Accelerated Bone Healing in Calvarial and Femoral Defects with Injectable Microcarriers that Mimic the Osteogenic Niche

Osteo-enhanced human mesenchymal stem cells (OEhMSCs) secrete an osteogenic cell matrix (OCM) that mimics the composition of anabolic bone tissue and strongly enhances OEhMSC retention and subsequent bone repair in vivo. Here we demonstrate a system for rapid production of gelatin methacrylate microcarriers coated with decellularized OCM (OCM-GelMA) to serve as an injectable bone graft material with high osteogenic potential comparable to a clinically utilized gold standard, bone morphogenic protein 2 (BMP-2). OEhMSCs seeded onto OCM-GelMA secreted high levels of osteogenic and angiogenic cytokines and expressed higher levels of BMP-2 relative to OEhMSCs on bare GelMA microcarriers. OEhMSCs co-administered with OCM-GelMA microcarriers resulted in enhanced healing of murine critical-sized calvarial defects, which was comparable to that achieved with a BMP-2-laden gelatin sponge control. When tested in a murine femoral defect model, OCM-GelMA co-administered with OEhMSCs also induced profound bone growth within the defect. We submit that OCM-GelMA promotes OEhMSC paracrine release to accelerate bone repair, indicating their potential as a bone graft for use in minimally invasive surgery.

Download Full-text

Bone graft substitutes for the promotion of spinal arthrodesis

Neurosurgical FOCUS ◽

10.3171/foc.2001.10.4.5 ◽

2001 ◽

Vol 10 (4) ◽

pp. 1-5 ◽

Cited By ~ 9

Author(s):

Gregory A. Helm ◽

Hayan Dayoub ◽

John A. Jane

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Bone Graft ◽

Bone Repair ◽

Bone Growth ◽

Transforming Growth Factor ◽

Local Bone ◽

Bone Graft Substitutes ◽

Autologous Bone

In the prototypical method for inducing spinal fusion, autologous bone graft is harvested from the iliac crest or local bone removed during the spinal decompression. Although autologous bone remains the “gold standard” for stimulating bone repair and regeneration, modern molecular biology and bioengineering techniques have produced unique materials that have potent osteogenic activities. Recombinant human osteogenic growth factors, such as bone morphogenetic proteins, transforming growth factor–β, and platelet-derived growth factor are now produced in highly concentrated and pure forms and have been shown to be extremely potent bone-inducing agents when delivered in vivo in rats, dogs, primates, and humans. The delivery of pluripotent mesenchymal stem cells (MSCs) to regions requiring bone formation is also compelling, and it has been shown to be successful in inducing osteogenesis in numerous pre-clinical studies in rats and dogs. Finally, the identification of biological and nonbiological scaffolding materials is a crucial component of future bone graft substitutes, not only as a delivery vehicle for bone growth factors and MSCs but also as an osteoconductive matrix to stimulate bone deposition directly. In this paper, the currently available bone graft substitutes will be reviewed and the authors will discuss the novel therapeutic approaches that are currently being developed for use in the clinical setting.

Download Full-text

Preliminary Animal Study on Bone Formation Ability of Commercialized Particle-Type Bone Graft with Increased Operability by Hydrogel

Materials ◽

10.3390/ma14164464 ◽

2021 ◽

Vol 14 (16) ◽

pp. 4464

Author(s):

So-Yeun Kim ◽

You-Jin Lee ◽

Won-Tak Cho ◽

Su-Hyun Hwang ◽

Soon-Chul Heo ◽

...

Keyword(s):

Bone Formation ◽

Bone Graft ◽

Cellular Response ◽

Human Mesenchymal Stem Cells ◽

Study Groups ◽

Control Group ◽

Graft Material ◽

Defect Sites ◽

Significant Difference

The purpose of this study was to evaluate the bone-generating ability of a new bovine-derived xenograft (S1-XB) containing hydrogel. For control purposes, we used Bio-Oss and Bone-XB bovine-derived xenografts. S1-XB was produced by mixing Bone-XB and hydrogel. Cell proliferation and differentiation studies were performed to assess cytotoxicities and cell responses. For in vivo study, 8 mm-sized cranial defects were formed in 16 rabbits, and then the bone substitutes were transplanted into defect sites in the four study groups, that is, a Bio-Oss group, a Bone-XB group, an S1-XB group, and a control (all n = 4); in the control group defects were left empty. Eight weeks after surgery, new bone formation areas were measured histomorphometrically. In the cell study, extracts of Bio-Oss, Bone-XB, and S1-XB showed good results in terms of the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and no cytotoxic reaction was evident. No significant difference was observed between mean new bone areas in the Bio-Oss (36.93 ± 4.27%), Bone-XB (35.07 ± 3.23%), and S1-XB (30.80 ± 6.41%) groups, but new bone area was significantly smaller in the control group (18.73 ± 5.59%) (p < 0.05). Bovine-derived bone graft material containing hydrogel (S1-XB) had a better cellular response and an osteogenic effect similar to Bio-Oss.

Download Full-text

In Vivo Study for Clinical Application of Dental Stem Cell Therapy Incorporated with Dental Titanium Implants

Materials ◽

10.3390/ma14020381 ◽

2021 ◽

Vol 14 (2) ◽

pp. 381

Author(s):

Hyunmin Choi ◽

Kyu-Hyung Park ◽

Narae Jung ◽

June-Sung Shim ◽

Hong-Seok Moon ◽

...

Keyword(s):

Stem Cells ◽

Bone Formation ◽

Alveolar Bone ◽

Human Mesenchymal Stem Cells ◽

Titanium Implants ◽

Osteogenic Potential ◽

Induction Medium ◽

Radiographic Analysis ◽

New Bone Formation

The aim of this study was to investigate the behavior of dental-derived human mesenchymal stem cells (d-hMSCs) in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo. d-hMSCs derived from alveolar bone were established and cultured on machined, sandblasted and acid-etched (SLA)-treated titanium discs with and without osteogenic induction medium. Their morphological and osteogenic potential was assessed by scanning electron microscopy (SEM) and real-time polymerase chain reaction (RT-PCR) via mixing of 5 × 106 of d-hMSCs with 1 mL of Metrigel and 20 μL of gel-cell mixture, which was dispensed into the defect followed by the placement of customized mini-implants (machined, SLA-treated implants) in New Zealand white rabbits. Following healing periods of 2 weeks and 12 weeks, the obtained samples in each group were analyzed radiographically, histomorphometrically and immunohistochemically. The quantitative change in osteogenic differentiation of d-hMSCs was identified according to the type of surface treatment. Radiographic analysis revealed that an increase in new bone formation was statistically significant in the d-hMSCs group. Histomorphometric analysis was in accordance with radiographic analysis, showing the significantly increased new bone formation in the d-hMSCs group regardless of time of sacrifice. Human nuclei A was identified near the area where d-hMSCs were implanted but the level of expression was found to be decreased as time passed. Within the limitations of the present study, in this animal model, the transplantation of d-hMSCs enhanced the new bone formation around an implant and the survival and function of the stem cells was experimentally proven up to 12 weeks post-sacrifice.

Download Full-text

Assessment of α-calcium sulfate hemihydrate/nanocellulose composite bone graft material for bone healing in a rabbit femoral condyle model

Materials Express ◽

10.1166/mex.2021.2060 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1497-1504

Author(s):

Jinlong Liu ◽

Yicai Zhang ◽

Lin Qiu ◽

Yujuan Zhang ◽

Bin Gao

Keyword(s):

Bone Graft ◽

Calcium Sulfate ◽

Biological Activities ◽

Femoral Condyle ◽

Three Dimensional ◽

Graft Material ◽

Bone Graft Material ◽

Calcium Sulfate Hemihydrate ◽

Composite Bone

The material properties of nanocellulose (NC) can effectively enhance the structural stability of composite materials. However, the research related to NC/α-calcium sulfate hemihydrate (CSH) composites is largely lacking. In this paper, we explore the combination of these two materials and determine their elaborate biological activities in vivo. Using α-CSH as the matrix, the composite bone graft materials were produced according to different proportions of NC. Then the mechanical strength of the composite bone graft was measured, and the results were analyzed by X-ray diffraction and scanning electron microscopy (SEM). To conduct the material in vivo evaluation, 0% (CN0) and 0.75% (CN0.75) NC/α-CSH composite bone graft materials were implanted into a femoral condyle defect model. The results indicated that NC could significantly enhance the mechanical properties of α-CSH. The SEM analysis indicated that the NC shuttled between the crystal gaps and formed a three-dimensional network structure, which was firmly combined with the crystal structure. Meanwhile, the CN0.75 scaffold remained at 12 weeks postoperation, which provided a long-term framework for new bone formation. Overall, our findings demonstrate that, with a 0.75% NC/α-CSH composite demonstrating good potential as a bone graft material for clinical bone grafting.

Download Full-text

Influence of Maitake (Grifola frondosa) Particle Sizes on Human Mesenchymal Stem Cells and In Vivo Evaluation of Their Therapeutic Potential

BioMed Research International ◽

10.1155/2020/8193971 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Dinesh K. Patel ◽

Yu-Ri Seo ◽

Sayan Deb Dutta ◽

Ok Hwan Lee ◽

Ki-Taek Lim

Keyword(s):

Therapeutic Potential ◽

Human Mesenchymal Stem Cells ◽

Grifola Frondosa ◽

Osteogenic Potential ◽

Calcium Deposition ◽

Particle Sizes ◽

In Vivo Evaluation ◽

Rat Serum ◽

Gene Markers

Maitake (Grifola frondosa) mushroom has received an enormous amount of attention as a dietary supplement due to its high nutritional values. The particle sizes of G. frondosa mushrooms were monitored by a classifying mill. β-Glucans are the bioactive component of the mushroom, and it was revealed through Fourier transform infrared spectroscopy (FTIR), proton and carbon nuclear magnetic resonance (1H and 13C-NMR), matrix-assisted laser desorption/ionization, and time-of-flight (MALDI-TOF) spectrometry. The biocompatibility of G. frondosa particles, as well as induced osteogenesis of hMSCs, was evaluated through WST-1 assay and alizarin staining (ARS) technique, respectively. Notably, enhanced cell viability was noted in the presence of G. frondosa. Significantly improved calcium deposition has observed from hMSCs with G. frondosa, suggesting to their mineralization potential. The expression of osteogenic related gene markers was examined in the presence of G. frondosa through real-time polymerase chain reaction (qPCR) technique. The upregulation of osteogenic gene markers in the presence of G. frondosa particles was indicating their superior osteogenic potential. Besides, G. frondosa also activated the secretion of various kinds of proteins from the hMSCs indicating their potential for tissue engineering applications. Enhanced secretion of different immunoglobulins was observed in rat serum in the presence of G. frondosa, further demonstrating their therapeutic nature. Therefore, G. frondosa is effective for enhanced osteogenesis and can be utilized as a natural, edible, and osteogenic agent.

Download Full-text

Osteogenic Potential Using a Malleable, Biodegradable Composite Added Traditional Chinese Medicine: in vitro and in vivo Evaluations

The American Journal of Chinese Medicine ◽

10.1142/s0192415x06004351 ◽

2006 ◽

Vol 34 (05) ◽

pp. 873-886 ◽

Cited By ~ 6

Author(s):

Chun-Hsu Yao ◽

Bai-Shuan Liu ◽

Chau-Guey Liu ◽

Yueh-Sheng Chen

Keyword(s):

Bone Substitute ◽

Bone Growth ◽

In Vitro Study ◽

Osteogenic Potential ◽

Calvarial Bone ◽

Large Defect ◽

Biodegradable Composite ◽

Calvarial Bone Defect

The purpose of this investigation was to prepare and evaluate the feasibility and biocompatibility of a new composite as a large defect bone substitute. The new GTGG was mainly composed of tricalcium phosphate ceramic particles and glutaraldehyde crosslinked gelatin in which Gui-Lu-Jiao was added (a mixture of Cervi Colla Cornus and Colla Plastri Testudinis). In the in vitro study, rat's calvaria osteoblasts were used to study bone characteristics upon exposure to different concentrations of the Gui-Lu-Jiao solution. In the in vivo study, GTGG composites were implanted into the defects of calvarial bones in mature New Zealand rabbits to test their osteogenerative characteristics. As a result, we found that Gui-Lu-Jiao added to the culture could promote the proliferation of osteoblasts. In addition, GTGG could induce a large amount of new bone growth in the rabbit's calvarial bone defect. Therefore, the GTGG composite might be a potential bone substitute.

Download Full-text

Treatment for Wear and Osteolysis in Well-Fixed Uncemented TKR

ISRN Orthopedics ◽

10.1155/2013/398298 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Leah Nunez ◽

Brandon Broome ◽

Tom Pace ◽

Melinda Harman

Keyword(s):

Bone Graft ◽

Bone Grafting ◽

Case Series ◽

Graft Material ◽

Polyethylene Insert ◽

Total Knee Replacements ◽

Uncemented Prosthesis ◽

Viable Solution ◽

Total Knee

Background. Traditionally, osteolysis around total knee replacements (TKRs) is treated with complete revision. In certain subsets, polyethylene insert exchange and bone grafting may be applicable. This study reports the clinical outcomes for selective bone grafting in patients with osteolysis without complete revision of the TKR. Methods. This retrospective study analyzes 10 TKRs (9 patients, 66.5 ± 6.1 years old) presenting with osteolysis and revised after 8.7 ± 1.9 years of in vivo function. At index TKR, all patients were implanted with uncemented prosthesis and modular polyethylene insert with anteroposterior articular constraint (Ultracongruent, Natural Knee II, Sulzer Medica). The surgical technique for treating the osteolysis included removal of necrotic bone tissue using curettage, filling of the defect with bone graft materials, and polyethylene insert exchange. Results. Patients have not exhibited any further complications associated with osteolysis after 5.1 ± 2.4 years of followup. Routine radiographic exams show total incorporation of the graft material into the previously lytic regions in all patients. Conclusion. In some TKRs with osteolysis and firmly fixed components, the removal of lytic tissue and subsequent defect filling with bone graft materials can be a viable solution. This case series shows complete resolution of osteolysis in all patients with no complications.

Download Full-text

Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite

International Journal of Molecular Sciences ◽

10.3390/ijms23010283 ◽

2021 ◽

Vol 23 (1) ◽

pp. 283

Author(s):

Christian Deininger ◽

Andrea Wagner ◽

Patrick Heimel ◽

Elias Salzer ◽

Xavier Monforte Vila ◽

...

Keyword(s):

Bone Repair ◽

Bone Morphogenetic Protein 2 ◽

Great Promise ◽

Calcium Phosphate Coating ◽

Graft Material ◽

Morphogenetic Protein ◽

Silk Scaffolds ◽

Cost Efficient

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.

Download Full-text

Human Adipose-Derived Mesenchymal Stem Cells-Incorporated Silk Fibroin as a Potential Bio-Scaffold in Guiding Bone Regeneration

Polymers ◽

10.3390/polym12040853 ◽

2020 ◽

Vol 12 (4) ◽

pp. 853 ◽

Cited By ~ 1

Author(s):

Dewi Sartika ◽

Chih-Hsin Wang ◽

Ding-Han Wang ◽

Juin-Hong Cherng ◽

Shu-Jen Chang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Silk Fibroin ◽

Bone Repair ◽

Matrix Deposition ◽

Calvarial Defects

Recently, stem cell-based bone tissue engineering (BTE) has been recognized as a preferable and clinically significant strategy for bone repair. In this study, a pure 3D silk fibroin (SF) scaffold was fabricated as a BTE material using a lyophilization method. We aimed to investigate the efficacy of the SF scaffold with and without seeded human adipose-derived mesenchymal stem cells (hASCs) in facilitating bone regeneration. The effectiveness of the SF-hASCs scaffold was evaluated based on physical characterization, biocompatibility, osteogenic differentiation in vitro, and bone regeneration in critical rat calvarial defects in vivo. The SF scaffold demonstrated superior biocompatibility and significantly promoted osteogenic differentiation of hASCs in vitro. At six and twelve weeks postimplantation, micro-CT showed no statistical difference in new bone formation amongst all groups. However, histological staining results revealed that the SF-hASCs scaffold exhibited a better bone extracellular matrix deposition in the defect regions compared to other groups. Immunohistochemical staining confirmed this result; expression of osteoblast-related genes (BMP-2, COL1a1, and OCN) with the SF-hASCs scaffold treatment was remarkably positive, indicating their ability to achieve effective bone remodeling. Thus, these findings demonstrate that SF can serve as a potential carrier for stem cells, to be used as an osteoconductive bioscaffold for BTE applications.

Download Full-text

Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model

Bone and Joint Research ◽

10.1302/2046-3758.86.bjr-2018-0224.r2 ◽

2019 ◽

Vol 8 (6) ◽

pp. 266-274

Author(s):

I. Palmer ◽

S. A. Clarke ◽

F. J Buchanan

Keyword(s):

Calcium Phosphate ◽

Bone Repair ◽

Bone Growth ◽

Calcium Release ◽

Release Kinetics ◽

Rabbit Model ◽

Tissue Response ◽

Ph Change ◽

Irradiation Technology

Objectives Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. Methods ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. Results Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. Conclusion The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of β-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices. Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266–274. DOI: 10.1302/2046-3758.86.BJR-2018-0224.R2.

Download Full-text