Mechano-Biological Computer Model of Scaffold-Supported Bone Regeneration: Effect of Bone Graft and Scaffold Structure on Large Bone Defect Tissue Patterning

AbstractInsufficient blood vessel supply is a primary limiting factor for regenerative approaches to large bone defect repair. Recombinant BMP-2 delivery induces robust bone formation and has been observed to enhance neovascularization, but whether the angiogenic effects of BMP-2 are due to direct endothelial cell stimulation or to indirect paracrine signaling remains unclear. Here, we evaluated the effects of BMP-2 delivery on vascularized bone regeneration and tested whether BMP-2 induces neovascularization directly or indirectly. We found that delivery of BMP-2 (5 μg) enhanced both bone formation and neovascularization in critically sized (8 mm) rat femoral bone defects; however, BMP-2 did not directly stimulate angiogenesis in vitro. In contrast, conditioned medium from both mesenchymal progenitor cells and osteoblasts induced angiogenesis in vitro, suggesting a paracrine mechanism of BMP-2 action. Consistent with this inference, co-delivery of BMP-2 with endothelial colony forming cells (ECFCs) to a heterotopic site, distant from the bone marrow niche, induced ossification but had no effect on neovascularization. Taken together, these data suggest that BMP-2 induces neovascularization during bone regeneration primarily through paracrine activation of osteoprogenitor cells.

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In vivo study on the healing of bone defect treated with non-thermal atmospheric pressure gas discharge plasma

PLoS ONE ◽

10.1371/journal.pone.0255861 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0255861

Author(s):

Akiyoshi Shimatani ◽

Hiromitsu Toyoda ◽

Kumi Orita ◽

Yoshihiro Hirakawa ◽

Kodai Aoki ◽

...

Keyword(s):

Plasma Treatment ◽

Bone Regeneration ◽

Bone Defect ◽

Atmospheric Pressure ◽

Atmospheric Pressure Plasma ◽

Control Group ◽

Untreated Control Group ◽

Large Bone Defect ◽

X Ray ◽

Large Bone

Medical treatment using non-thermal atmospheric pressure plasma (NTAPP) is rapidly gaining recognition. NTAPP is thought to be a new therapeutic method because it could generate highly reactive species in an ambient atmosphere which could be exposed to biological targets (e.g., cells and tissues). If plasma-generated reactive species could stimulate bone regeneration, NTAPP can provide a new treatment opportunity in regenerative medicine. Here, we investigated the impact of NTAPP on bone regeneration using a large bone defect in New Zealand White rabbits and a simple atmospheric pressure plasma (helium microplasma jet). We observed the recovery progress of the large bone defects by X-ray imaging over eight weeks after surgery. The X-ray results showed a clear difference in the occupancy of the new bone of the large bone defect among groups with different plasma treatment times, whereas the new bone occupancy was not substantial in the untreated control group. According to the results of micro-computed tomography analysis at eight weeks, the most successful bone regeneration was achieved using a plasma treatment time of 10 min, wherein the new bone volume was 1.51 times larger than that in the plasma untreated control group. Using H&E and Masson trichrome stains, nucleated cells were uniformly observed, and no inclusion was confirmed, respectively, in the groups of plasma treatment. We concluded the critical large bone defect were filled with new bone. Overall, these results suggest that NTAPP is promising for fracture treatment.

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In vivo study on the healing of bone defect treated with non-thermal atmospheric pressure gas discharge plasma

10.1101/2021.08.09.455731 ◽

2021 ◽

Author(s):

Akiyoshi Shimatani ◽

Hiromitsu Toyoda ◽

Kumi Orita ◽

Yoshihiro Hirakawa ◽

Kodai Aoki ◽

...

Keyword(s):

Bone Regeneration ◽

Bone Defect ◽

Atmospheric Pressure ◽

Discharge Plasma ◽

Gas Discharge ◽

Control Group ◽

Large Bone Defect ◽

X Ray ◽

Gas Discharge Plasma ◽

Large Bone

Medical treatment using non-thermal atmospheric pressure gas discharge plasma is rapidly gaining recognition. Gas discharge plasma is thought to generate highly reactive species in an ambient atmosphere, which could be exposed to biological targets (e.g., cells and tissues). If plasma-generated reactive species could stimulate bone regeneration, gas discharge plasma could provide a new treatment opportunity in regenerative medicine. We investigated the impact of plasma on bone regeneration using a large bone defect in model rabbits and simple atmospheric pressure plasma (helium microplasma jet). We tracked the recovery progress of the large bone defects by X-ray imaging over eight weeks. The X-ray results showed a clear difference in the filling of the large bone defect among groups with different plasma treatment times, whereas filling was not substantial in the untreated control group. According to the results of micro-computed tomography analysis at eight weeks, the most successful bone regeneration was achieved using a plasma treatment time of 10 min, wherein the new bone volume was 1.51 times larger than that in the control group. Overall, these results suggest that non-thermal atmospheric pressure gas discharge plasma is promising for fracture treatment.

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Three-dimensional-printed individualized porous implants: A new “implant-bone” interface fusion concept for large bone defect treatment

Bioactive Materials ◽

10.1016/j.bioactmat.2021.03.030 ◽

2021 ◽

Vol 6 (11) ◽

pp. 3659-3670

Author(s):

Teng Zhang ◽

Qingguang Wei ◽

Hua Zhou ◽

Zehao Jing ◽

Xiaoguang Liu ◽

...

Keyword(s):

Bone Defect ◽

Three Dimensional ◽

Large Bone Defect ◽

Bone Interface ◽

Fusion Concept ◽

Bone Defect Treatment ◽

Large Bone

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Leucocyte- and Platelet-Rich Fibrin Block: Its Use for the Treatment of a Large Cyst with Implant-Based Rehabilitation

Medicina ◽

10.3390/medicina57020180 ◽

2021 ◽

Vol 57 (2) ◽

pp. 180 ◽

Cited By ~ 1

Author(s):

Rodolfo Mauceri ◽

Denise Murgia ◽

Orazio Cicero ◽

Luigi Paternò ◽

Luca Fiorillo ◽

...

Keyword(s):

Bone Regeneration ◽

Bone Defect ◽

Bone Healing ◽

Bone Substitute ◽

Alveolar Bone ◽

Critical Size ◽

Large Bone ◽

Alveolar Bone Defect ◽

Positive Results ◽

Autologous Platelet

The management of critical-size bone defects is still demanding. Recently, autologous platelet concentrates in combination with bone substitute have been applied and reported in a few studies. Our aim is to report the healing of a critical-size alveolar bone defect treated with a new bone regeneration technique by means of L-PRF and L-PRF blocks. A 45-year-old woman presented a large cystic lesion; the extraction of three teeth, a cyst removal procedure, and bone regeneration procedures with L-PRF and L-PRF blocks were planned. The L-PRF block was prepared by mixing a bone substitute with a piece of L-PRF membrane and liquid fibrinogen. Additionally, after bone healing an implant-based rehabilitation was optimally performed. On the basis of the positive results, in terms of bone healing and tissue regeneration in a large bone defect, the application of L-PRF and L-PRF blocks, in agreement with the scarce literature, is suggested as a feasible procedure in selected cases.

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