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State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells

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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 (31 August 2022) | Viewed by 29161

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Special Issue Editor

Dr. Koroush Kabir

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Guest Editor

Medizinische Fakultät, 53127 Bonn, Germany
Interests: orthopaedics; aseptic loosening; wear particles; macrophages; nanoparticles

Special Issue Information

Dear Colleagues,

Despite rapid advancements in regenerative therapy, bone regeneration for congenital and large bone defects is still challenging in the fields of dentistry, plastic surgery, and orthopedic surgery. Providing an optimal and ideal local environment for endogenous and exogenous cells is inevitable to overcome these challenges. Highly functional biomaterials enable the generation of a controlled environment. Furthermore, in vitro preconditioning of cells can facilitate the modulation of the local environment for bone regeneration. In this Special Issue, we aim to provide beneficial findings for the preparation and application of functional materials to effectively augment bone regeneration and elucidate novel mechanisms underlying the generation of an optimal environment for bone regeneration. Original research papers and mini- and full reviews are welcome.

Potential topics include, but are not limited to the following:

Modification of the scaffold or surface on materials for the spatiotemporal regulation of cell invasion and differentiation;
Enhancement of the accuracy on the delivery and controlled-release of drugs;
Regulation of anti-oxidant and anti-inflammatory effects;
Effective methods to prepare cells for use in bone and osteochondral regeneration;
Design and preparation of highly anti-bacterial materials;
Cost-effective strategies for functionalizing biomaterials;
Development of ecofriendly functional materials.

Dr. Koroush Kabir
Guest Editor

Manuscript Submission Information

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Published Papers (14 papers)

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15 pages, 3788 KiB

Open AccessArticle

Evaluation of Serum Albumin-Coated Bone Allograft for Bone Regeneration: A Seven-Year Follow-Up Study of 26 Cases

by Kata K. Gyulay, Péter Karászi, Mátyás Rédei, Petra Sólymos, Károly Schandl, Zsombor Lacza and Dénes B. Horváthy

Int. J. Mol. Sci. 2023, 24(11), 9232; https://doi.org/10.3390/ijms24119232 - 25 May 2023

Cited by 3 | Viewed by 1448

Abstract

We have previously reported that serum albumin-coated bone allograft (BoneAlbumin, BA) is an effective bone substitute. It improves bone regeneration at the patellar and tibial donor sites six months after harvesting bone-patellar tendon-bone (BPTB) autografts for primary anterior cruciate ligament reconstruction (ACLR). In the present study, we examined these donor sites seven years after implantation. The study group (N = 10) received BA-enhanced autologous cancellous bone at the tibial and BA alone at the patellar site. The control group (N = 16) received autologous cancellous bone at the tibial and blood clot at the patellar site. We evaluated subcortical density, cortical thickness, and bone defect volume via CT scans. At the patellar site, subcortical density was significantly higher in the BA group at both time points. There was no significant difference in cortical thickness between the two groups at either donor site. The control group’s bone defect significantly improved and reached the BA group’s values at both sites by year seven. Meanwhile, the bone defects in the BA group did not change significantly and were comparable to the six-month measurements. No complications were observed. There are two limitations in this study: The number of patients recruited is small, and the randomization of the patients could have improved the quality of the study as the control group patients were older compared to the study group patients. Our 7-year results seem to demonstrate that BA is a safe and effective bone substitute that supports faster regeneration of donor sites and results in good-quality bone tissue at the time of ACLR with BPTB autografts. However, studies with a larger number of patients are required to definitively confirm the preliminary results of our study. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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12 pages, 8203 KiB

Open AccessArticle

4-Hexylresorcinol Treatment before Degumming Increases the β-Sheet Structure of Silk Sericin and BMP-2 Expression in RAW264.7 Cells

by Ji Hae Lee, HaeYong Kweon, Ji-Hyeon Oh, Yei-Jin Kang, Dae-Won Kim, Won-Geun Yang, Weon-Sik Chae and Seong-Gon Kim

Int. J. Mol. Sci. 2023, 24(1), 150; https://doi.org/10.3390/ijms24010150 - 21 Dec 2022

Cited by 3 | Viewed by 1214

Abstract

Silk sericin is a degumming product used by the silk industry. The degumming process can affect the protein structure and molecular weight of silk sericin. The present study examined how pretreatment with 4-hexylresorcinol (4HR) affects the biomedical properties of silk sericin. Before the degumming process, silkworm cocoons were treated with 4HR solution. The protein structure of the final degumming product was evaluated by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy. Untreated silk sericin (S) and silk sericin pretreated with 4HR (S+4HR) were added to RAW264.7 cells, and the expression of BMP-2 was determined. The bone-regenerating capacity of S+4HR was evaluated using the critical-sized rat calvarial defect model. Compared with S, S+4HR showed an increase in β-sheet structures. Administration of S+4HR to RAW264.7 cells increased expression of BMP-2, mainly via the TLR-mediated signaling pathway. Bone volume, as measured by micro-computerized tomography, was significantly greater in the S+4HR group than in the S, gelatin alone, and unfilled control groups (p < 0.05 each). Expression of BMP-2 and runx2 in tissue specimens was significantly higher following treatment with S+4HR than with S (p < 0.05). Taken together, these findings show that 4HR pretreatment before the degumming process increased the β-sheet structure of silk sericin, as well as inducing BMP-2 expression and bone regeneration ability. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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17 pages, 2919 KiB

Open AccessArticle

A Tissue Engineering Acoustophoretic (TEA) Set-up for the Enhanced Osteogenic Differentiation of Murine Mesenchymal Stromal Cells (mMSCs)

by Hui Zhang, Nirina Beilfuss, Urszula Zabarylo, Kay Raum and Regina Puts

Int. J. Mol. Sci. 2022, 23(19), 11473; https://doi.org/10.3390/ijms231911473 - 29 Sep 2022

Cited by 2 | Viewed by 1813

Abstract

Quickly developing precision medicine and patient-oriented treatment strategies urgently require novel technological solutions. The randomly cell-populated scaffolds usually used for tissue engineering often fail to mimic the highly anisotropic characteristics of native tissue. In this work, an ultrasound standing-wave-based tissue engineering acoustophoretic (TEA) set-up was developed to organize murine mesenchymal stromal cells (mMSCs) in an in situ polymerizing 3-D fibrin hydrogel. The resultant constructs, consisting of 17 cell layers spaced at 300 µm, were obtained by continuous wave ultrasound applied at a 2.5 MHz frequency. The patterned mMSCs preserved the structured behavior within 10 days of culturing in osteogenic conditions. Cell viability was moderately increased 1 day after the patterning; it subdued and evened out, with the cells randomly encapsulated in hydrogels, within 21 days of culturing. Cells in the structured hydrogels exhibited enhanced expression of certain osteogenic markers, i.e., Runt-related transcription factor 2 (RUNX2), osterix (Osx) transcription factor, collagen-1 alpha1 (COL1A1), osteopontin (OPN), osteocalcin (OCN), and osteonectin (ON), as well as of certain cell-cycle-progression-associated genes, i.e., Cyclin D1, cysteine-rich angiogenic inducer 61 (CYR61), and anillin (ANLN), when cultured with osteogenic supplements and, for ANLN, also in the expansion media. Additionally, OPN expression was also augmented on day 5 in the patterned gels cultured without the osteoinductive media, suggesting the pro-osteogenic influence of the patterned cell organization. The TEA set-up proposes a novel method for non-invasively organizing cells in a 3-D environment, potentially enhancing the regenerative properties of the designed anisotropic constructs for bone healing. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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13 pages, 4067 KiB

Open AccessArticle

Structural Design and Finite Element Simulation Analysis of Grade 3 Graded Porous Titanium Implant

by Bowen Liu, Wei Xu, Mingying Chen, Dongdong Chen, Guyu Sun, Ce Zhang, Yu Pan, Jinchao Lu, Enbo Guo and Xin Lu

Int. J. Mol. Sci. 2022, 23(17), 10090; https://doi.org/10.3390/ijms231710090 - 3 Sep 2022

Cited by 7 | Viewed by 1403

Abstract

The metal titanium is often used as a dental implant material, and the elastic modulus of solid titanium implants does not match the biological bone tissue, which can easily produce a stress shielding effect and cause implant failure. In this paper, a three-level gradient porous structure implant was designed, and its mechanical and biological adaptability were studied by finite element simulation analysis. Combined with the comprehensive evaluation of the mechanical and biological properties of implants of various structures, the analysis found that a porous implant with porosity of 59.86% of the gradient was the best structure. The maximum equivalent stress of this structure in the mandible that simulated the oral environment was 154.34 MPa, which was less than half of its theoretical compression yield strength. The strain of the surrounding bone tissue lies in the bone compared with other structures, the proportion of the active state of plastic construction is larger, at 10.51%, and the fretting value of this structure and the bone tissue interface is the smallest, at only 10 μm. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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19 pages, 3527 KiB

Open AccessArticle

Dentin Particulate for Bone Regeneration: An In Vitro Study

by Giulia Brunello, Federica Zanotti, Gerard Scortecci, Lari Sapoznikov, Stefano Sivolella and Barbara Zavan

Int. J. Mol. Sci. 2022, 23(16), 9283; https://doi.org/10.3390/ijms23169283 - 18 Aug 2022

Cited by 5 | Viewed by 1975

Abstract

The aim of this in vitro study was to investigate the commitment and behavior of dental pulp stem cells (DPSCs) seeded onto two different grafting materials, human dentin particulate (DP) and deproteinized bovine bone matrix (BG), with those cultured in the absence of supplements. Gene expression analyses along with epigenetic and morphological tests were carried out to examine odontogenic and osteogenic differentiation and cell proliferation. Compressive testing of the grafting materials seeded with DPSCs was performed as well. DPSC differentiation into odontoblast-like cells was identified from the upregulation of odontogenic markers (DSPP and MSX) and osteogenic markers (RUNX2, alkaline phosphatase, osteonectin, osteocalcin, collagen type I, bmp2, smad5/8). Epigenetic tests confirmed the presence of miRNAs involved in odontogenic or osteogenic commitment of DPSCs cultured for up to 21 days on DP. Compressive strength values obtained from extracellular matrix (ECM) synthesized by DPSCs showed a trend of being higher when seeded onto DP than onto BG. High expression of VEGF factor, which is related to angiogenesis, and of dentin sialoprotein was observed only in the presence of DP. Morphological analyses confirmed the typical phenotype of adult odontoblasts. In conclusion, the odontogenic and osteogenic commitment of DPSCs and their respective functions can be achieved on DP, which enables exceptional dentin and bone regeneration. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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15 pages, 2972 KiB

Open AccessArticle

Perforated Hydrogels Consisting of Cholesterol-Bearing Pullulan (CHP) Nanogels: A Newly Designed Scaffold for Bone Regeneration Induced by RANKL-Binding Peptides and BMP-2

by Cangyou Xie, Michiko Satake-Ozawa, Fatma Rashed, Masud Khan, Masaomi Ikeda, Shunya Hayashi, Shinichi Sawada, Yoshihiro Sasaki, Tohru Ikeda, Yoshiyuki Mori, Kazunari Akiyoshi and Kazuhiro Aoki

Int. J. Mol. Sci. 2022, 23(14), 7768; https://doi.org/10.3390/ijms23147768 - 14 Jul 2022

Cited by 4 | Viewed by 2205

Abstract

The receptor activator of NF-κB ligand (RANKL)-binding peptide, OP3-4, is known to stimulate bone morphogenetic protein (BMP)-2-induced bone formation, but peptides tend to aggregate and lose their bioactivity. Cholesterol-bearing pullulan (CHP) nanogel scaffold has been shown to prevent aggregation of peptides and to allow their sustained release and activity; however, the appropriate design of CHP nanogels to conduct local bone formation needs to be developed. In the present study, we investigated the osteoconductive capacity of a newly synthesized CHP nanogel, CHPA using OP3-4 and BMP-2. We also clarified the difference between perforated and nonperforated CHPA impregnated with the two signaling molecules. Thirty-six, five-week-old male BALB/c mice were used for the calvarial defect model. The mice were euthanized at 6 weeks postoperatively. A higher cortical bone mineral content and bone formation rate were observed in the perforated scaffold in comparison to the nonperforated scaffold, especially in the OP3-4/BMP-2 combination group. The degradation rate of scaffold material in the perforated OP3-4/BMP-2 combination group was lower than that in the nonperforated group. These data suggest that perforated CHPA nanogel could lead to local bone formation induced by OP3-4 and BMP–2 and clarified the appropriate degradation rate for inducing local bone formation when CHPA nanogels are designed to be perforated. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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13 pages, 4291 KiB

Open AccessArticle

Bone Tissue Engineering in Rat Calvarial Defects Using Induced Bone-like Tissue by rhBMPs from Immature Muscular Tissues In Vitro

by Tatsuhide Hayashi, Masaki Asakura, Mayu Kawase, Masakazu Matsubara, Yasuaki Uematsu, Akimichi Mieki and Tatsushi Kawai

Int. J. Mol. Sci. 2022, 23(13), 6927; https://doi.org/10.3390/ijms23136927 - 22 Jun 2022

Cited by 1 | Viewed by 1965

Abstract

This study aimed to induce bone-like tissue from immature muscular tissue (IMT) in vitro using commercially available recombinant human bone morphogenetic protein (rhBMP)-2, rhBMP-4, and rhBMP-7, and then implanting this tissue into a calvarial defect in rats to assess healing. IMTs were extracted from 20-day-old Sprague-Dawley (SD) fetal rats, placed on expanded polytetrafluoroethylene (ePTFE) with 10 ng/μL each of rhBMP-2, BMP-4, and BMP-7, and cultured for two weeks. The specimens were implanted into calvarial defects in 3-week-old SD rats for up to three weeks. Relatively strong radiopacity was observed on micro-CT two weeks after culture, and bone-like tissue, comprising osteoblastic cells and osteoids, was partially observed by H&E staining. Calcium, phosphorus, and oxygen were detected in the extracellular matrix using an electron probe micro analyzer, and X-ray diffraction patterns and Fourier transform infrared spectroscopy spectra of the specimen were found to have typical apatite crystal peaks and spectra, respectively. Furthermore, partial strong radiopacity and ossification were confirmed one week after implantation, and a dominant novel bone was observed after two weeks in the defect site. Thus, rhBMP-2, BMP-4, and BMP-7 differentiated IMT into bone-like tissue in vitro, and this induced bone-like tissue has ossification potential and promotes the healing of calvarial defects. Our results suggest that IMT is an effective tissue source for bone tissue engineering. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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19 pages, 10782 KiB

Open AccessArticle

Regression Analysis of the Dielectric and Morphological Properties for Porous Nanohydroxyapatite/Starch Composites: A Correlative Study

by Chong You Beh, Ee Meng Cheng, Nashrul Fazli Mohd Nasir, Mohd Shukry Abdul Majid, Shing Fhan Khor, Mohd Ridzuan Mohd Jamir, Emma Ziezie Mohd Tarmizi and Kim Yee Lee

Int. J. Mol. Sci. 2022, 23(10), 5695; https://doi.org/10.3390/ijms23105695 - 19 May 2022

Cited by 1 | Viewed by 1443

Abstract

This paper aims to investigate the dielectric properties, i.e., dielectric constant (ε′), dielectric loss factor (ε″), dielectric tangent loss (tan δ), electrical conductivity (σ), and penetration depth (D_p), of the porous nanohydroxyapatite/starch composites in the function of starch proportion, pore size, and porosity over a broad band frequency range of 5 MHz–12 GHz. The porous nanohydroxyapatite/starch composites were fabricated using different starch proportions ranging from 30 to 90 wt%. The results reveal that the dielectric properties and the microstructural features of the porous nanohydroxyapatite/starch composites can be enhanced by the increment in the starch proportion. Nevertheless, the composite with 80 wt% of starch proportion exhibit low dielectric properties (ε′, ε″, tan δ, and σ) and a high penetration depth because of its highly interconnected porous microstructures. The dielectric properties of the porous nanohydroxyapatite/starch composites are highly dependent on starch proportion, average pore size, and porosity. The regression models are developed to express the dielectric properties of the porous nanohydroxyapatite/starch composites (R² > 0.96) in the function of starch proportion, pore size, and porosity from 1 to 11 GHz. This dielectric study can facilitate the assessment of bone scaffold design in bone tissue engineering applications. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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19 pages, 3940 KiB

Open AccessArticle

Graphene Oxide Framework Structures and Coatings: Impact on Cell Adhesion and Pre-Vascularization Processes for Bone Grafts

by Fanlu Wang, Lena Marie Saure, Fabian Schütt, Felix Lorich, Florian Rasch, Ali Shaygan Nia, Xinliang Feng, Andreas Seekamp, Tim Klüter, Hendrik Naujokat, Rainer Adelung and Sabine Fuchs

Int. J. Mol. Sci. 2022, 23(6), 3379; https://doi.org/10.3390/ijms23063379 - 21 Mar 2022

Cited by 4 | Viewed by 2235

Abstract

Graphene oxide (GO) is a promising material for bone tissue engineering, but the validation of its molecular biological effects, especially in the context of clinically applied materials, is still limited. In this study, we compare the effects of graphene oxide framework structures (F-GO) and reduced graphene oxide-based framework structures (F-rGO) as scaffold material with a special focus on vascularization associated processes and mechanisms in the bone. Highly porous networks of zinc oxide tetrapods serving as sacrificial templates were used to create F-GO and F-rGO with porosities >99% consisting of hollow interconnected microtubes. Framework materials were seeded with human mesenchymal stem cells (MSC), and the cell response was evaluated by confocal laser scanning microscopy (CLSM), deoxyribonucleic acid (DNA) quantification, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and alkaline phosphatase activity (ALP) to define their impact on cellular adhesion, osteogenic differentiation, and secretion of vascular growth factors. F-GO based scaffolds improved adhesion and growth of MSC as indicated by CLSM and DNA quantification. Further, F-GO showed a better vascular endothelial growth factor (VEGF) binding capacity and improved cell growth as well as the formation of microvascular capillary-like structures in co-cultures with outgrowth endothelial cells (OEC). These results clearly favored non-reduced graphene oxide in the form of F-GO for bone regeneration applications. To study GO in the context of a clinically used implant material, we coated a commercially available xenograft (Bio-Oss^® block) with GO and compared the growth of MSC in monoculture and in coculture with OEC to the native scaffold. We observed a significantly improved growth of MSC and formation of prevascular structures on coated Bio-Oss^®, again associated with a higher VEGF binding capacity. We conclude that graphene oxide coating of this clinically used, but highly debiologized bone graft improves MSC cell adhesion and vascularization. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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16 pages, 3578 KiB

Open AccessArticle

Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways

by Xuan Liu, Li Diao, Yudie Zhang, Xue Yang, Junnan Zhou, Yuhang Mao, Xiaotian Shi, Fuli Zhao and Mei Liu

Int. J. Mol. Sci. 2022, 23(5), 2868; https://doi.org/10.3390/ijms23052868 - 5 Mar 2022

Cited by 7 | Viewed by 2270

Abstract

Wear particle-induced aseptic loosening is the most common complication of total joint arthroplasty (TJA). Excessive osteoclast formation and bone resorptive activation have been considered to be responsible for extensive bone destruction and prosthesis failure. Therefore, identification of anti-osteoclastogenesis agents is a potential therapy strategy for the treatment of aseptic loosening and other osteoclast-related osteolysis diseases. In the present study, we reported, for the first time, that piperlongumine (PL), a key alkaloid compound from Piper longum fruits, could significantly suppress the formation and activation of osteoclasts. Furthermore, PL effectively decreased the mRNA expressions of osteoclastic marker genes such as tartrate-resistant acid phosphatase (TRAP), calcitonin receptor (CTR), and cathepsin K (CTSK). In addition, PL suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced activations of MAPKs (ERK, JNK and p38) and NF-κB, which down-regulated the protein expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Using a titanium (Ti) particle-induced calvarial osteolysis model, we demonstrated that PL could ameliorate Ti particle-induced bone loss in vivo. These data provide strong evidence that PL has the potential to treat osteoclast-related diseases including periprosthetic osteolysis (PPO) and aseptic loosening. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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13 pages, 7765 KiB

Open AccessArticle

Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects

by Shabnam I. Ibragimova, Ekaterina V. Medvedeva, Irina A. Romanova, Leonid P. Istranov, Elena V. Istranova, Aleksey V. Lychagin, Andrey A. Nedorubov, Peter S. Timashev, Vladimir I. Telpukhov and Andrei S. Chagin

Int. J. Mol. Sci. 2022, 23(1), 292; https://doi.org/10.3390/ijms23010292 - 28 Dec 2021

Cited by 4 | Viewed by 2442

Abstract

Articular cartilage is a highly organized tissue that has a limited ability to heal. Tissue engineering is actively exploited for joint tissue reconstruction in numerous cases of articular cartilage degeneration associated with trauma, arthrosis, rheumatoid arthritis, and osteoarthritis. However, the optimal scaffolds for cartilage repair are not yet identified. Here we have directly compared five various scaffolds, namely collagen-I membrane, collagen-II membrane, decellularized cartilage, a cellulose-based implant, and commercially available Chondro-Gide^® (Geistlich Pharma AG, Wolhusen, Switzerland) collagen membrane. The scaffolds were implanted in osteochondral full-thickness defects, formed on adult Wistar rats using a hand-held cutter with a diameter of 2.0 mm and a depth of up to the subchondral bone. The congruence of the articular surface was almost fully restored by decellularized cartilage and collagen type II-based scaffold. The most vivid restoration was observed 4 months after the implantation. The formation of hyaline cartilage was not detected in any of the groups. Despite cellular infiltration into scaffolds being observed in each group except cellulose, neither chondrocytes nor chondro-progenitors were detected. We concluded that for restoration of hyaline cartilage, scaffolds have to be combined either with cellular therapy or morphogens promoting chondrogenic differentiation. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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13 pages, 5822 KiB

Open AccessArticle

Bone Regeneration of a 3D-Printed Alloplastic and Particulate Xenogenic Graft with rhBMP-2

by Ji-In Ryu, Byoung-Eun Yang, Sang-Min Yi, Hyo Geun Choi, Sung-Woon On, Seok Jin Hong, Ho-Kyung Lim and Soo-Hwan Byun

Int. J. Mol. Sci. 2021, 22(22), 12518; https://doi.org/10.3390/ijms222212518 - 20 Nov 2021

Cited by 7 | Viewed by 2389

Abstract

This study aimed to evaluate the bone regeneration capacity of a customized alloplastic material and xenograft with recombinant human bone morphogenetic protein-2 (rhBMP-2). We prepared hydroxyapatite (HA)/tricalcium phosphate (TCP) pure ceramic bone blocks made using a 3D printing system and added rhBMP-2 to both materials. In eight beagle dogs, a total of 32 defects were created on the lower jaws. The defective sites of the negative control group were left untreated (N group; 8 defects), and those in the positive control group were filled with particle-type Bio-Oss (P group; 12 defects). The defect sites in the experimental group were filled with 3D-printed synthetic bone blocks (3D group; 12 defects). Radiographic and histological evaluations were performed after healing periods of 6 and 12 weeks and showed no significant difference in new bone formation and total bone between the P and 3D groups. The 3D-printed custom HA/TCP graft with rhBMP-2 showed bone regeneration effects similar to that of particulate Bio-Oss with rhBMP-2. Through further study and development, the application of 3D-printed customized alloplastic grafts will be extended to various fields of bone regeneration. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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Review

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16 pages, 3315 KiB

Open AccessReview

Chondrocytes In Vitro Systems Allowing Study of OA

by Ewa Bednarczyk

Int. J. Mol. Sci. 2022, 23(18), 10308; https://doi.org/10.3390/ijms231810308 - 7 Sep 2022

Cited by 5 | Viewed by 2127

Abstract

Osteoarthritis (OA) is an extremely complex disease, as it combines both biological-chemical and mechanical aspects, and it also involves the entire joint consisting of various types of tissues, including cartilage and bone. This paper describes the methods of conducting cell cultures aimed at searching for the mechanical causes of OA development, therapeutic solutions, and methods of preventing the disease. It presents the systems for the cultivation of cartilage cells depending on the level of their structural complexity, and taking into account the most common solutions aimed at recreating the most important factors contributing to the development of OA, that is mechanical loads. In-vitro systems used in tissue engineering to investigate the phenomena associated with OA were specified depending on the complexity and purposefulness of conducting cell cultures. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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17 pages, 1502 KiB

Open AccessReview

Modern Approaches to Acellular Therapy in Bone and Dental Regeneration

by Alexey A. Ivanov, Alla V. Kuznetsova, Olga P. Popova, Tamara I. Danilova and Oleg O. Yanushevich

Int. J. Mol. Sci. 2021, 22(24), 13454; https://doi.org/10.3390/ijms222413454 - 15 Dec 2021

Cited by 7 | Viewed by 2713

Abstract

An approach called cell-free therapy has rapidly developed in regenerative medicine over the past decade. Understanding the molecular mechanisms and signaling pathways involved in the internal potential of tissue repair inspires the development of new strategies aimed at controlling and enhancing these processes during regeneration. The use of stem cell mobilization, or homing for regeneration based on endogenous healing mechanisms, prompted a new concept in regenerative medicine: endogenous regenerative medicine. The application of cell-free therapeutic agents leading to the recruitment/homing of endogenous stem cells has advantages in overcoming the limitations and risks associated with cell therapy. In this review, we discuss the potential of cell-free products such as the decellularized extracellular matrix, growth factors, extracellular vesicles and miRNAs in endogenous bone and dental regeneration. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Materials for Bone Regeneration: Biomaterials and Cells)

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