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Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue

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A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Biomaterials".

Deadline for manuscript submissions: closed (20 December 2024) | Viewed by 33147

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Special Issue Editors

Dr. Dante Dallari

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Guest Editor

IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
Interests: orthopedics; prosthetic and revision surgery of hip and knee; preclinical and clinical translation; reconstructive surgery; innovative techniques in orthopedic surgery

Dr. Marco Govoni

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Guest Editor

Reconstructive Orthopaedic Surgery and Innovative Techniques—Musculoskeletal Tissue Bank, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
Interests: tissue engineering and regenerative medicine; musculoskeletal system; multiscale technological devices; bioreactors
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Special Issue Information

Dear Colleagues,

Musculoskeletal tissue is a complex system that comprises bone, cartilage, tendon, ligament, and muscle, as well as their interfaces, and mainly supports body shape, structure, and locomotion. Over the years, several materials have been evaluated as an option for musculoskeletal apparatus defect repair and regeneration. Commonly used natural materials for tissue replacement include autografts and allografts. Although they possess structure, composition, and mechanical properties similar to those of the host tissue, the limited availability of autografts, and the risk of potential disease transmission associated with allografts, has pushed scientists to search for alternative graft options both in terms of synthetic and biological materials. In addition, most musculoskeletal substitutes are formed as a composite of allografts, such as bone chips, demineralized bone matrix, and one or more materials from an extensive list that includes degradable and non-degradable polymers, xenografts as calcified matrices, bioactive glass, acellularized matrices, collagen, and silk. Moreover, forces exerted on the implant materials consist of tensile, compressive, or shear components. Because the musculoskeletal apparatus can modify its structure in response to forces exerted on it, implant materials must be designed to account for this. Another relevant issue deals with the integration of natural or synthetic substitutes with host tissue, which was found to be jeopardized in several long-term follow-up studies. Hence, the enhancement of biological host-integration properties and the mechanical characteristics of implants require a multidisciplinary approach in order to obtain comprehensive knowledge of grafts that can be safely and effectively used for musculoskeletal tissue engineering. Biocompatibility, degradability, mechanical integrity, and the ability to deliver inductive factors and cells are just a few of the issues needing to be addressed for reconstructive purposes. Therefore, in this Special Issue we aim to stimulate researchers around the world to share their interesting and promising works on various aspects of natural grafts and biomaterials, or a combination of both, for musculoskeletal tissue engineering protocols. To this aim, we invite original research articles, comprehensive reviews, and significant preliminary communications. Contributions describing current challenges and future outlook on emerging reconstructive and regenerative applications for bone, cartilage, muscle, tendon and ligaments are also welcome.

Dr. Dante Dallari
Dr. Marco Govoni
Guest Editors

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Keywords

autografts
allografts
xenografts
biomaterials
prosthetics
multi-phase scaffolds
musculoskeletal tissue engineering
bone tissue reconstruction and/or regeneration
cartilage tissue reconstruction and/or regeneration
tendon and/or ligament tissue reconstruction and/or regeneration

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Published Papers (11 papers)

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Research

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11 pages, 16037 KiB

Open AccessEditor’s ChoiceArticle

Human Bone-Marrow-Derived Stem-Cell-Seeded 3D Chitosan–Gelatin–Genipin Scaffolds Show Enhanced Extracellular Matrix Mineralization When Cultured under a Perfusion Flow in Osteogenic Medium

by Gabriele Boretti, Emanuele Giordano, Mariana Ionita, George Mihail Vlasceanu, Ólafur Eysteinn Sigurjónsson, Paolo Gargiulo and Joseph Lovecchio

Materials 2023, 16(17), 5898; https://doi.org/10.3390/ma16175898 - 29 Aug 2023

Cited by 3 | Viewed by 2028

Abstract

Tissue-engineered bone tissue grafts are a promising alternative to the more conventional use of natural donor bone grafts. However, choosing an appropriate biomaterial/scaffold to sustain cell survival, proliferation, and differentiation in a 3D environment remains one of the most critical issues in this domain. Recently, chitosan/gelatin/genipin (CGG) hybrid scaffolds have been proven as a more suitable environment to induce osteogenic commitment in undifferentiated cells when doped with graphene oxide (GO). Some concern is, however, raised towards the use of graphene and graphene-related material in medical applications. The purpose of this work was thus to check if the osteogenic potential of CGG scaffolds without added GO could be increased by improving the medium diffusion in a 3D culture of differentiating cells. To this aim, the level of extracellular matrix (ECM) mineralization was evaluated in human bone-marrow-derived stem cell (hBMSC)-seeded 3D CGG scaffolds upon culture under a perfusion flow in a dedicated custom-made bioreactor system. One week after initiating dynamic culture, histological/histochemical evaluations of CGG scaffolds were carried out to analyze the early osteogenic commitment of the culture. The analyses show the enhanced ECM mineralization of the 3D perfused culture compared to the static counterpart. The results of this investigation reveal a new perspective on more efficient clinical applications of CGG scaffolds without added GO. Full article

(This article belongs to the Special Issue Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue)

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14 pages, 1515 KiB

Open AccessFeature PaperArticle

Nanomechanical Mapping of Hard Tissues by Atomic Force Microscopy: An Application to Cortical Bone

by Marco Bontempi, Francesca Salamanna, Rosario Capozza, Andrea Visani, Milena Fini and Alessandro Gambardella

Materials 2022, 15(21), 7512; https://doi.org/10.3390/ma15217512 - 26 Oct 2022

Cited by 11 | Viewed by 2609

Abstract

Force mapping of biological tissues via atomic force microscopy (AFM) probes the mechanical properties of samples within a given topography, revealing the interplay between tissue organization and nanometer-level composition. Despite considerable attention to soft biological samples, constructing elasticity maps on hard tissues is not routine for standard AFM equipment due to the difficulty of interpreting nanoindentation data in light of the available models of surface deformation. To tackle this issue, we proposed a protocol to construct elasticity maps of surfaces up to several GPa in moduli by AFM nanoindentation using standard experimental conditions (air operation, nanometrically sharp spherical tips, and cantilever stiffness below 30 N/m). We showed how to process both elastic and inelastic sample deformations simultaneously and independently and quantify the degree of elasticity of the sample to decide which regime is more suitable for moduli calculation. Afterwards, we used the frequency distributions of Young’s moduli to quantitatively assess differences between sample regions different for structure and composition, and to evaluate the presence of mechanical inhomogeneities. We tested our method on histological sections of sheep cortical bone, measuring the mechanical response of different osseous districts, and mapped the surface down to the single collagen fibril level. Full article

(This article belongs to the Special Issue Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue)

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15 pages, 1466 KiB

Open AccessArticle

Optimization of In Situ Indentation Protocol to Map the Mechanical Properties of Articular Cartilage

by Matteo Berni, Paolo Erani, Nicola Francesco Lopomo and Massimiliano Baleani

Materials 2022, 15(18), 6425; https://doi.org/10.3390/ma15186425 - 16 Sep 2022

Cited by 3 | Viewed by 2225

Abstract

Tissue engineering aims at developing complex composite scaffolds for articular cartilage repair. These scaffolds must exhibit a mechanical behavior similar to the whole osteochondral unit. In situ spherical indentation allows us to map the mechanical behavior of articular cartilage, avoiding removal of the underlying bone tissue. Little is known about the impact of grid spacing, indenter diameter, and induced deformation on the cartilage response to indentation. We investigated the impact of grid spacing (range: a to 3a, where a is the radius of the contact area between cartilage and indenter), indenter diameter (range: 1 to 8 mm), and deformation induced by indentation (constant indentation depth versus constant nominal deformation) on cartilage response. The bias induced by indentations performed in adjacent grid points was minimized with a 3a grid spacing. The cartilage response was indenter-dependent for diameters ranging between 1 and 6 mm with a nominal deformation of 15%. No significant differences were found using 6 mm and 8 mm indenters. Six mm and 8 mm indenters were used to map human articular cartilage with a grid spacing equal to 3a. Instantaneous elastic modulus E₀ was calculated for constant indentation depth and constant nominal deformation. E₀ value distribution did not change significantly by switching the two indenters, while dispersion decreased by 5–6% when a constant nominal deformation was applied. Such an approach was able to discriminate changes in tissue response due to doubling the indentation rate. The proposed procedure seems to reduce data dispersion and properly determine cartilage mechanical properties to be compared with those of complex composite scaffolds. Full article

(This article belongs to the Special Issue Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue)

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10 pages, 1824 KiB

Open AccessArticle

Fiber Thickness and Porosity Control in a Biopolymer Scaffold 3D Printed through a Converted Commercial FDM Device

by Joseph Lovecchio, Marilisa Cortesi, Marco Zani, Marco Govoni, Dante Dallari and Emanuele Giordano

Materials 2022, 15(7), 2394; https://doi.org/10.3390/ma15072394 - 24 Mar 2022

Cited by 10 | Viewed by 3298

Abstract

3D printing has opened exciting new opportunities for the in vitro fabrication of biocompatible hybrid pseudo-tissues. Technologies based on additive manufacturing herald a near future when patients will receive therapies delivering functional tissue substitutes for the repair of their musculoskeletal tissue defects. In particular, bone tissue engineering (BTE) might extensively benefit from such an approach. However, designing an optimal 3D scaffold with adequate stiffness and biodegradability properties also guaranteeing the correct cell adhesion, proliferation, and differentiation, is still a challenge. The aim of this work was the rewiring of a commercial fuse deposition modeling (FDM) 3D printer into a 3D bioplotter, aiming at obtaining scaffold fiber thickness and porosity control during its manufacturing. Although it is well-established that FDM is a fast and low-price technology, the high temperatures required for printing lead to limitations in the biomaterials that can be used. In our hands, modifying the printing head of the FDM device with a custom-made holder has allowed to print hydrogels commonly used for embedding living cells. The results highlight a good resolution, reproducibility and repeatability of alginate/gelatin scaffolds obtained via our custom 3D bioplotter prototype, showing a viable strategy to equip a small-medium laboratory with an instrument for manufacturing good-quality 3D scaffolds for cell culture and tissue engineering applications. Full article

(This article belongs to the Special Issue Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue)

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19 pages, 3537 KiB

Open AccessArticle

Brillouin and Raman Micro-Spectroscopy: A Tool for Micro-Mechanical and Structural Characterization of Cortical and Trabecular Bone Tissues

by Martina Alunni Cardinali, Assunta Morresi, Daniele Fioretto, Leonardo Vivarelli, Dante Dallari and Marco Govoni

Materials 2021, 14(22), 6869; https://doi.org/10.3390/ma14226869 - 14 Nov 2021

Cited by 13 | Viewed by 2749

Abstract

Human bone is a specialized tissue with unique material properties, providing mechanical support and resistance to the skeleton and simultaneously assuring capability of adaptation and remodelling. Knowing the properties of such a structure down to the micro-scale is of utmost importance, not only for the design of effective biomimetic materials but also to be able to detect pathological alterations in material properties, such as micro-fractures or abnormal tissue remodelling. The Brillouin and Raman micro-spectroscopic (BRmS) approach has the potential to become a first-choice technique, as it is capable of simultaneously investigating samples’ mechanical and structural properties in a non-destructive and label-free way. Here, we perform a mapping of cortical and trabecular bone sections of a femoral epiphysis, demonstrating the capability of the technique for discovering the morpho-mechanics of cells, the extracellular matrix, and marrow constituents. Moreover, the interpretation of Brillouin and Raman spectra merged with an approach of data mining is used to compare the mechanical alterations in specimens excised from distinct anatomical areas and subjected to different sample processing. The results disclose in both cases specific alterations in the morphology and/or in the tissue chemical make-up, which strongly affects bone mechanical properties, providing a method potentially extendable to other important biomedical issues. Full article

(This article belongs to the Special Issue Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue)

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13 pages, 31898 KiB

Open AccessArticle

Determination of the Spatial Anisotropy of the Surface MicroStructures of Different Implant Materials: An Atomic Force Microscopy Study

by Alessandro Gambardella, Gregorio Marchiori, Melania Maglio, Alessandro Russo, Chiara Rossi, Andrea Visani and Milena Fini

Materials 2021, 14(17), 4803; https://doi.org/10.3390/ma14174803 - 24 Aug 2021

Cited by 5 | Viewed by 3230

Abstract

Many biomaterials’ surfaces exhibit directional properties, i.e., possess spatial anisotropy on a range of spatial scales spanning from the domain of the naked eye to the sub-micrometer level. Spatial anisotropy of surface can influence the mechanical, physicochemical, and morphological characteristics of the biomaterial, thus affecting its functional behavior in relation, for example, to the host tissue response in regenerative processes, or to the efficacy of spatially organized surface patterns in avoiding bacterial attachment. Despite the importance of the availability of quantitative data, a comprehensive characterization of anisotropic topographies is generally a hard task due to the proliferation of parameters and inherent formal complications. This fact has led so far to excessive simplification that has often prevented researchers from having comparable results. In an attempt to overcome these issues, in this work a systematic and multiscale approach to spatial anisotropy is adopted, based on the determination of only two statistical parameters of surface, namely the texture aspect ratio S_tr and the roughness exponent H, extracted from atomic force microscopy images of the surface. The validity on this approach is tested on four commercially available implant materials, namely titanium alloy, polyethylene, polyetheretherketone and polyurethane, characterized by textured surfaces obtained after different machining. It is found that the “two parameters” approach is effective in describing the anisotropy changes on surfaces with complex morphology, providing a simple quantitative route for characterization and design of natural and artificial textured surfaces at spatial scales relevant to a wide range of bio-oriented applications. Full article

(This article belongs to the Special Issue Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue)

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10 pages, 1498 KiB

Open AccessArticle

The Impact of Contaminating Poly (Methyl Methacrylate) (PMMA) Bone Cements on Their Compressive Strength

by Jakub Szabelski, Robert Karpiński, Przemysław Krakowski and Józef Jonak

Materials 2021, 14(10), 2555; https://doi.org/10.3390/ma14102555 - 14 May 2021

Cited by 18 | Viewed by 2145

Abstract

This study presents an analysis of the impact of doping bone cement with saline. The two-ingredient cement, made right before the surgery, is subject to various kinds of organic contaminants and liquids used in the operating area, such as saline used to cleanse or cool it, during the process of mounting the prosthesis or bone-filling procedures. The processes of experimental destructive testing and statistical analysis have shown that, depending on the degree of saline doping, the static compressive strength parameters may greatly improve (with a low degree of contamination) or significantly worsen (when the contamination degree is higher). The limit value of the degree of salt admixture was estimated (2%), with which no statistically significant differences were observed in the cement strength in relation to the strength of non-contaminated cement. Full article

(This article belongs to the Special Issue Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue)

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Review

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19 pages, 848 KiB

Open AccessEditor’s ChoiceReview

The Intraoperative Use of Defensive Antibacterial Coating (DAC^®) in the Form of a Gel to Prevent Peri-Implant Infections in Orthopaedic Surgery: A Clinical Narrative Review

by Daniele Pressato, Angela Battista, Marco Govoni, Leonardo Vivarelli, Dante Dallari and Antonio Pellegrini

Materials 2023, 16(15), 5304; https://doi.org/10.3390/ma16155304 - 28 Jul 2023

Cited by 6 | Viewed by 2546

Abstract

Periprosthetic joint infections (PJIs) in arthroplasty and osteosynthesis-associated infections (OAIs) in reconstructive surgery still represent a challenging complication in orthopaedics and traumatology causing a burden worsening the patient’s quality of life, for caregiver and treating physicians, and for healthcare systems. PJIs and OAIs are the result of bacterial adhesion over an implant surface with subsequent biofilm formation. Therefore, the clinical pathological outcome is a difficult-to-eradicate persistent infection. Strategies to treat PJIs and OAIs involve debridement, the replacement of internal fixators or articular prostheses, and intravenous antibiotics. However, long treatments and surgical revision cause discomfort for patients; hence, the prevention of PJIs and OAIs represents a higher priority than treatment. Local antibiotic treatments through coating-release systems are becoming a smart approach to prevent this complication. Hydrophilic coatings, loaded with antibiotics, simultaneously provide a barrier effect against bacterial adhesion and allow for the local delivery of an antibiotic. The intraoperative use of a hyaluronan (HY)-derivative coating in the form of a gel, loaded with antibiotics to prevent PJI, has recently raised interest in orthopaedics. Current evidence supports the use of this coating in the prophylaxis of PJI and IRIs in terms of clinical outcomes and infection reduction. Thus, the purpose of this narrative review is to assess the use of a commercially available HY derivative in the form of a gel, highlighting the characteristics of this biomaterial, which makes it attractive for the management of PJIs and IRIs in orthopaedics and traumatology. Full article

(This article belongs to the Special Issue Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue)

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10 pages, 1602 KiB

Open AccessReview

Uncemented Cups and Impaction Bone Grafting for Acetabular Bone Loss in Revision Hip Arthroplasty: A Review of Rationale, Indications, and Outcomes

by Rocco D’Apolito and Luigi Zagra

Materials 2022, 15(10), 3728; https://doi.org/10.3390/ma15103728 - 23 May 2022

Cited by 6 | Viewed by 3562 | Correction

Abstract

Total hip arthroplasty (THA) is increasingly performed in young patients and the number of revisions is estimated to rise over time. Acetabular osteolysis and bone loss are frequently encountered during revision and may be classified and treated in different ways. Impaction bone grafting (IBG) with morselized allograft offers a viable option. IBG was introduced over 40 years ago in combination with cemented cups, and is also used with uncemented cups. The impacted bone chips act as a void filler to restore bone stock; once incorporated they are substituted by host bone. Surgery entails assessment of the defect, acetabular preparation, preparation of the morselized graft, impaction of the graft, and cup implantation. Satisfactory medium- and long-term results have now been reported in most studies. With the advent of high-porosity cups, indications have been extended, enhancing the potential of IBG, in which primary stability of the cup to the host bone is essential for a successful procedure. Synthetic bone substitutes have also been used in combination with allogenic grafts and may extend the original technique for which long-term studies are warranted. Full article

(This article belongs to the Special Issue Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue)

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19 pages, 660 KiB

Open AccessReview

Commercial Bone Grafts Claimed as an Alternative to Autografts: Current Trends for Clinical Applications in Orthopaedics

by Marco Govoni, Leonardo Vivarelli, Alessandro Mazzotta, Cesare Stagni, Alessandra Maso and Dante Dallari

Materials 2021, 14(12), 3290; https://doi.org/10.3390/ma14123290 - 14 Jun 2021

Cited by 41 | Viewed by 5377

Abstract

In the last twenty years, due to an increasing medical and market demand for orthopaedic implants, several grafting options have been developed. However, when alternative bone augmentation materials mimicking autografts are searched on the market, commercially available products may be grouped into three main categories: cellular bone matrices, growth factor enhanced bone grafts, and peptide enhanced xeno-hybrid bone grafts. Firstly, to obtain data for this review, the search engines Google and Bing were employed to acquire information from reports or website portfolios of important competitors in the global bone graft market. Secondly, bibliographic databases such as Medline/PubMed, Web of Science, and Scopus were also employed to analyse data from preclinical/clinical studies performed to evaluate the safety and efficacy of each product released on the market. Here, we discuss several products in terms of osteogenic/osteoinductive/osteoconductive properties, safety, efficacy, and side effects, as well as regulatory issues and costs. Although both positive and negative results were reported in clinical applications for each class of products, to date, peptide enhanced xeno-hybrid bone grafts may represent the best choice in terms of risk/benefit ratio. Nevertheless, more prospective and controlled studies are needed before approval for routine clinical use. Full article

(This article belongs to the Special Issue Synthetic and Biologic Materials for Prosthetic and Reconstructive Applications for Musculoskeletal Tissue)

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