METHODS: Systematic review.
OBJECTIVE: The study\'s primary objective was to determine how osteobiologic choice affects fusion rates in patients undergoing anterior cervical discectomy and fusion (ACDF). The study\'s secondary objectives were to 1) determine the optimal timing of fusion assessment following ACDF and 2) determine if osteobiologic type affects the timing and optimal modality of fusion assessment.
METHODS: A systematic search of PubMed/MEDLINE was conducted for literature published from 2000 through October 2020 comparing anterior fusion in the cervical spine with various osteobiologics. Both comparative studies and case series of ≥10 patients were included.
RESULTS: A total of 74 studies met the inclusion criteria. Seventeen studies evaluated the efficacy of autograft on fusion outcomes, and 23 studies assessed the efficacy of allograft on fusion outcomes. 3 studies evaluated the efficacy of demineralized bone matrix, and seven assessed the efficacy of rhBMP-2 on fusion outcomes. Other limited studies evaluated the efficacy of ceramics and bioactive glasses on fusion outcomes, and 4 assessed the efficacy of stem cell products. Most studies utilized dynamic radiographs for the assessment of fusion. Overall, there was a general lack of supportive data to determine the optimal timing of fusion assessment meaningfully or if osteobiologic type influenced fusion timing.
CONCLUSIONS: Achieving fusion following ACDF appears to remain an intricate interplay between host biology and various surgical factors, including the selection of osteobiologics. While alternative osteobiologics to autograft exist and may produce acceptable fusion rates, limitations in study methodology prevent any definitive conclusions from existing literature.

METHODS: Systematic review.
OBJECTIVE: To assess the available evidence related to dose-dependent effectiveness (i.e., bone fusion) and morbidity of osteobiologics used in anterior cervical discectomy and fusion (ACDF).
METHODS: Studies with more than 9 adult patients with degenerated/herniated cervical discs operated for one-to four-levels ACDF reporting used osteobiologics doses, fusion rates at six months or later, and related comorbidities were included. PubMed, EMBASE, ClinicalTrials, and Cochrane were searched through September 2021. Data extracted in spread sheet and risk of bias assessed using MINORS and Rob-2.
RESULTS: Sixteen studies were selected and sub-grouped into BMP and non-BMP osteobiologics. For the 10 BMP studies, doses varied from 0.26 to 2.1 mg in 649 patients with fusion rates of 95.3 to 100% at 12 months. For other osteobiologics, each of six studies reported one type of osteobiologic in certain dose/concentration/volume in a total of 580 patients with fusion rates of 6.8 to 96.9% at 12 months. Risk of bias was low in three of the 13 non-randomized (18.75%) and in all the three randomized studies (100%).
CONCLUSIONS: Taking into account the inconsistent reporting within available literature, for BMP usage in ACDF, doses lower than 0.7 mg per level can achieve equal successful fusion rates as higher doses, and there is no complication-free dose proved yet. It seems that the lower the dose the lower the incidence of serious complications. As for non-BMP osteobiologics the studies are very limited for each osteobiologic and thus conclusions must be drawn individually and with caution.

METHODS: Systematic Review of the Literature.
OBJECTIVE: The purpose of this study was to perform a systematic review describing fusion rates for anterior cervical discectomy and fusion (ACDF) using autograft vs various interbody devices augmented with different osteobiologic materials.
METHODS: A systematic review limited to the English language was performed in Medline, Embase and Cochrane library using Medical Subject Heading (MeSH) terms. Studies that evaluated fusion after ACDF using autografts and osteobiologics combined with PEEK, carbon fibre, or metal cages were searched for. Articles in full text that met the criteria were included in the review. The main outcomes evaluated were the time taken to merge, the definition of the fusion assessment, and the modality of the fusion assessment. The risk of bias of each article was assessed by the MINORS score or ROB 2.0 depending on the randomisation process.
RESULTS: The total number of references reviewed was six hundred and eighty-two. After applying the inclusion criteria, 54 were selected for the retrieval of the full text. Eight studies were selected and included for final analysis in this study. Fusion rates were reported between 83.3% and 100% for autograft groups compared to 46.5% and 100% for various interbody device/osteobiological combinations. The overall quality of the evidence in all radiographic fusion studies was considered insufficient due to a serious risk of bias.
CONCLUSIONS: Mechanical interbody devices augmented with osteobiologics performed similarly to autografts in terms of reliability and efficacy. Their time to fusion and fusion rate were comparable to autografts at the end of the final follow-up.

METHODS: Systematic review and meta-analysis.
OBJECTIVE: To compare clinical and radiographic outcomes as well as complications of unplated vs plated anterior cervical discectomy and fusion (ACDF) surgery considering the role of osteobiologics in single- and multi-level procedures.
METHODS: A systematic search of PubMed/MEDLINE, Scopus, CINAHL, EMBASE, CENTRAL, Cochrane and ClinicalTrials.gov databases was performed. Briefly, we sought to identify studies comparing unplated vs. plated ACDF for cervical degenerative disc disease reporting the use of osteobiologics in terms of clinical outcomes, radiographic fusion, and complications. Data on study population, follow-up time, type of cage and plate used, type of osteobiologic employed, number of levels treated, patient-reported outcomes (PROs), radiographic outcomes and complications were collected and compared. Relevant information was pooled for meta-analyses.
RESULTS: Thirty-eight studies met the inclusion criteria. No significant difference was found in terms of clinical outcomes between groups. Unplated ACDF was characterized by reduced blood loss, operation time and length of hospital stay. Fusion was achieved by the majority of patients in both groups, with no evidence of any specific contribution depending on the osteobiologics used. Dysphagia was more commonly associated with anterior plating, while cage subsidence prevailed in the unplated group.
CONCLUSIONS: Unplated and plated ACDF seem to provide similar outcomes irrespective of the osteobiologic used, with minor differences with doubtful clinical significance. However, the heterogeneity and high risk of bias affecting included studies markedly prevent significant conclusions.

Study Design: Systematic literature reviewObjective: To critically analyze the literature and describe the complications associated with the use of allograft in 1- or 2- level anterior cervical discectomy and fusion (ACDF)Methods: A systematic search of PubMed/MEDLINE, EMBASE, and ClinicalTrials.gov databases was conducted for literature published between January 2000 and August 2020 reporting complications associated with the use of allograft in 1- or 2- level ACDF.Results: From 584 potentially relevant citations, 21 met the inclusion criteria (4 randomized controlled trials (RCT), 4 prospective, and 13 retrospective studies). The patient number varied between 26 and 463 in comparative studies (RCT and non-RCT) and between 29 and 345 in non-comparative studies. Fusion rate was reported in 14 studies and ranged between 68.5-100%. The most frequently reported complication was post-operative dysphagia or dysphonia, with incidences ranging between .5% and 14.4%. Revision surgery was the second most reported complication (14 studies) and ranged between 0% and 10.3%. Wound-related complications were reported in 6 studies and ranged between 0% and 22.8%.Conclusion: The overall reporting of complications was low with very few comparative studies. Reported complications with allografts are within the range of other osteobiologics and autografts and in most cases may not attributable to the use of osteobiologics and may be complications of the procedure itself. Comparative studies with a more robust methodology analyzing complications with allograft and other osteobiologics are needed to inform current practice with strong recommendations.

METHODS: Systematic review.
OBJECTIVE: Examine the clinical evidence for the use of osteobiologics in hybrid surgery (combined anterior cervical discectomy and fusion (ACDF) and total disc replacement (TDR)) in patients with multilevel cervical degenerative disc disease (DDD).
METHODS: PubMed and Embase were searched between January 2000 and August 2020. Clinical studies investigating 18-80 year old patients with multilevel cervical DDD who underwent hybrid surgery with or without the use of osteobiologics were considered eligible. Two reviewers independently screened and assessed the identified articles. The methodological index for non-randomized studies (MINORS) tool and the risk of bias (RoB 2.0) assessment tool were used to assess risk of bias. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to evaluate quality of evidence across studies per outcome.
RESULTS: Eleven studies were included. A decrease in cervical range of motion was observed in most studies for both the hybrid surgery and the control groups consisting of stand-alone ACDF or TDR. Fusion rates of 70-100% were reported in both the hybrid surgery and control groups consisting of stand-alone ACDF. The hybrid surgery group performed better or comparable to the control group in terms of adjacent segment degeneration. Studies reported an improvement in visual analogue scale for pain and neck disability index values after surgery compared to preoperative scores for both treatment groups. The included studies had moderate methodological quality.
CONCLUSIONS: There is insufficient evidence for assessing the use of osteobiologics in multilevel hybrid surgery and additional high quality and controlled research is deemed essential.

METHODS: Systematic Review.
OBJECTIVE: To review the literature for complications and outcomes after the implantation of cellular bone matrix (CBM) during spine fusion.
METHODS: The PubMed database was queried from inception to January 31, 2023 for any articles that discussed the role of and identified a specific CBM in spinal fusion procedures. Adverse events, reoperations, methods, and fusion rates were collected from all studies and reported.
RESULTS: Six hundred articles were identified, of which 19 were included that reported outcomes of 7 different CBM products. Seven studies evaluated lumbar fusion, 11 evaluated cervical fusion, and 1 study reported adverse events of a single CBM product. Only 4 studies were comparative studies while others were limited to case series. Fusion rates ranged from 68% to 98.7% in the lumbar spine and 87% to 100% in the cervical spine, although criteria for radiographic fusion was variable. While 7 studies reported no adverse events, there was no strict consensus on what constituted a complication. One study reported catastrophic disseminated tuberculosis from donor contaminated CBM. The authors of 14 studies had conflicts of interest with either the manufacturer or distributor for their analyzed CBM.
CONCLUSIONS: Current evidence regarding the use of cellular bone matrix as an osteobiologic during spine surgery is weak and limited to low-grade non-comparative studies subject to industry funding. While reported fusion rates are high, the risk of severe complications should not be overlooked. Further large clinical trials are required to elucidate whether the CBMs offer any benefits that outweigh the risks.

METHODS: This study constitutes a systematic review of the literature.
OBJECTIVE: The aim of this study was to identify and present all available studies that report on the costs of osteobiologics used in anterior cervical discectomy and fusion (ACDF).
METHODS: The literature was systematically reviewed to identify studies with specific inclusion criteria: (1) randomized controlled trials and observational studies, (2) in adult patients, (3) with herniated disc(s) or degenerative cervical spine disease, (4) reporting on either direct or indirect costs of using specific osteobiologics in an ACDF operation. (5) Only studies in English were included. The quality of the included studies was assessed using the MINORS and RoB 2.0 tools.
RESULTS: Overall, 14 articles were included; one randomized controlled trial and 13 observational studies. The most commonly used osteobiologics other than autograft/iliac crest bone graft (ICBG) were allograft and bone morphogenetic protein (BMP). None of the studies was reported to be industry-supported. There was considerable heterogeneity on the reported costs. Overall, most studies reported on surgery-related costs, such as anesthesia, operating room, surgical materials and surgeon\'s fee. Only two studies, both using allograft, reported the exact cost of the osteobiologic used (450 GBP, $700). Some of the studies reported on the cost of care during hospitalization for the surgical operation, such as radiology studies, emergency room costs, cardiologic evaluation, laboratory studies, pharmacy costs, and room costs. Only a few studies reported on the cost of follow-up, reoperation, and physical therapy and rehabilitation.
CONCLUSIONS: Based on the data of this current systematic review, no recommendations can be made regarding the cost-effectiveness of using osteobiologics in ACDF. Given the high costs of osteobiologics, this remains a topic of importance. The design of future studies on the subject should include cost effectiveness.

The aim of the current review is to summarize the current evidence on graft materials used in fusion procedures for spinal deformity corrections.
PubMed, Embase, and Cochrane Library were searched for relevant published observational studies and clinical trials using osteobiologics and biomaterials in spinal deformity surgery.
The use of autograft in deformity correction surgeries has been reported in a limited number of studies, with the harvest sites including iliac crest, ribs, and local bone. Various allografts and biologics have been used in the treatment of spinal deformities including idiopathic and degenerative scoliosis, either as stand alone or in combination with autograft. Limited number of studies reported no differences in fusion rates or outcomes. Use of rh-BMP2 in anterior, posterior or front/back approaches showed higher fusion rates than other graft materials in patients with spinal deformities. Due to the limited number of quality studies included in the review, as well as alternative factors, such as costs, availability, and surgeon expertise/preference, no definitive conclusion or recommendations can be made as to the ideal graft choice in spinal deformity surgery.
Most commonly used grafts included autograft, allograft and rh-BMP2, with new biologics and biomaterials constantly emerging in the market. Limited number of high-quality comparative studies and heterogeneity in study design prevented direct comparisons that can lead to meaningful recommendations. Further studies are needed to prove superiority of any single graft material and/or biologic that is also cost-effective and safe.

OBJECTIVE: With the advances in biological technologies over the past 20 years, a number of new therapies to promote bone healing have been introduced. Particularly in the spinal surgery field, more unprecedented biological therapeutics become available to enhance spinal fusion success rate along with advanced instrumentation approaches. Yet surgeons may not have been well informed about their safety and efficacy profiles in order to improve clinical practices. Therefore there is a need to summarize the evidence and bring the latest progress to surgeons for better clinical services for patients.
METHODS: We comprehensively reviewed the literatures in regard to the biological therapeutics for enhancement of spinal fusion published in the last two decades.
RESULTS: Autograft bone is still the gold standard for bone grafting in spinal fusion surgery due to its good osteoconductive, osteoinductive, and osteogenic abilities. Accumulating evidence suggests that adding rhBMPs in combination with autograft effectively promotes the fusion rate and improves surgical outcomes. However, the stimulating effect on spinal fusion of other growth factors, including PDGF, VEGF, TGF-beta, and FGF, is not convincing, while Nell-1 and activin A exhibited preliminary efficacy. In terms of systemic therapeutic approaches, the osteoporosis drug Teriparatide has played a positive role in promoting bone healing after spinal surgery, while new medications such as denosumab and sclerostin antibodies still need further validation. Currently, other treatment, such as controlled-release formulations and carriers, are being studied for better releasing profile and the administration convenience of the active ingredients.
CONCLUSIONS: As the world\'s population continues to grow older, the number of spinal fusion cases grows substantially due to increased surgical needs for spinal degenerative disease (SDD). Critical advancements in biological therapeutics that promote spinal fusion have brought better clinical outcomes to patients lately. With the accumulation of higher-level evidence, the safety and efficacy of present and emerging products are becoming more evident. These emerging therapeutics will shift the landscape of perioperative therapy for the enhancement of spinal fusion.