Autologous blood coagulum containing rhBMP6 induces new bone formation to promote anterior lumbar interbody fusion (ALIF) and posterolateral lumbar fusion (PLF) of spine in sheep

Grgurević, Lovorka; Erjavec, Igor; Gupta, Munish C.; Pećin, Marko; Bordukalo-Niksic, Tatjana; Štoković, Nikola; Vnuk, Dražen; Farkaš, Vladimı́r; Capak, Hrvoje; Milošević, Milan; Špoljar, Jadranka Bubić; Perić, Mihaela; Vučković, Mirta; Matičić, Dražen; Windhager, Reinhard; Oppermann, Hermann; Sampath, T. Kuber; Vukičević, Slobodan

doi:10.1016/j.bone.2020.115448

Cited by 28 publications

(43 citation statements)

References 61 publications

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“…For signaling BMP6 uses ALK2, ALK3 and ALK6 BMP type I receptors and it increases the expression of bone differentiation markers in cell cultures 131,140 . ABC also decreases inflammation and foreign body cell accumulation when combined with allograft or calcium phosphate ceramics in PLF animal studies 132,135,136,153 . BMP6 in blood remains active for approximately 7 days and could not be detected in the remaining serum after the formation of the autologous blood coagulum 12,115,131 .…”

Section: Bmp6 Quantity Needed For Treatment Of Mice Lacking Bmp6 Genementioning

confidence: 99%

“…1), promotes diaphyseal segmental defects healing and induces PLF in rabbits 131,132 (Fig. 3) and sheep 135 (Fig. 4).…”

Section: Bmp6 Quantity Needed For Treatment Of Mice Lacking Bmp6 Genementioning

confidence: 99%

“…The novel ABGS osteogenic device accelerates bone repair and contains compatible blood coagulum carrier, thus limiting inflammatory reaction contrary to other BMP based bone devices. BMP6 is used in a small dose with the ABC carrier and enhanced bone formation in preclinical studies 14,[135][136][137][138] (Figs. 1, 3, and 4).…”

Section: Commercial Bmp-based Bone Implantsmentioning

confidence: 99%

“…To improve biomechanical properties of ABGS, compression resistant matrix (CRM) might be added to ABGS implants in selected indications which require larger implants including PLF and segmental defects of long bones 132 . Allograft was the first CRM tested in combination with ABGS in rabbit and sheep PLF models 132,135 . Following the successful outcome of these preclinical studies, ABGS formulation with allograft particles as a CRM is being currently tested in PLF clinical study in patients with degenerative disc disease.…”

Section: Compression Resistant Matrixmentioning

confidence: 99%

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Bone morphogenetic proteins: From discovery to development of a novel autologous bone graft substitute consisting of recombinant human BMP6 delivered in autologous blood coagulum carrier

Vukičević¹,

Perić²,

Oppermann³

et al. 2020

Rad Hrvatske akademije znanosti i umjetnosti

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Bone Morphogenetic Proteins (BMPs) are growth and differentiation factors within the TGFβ superfamily of proteins. They induce ectopic and orthotopic endochondral bone formation and are involved in the regulation of cell proliferation, differentiation, apoptosis and mesenchymal-epithelial interactions in critical morphogenetic processes of tissues beyond bone. BMP2 and BMP7 osteogenic devices have been approved for enhancing healing in patients with long bone defects and anterior spinal fusion procedures. However, due to a high price and various serious adverse events including heterotopic ossification, retrograde ejaculation and pain their clinical use have been limited. In this review we discuss the BMP discovery, biology and their use in clinical studies with particular reference to the newly developed BMP6 based autologous bone graft substitute (ABGS). A novel ABGS consisting of an autologous bone coagulum (ABC) carrier with dispersed BMP6 to initiate the differentiation of mesenchymal cells into endochondral bone. The ABC met the conditions for an optimal delivery system for BMP6 due to handling simplicity, without an immunogenic and inflammatory response at the implantation site. Addition of allograft or synthetic ceramics to ABGS demonstrated in animal models significantly increased volume

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Section: Bmp6 Quantity Needed For Treatment Of Mice Lacking Bmp6 Genementioning

confidence: 99%

“…1), promotes diaphyseal segmental defects healing and induces PLF in rabbits 131,132 (Fig. 3) and sheep 135 (Fig. 4).…”

Section: Bmp6 Quantity Needed For Treatment Of Mice Lacking Bmp6 Genementioning

confidence: 99%

Section: Commercial Bmp-based Bone Implantsmentioning

confidence: 99%

Section: Compression Resistant Matrixmentioning

confidence: 99%

See 2 more Smart Citations

Bone morphogenetic proteins: From discovery to development of a novel autologous bone graft substitute consisting of recombinant human BMP6 delivered in autologous blood coagulum carrier

Vukičević¹,

Perić²,

Oppermann³

et al. 2020

Rad Hrvatske akademije znanosti i umjetnosti

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“…We have recently developed an autologous bone graft substitute (ABGS) comprised of BMP6 delivered within an autologous blood coagulum to which a compression-resistant matrix, such as allograft or synthetic ceramics, can be added [22,73,74,76,[86][87][88][89][90][91][92]. Moreover, the volume of newly induced bone increased with the elevation of the CRM amount, which might be attributed to the enlargement in an overall surface area [73].…”

Section: Bone Regeneration By Bone Morphogenetic Protein Devicesmentioning

confidence: 99%

Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies

et al. 2021

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Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.

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Evaluation of lumbar spinal fusion utilizing recombinant human platelet derived growth factor‐B chain homodimer (rhPDGF‐BB) combined with a bovine collagen/β‐tricalcium phosphate (β‐TCP) matrix in an ovine model

et al. 2021

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Background context While the clinical effectiveness of recombinant human Platelet Derived Growth Factor‐B chain homodimer combined with collagen and β‐tricalcium phosphate (rhPDGF‐BB + collagen/β‐TCP) treatment for indications involving hindfoot and ankle is well‐established, it is not approved for use in spinal interbody fusion, and the use of autograft remains the gold standard. Purpose The purpose of this study was to compare the effects of rhPDGF‐BB + collagen/β‐TCP treatment on lumbar spine interbody fusion in an ovine model to those of autograft bone and collagen/β‐TCP treatments using biomechanical, radiographic, and histological assessment techniques. Study design Thirty‐two skeletally mature Columbian Rambouillet sheep were used to evaluate the safety and effectiveness of rhPDGF‐BB + collagen/β‐TCP matrix in a lumbar spinal fusion model. Interbody polyetheretherketone (PEEK) cages contained either autograft, rhPDGF‐BB + collagen/β‐TCP, collagen/β‐TCP matrix, or left empty. Methods Animals were sacrificed 8‐ or 16‐weeks post‐surgery. Spinal fusion was evaluated via post‐sacrifice biomechanical, micro‐computed tomography (μCT), and histological analysis. Outcomes were statistically compared using a two‐way analysis of variance (ANOVA) with an alpha value of 0.05 and a Tukey post‐hoc test. Results There were no statistically significant differences between groups within treatment timepoints for flexion‐extension, lateral bending, or axial rotation range of motion, neutral zone, neutral zone stiffness, or elastic zone stiffness. μCT bone volume fraction was significantly greater between treatment groups independent of timepoint where Autograft and rhPDGF‐BB + collagen/β‐TCP treatments demonstrated significantly greater bone volume fraction as compared to collagen/β‐TCP (P = .026 and P = .038, respectively) and Empty cage treatments (P = .002 and P = .003, respectively). μCT mean bone density fraction was most improved in rhPDGF‐BB + collagen/β‐TCP specimens at the 8 week and 16‐week timepoints as compared to all other treatment groups. There were no statistically significant differences in histomorphometric measurements of bone, soft tissue, or empty space between rhPDGF‐BB + collagen/β‐TCP and autograft treatments. Conclusions The results of this study indicate that the use of rhPDGF‐BB combined with collagen/β‐TCP promotes spinal fusion comparable to that of autograft bone. Clinical significance The data indicate that rhPDGF‐BB combined with collagen/β‐TCP promotes spinal fusion comparably to autograft bone treatment and may offer a viable alternative in large animal spinal fusion. Future prospective clinical studies are necessary to fully understand the role of rhPDGF‐BB combined with collagen/β‐TCP in human spinal fusion healing.

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Autologous blood coagulum containing rhBMP6 induces new bone formation to promote anterior lumbar interbody fusion (ALIF) and posterolateral lumbar fusion (PLF) of spine in sheep

Cited by 28 publications

References 61 publications

Bone morphogenetic proteins: From discovery to development of a novel autologous bone graft substitute consisting of recombinant human BMP6 delivered in autologous blood coagulum carrier

Bone morphogenetic proteins: From discovery to development of a novel autologous bone graft substitute consisting of recombinant human BMP6 delivered in autologous blood coagulum carrier

Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies

Evaluation of lumbar spinal fusion utilizing recombinant human platelet derived growth factor‐B chain homodimer (rhPDGF‐BB) combined with a bovine collagen/β‐tricalcium phosphate (β‐TCP) matrix in an ovine model

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