Comparing cellular bone matrices for posterolateral spinal fusion in a rat model

Lin, Cliff; Zhang, Nianli; Waldorff, Erik I.; Punsalan, Paolo Antonio R.; Wang, David; Semler, Eric J.; Ryaby, James T.; Yoo, Jung U.; Johnstone, Brian

doi:10.1002/jsp2.1084

Cited by 11 publications

(8 citation statements)

References 40 publications

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“…Autologous iliac cres bone graft (ICBG) remains the gold standard for spinal fusion, but its harvest is associated with long‐term donor site pain in up to 25% of patients 3 . A variety of alternative bone graft options are available (allograft, demineralized bone matrix, and cellular bone matrices), but none have proven to be suitable and effective substitutes for ICBG in the posterolateral spine 4,5 . Alternatively, biologic bone grafts substitutes such as bone morphogenetic protein (BMP) can be used either as an adjunct to autograft/allograft or it can be used as a standalone osteoinductive agent.…”

Section: Introductionmentioning

confidence: 99%

The temporal and spatial expression of sclerostin and Wnt signaling factors during the maturation of posterolateral lumbar spine fusions

et al. 2020

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The bone healing environment in the posterolateral spine following arthrodesis surgery is one of the most challenging in all of orthopedics and our understanding of the molecular signaling pathways mediating osteogenesis during spinal fusion is limited. In this study, the spatial and temporal expression pattern of Wnt signaling factors and inhibitors during spinal fusion was assessed for the first time. Bilateral posterolateral spine arthrodesis with autologous iliac crest bone graft was performed on 21 New Zealand White rabbits. At 1-, 2-, 3-, 4-, and 6-weeks, the expression of sclerostin and a variety of canonical and noncanonical Wnts signaling factors was measured by qRT-PCR from tissue separately collected from the transverse processes, the Outer and Inner Zones of the fusion mass, and the adjancent paraspinal muscle. Immunohistochemistry for sclerostin protein was also performed. Sclerostin and many Wnt factors, especially Wnt3a and Wnt5a, were found to have distinct spatial and temporal expression patterns. For example, harvesting ICBG caused a significant increase in sclerostin expression. Furthermore, the paraspinal muscle immediately adjacent to the transplanted ICBG also had significant increases in sclerostin expression at 3 weeks, suggesting new potential mechanisms for pseudarthroses following spinal arthrodesis. The presented work is the first description of the spatial and temporal expression of sclerostin and Wnt signaling factors in the developing spine fusion, filling an important knowledge gap in the basic biology of spinal fusion and potentially aiding in the development of novel biologics to increase spinal fusion rates.

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Section: Introductionmentioning

confidence: 99%

The temporal and spatial expression of sclerostin and Wnt signaling factors during the maturation of posterolateral lumbar spine fusions

et al. 2020

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“…In the first study, 6 commercially available ACBMs (Trin-ity ELITE, ViviGen, Cellentra, Osteocel Pro, BIO 4 , and Map3) were compared with ICBG from syngeneic rats. 13 At 6 weeks, fusion rates by manual palpation were as follows: 5/15 in the ICBG group, 11/15 in the Cellentra group, 8/15 in the Trinity ELITE group, 2/15 in the Vivi-Gen group, and 0/15 in the Osteocel Pro, BIO 4 , and Map3 groups. Cellentra and Trinity ELITE also showed significantly greater bone volume increases than other implants (73% and 65%, respectively), seen on micro-CT as well as on histological analysis.…”

Section: Studies Comparing Acbm Productsmentioning

confidence: 93%

“…All human clinical studies and animal research in which ACBMs were used as bone substitutes or BGEs and where clinical and/or radiological outcome data were provided were included. The final 18 selected articles for the systematic review included 5 publications pertaining to animal research, [11][12][13][14][15] 5 publications pertaining to ACBM use in cervical spine surgery in human subjects, [16][17][18][19][20] and 8 publications pertaining to ACBM use in lumbar spine surgery in human subjects. [21][22][23][24][25][26][27][28] Tables 2 and 3 detail the study characteristics, patient profiles, and study outcomes for ACBM use in human clinical studies in cervical spine and lumbar spine surgery, respectively.…”

Section: Pubmed Search and Characteristics Of Selected Studiesmentioning

confidence: 99%

Investigating the efficacy of allograft cellular bone matrix for spinal fusion: a systematic review of the literature

Diaz¹,

Savardekar²,

Brougham³

et al. 2021

Neurosurgical Focus

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OBJECTIVE The use of allograft cellular bone matrices (ACBMs) in spinal fusion has expanded rapidly over the last decade. Despite little objective data on its effectiveness, ACBM use has replaced the use of traditional autograft techniques, namely iliac crest bone graft (ICBG), in many centers. METHODS In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted of the PubMed, Cochrane Library, Scopus, and Web of Science databases of English-language articles over the time period from January 2001 to December 2020 to objectively assess the effectiveness of ACBMs, with an emphasis on the level of industry involvement in the current body of literature. RESULTS Limited animal studies (n = 5) demonstrate the efficacy of ACBMs in spinal fusion, with either equivalent or increased rates of fusion compared to autograft. Clinical human studies utilizing ACBMs as bone graft expanders or bone graft substitutes (n = 5 for the cervical spine and n = 8 for the lumbar spine) demonstrate the safety of ACBMs in spinal fusion, but fail to provide conclusive level I, II, or III evidence for its efficacy. Additionally, human studies are plagued with several limiting factors, such as small sample size, lack of prospective design, lack of randomization, absence of standardized assessment of fusion, and presence of industry support/relevant conflict of interest. CONCLUSIONS There exist very few objective, unbiased human clinical studies demonstrating ACBM effectiveness or superiority in spinal fusion. Impartial, well-designed prospective studies are needed to offer evidence-based best practices to patients in this domain.

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“…One recent study compared 6-week fusion outcomes of 6 commercially available human CBMs (Cellentra, Trinity, Vivi-Gen, Osteocel, map3, and Bio4) after use for augmenting spinal fusion in athymic rats. 48 Analysis of microCT performed in 15 euthanized animals revealed stable fusion in 11, 8, 2, 0, 0, and 0 for the 6 CBM products, respectively. 48 The authors concluded that the Trinity and Cellentra products achieved significantly better fusion rates in this particular animal model.…”

Section: Current Limitations To Implementation Of Cbmsmentioning

confidence: 94%

Existing clinical evidence on the use of cellular bone matrix grafts in spinal fusion: updated systematic review of the literature

Darveau¹,

Leary²,

Persad-Paisley³

et al. 2021

Neurosurgical Focus

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OBJECTIVE Spinal fusion surgery is increasingly common; however, pseudarthrosis remains a common complication affecting as much as 15% of some patient populations. Currently, no clear consensus on the best bone graft materials to use exists. Recent advances have led to the development of cell-infused cellular bone matrices (CBMs), which contain living components such as mesenchymal stem cells (MSCs). Relatively few clinical outcome studies on the use of these grafts exist, although the number of such studies has increased in the last 5 years. In this study, the authors aimed to summarize and critically evaluate the existing clinical evidence on commercially available CBMs in spinal fusion and reported clinical outcomes. METHODS The authors performed a systematic search of the MEDLINE and PubMed electronic databases for peer-reviewed, English-language original articles (1970–2020) in which the articles’ authors studied the clinical outcomes of CBMs in spinal fusion. The US National Library of Medicine electronic clinical trials database (www.ClinicalTrials.gov) was also searched for relevant ongoing clinical trials. RESULTS Twelve published studies of 6 different CBM products met inclusion criteria: 5 studies of Osteocel Plus/Osteocel (n = 354 unique patients), 3 of Trinity Evolution (n = 114), 2 of ViviGen (n = 171), 1 of map3 (n = 41), and 1 of VIA Graft (n = 75). All studies reported high radiographic fusion success rates (range 87%–100%) using these CBMs. However, this literature was overwhelmingly limited to single-center, noncomparative studies. Seven studies disclosed industry funding or conflicts of interest (COIs). There are 4 known trials of ViviGen (3 trials) and Bio4 (1 trial) that are ongoing. CONCLUSIONS CBMs are a promising technology with the potential of improving outcome after spinal fusion. However, while the number of studies conducted in humans has tripled since 2014, there is still insufficient evidence in the literature to recommend for or against CBMs relative to cheaper alternative materials. Comparative, multicenter trials and outcome registries free from industry COIs are indicated.

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Comparing cellular bone matrices for posterolateral spinal fusion in a rat model

Cited by 11 publications

References 40 publications

The temporal and spatial expression of sclerostin and Wnt signaling factors during the maturation of posterolateral lumbar spine fusions

The temporal and spatial expression of sclerostin and Wnt signaling factors during the maturation of posterolateral lumbar spine fusions

Investigating the efficacy of allograft cellular bone matrix for spinal fusion: a systematic review of the literature

Existing clinical evidence on the use of cellular bone matrix grafts in spinal fusion: updated systematic review of the literature

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