Biomaterials in Bone Regeneration: Challenges to Guarantee Appropriate Biological Features

A special issue of Biomimetics (ISSN 2313-7673). This special issue belongs to the section "Biomimetics of Materials and Structures".

Deadline for manuscript submissions: closed (20 December 2022) | Viewed by 32345

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Guest Editor
Department of Industrial Engineering, University of Padua, Via Marzolo 9, 35131 Padua, Italy
Interests: synthesis, purification, and characterization of peptides; identification of bioactive peptides (adhesive, pro-angiogenic, antitumor and growth factors); covalent functionalization of biomaterials (metals, ceramics, synthetic polymers, natural polymers); conjugation of bioactive peptide to decellularized matrices; residual detergent determination in decellularize tissues; bioactive hybrid materials; bioactive and biomimetic materials for bone, nervous and cardiac tissue engineering; self-assembling peptides; chemoselective ligation; peptide nucleic acids probe for biosensing; recognition between substrates and proteolytic enzymes; peptide hydrogels; electrospun scaffolds; matrices for the development of in vitro tumor tissues

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Guest Editor
Department of Industrial Engineering, University of Padua, Via Marzolo 9, 35131 Padua, Italy
Interests: synthesis, purification, and characterization of peptides; identification of bioactive peptides (adhesive, pro-angiogenic, antitumor and growth factors); covalent functionalization of biomaterials (metals, ceramics, synthetic polymers, natural polymers); conjugation of bioactive peptide to decellularized matrices; residual detergent determination in decellularize tissues; bioactive hybrid materials; bioactive and biomimetic materials for bone, nervous and cardiac tissue engineering; self-assembling peptides; chemoselective ligation; peptide nucleic acids probe for biosensing; recognition between substrates and proteolytic enzymes; peptide hydrogels; electrospun scaffolds; matrices for the development of in vitro tumor tissues

Special Issue Information

Dear Colleagues,

The development of load-bearing bone substitutes capable of reabsorption responds to the need to intervene with increasingly favorable outcomes in numerous bone pathologies, and at the same time offers new stimuli and new challenges in an area of research among the most lively and advanced in the universe of tissue grafts. Starting from traditional materials such as ceramics and polymers, it is possible to range within new issues such as the use of natural polymers, new synthetic polymers, hydrogels, composite materials, and engineered bone tissues even proposed in Nature-inspired architectures thanks to electrospinning or 3D-printing techniques. The current challenges mainly concern ensuring appropriate biological properties for stimulating the adhesion, proliferation, and differentiation of specific cell populations in addition to the vascularization of the graft. Strategies for promoting the bio-functionality of prostheses are increasingly enriching with new methods such as gene delivery, the delivery of bio-factors, and the nanometric topography of the scaffolds. This Special Issue is an opportunity for comparison among authors who have been dealing with these topics and provides a stimulus for young researchers who are entering this fascinating field to provide their contribution to reach ever more ambitious milestones.

Dr. Monica Dettin
Dr. Annj Zamuner
Guest Editors

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Keywords

  • bone
  • biomaterials
  • gene delivery
  • growth factor
  • adhesion motifs
  • hydrogel
  • vascularization
  • peptide
  • biodegradability

Published Papers (16 papers)

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Research

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14 pages, 10906 KiB  
Article
Bioconjugation of Carbohydrates to Gelatin Sponges Promoting 3D Cell Cultures
by Antonietta Pepe, Antonio Laezza, Angela Ostuni, Alessandra Scelsi, Alessandro Laurita and Brigida Bochicchio
Biomimetics 2023, 8(2), 193; https://doi.org/10.3390/biomimetics8020193 - 06 May 2023
Cited by 1 | Viewed by 1593
Abstract
Gelatin sponges are widely employed as hemostatic agents, and are gaining increasing interest as 3D scaffolds for tissue engineering. To broaden their possible application in the field of tissue engineering, a straightforward synthetic protocol able to anchor the disaccharides, maltose and lactose, for [...] Read more.
Gelatin sponges are widely employed as hemostatic agents, and are gaining increasing interest as 3D scaffolds for tissue engineering. To broaden their possible application in the field of tissue engineering, a straightforward synthetic protocol able to anchor the disaccharides, maltose and lactose, for specific cell interactions was developed. A high conjugation yield was confirmed by 1H-NMR and FT-IR spectroscopy, and the morphology of the resulting decorated sponges was characterized by SEM. After the crosslinking reaction, the sponges preserve their porous structure as ascertained by SEM. Finally, HepG2 cells cultured on the decorated gelatin sponges show high viability and significant differences in the cellular morphology as a function of the conjugated disaccharide. More spherical morphologies are observed when cultured on maltose-conjugated gelatin sponges, while a more flattened aspect is discerned when cultured onto lactose-conjugated gelatin sponges. Considering the increasing interest in small-sized carbohydrates as signaling cues on biomaterial surfaces, systematic studies on how small carbohydrates might influence cell adhesion and differentiation processes could take advantage of the described protocol. Full article
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20 pages, 17737 KiB  
Article
Proteolytically Resistant Bioactive Peptide-Grafted Sr/Mg-Doped Hardystonite Foams: Comparison of Two Covalent Functionalization Strategies
by Annj Zamuner, Elena Zeni, Hamada Elsayed, Michele Di Foggia, Paola Taddei, Antonella Pasquato, Lucy Di Silvio, Enrico Bernardo, Paola Brun and Monica Dettin
Biomimetics 2023, 8(2), 185; https://doi.org/10.3390/biomimetics8020185 - 29 Apr 2023
Cited by 1 | Viewed by 1417
Abstract
Hardystonite-based (HT) bioceramic foams were easily obtained via thermal treatment of silicone resins and reactive oxide fillers in air. By using a commercial silicone, incorporating strontium oxide and magnesium oxide precursors (as well as CaO and ZnO), and treating it at 1100 °C, [...] Read more.
Hardystonite-based (HT) bioceramic foams were easily obtained via thermal treatment of silicone resins and reactive oxide fillers in air. By using a commercial silicone, incorporating strontium oxide and magnesium oxide precursors (as well as CaO and ZnO), and treating it at 1100 °C, a complex solid solution (Ca1.4Sr0.6Zn0.85Mg0.15Si2O7) that has superior biocompatibility and bioactivity properties compared to pure hardystonite (Ca2ZnSi2O7) can be obtained. Proteolytic-resistant adhesive peptide mapped on vitronectin (D2HVP), was selectively grafted to Sr/Mg-doped HT foams using two different strategies. Unfortunately, the first method (via protected peptide) was unsuitable for acid-sensitive materials such as Sr/Mg-doped HT, resulting in the release of cytotoxic levels of Zinc over time, with consequent negative cellular response. To overcome this unexpected result, a novel functionalization strategy requiring aqueous solution and mild conditions was designed. Sr/Mg-doped HT functionalized with this second strategy (via aldehyde peptide) showed a dramatic increase in human osteoblast proliferation at 6 days compared to only silanized or non-functionalized samples. Furthermore, we demonstrated that the functionalization treatment does not induce any cytotoxicity. Functionalized foams enhanced mRNA-specific transcript levels coding IBSP, VTN, RUNX2, and SPP1 at 2 days post-seeding. In conclusion, the second functionalization strategy proved to be appropriate for this specific biomaterial and was effective at enhancing the material’s bioactivity. Full article
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16 pages, 16822 KiB  
Article
Structural Mechanical Properties of 3D Printing Biomimetic Bone Replacement Materials
by Xueman Lv, Shuo Wang, Zihe Xu, Xuanting Liu, Guoqin Liu, Feipeng Cao and Yunhai Ma
Biomimetics 2023, 8(2), 166; https://doi.org/10.3390/biomimetics8020166 - 19 Apr 2023
Cited by 3 | Viewed by 1478
Abstract
One of the primary challenges in developing bone substitutes is to create scaffolds with mechanical properties that closely mimic those of regenerated tissue. Scaffolds that mimic the structure of natural cancellous bone are believed to have better environmental adaptability. In this study, we [...] Read more.
One of the primary challenges in developing bone substitutes is to create scaffolds with mechanical properties that closely mimic those of regenerated tissue. Scaffolds that mimic the structure of natural cancellous bone are believed to have better environmental adaptability. In this study, we used the porosity and thickness of pig cancellous bone as biomimetic design parameters, and porosity and structural shape as differential indicators, to design a biomimetic bone beam scaffold. The mechanical properties of the designed bone beam model were tested using the finite element method (FEM). PCL/β-TCP porous scaffolds were prepared using the FDM method, and their mechanical properties were tested. The FEM simulation results were compared and validated, and the effects of porosity and pore shape on the mechanical properties were analyzed. The results of this study indicate that the PCL/β-TCP scaffold, prepared using FDM 3D printing technology for cancellous bone tissue engineering, has excellent integrity and stability. Predicting the structural stability using FEM is effective. The triangle pore structure has the most stability in both simulations and tests, followed by the rectangle and honeycomb shapes, and the diamond structure has the worst stability. Therefore, adjusting the porosity and pore shape can change the mechanical properties of the composite scaffold to meet the mechanical requirements of customized tissue engineering. Full article
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13 pages, 5521 KiB  
Article
Influence of a Physiologically Formed Blood Clot on Pre-Osteoblastic Cells Grown on a BMP-7-Coated Nanoporous Titanium Surface
by Leonardo Raphael Zuardi, Cleide Lúcia Araújo Silva, Eduardo Magalhães Rego, Giovana Vacilotto Carneiro, Silvia Spriano, Antonio Nanci and Paulo Tambasco de Oliveira
Biomimetics 2023, 8(1), 123; https://doi.org/10.3390/biomimetics8010123 - 16 Mar 2023
Cited by 2 | Viewed by 3096
Abstract
Titanium (Ti) nanotopography modulates the osteogenic response to exogenous bone morphogenetic protein 7 (BMP-7) in vitro, supporting enhanced alkaline phosphatase mRNA expression and activity, as well as higher osteopontin (OPN) mRNA and protein levels. As the biological effects of OPN protein are modulated [...] Read more.
Titanium (Ti) nanotopography modulates the osteogenic response to exogenous bone morphogenetic protein 7 (BMP-7) in vitro, supporting enhanced alkaline phosphatase mRNA expression and activity, as well as higher osteopontin (OPN) mRNA and protein levels. As the biological effects of OPN protein are modulated by its proteolytic cleavage by serum proteases, this in vitro study evaluated the effects on osteogenic cells in the presence of a physiological blood clot previously formed on a BMP-7-coated nanostructured Ti surface obtained by chemical etching (Nano-Ti). Pre-osteoblastic MC3T3-E1 cells were cultured during 5 days on recombinant mouse (rm) BMP-7-coated Nano-Ti after it was implanted in adult female C57BI/6 mouse dorsal dermal tissue for 18 h. Nano-Ti without blood clot or with blood clot at time 0 were used as the controls. The presence of blood clots tended to inhibit the expression of key osteoblast markers, except for Opn, and rmBMP-7 functionalization resulted in a tendency towards relatively greater osteoblastic differentiation, which was corroborated by runt-related transcription factor 2 (RUNX2) amounts. Undetectable levels of OPN and phosphorylated suppressor of mothers against decapentaplegic (SMAD) 1/5/9 were noted in these groups, and the cleaved form of OPN was only detected in the blood clot immediately prior to cell plating. In conclusion, the strategy to mimic in vitro the initial interfacial in vivo events by forming a blood clot on a Ti nanoporous surface resulted in the inhibition of pre-osteoblastic differentiation, which was minimally reverted with an rmBMP-7 coating. Full article
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16 pages, 4558 KiB  
Article
Facts to Consider in Developing Materials That Emulate the Upper Jawbone: A Microarchitecture Study Showing Unique Characteristics at Four Different Sites
by Ee Lian Lim, Wei Cheong Ngeow, Kathreena Kadir and Murali Naidu
Biomimetics 2023, 8(1), 115; https://doi.org/10.3390/biomimetics8010115 - 10 Mar 2023
Cited by 1 | Viewed by 1280
Abstract
The maxilla is generally acknowledged as being more trabecular than the mandible. Allograft currently available for use in the maxillofacial region is harvested from the hip and long bones, irrespective of their local characteristics, and grafted onto the jawbones. Other alternative are autograft [...] Read more.
The maxilla is generally acknowledged as being more trabecular than the mandible. Allograft currently available for use in the maxillofacial region is harvested from the hip and long bones, irrespective of their local characteristics, and grafted onto the jawbones. Other alternative are autograft or commercially available bone substitutes. Due to their inherent differences, an in-depth understanding of the bone microarchitecture is important to develop the most compatible graft for use at the maxilla. This cross-sectional study aimed to determine the microstructures of bone harvested from different sites of the maxilla, to be used for standard setting. Forty-nine specimens from seven human cadavers were harvested from the zygomatic buttress, anterior maxillary sinus wall, anterior nasal spine and anterior palate. Each bone block, measuring of 10 mm × 5 mm, was harvested using rotary instruments. Bone analysis was performed following micro-computed tomography to obtain trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular thickness (Tb.Th), and bone volume fraction (BV/TV). There were site-related differences, with BV/TV that ranged between 37.38% and 85.83%. The Tb.N was the lowest at the palate (1.12 (mm−1)) and highest at the anterior maxillary sinus wall (1.41 (mm−1)) region. The palate, however, had the highest trabecular separation value (Tb.Sp) at 0.47 mm. The TB.Th was the lowest at the anterior nasal spine (0.34 mm) but both the zygoma and anterior maxillary sinus regions shared the highest Tb.Th (0.44 mm). Except for having the lowest Th.Sp (0.35 mm), the anterior maxillary sinus wall consistently showed higher values together with the zygomatic buttress in all other parameters. Concurring with current clinical practice of harvesting autograft from the zygomatic buttress and anterior maxillary sinus wall, their bony characteristic serve as the microarchitecture standard to adopt when developing new bone graft materials for use in the maxilla. Full article
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13 pages, 3342 KiB  
Article
Fabrication of 3D Bioprinted Bi-Phasic Scaffold for Bone–Cartilage Interface Regeneration
by Hongyi Chen, Giovanni Gonnella, Jie Huang and Lucy Di-Silvio
Biomimetics 2023, 8(1), 87; https://doi.org/10.3390/biomimetics8010087 - 21 Feb 2023
Cited by 5 | Viewed by 1936
Abstract
Treatments for osteochondral defects (OCDs) are mainly palliative and, with the increase in this pathology seen among both young and elderly people, an alternative treatment modality is sought. Many tissue-engineered strategies have been explored for regenerating the cartilage–bone interface; however, they generally fall [...] Read more.
Treatments for osteochondral defects (OCDs) are mainly palliative and, with the increase in this pathology seen among both young and elderly people, an alternative treatment modality is sought. Many tissue-engineered strategies have been explored for regenerating the cartilage–bone interface; however, they generally fall short of being ideal. Although cell-laden hydrogel scaffolds are a common approach for bone and cartilage tissue regeneration, they usually lack homogenous cell dispersion and patient specificity. In this study, a biphasic 3D bioprinted composite scaffold was fabricated for cartilage–bone interface regeneration. To overcome the shortcoming of both materials, alginate–gelatin (A–G) hydrogel was used to confer a naturally occurring environment for the cells and polycaprolactone (PCL) was used to enhance mechanical stability, thus maximizing the overall performance. Hydroxyapatite fillers were added to the PCL in the bone phase of the scaffold to improve its bioactivity. Physical and biological evaluation of scaffolds in both phases was assessed. The scaffolds demonstrated a desirable biological response both singly and in the combined PCL/A-G scaffolds, in both the short term and longer term, showing promise as an interfacial material between cartilage and bone. Full article
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12 pages, 3411 KiB  
Article
Long-Term Changes in Adipose Tissue in the Newly Formed Bone Induced by Recombinant Human BMP-2 In Vivo
by Hyouk-Keun Jee, Woo-Young Jeon, Han-Wool Kwak and Hyun Seok
Biomimetics 2023, 8(1), 33; https://doi.org/10.3390/biomimetics8010033 - 13 Jan 2023
Cited by 2 | Viewed by 1424
Abstract
Recombinant human bone morphogenetic protein-2 (rhBMP-2) induces osteogenesis and adipogenesis in bone scaffolds. We evaluated rhBMP-2-induced long-term changes in adipose tissue in the newly formed bone in different scaffolds forms. Bovine bone particles and blocks were grafted along with rhBMP-2 in the subperiosteal [...] Read more.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) induces osteogenesis and adipogenesis in bone scaffolds. We evaluated rhBMP-2-induced long-term changes in adipose tissue in the newly formed bone in different scaffolds forms. Bovine bone particles and blocks were grafted along with rhBMP-2 in the subperiosteal space of a rat calvarial bone, and the formation of new bone and adipose tissue were evaluated at 6 and 16 weeks after the surgery. The bone mineral density (BMD) and trabecular thickness (TbTh) of the 16w particle group were significantly higher than those of the 6w particle group (p = 0.018 and 0.012, respectively). The BMD and TbTh gradually increased in the particle group from weeks 6 to 16. The average adipose tissue volume (ATV) of the 6w particle group was higher than that of the 16w particle group, although the difference was not significant (p > 0.05), and it decreased gradually. There were no significant changes in the bone volume (BV) and BMD between the 6w and 16w block groups. Histological analysis revealed favorable new bone regeneration in all groups. Adipose tissue was formed between the bone particles and at the center in the particle and block groups, respectively. The adipose tissue space decreased, and the proportion of new bone increased in the 16w particle group compared to that in the 6w group. To summarize, in the particle group, the adipose tissue decreased in a time-dependent manner, BMD and TbTh increased, and new bone formation increased from 6 to 16 weeks. These results suggest that rhBMP-2 effectively induces new bone formation in the long term in particle bone scaffolds. Full article
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10 pages, 7447 KiB  
Article
Elastic Fibers and F-Box and WD-40 Domain-Containing Protein 2 in Bovine Periosteum and Blood Vessels
by Mari Akiyama
Biomimetics 2023, 8(1), 7; https://doi.org/10.3390/biomimetics8010007 - 23 Dec 2022
Cited by 1 | Viewed by 1328
Abstract
Elastic fibers form vessel walls, and elastic fiber calcification causes serious vascular diseases. Elastin is a well-known elastic fiber component; however, the insoluble nature of elastic fibers renders elastic fiber component analysis difficult. A previous study investigated F-box and WD-40 domain-containing protein 2 [...] Read more.
Elastic fibers form vessel walls, and elastic fiber calcification causes serious vascular diseases. Elastin is a well-known elastic fiber component; however, the insoluble nature of elastic fibers renders elastic fiber component analysis difficult. A previous study investigated F-box and WD-40 domain-containing protein 2 (FBXW2) in the cambium layer of bovine periosteum and hypothesized that fiber structures of FBXW2 are coated with osteocalcin during explant culture. Here, FBXW2 was expressed around some endothelial cells but not in all microvessels of the bovine periosteum. The author hypothesized that FBXW2 is expressed only in blood vessels with elastic fibers. Immunostaining and Elastica van Gieson staining indicated that FBXW2 was expressed in the same regions as elastic fibers and elastin in the cambium layer of the periosteum. Alpha-smooth muscle actin (αSMA) was expressed in microvessels and periosteum-derived cells. Immunostaining and observation of microvessels with serial sections revealed that osteocalcin was not expressed around blood vessels at 6 and 7 weeks. However, blood vessels and periosteum connoted elastic fibers, FBXW2, and αSMA. These findings are expected to clarify the processes involved in the calcification of elastic fibers in blood vessels. Full article
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16 pages, 1705 KiB  
Article
The Effect of Argon Plasma Surface Treatment on Poly(lactic-co-glycolic acid)/Collagen-Based Biomaterials for Bone Tissue Engineering
by Phat T. Vu, Jackson P. Conroy and Amy M. Yousefi
Biomimetics 2022, 7(4), 218; https://doi.org/10.3390/biomimetics7040218 - 29 Nov 2022
Cited by 5 | Viewed by 2136
Abstract
Nonunion bone fractures can impact the quality of life and represent a major economic burden. Scaffold-based tissue engineering has shown promise as an alternative to bone grafting. Achieving desirable bone reconstruction requires appropriate surface properties, together with optimizing the internal architecture of 3D [...] Read more.
Nonunion bone fractures can impact the quality of life and represent a major economic burden. Scaffold-based tissue engineering has shown promise as an alternative to bone grafting. Achieving desirable bone reconstruction requires appropriate surface properties, together with optimizing the internal architecture of 3D scaffolds. This study presents the surface modification of poly(lactic-co-glycolic acid) (PLGA), collagen, and PLGA-collagen via an argon plasma treatment. Argon plasma can modify the surface chemistry and topography of biomaterials and improve in vivo integration. Solvent-cast films were prepared using 1,1,1,3,3,3-hexafluoro-2-propanol and characterized via differential scanning calorimetry, thermogravimetric analysis, contact angle measurement, and critical surface tension analysis. For PLGA films, the water contact angle dropped from 70° to 42°, whereas the diiodomethane contact angle reduced from 53° to 32° after the plasma treatment. A set of PLGA-collagen formulations were loaded with nanohydroxyapatite (nHA) and polyethylene glycol (PEG) to enhance their osteoconductivity and hydrophilicity. Then, 3D scaffolds were fabricated using a 3D Bioplotter and characterized via Fourier-transform infrared (FTIR) spectroscopy. A bicinchoninic acid assay (BCA) was used to compare the protein release from the untreated and plasma-treated scaffolds into phosphate-buffered saline (PBS). The plasma-treated scaffolds had a lower protein release, and the difference compared to the untreated scaffolds was statistically significant. Full article
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16 pages, 5045 KiB  
Article
Effect of the Antimicrobial Agents Peppermint Essential Oil and Silver Nanoparticles on Bone Cement Properties
by Alina Robu, Aurora Antoniac, Robert Ciocoiu, Elena Grosu, Julietta V. Rau, Marco Fosca, Ivan I. Krasnyuk, Jr., Gratiela Gradisteanu Pircalabioru, Veronica Manescu (Paltanea), Iulian Antoniac and Sebastian Gradinaru
Biomimetics 2022, 7(3), 137; https://doi.org/10.3390/biomimetics7030137 - 17 Sep 2022
Cited by 4 | Viewed by 2182
Abstract
The main problems directly linked with the use of PMMA bone cements in orthopedic surgery are the improper mechanical bond between cement and bone and the absence of antimicrobial properties. Recently, more research has been devoted to new bone cement with antimicrobial properties [...] Read more.
The main problems directly linked with the use of PMMA bone cements in orthopedic surgery are the improper mechanical bond between cement and bone and the absence of antimicrobial properties. Recently, more research has been devoted to new bone cement with antimicrobial properties using mainly antibiotics or other innovative materials with antimicrobial properties. In this paper, we developed modified PMMA bone cement with antimicrobial properties proposing some experimental antimicrobial agents consisting of silver nanoparticles incorporated in ceramic glass and hydroxyapatite impregnated with peppermint oil. The impact of the addition of antimicrobial agents on the structure, mechanical properties, and biocompatibility of new PMMA bone cements was quantified. It has been shown that the addition of antimicrobial agents improves the flexural strength of the traditional PMMA bone cement, while the yield strength values show a decrease, most likely because this agent acts as a discontinuity inside the material rather than as a reinforcing agent. In the case of all samples, the addition of antimicrobial agents had no significant influence on the thermal stability. The new PMMA bone cement showed good biocompatibility and the possibility of osteoblast proliferation (MTT test) along with a low level of cytotoxicity (LDH test). Full article
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17 pages, 8155 KiB  
Article
Injectability, Processability, Drug Loading, and Antibacterial Activity of Gentamicin-Impregnated Mesoporous Bioactive Glass Composite Calcium Phosphate Bone Cement In Vitro
by Ming-Hsien Hu, Pei-Yi Chu, Ssu-Meng Huang, Bo-Sin Shih, Chia-Ling Ko, Jin-Jia Hu and Wen-Cheng Chen
Biomimetics 2022, 7(3), 121; https://doi.org/10.3390/biomimetics7030121 - 28 Aug 2022
Cited by 13 | Viewed by 3382
Abstract
Calcium phosphate cement (CPC) is similar to bone in composition and has plasticity, while mesoporous bioactive glass (MBG) has the advantage of releasing Si, which can promote osteogenic properties and drug loading capacity. A sol–gel-prepared MBG micro-powder (mMBG) and further impregnated antibiotic gentamicin [...] Read more.
Calcium phosphate cement (CPC) is similar to bone in composition and has plasticity, while mesoporous bioactive glass (MBG) has the advantage of releasing Si, which can promote osteogenic properties and drug loading capacity. A sol–gel-prepared MBG micro-powder (mMBG) and further impregnated antibiotic gentamicin sulfate (Genta@mMBG: 2, 3, and 4 mg/mL) antibiotic were added to CPC at different weight ratios (5, 10, and 15 wt.%) to study CPC’s potential clinical applications. Different ratios of mMBG/CPC composite bone cement showed good injectability and disintegration resistance, but with increasing mMBG addition, the working/setting time and compressive strength decreased. The maximum additive amount was 10 wt.% mMBG due to the working time of ~5 min, the setting time of ~10 min, and the compressive strength of ~51 MPa, indicating that it was more suitable for clinical surgical applications than the other groups. The 2Genta@mMBG group loaded with 2 mg/mL gentamicin had good antibacterial activity, and the 10 wt.% 2Genta@mMBG/CPC composite bone cement still had good antibacterial activity but reduced the initial release of Genta. 2Genta@mMBG was found to have slight cytotoxicity, so 2Genta@mMBG was composited into CPC to improve the biocompatibility and to endow CPC with more advantages for clinical application. Full article
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Review

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45 pages, 9598 KiB  
Review
Bone Regeneration Induced by Patient-Adapted Mg Alloy-Based Scaffolds for Bone Defects: Present and Future Perspectives
by Veronica Manescu (Paltanea), Iulian Antoniac, Aurora Antoniac, Dan Laptoiu, Gheorghe Paltanea, Robert Ciocoiu, Iosif Vasile Nemoianu, Lucian Gheorghe Gruionu and Horatiu Dura
Biomimetics 2023, 8(8), 618; https://doi.org/10.3390/biomimetics8080618 - 17 Dec 2023
Cited by 1 | Viewed by 1846
Abstract
Treatment of bone defects resulting after tumor surgeries, accidents, or non-unions is an actual problem linked to morbidity and the necessity of a second surgery and often requires a critical healthcare cost. Although the surgical technique has changed in a modern way, the [...] Read more.
Treatment of bone defects resulting after tumor surgeries, accidents, or non-unions is an actual problem linked to morbidity and the necessity of a second surgery and often requires a critical healthcare cost. Although the surgical technique has changed in a modern way, the treatment outcome is still influenced by patient age, localization of the bone defect, associated comorbidities, the surgeon approach, and systemic disorders. Three-dimensional magnesium-based scaffolds are considered an important step because they can have precise bone defect geometry, high porosity grade, anatomical pore shape, and mechanical properties close to the human bone. In addition, magnesium has been proven in in vitro and in vivo studies to influence bone regeneration and new blood vessel formation positively. In this review paper, we describe the magnesium alloy’s effect on bone regenerative processes, starting with a short description of magnesium’s role in the bone healing process, host immune response modulation, and finishing with the primary biological mechanism of magnesium ions in angiogenesis and osteogenesis by presenting a detailed analysis based on a literature review. A strategy that must be followed when a patient-adapted scaffold dedicated to bone tissue engineering is proposed and the main fabrication technologies are combined, in some cases with artificial intelligence for Mg alloy scaffolds, are presented with examples. We emphasized the microstructure, mechanical properties, corrosion behavior, and biocompatibility of each study and made a basis for the researchers who want to start to apply the regenerative potential of magnesium-based scaffolds in clinical practice. Challenges, future directions, and special potential clinical applications such as osteosarcoma and persistent infection treatment are present at the end of our review paper. Full article
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32 pages, 5683 KiB  
Review
A Review on Manufacturing Processes of Biocomposites Based on Poly(α-Esters) and Bioactive Glass Fillers for Bone Regeneration
by Xavier Lacambra-Andreu, Abderrahim Maazouz, Khalid Lamnawar and Jean-Marc Chenal
Biomimetics 2023, 8(1), 81; https://doi.org/10.3390/biomimetics8010081 - 14 Feb 2023
Cited by 1 | Viewed by 2334
Abstract
The incorporation of bioactive and biocompatible fillers improve the bone cell adhesion, proliferation and differentiation, thus facilitating new bone tissue formation upon implantation. During these last 20 years, those biocomposites have been explored for making complex geometry devices likes screws or 3D porous [...] Read more.
The incorporation of bioactive and biocompatible fillers improve the bone cell adhesion, proliferation and differentiation, thus facilitating new bone tissue formation upon implantation. During these last 20 years, those biocomposites have been explored for making complex geometry devices likes screws or 3D porous scaffolds for the repair of bone defects. This review provides an overview of the current development of manufacturing process with synthetic biodegradable poly(α-ester)s reinforced with bioactive fillers for bone tissue engineering applications. Firstly, the properties of poly(α-ester), bioactive fillers, as well as their composites will be defined. Then, the different works based on these biocomposites will be classified according to their manufacturing process. New processing techniques, particularly additive manufacturing processes, open up a new range of possibilities. These techniques have shown the possibility to customize bone implants for each patient and even create scaffolds with a complex structure similar to bone. At the end of this manuscript, a contextualization exercise will be performed to identify the main issues of process/resorbable biocomposites combination identified in the literature and especially for resorbable load-bearing applications. Full article
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21 pages, 5065 KiB  
Review
Tantalum as Trabecular Metal for Endosseous Implantable Applications
by Filippo Carraro and Andrea Bagno
Biomimetics 2023, 8(1), 49; https://doi.org/10.3390/biomimetics8010049 - 23 Jan 2023
Cited by 3 | Viewed by 2130
Abstract
During the last 20 years, tantalum has known ever wider applications for the production of endosseous implantable devices in the orthopedic and dental fields. Its excellent performances are due to its capacity to stimulate new bone formation, thus improving implant integration and stable [...] Read more.
During the last 20 years, tantalum has known ever wider applications for the production of endosseous implantable devices in the orthopedic and dental fields. Its excellent performances are due to its capacity to stimulate new bone formation, thus improving implant integration and stable fixation. Tantalum’s mechanical features can be mainly adjusted by controlling its porosity thanks to a number of versatile fabrication techniques, which allow obtaining an elastic modulus similar to that of bone tissue, thus limiting the stress-shielding effect. The present paper aims at reviewing the characteristics of tantalum as a solid and porous (trabecular) metal, with specific regard to biocompatibility and bioactivity. Principal fabrication methods and major applications are described. Moreover, the osteogenic features of porous tantalum are presented to testify its regenerative potential. It can be concluded that tantalum, especially as a porous metal, clearly possesses many advantageous characteristics for endosseous applications but it presently lacks the consolidated clinical experience of other metals such as titanium. Full article
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12 pages, 5744 KiB  
Case Report
Guided Bone Regeneration with Occlusive Titanium Barrier: A Case Report and Clinical Considerations
by Lucio Milillo and Massimo Petruzzi
Biomimetics 2023, 8(1), 106; https://doi.org/10.3390/biomimetics8010106 - 06 Mar 2023
Cited by 1 | Viewed by 1476
Abstract
The need to obtain adequate bone volumes for prosthetic rehabilitation supported by implants, using different techniques and materials, represents an urgent need in modern dentistry. We report a case regarding the management of implant-prosthetic rehabilitation of the first and second upper right molars, [...] Read more.
The need to obtain adequate bone volumes for prosthetic rehabilitation supported by implants, using different techniques and materials, represents an urgent need in modern dentistry. We report a case regarding the management of implant-prosthetic rehabilitation of the first and second upper right molars, in which no less than 4 mm of crestal bone remained to insert two implants. Regeneration of the residual bone was previously performed using a customized titanium barrier and a filler of a blood clot with tricalcium beta phosphate. The bone gain (3 mm) was evaluated by comparing CBCT images, while the implant stability (mean 70) was assessed with the ISQ measurement. A regenerated bone sample was taken for histological analysis. Guided bone regeneration obtained with a titanium barrier and blood clot allowed for the insertion of stable implants in a mature bone without heterologous material. Full article
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12 pages, 1855 KiB  
Perspective
Metal–Organic Frameworks (MOFs) and Their Composites as Emerging Biomaterials for Osteoarthritis Treatment
by Hoi-Lam Wong, Chung-Yin Tsang and Sebastian Beyer
Biomimetics 2023, 8(1), 97; https://doi.org/10.3390/biomimetics8010097 - 27 Feb 2023
Cited by 3 | Viewed by 2034
Abstract
Metal-Organic Frameworks (MOFs) have emerged as a novel component in biomaterial formulations over the past 5 years. The bioactivity of MOFs in bone or cartilage tissue is mediated through the sustained delivery of metal ions, bioactive ligands, or drug molecules that are loaded [...] Read more.
Metal-Organic Frameworks (MOFs) have emerged as a novel component in biomaterial formulations over the past 5 years. The bioactivity of MOFs in bone or cartilage tissue is mediated through the sustained delivery of metal ions, bioactive ligands, or drug molecules that are loaded into the porous MOF structures. Alternatively, bioactivity may also originate from structure-specific properties. The latter includes the availability and accessibility of open metal coordination sites for the catalytic conversion of biomolecules into active agents. This narrative highlight aims to inspire strategies to utilize MOFs for treating osteoarthritis (OA), with a special focus on augmenting hydrogel-based biomaterials with MOFs. The added value of MOFs in these hydrogel formulations is discussed, and the biological efficacy is compared to approaches applying classical injectable biomaterials for OA treatment. Possible future directions and pitfalls of these novel MOF–hydrogel composites are emphasized to assist future transition of MOFs into clinical applications. Full article
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