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Scaffolds and Implants for Bone Regeneration

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A special issue of Journal of Functional Biomaterials (ISSN 2079-4983). This special issue belongs to the section "Bone Biomaterials".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 25998

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Special Issue Editors

Dr. Kunyu Zhang

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School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou 510006, China
Interests: biomaterials; hydrogels; tissue engineering; regenerative medicine; mechanobiology; drug/gene delivery
Special Issues, Collections and Topics in MDPI journals

Dr. Qian Feng

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Guest Editor

Bioengineering College, Chongqing University, Chongqing 400044, China
Interests: hydrogels for regenerative medicine; hydrogels for flexible sensors
Special Issues, Collections and Topics in MDPI journals

Dr. Yongsheng Yu

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Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
Interests: peptides; hydrogels; targeted therapy; regenerative medicine; antibiosis

Dr. Boguang Yang

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Guest Editor

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China
Interests: hydrogels; musculoskeletal tissue engineering; mechanobiology

Special Issue Information

Dear Colleagues,

Bone defects caused by trauma, tumor, infection and a variety of congenital diseases are among the most common orthopedic disorders, and the clinical management of non-union bone defects is still a challenge for orthopedic surgeons. In recent years, bone implants based on metals, ceramics, and polymers have been widely utilized and helped millions of patients. However, the rapid growth of the elderly demographic has tremendously intensified the occurrence of bone trauma cases, requiring once again the further development of effective strategies for bone reconstruction and regeneration. Therefore, the development of scaffolds and implants with new compositions, three-dimensional configurations, proper mechanical properties, and particular interactions with cells is highly expected. These new biomaterials may effectively promote bone regeneration and thus have a significant impact on individual patients and health care systems.

In this Special Issue, we would like to present an innovative perspective for the scaffolds and implants for bone regeneration. Topics will include but not be limited to: scaffold design and fabrication; biocompatibility and biodegradability; host response to implants; cell–scaffold interactions; and scaffold-based drug delivery. Both original research articles and reviews are very welcome.

Dr. Kunyu Zhang
Dr. Qian Feng
Dr. Yongsheng Yu
Dr. Boguang Yang
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Functional Biomaterials is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

biomaterials
scaffolds
implants
hydrogels
metals
ceramics
bone regeneration
tissue engineering
stem cells
immune cells

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Published Papers (10 papers)

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Research

14 pages, 2953 KiB

Open AccessArticle

Characterization of Trabecular Bone Microarchitecture and Mechanical Properties Using Bone Surface Curvature Distributions

by Pengwei Xiao, Caroline Schilling and Xiaodu Wang

J. Funct. Biomater. 2024, 15(8), 239; https://doi.org/10.3390/jfb15080239 - 22 Aug 2024

Viewed by 1125

Abstract

Understanding bone surface curvatures is crucial for the advancement of bone material design, as these curvatures play a significant role in the mechanical behavior and functionality of bone structures. Previous studies have demonstrated that bone surface curvature distributions could be used to characterize bone geometry and have been proposed as key parameters for biomimetic microstructure design and optimization. However, understanding of how bone surface curvature distributions correlate with bone microstructure and mechanical properties remains limited. This study hypothesized that bone surface curvature distributions could be used to predict the microstructure as well as mechanical properties of trabecular bone. To test the hypothesis, a convolutional neural network (CNN) model was trained and validated to predict the histomorphometric parameters (e.g., BV/TV, BS, Tb.Th, DA, Conn.D, and SMI), geometric parameters (e.g., plate area PA, plate thickness PT, rod length RL, rod diameter RD, plate-to-plate nearest neighbor distance NND_PP, rod-to-rod nearest neighbor distance NND_RR, plate number PN, and rod number RN), as well as the apparent stiffness tensor of trabecular bone using various bone surface curvature distributions, including maximum principal curvature distribution, minimum principal curvature distribution, Gaussian curvature distribution, and mean curvature distribution. The results showed that the surface curvature distribution-based deep learning model achieved high fidelity in predicting the major histomorphometric parameters and geometric parameters as well as the stiffness tenor of trabecular bone, thus supporting the hypothesis of this study. The findings of this study underscore the importance of incorporating bone surface curvature analysis in the design of synthetic bone materials and implants. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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17 pages, 10665 KiB

Open AccessEditor’s ChoiceArticle

Femtosecond Laser Irradiation to Zirconia Prior to Calcium Phosphate Coating Enhances Osteointegration of Zirconia in Rabbits

by Hirotaka Mutsuzaki, Hidehiko Yashiro, Masayuki Kakehata, Ayako Oyane and Atsuo Ito

J. Funct. Biomater. 2024, 15(2), 42; https://doi.org/10.3390/jfb15020042 - 11 Feb 2024

Cited by 1 | Viewed by 4974

Abstract

Calcium phosphate (CaP) coating of zirconia and zirconia-based implants is challenging, due to their chemical instability and susceptibility to thermal and mechanical impacts. A 3 mol% yttrium-stabilized tetragonal zirconia polycrystal was subjected to femtosecond laser (FsL) irradiation to form micro- and submicron surface architectures, prior to CaP coating using pulsed laser deposition (PLD) and low-temperature solution processing. Untreated zirconia, CaP-coated zirconia, and FsL-irradiated and CaP-coated zirconia were implanted in proximal tibial metaphyses of male Japanese white rabbits for four weeks. Radiographical analysis, push-out test, alizarin red staining, and histomorphometric analysis demonstrated a much improved bone-bonding ability of FsL-irradiated and CaP-coated zirconia over CaP-coated zirconia without FsL irradiation and untreated zirconia. The failure strength of the FsL-irradiated and CaP-coated zirconia in the push−out test was 6.2–13.1-times higher than that of the CaP-coated zirconia without FsL irradiation and untreated zirconia. Moreover, the adhesion strength between the bone and FsL-irradiated and CaP-coated zirconia was as high as that inducing host bone fracture in the push-out tests. The increased bone-bonding ability was attributed to the micro-/submicron surface architectures that enhanced osteoblastic differentiation and mechanical interlocking, leading to improved osteointegration. FsL irradiation followed by CaP coating could be useful for improving the osteointegration of cement-less zirconia-based joints and zirconia dental implants. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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17 pages, 4864 KiB

Open AccessEditor’s ChoiceArticle

Human Whole Blood Interactions with Craniomaxillofacial Reconstruction Materials: Exploring In Vitro the Role of Blood Cascades and Leukocytes in Early Healing Events

by Viviana R. Lopes, Ulrik Birgersson, Vivek Anand Manivel, Gry Hulsart-Billström, Sara Gallinetti, Conrado Aparicio and Jaan Hong

J. Funct. Biomater. 2023, 14(7), 361; https://doi.org/10.3390/jfb14070361 - 11 Jul 2023

Viewed by 1593

Abstract

The present study investigated early interactions between three alloplastic materials (calcium phosphate (CaP), titanium alloy (Ti), and polyetheretherketone (PEEK) with human whole blood using an established in vitro slide chamber model. After 60 min of contact with blood, coagulation (thrombin–antithrombin complexes, TAT) was initiated on all test materials (Ti > PEEK > CaP), with a significant increase only for Ti. All materials showed increased contact activation, with the KK–AT complex significantly increasing for CaP (p < 0.001), Ti (p < 0.01), and PEEK (p < 0.01) while only CaP demonstrated a notable rise in KK-C1INH production (p < 0.01). The complement system had significant activation across all materials, with CaP (p < 0.0001, p < 0.0001) generating the most pronounced levels of C3a and sC5b-9, followed by Ti (p < 0.001, p < 0.001) and lastly, PEEK (p < 0.001, p < 0.01). This activation correlated with leukocyte stimulation, particularly myeloperoxidase release. Consequently, the complement system may assume a more significant role in the early stages post implantation in response to CaP materials than previously recognized. Activation of the complement system and the inevitable activation of leukocytes might provide a more favorable environment for tissue remodeling and repair than has been traditionally acknowledged. While these findings are limited to the early blood response, complement and leukocyte activation suggest improved healing outcomes, which may impact long-term clinical outcomes. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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20 pages, 4165 KiB

Open AccessEditor’s ChoiceArticle

Surface Modified β-Ti-18Mo-6Nb-5Ta (wt%) Alloy for Bone Implant Applications: Composite Characterization and Cytocompatibility Assessment

by Michael Escobar, Oriol Careta, Nora Fernández Navas, Aleksandra Bartkowska, Ludovico Andrea Alberta, Jordina Fornell, Pau Solsona, Thomas Gemming, Annett Gebert, Elena Ibáñez, Andreu Blanquer, Carme Nogués, Jordi Sort and Eva Pellicer

J. Funct. Biomater. 2023, 14(2), 94; https://doi.org/10.3390/jfb14020094 - 9 Feb 2023

Cited by 1 | Viewed by 2072

Abstract

Commercially available titanium alloys such as Ti-6Al-4V are established in clinical use as load-bearing bone implant materials. However, concerns about the toxic effects of vanadium and aluminum have prompted the development of Al- and V-free β-Ti alloys. Herein, a new alloy composed of non-toxic elements, namely Ti-18Mo-6Nb-5Ta (wt%), has been fabricated by arc melting. The resulting single β-phase alloy shows improved mechanical properties (Young’s modulus and hardness) and similar corrosion behavior in simulated body fluid when compared with commercial Ti-6Al-4V. To increase the cell proliferation capability of the new biomaterial, the surface of Ti-18Mo-6Nb-5Ta was modified by electrodepositing calcium phosphate (CaP) ceramic layers. Coatings with a Ca/P ratio of 1.47 were obtained at pulse current densities, −j_c, of 1.8–8.2 mA/cm², followed by 48 h of NaOH post-treatment. The thickness of the coatings has been measured by scanning electron microscopy from an ion beam cut, resulting in an average thickness of about 5 μm. Finally, cytocompatibility and cell adhesion have been evaluated using the osteosarcoma cell line Saos-2, demonstrating good biocompatibility and enhanced cell proliferation on the CaP-modified Ti-18Mo-6Nb-5Ta material compared with the bare alloy, even outperforming their CaP-modified Ti-6-Al-4V counterparts. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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16 pages, 3405 KiB

Open AccessArticle

Increased UHMWPE Particle-Induced Osteolysis in Fetuin-A-Deficient Mice

by Christina Polan, Christina Brenner, Monika Herten, Gero Hilken, Florian Grabellus, Heinz-Lothar Meyer, Manuel Burggraf, Marcel Dudda, Willi Jahnen-Dechent, Christian Wedemeyer and Max Daniel Kauther

J. Funct. Biomater. 2023, 14(1), 30; https://doi.org/10.3390/jfb14010030 - 4 Jan 2023

Viewed by 2090

Abstract

Particle-induced osteolysis is a major cause of aseptic prosthetic loosening. Implant wear particles stimulate tissue macrophages inducing an aseptic inflammatory reaction, which ultimately results in bone loss. Fetuin-A is a key regulator of calcified matrix metabolism and an acute phase protein. We studied the influence of fetuin-A on particle-induced osteolysis in an established mouse model using fetuin-A-deficient mice. Ten fetuin-A-deficient (Ahsg^−/−) mice and ten wild-type animals (Ahsg^+/+) were assigned to test group receiving ultra-high molecular weight polyethylene (UHMWPE) particle implantation or to control group (sham surgery). After 14 days, bone metabolism parameters RANKL, osteoprotegerin (OPG), osteocalcin (OC), alkaline phosphatase (ALP), calcium, phosphate, and desoxypyridinoline (DPD) were examined. Bone volume was determined by microcomputed tomography (μCT); osteolytic regions and osteoclasts were histomorphometrically analyzed. After particle treatment, bone resorption was significantly increased in Ahsg^−/− mice compared with corresponding Ahsg^+/+ wild-type mice (p = 0.007). Eroded surface areas in Ahsg^−/− mice were significantly increased (p = 0.002) compared with Ahsg^+/+ mice, as well as the number of osteoclasts compared with control (p = 0.039). Fetuin-A deficiency revealed increased OPG (p = 0.002), and decreased levels of DPD (p = 0.038), OC (p = 0.036), ALP (p < 0.001), and Ca (p = 0.001) compared with wild-type animals. Under osteolytic conditions in Ahsg^−/− mice, OPG was increased (p = 0.013), ALP (p = 0.015) and DPD (p = 0.012) were decreased compared with the Ahsg^+/+ group. Osteolytic conditions lead to greater bone loss in fetuin-A-deficient mice compared with wild-type mice. Reduced fetuin-A serum levels may be a risk factor for particle-induced osteolysis while the protective effect of fetuin-A might be a future pathway for prophylaxis and treatment. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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11 pages, 1783 KiB

Open AccessArticle

Autologous Matrix-Induced Chondrogenesis (AMIC) for Focal Chondral Lesions of the Knee: A 2-Year Follow-Up of Clinical, Proprioceptive, and Isokinetic Evaluation

by Paweł Bąkowski, Kamilla Grzywacz, Agnieszka Prusińska, Kinga Ciemniewska-Gorzela, Justus Gille and Tomasz Piontek

J. Funct. Biomater. 2022, 13(4), 277; https://doi.org/10.3390/jfb13040277 - 6 Dec 2022

Cited by 2 | Viewed by 1867

Abstract

(1) Background: The autologous matrix-induced chondrogenesis (AMIC) is a bio-orthopedic treatment for articular cartilage damage. It combines microfracture surgery with the application of a collagen membrane. The aim of the present study was to report a medium-term follow-up of patients treated with AMIC for focal chondral lesions. (2) Methods: Fourty-eight patients treated surgically and 21 control participants were enrolled in the study. To evaluate the functional outcomes, the proprioceptive (postural stability, postural priority) and isokinetic (peak value of maximum knee extensor and flexor torque in relation to body mass and the total work) measurements were performed. To evaluate the clinical outcomes, the Lysholm score and the IKDC score were imposed. (3) Results: Compared to the preoperative values, there was significant improvement in the first 2 years after intervention in the functional as well as subjective outcome measures. (4) Conclusions: AMIC showed durable results in aligned knees. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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17 pages, 6279 KiB

Open AccessArticle

Poly (Butylene Succinate)/Silicon Nitride Nanocomposite with Optimized Physicochemical Properties, Biocompatibility, Degradability, and Osteogenesis for Cranial Bone Repair

by Qinghui Zhao and Shaorong Gao

J. Funct. Biomater. 2022, 13(4), 231; https://doi.org/10.3390/jfb13040231 - 8 Nov 2022

Cited by 6 | Viewed by 1776

Abstract

Congenital disease, tumors, infections, and trauma are the main reasons for cranial bone defects. Herein, poly (butylene succinate) (PB)/silicon nitride (Si₃N₄) nanocomposites (PSC) with Si3N4 content of 15 w% (PSC15) and 30 w% (PSC30) were fabricated for cranial bone repair. Compared with PB, the compressive strength, hydrophilicity, surface roughness, and protein absorption of nanocomposites were increased with the increase in Si₃N₄ content (from 15 w% to 30 w%). Furthermore, the cell adhesion, multiplication, and osteoblastic differentiation on PSC were significantly enhanced with the Si₃N₄ content increasing in vitro. PSC30 exhibited optimized physicochemical properties (compressive strength, surface roughness, hydrophilicity, and protein adsorption) and cytocompatibility. The m-CT and histological results displayed that the new bone formation for SPC30 obviously increased compared with PB, and PSC30 displayed proper degradability (75.3 w% at 12 weeks) and was gradually replaced by new bone tissue in vivo. The addition of Si₃N₄ into PB not only optimized the surface performances of PSC but also improved the degradability of PSC, which led to the release of Si ions and a weak alkaline environment that significantly promoted cell response and tissue regeneration. In short, the enhancements of cellular responses and bone regeneration of PSC30 were attributed to the synergism of the optimized surface performances and slow release of Si ion, and PSC30 were better than PB. Accordingly, PSC30, with good biocompatibility and degradability, displayed a promising and huge potential for cranial bone construction. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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27 pages, 14441 KiB

Open AccessArticle

A Three-Dimensional Printed Polycaprolactone–Biphasic-Calcium-Phosphate Scaffold Combined with Adipose-Derived Stem Cells Cultured in Xenogeneic Serum-Free Media for the Treatment of Bone Defects

by Woraporn Supphaprasitt, Lalita Charoenmuang, Nuttawut Thuaksuban, Prawichaya Sangsuwan, Narit Leepong, Danaiya Supakanjanakanti, Surapong Vongvatcharanon, Trin Suwanrat and Woraluk Srimanok

J. Funct. Biomater. 2022, 13(3), 93; https://doi.org/10.3390/jfb13030093 - 15 Jul 2022

Cited by 5 | Viewed by 2526

Abstract

The efficacy of a three-dimensional printed polycaprolactone–biphasic-calcium-phosphate scaffold (PCL–BCP TDP scaffold) seeded with adipose-derived stem cells (ADSCs), which were cultured in xenogeneic serum-free media (XSFM) to enhance bone formation, was assessed in vitro and in animal models. The ADSCs were isolated from the buccal fat tissue of six patients using enzymatic digestion and the plastic adherence method. The proliferation and osteogenic differentiation of the cells cultured in XSFM when seeded on the scaffolds were assessed and compared with those of cells cultured in a medium containing fetal bovine serum (FBS). The cell–scaffold constructs were cultured in XSFM and were implanted into calvarial defects in thirty-six Wistar rats to assess new bone regeneration. The proliferation and osteogenic differentiation of the cells in the XSFM medium were notably better than that of the cells in the FBS medium. However, the efficacy of the constructs in enhancing new bone formation in the calvarial defects of rats was not statistically different to that achieved using the scaffolds alone. In conclusion, the PCL–BCP TDP scaffolds were biocompatible and suitable for use as an osteoconductive framework. The XSFM medium could support the proliferation and differentiation of ADSCs in vitro. However, the cell–scaffold constructs had no benefit in the enhancement of new bone formation in animal models. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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20 pages, 1328 KiB

Open AccessEditor’s ChoiceArticle

The Implant Proteome—The Right Surgical Glue to Fix Titanium Implants In Situ

by Marcus Jäger, Agnieszka Latosinska, Monika Herten, André Busch, Thomas Grupp and Andrea Sowislok

J. Funct. Biomater. 2022, 13(2), 44; https://doi.org/10.3390/jfb13020044 - 15 Apr 2022

Cited by 3 | Viewed by 2961

Abstract

Titanium implants are frequently applied to the bone in orthopedic and trauma surgery. Although these biomaterials are characterized by excellent implant survivorship and clinical outcomes, there are almost no data available on the initial protein layer binding to the implant surface in situ. This study aims to investigate the composition of the initial protein layer on endoprosthetic surfaces as a key initiating step in osseointegration. In patients qualified for total hip arthroplasty, the implants are inserted into the femoral canal, fixed and subsequently explanted after 2 and 5 min. The proteins adsorbed to the surface (the implant proteome) are analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS). A statistical analysis of the proteins’ alteration with longer incubation times reveals a slight change in their abundance according to the Vroman effect. The pathways involved in the extracellular matrix organization of bone, sterile inflammation and the beginning of an immunogenic response governed by neutrophils are significantly enriched based on the analysis of the implant proteome. Those are generally not changed with longer incubation times. In summary, proteins relevant for osseointegration are already adsorbed within 2 min in situ. A deeper understanding of the in situ protein–implant interactions in patients may contribute to optimizing implant surfaces in orthopedic and trauma surgery. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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16 pages, 4996 KiB

Open AccessEditor’s ChoiceArticle

Osseointegration at Implants Installed in Composite Bone: A Randomized Clinical Trial on Sinus Floor Elevation

by Mitsuo Kotsu, Karol Alí Apaza Alccayhuaman, Mauro Ferri, Giovanna Iezzi, Adriano Piattelli, Natalia Fortich Mesa and Daniele Botticelli

J. Funct. Biomater. 2022, 13(1), 22; https://doi.org/10.3390/jfb13010022 - 28 Feb 2022

Cited by 6 | Viewed by 2943

Abstract

Osseointegration of implants installed in conjunction with sinus floor elevation might be affected by the presence of residual graft. The implant surface characteristics and the protection of the access window using a collagen membrane might influence the osseointegration. To evaluate these factors, sinus floor elevation was performed in patients using a natural bovine bone grafting material. The access windows were either covered with a collagen membrane made of porcine corium (Mb group) or left uncovered (No-Mb group) and, after six months, two mini-implants with either a moderate rough or turned surfaces were installed. After 3 months, biopsies containing the mini-implants were retrieved, processed histologically, and analyzed. Twenty patients, ten in each group, were included in the study. The two mini-implants were retrieved from fourteen patients, six belonging to the Mb group, and eight to the No-Mb group. No statistically significant differences were found in osseointegration between groups. However, statistically significant differences were found between the two surfaces. It was concluded that implants with a moderately rough surface installed in a composite bone presented much higher osseointegration compared to those with a turned surface. The present study failed to show an effect of the use of a collagen membrane on the access window. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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