoma Saos-2 cells indicated that pSPIONs incorporation significantly stimulated cell adhesion, proliferation and alkaline phosphatase (ALP) expression when compared to CS/PVA/HA scaffolds. Thus, these results support that CS/PVA/HA/pSPIONs scaffolds with pSPIONs concentrations above or equal to 3.77 wt.% have the potential to be used for magnetic hyperthermia and bone regeneration. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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17 pages, 4307 KiB

Open AccessArticle

Preventing Antibiotic-Resistant Infections: Additively Manufactured Porous Ti6Al4V Biofunctionalized with Ag and Fe Nanoparticles

by Niko E. Putra, Marius A. Leeflang, Verena Ducret, Viorica Patrulea, Lidy E. Fratila-Apachitei, Karl Perron, Hua Ye, Jie Zhou, Iulian Apachitei and Amir A. Zadpoor

Int. J. Mol. Sci. 2022, 23(21), 13239; https://doi.org/10.3390/ijms232113239 - 31 Oct 2022

Cited by 5 | Viewed by 2096

Abstract

Implant-associated infections are highly challenging to treat, particularly with the emergence of multidrug-resistant microbials. Effective preventive action is desired to be at the implant site. Surface biofunctionalization of implants through Ag-doping has demonstrated potent antibacterial results. However, it may adversely affect bone regeneration at high doses. Benefiting from the potential synergistic effects, combining Ag with other antibacterial agents can substantially decrease the required Ag concentration. To date, no study has been performed on immobilizing both Ag and Fe nanoparticles (NPs) on the surface of additively manufactured porous titanium. We additively manufactured porous titanium and biofunctionalized its surface with plasma electrolytic oxidation using a Ca/P-based electrolyte containing Fe NPs, Ag NPs, and the combinations. The specimen’s surface morphology featured porous TiO₂ bearing Ag and Fe NPs. During immersion, Ag and Fe ions were released for up to 28 days. Antibacterial assays against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa showed that the specimens containing Ag NPs and Ag/Fe NPs exhibit bactericidal activity. The Ag and Fe NPs worked synergistically, even when Ag was reduced by up to three times. The biofunctionalized scaffold reduced Ag and Fe NPs, improving preosteoblasts proliferation and Ca-sensing receptor activation. In conclusion, surface biofunctionalization of porous titanium with Ag and Fe NPs is a promising strategy to prevent implant-associated infections and allow bone regeneration and, therefore, should be developed for clinical application. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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24 pages, 6427 KiB

Open AccessArticle

Bone-Targeting Nanoparticles of a Dendritic (Aspartic acid)₃-Functionalized PEG-PLGA Biopolymer Encapsulating Simvastatin for the Treatment of Osteoporosis in Rat Models

by Che-Wei Lin, Chih-Yun Lee, Sung-Yen Lin, Lin Kang, Yin-Chih Fu, Chung-Hwan Chen and Chih-Kuang Wang

Int. J. Mol. Sci. 2022, 23(18), 10530; https://doi.org/10.3390/ijms231810530 - 11 Sep 2022

Cited by 4 | Viewed by 1917

Abstract

Simvastatin (SIM) is a lipid-lowering drug that also promotes bone formation, but its high liver specificity may cause muscle damage, and the low solubility of lipophilic drugs limits the systemic administration of SIM, especially in osteoporosis (OP) studies. In this study, we utilized the bone-targeting moiety of dendritic oligopeptides consisting of three aspartic acid moieties (_dAsp₃) and amphiphilic polymers (poly(ethylene glycol)-block-poly(lactic-co-glycolic acid); PEG-PLGA) to create _dAsp₃-PEG-PLGA (APP) nanoparticles (NPs), which can carry SIM to treat OP. An in vivo imaging system showed that gold nanocluster (GNC)-PLGA/APP NPs had a significantly higher accumulation rate in representative bone tissues. In vivo experiments comparing low-dose SIM treatment (0.25 mg/kg per time, 2 times per week) showed that bone-targeting SIM/APP NPs could increase the bone formation effect compared with non-bone-targeting SIM/PP NPs in a local bone loss of hindlimb suspension (disuse) model, but did not demonstrate good bone formation in a postmenopausal (ovariectomized) model of systemic bone loss. The APP NPs could effectively target high mineral levels in bone tissue and were expected to reduce side effects in other organs affected by SIM. However, in vivo OP model testing showed that the same lower dose could not be used to treat different types of OP. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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13 pages, 3580 KiB

Open AccessArticle

Development of Injectable Calcium Sulfate and Self-Setting Calcium Phosphate Composite Bone Graft Materials for Minimally Invasive Surgery

by Yu-Hsun Chiu, I-Cheng Chen, Chen-Ying Su, Hsin-Hua Tsai, Tai-Horng Young and Hsu-Wei Fang

Int. J. Mol. Sci. 2022, 23(14), 7590; https://doi.org/10.3390/ijms23147590 - 08 Jul 2022

Cited by 4 | Viewed by 2548

Abstract

The demand of bone grafting is increasing as the population ages worldwide. Although bone graft materials have been extensively developed over the decades, only a few injectable bone grafts are clinically available and none of them can be extruded from 18G needles. To overcome the existing treatment limitations, the aim of this study is to develop ideal injectable implants from biomaterials for minimally invasive surgery. An injectable composite bone graft containing calcium sulfate hemihydrate, tetracalcium phosphate, and anhydrous calcium hydrogen phosphate (CSH/CaP paste) was prepared with different CSH/CaP ratios and different concentrations of additives. The setting time, injectability, mechanical properties, and biocompatibility were evaluated. The developed injectable CSH/CaP paste (CSH/CaP 1:1 supplemented with 6% citric acid and 2% HPMC) presented good handling properties, great biocompatibility, and adequate mechanical strength. Furthermore, the paste was demonstrated to be extruded from a syringe equipped with 18G needles and exerted a great potential for minimally invasive surgery. The developed injectable implants with tissue repairing potentials will provide an ideal therapeutic strategy for minimally invasive surgery to apply in the treatment of maxillofacial defects, certain indications in the spine, inferior turbinate for empty nose syndrome (ENS), or reconstructive rhinoplasty. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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Review

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17 pages, 673 KiB

Open AccessReview

The Challenge of Periprosthetic Joint Infection Diagnosis: From Current Methods to Emerging Biomarkers

by Corneliu Ovidiu Vrancianu, Bogdan Serban, Irina Gheorghe-Barbu, Ilda Czobor Barbu, Roxana Elena Cristian, Mariana Carmen Chifiriuc and Catalin Cirstoiu

Int. J. Mol. Sci. 2023, 24(5), 4320; https://doi.org/10.3390/ijms24054320 - 21 Feb 2023

Cited by 3 | Viewed by 2560

Abstract

Due to the increase in the life span and mobility at older ages, the number of implanted prosthetic joints is constantly increasing. However, the number of periprosthetic joint infections (PJIs), one of the most severe complications after total joint arthroplasty, also shows an increasing trend. PJI has an incidence of 1–2% in the case of primary arthroplasties and up to 4% in the case of revision operations. The development of efficient protocols for managing periprosthetic infections can lead to the establishment of preventive measures and effective diagnostic methods based on the results obtained after the laboratory tests. In this review, we will briefly present the current methods used in PJI diagnosis and the current and emerging synovial biomarkers used for the prognosis, prophylaxis, and early diagnosis of periprosthetic infections. We will discuss treatment failure that may result from patient factors, microbiological factors, or factors related to errors during diagnosis. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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20 pages, 1127 KiB

Open AccessReview

Bioengineering Approaches to Fight against Orthopedic Biomaterials Related-Infections

by Joana Barros, Fernando Jorge Monteiro and Maria Pia Ferraz

Int. J. Mol. Sci. 2022, 23(19), 11658; https://doi.org/10.3390/ijms231911658 - 01 Oct 2022

Cited by 8 | Viewed by 2174

Abstract

One of the most serious complications following the implantation of orthopedic biomaterials is the development of infection. Orthopedic implant-related infections do not only entail clinical problems and patient suffering, but also cause a burden on healthcare care systems. Additionally, the ageing of the world population, in particular in developed countries, has led to an increase in the population above 60 years. This is a significantly vulnerable population segment insofar as biomaterials use is concerned. Implanted materials are highly susceptible to bacterial and fungal colonization and the consequent infection. These microorganisms are often opportunistic, taking advantage of the weakening of the body defenses at the implant surface–tissue interface to attach to tissues or implant surfaces, instigating biofilm formation and subsequent development of infection. The establishment of biofilm leads to tissue destruction, systemic dissemination of the pathogen, and dysfunction of the implant/bone joint, leading to implant failure. Moreover, the contaminated implant can be a reservoir for infection of the surrounding tissue where microorganisms are protected. Therefore, the biofilm increases the pathogenesis of infection since that structure offers protection against host defenses and antimicrobial therapies. Additionally, the rapid emergence of bacterial strains resistant to antibiotics prompted the development of new alternative approaches to prevent and control implant-related infections. Several concepts and approaches have been developed to obtain biomaterials endowed with anti-infective properties. In this review, several anti-infective strategies based on biomaterial engineering are described and discussed in terms of design and fabrication, mechanisms of action, benefits, and drawbacks for preventing and treating orthopaedic biomaterials-related infections. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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16 pages, 1007 KiB

Open AccessReview

Polyphenol-Enriched Composite Bone Regeneration Materials: A Systematic Review of In Vitro Studies

by Kamila Checinska, Maciej Checinski, Katarzyna Cholewa-Kowalska, Maciej Sikora and Dariusz Chlubek

Int. J. Mol. Sci. 2022, 23(13), 7473; https://doi.org/10.3390/ijms23137473 - 05 Jul 2022

Cited by 4 | Viewed by 1958

Abstract

One of the possible alternatives for creating materials for the regeneration of bone tissue supporting comprehensive reconstruction is the incorporation of active substances whose controlled release will improve this process. This systematic review aimed to identify and synthesize in vitro studies that assess the suitability of polyphenolics as additives to polymer-ceramic composite bone regeneration materials. Data on experimental studies in terms of the difference in mechanical, wettability, cytocompatibility, antioxidant and anti-inflammatory properties of materials were synthesized. The obtained numerical data were compiled and analyzed in search of percentage changes of these parameters. The results of the systematic review were based on data from forty-six studies presented in nineteen articles. The addition of polyphenolic compounds to composite materials for bone regeneration improved the cytocompatibility and increased the activity of early markers of osteoblast differentiation, indicating a high osteoinductive potential of the materials. Polyphenolic compounds incorporated into the materials presumably give them high antioxidant properties and reduce the production of reactive oxygen species in macrophage cells, implying anti-inflammatory activity. The evidence was limited by the number of missing data and the heterogeneity of the data. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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32 pages, 10014 KiB

Open AccessReview

Silicon Nitride as a Biomedical Material: An Overview

by Xiaoyu Du, Seunghun S. Lee, Gurdial Blugan and Stephen J. Ferguson

Int. J. Mol. Sci. 2022, 23(12), 6551; https://doi.org/10.3390/ijms23126551 - 11 Jun 2022

Cited by 25 | Viewed by 3983

Abstract

Silicon nitride possesses a variety of excellent properties that can be specifically designed and manufactured for different medical applications. On the one hand, silicon nitride is known to have good mechanical properties, such as high strength and fracture toughness. On the other hand, the uniqueness of the osteogenic/antibacterial dualism of silicon nitride makes it a favorable bioceramic for implants. The surface of silicon nitride can simultaneously inhibit the proliferation of bacteria while supporting the physiological activities of eukaryotic cells and promoting the healing of bone tissue. There are hardly any biomaterials that possess all these properties concurrently. Although silicon nitride has been intensively studied as a biomedical material for years, there is a paucity of comprehensive data on its properties and medical applications. To provide a comprehensive understanding of this potential cornerstone material of the medical field, this review presents scientific and technical data on silicon nitride, including its mechanical properties, osteogenic behavior, and antibacterial capabilities. In addition, this paper highlights the current and potential medical use of silicon nitride and explains the bottlenecks that need to be addressed, as well as possible solutions. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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