Complications With Demineralized Bone Matrix, Hydroxyapatite and Beta-Tricalcium Phosphate in Single and Two-Level Anterior Cervical Discectomy and Fusion Surgery.

STUDY DESIGN: Systematic literature review. OBJECTIVES: To analyze the evidence available reporting complications in single or two-level anterior cervical discectomy and fusion (ACDF) using a demineralized bone matrix (DBM), hydroxyapatite (HA), or beta-tricalcium phosphate (ß-TCP). METHODS: A systematic review of the literature using PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases was performed in August 2020 to identify studies reporting complications in one or two-level ACDF surgery using DBM, HA, or ß-TCP. The study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 1857 patients were included, 981 male and 876 female, across 17 articles; 5 prospective, and 12 retrospectives. We noted heterogeneity among the included studies concerning the study design and combination of graft materials utilized in them. However, we noted a higher incidence of adjacent segment disease (17.7%) and pseudoarthrosis (9.3%) in fusion constructs using DBM. Studies using ß-TCP reported a higher incidence of pseudoarthrosis (28.2%) and implant failures (17.9%). CONCLUSIONS: Degenerative cervical conditions treated with one or two-level ACDF surgery using DBM, HA, or ß-TCP with or without cervical plating are associated with complications such as adjacent segment disease, dysphagia, and pseudarthrosis. However, consequent to the study designs and clinical heterogeneity of the studies, it is not possible to correlate these complications accurately with any specific graft material employed. Further well-designed prospective studies are needed to correctly know the related morbidity of each graft used for achieving fusion in ACDF.

A Comparative Study of HA/DBM Compounds Derived from Bovine and Porcine for Bone Regeneration.

This comparative study investigated the tissue regeneration and inflammatory response induced by xenografts comprised of hydroxyapatite (HA) and demineralized bone matrix (DBM) extracted from porcine (P) and bovine (B) sources. First, extraction of HA and DBM was independently conducted, followed by chemical and morphological characterization. Second, mixtures of HA/DBM were prepared in 50/50 and 60/40 concentrations, and the chemical, morphological, and mechanical properties were evaluated. A rat calvarial defect model was used to evaluate the tissue regeneration and inflammatory responses at 3 and 6 months. The commercial allograft DBM Puros® was used as a clinical reference. Different variables related to tissue regeneration were evaluated, including tissue thickness regeneration (%), amount of regenerated bone area (%), and amount of regenerated collagen area (%). The inflammatory response was evaluated by quantifying the blood vessel area. Overall, tissue regeneration from porcine grafts was superior to bovine. After 3 months of implantation, the tissue thickness regeneration in the 50/50P compound and the commercial DBM was significantly higher (~99%) than in the bovine materials (~23%). The 50/50P and DBM produced higher tissue regeneration than the naturally healed controls. Similar trends were observed for the regenerated bone and collagen areas. The blood vessel area was correlated with tissue regeneration in the first 3 months of evaluation. After 6 months of implantation, HA/DBM compounds showed less regenerated collagen than the DBM-only xenografts. In addition, all animal-derived xenografts improved tissue regeneration compared with the naturally healed defects. No clinical complications associated with any implanted compound were noted.

Extracellular matrix hydrogel derived from bovine bone is biocompatible in vitro and in vivo.

BACKGROUND: Nowadays, biomaterials used as a scaffold must be easy to deliver in the bone defect area. Extracellular matrix (ECM) hydrogels are highly hydrated polymers that can fill irregular shapes and act as bioactive materials. OBJECTIVE: This work aims to show the effects of ECM hydrogels derived from bovine bone (bECMh) on proliferation, cytotoxicity and expression of pro-inflammatory cytokines in three cells types involved in tissue regeneration, as well as biocompatibility in vivo. METHODS: In vitro, we used an extract of bECMh to test it on macrophages, fibroblasts, and adipose-derived mesenchymal stem cells (AD-MCSs). Cell proliferation was measured using the MTT assay, cytotoxicity was measured by quantifying lactate dehydrogenase release and the Live/Dead Cell Imaging assays. Concentrations of IL-6, IL-10, IL-12p70, MCP-1 and TNF-α were quantified in the supernatants using a microsphere-based cytometric bead array. For in vivo analysis, Wistar rats were inoculated into the dorsal sub-dermis with bECMh, taking as reference the midline of the back. The specimens were sacrificed at 24 h for histological study. RESULTS: In vitro, this hydrogel behaves as a dynamic biomaterial that increases fibroblast proliferation, induces the production of pro-inflammatory cytokines in macrophages, among which MCP-1 and TNF-α stand out. In vivo, bECMh allows the colonization of host fibroblast-like and polymorphonuclear cells, without tissue damage or inflammation. CONCLUSIONS: The results indicate that bECMh is a biocompatible material that could be used as a scaffold, alone or in conjunction with cells or functional biomolecules, enhancing proliferation and allowing the filling of bone defects to its further regeneration.

Bone substitutes and expanders in Spine Surgery: A review of their fusion efficacies.

STUDY DESIGN: A narrative review of literature. OBJECTIVE: This manuscript intends to provide a review of clinically relevant bone substitutes and bone expanders for spinal surgery in terms of efficacy and associated clinical outcomes, as reported in contemporary spine literature. SUMMARY OF BACKGROUND DATA: Ever since the introduction of allograft as a substitute for autologous bone in spinal surgery, a sea of literature has surfaced, evaluating both established and newly emerging fusion alternatives. An understanding of the available fusion options and an organized evidence-based approach to their use in spine surgery is essential for achieving optimal results. METHODS: A Medline search of English language literature published through March 2016 discussing bone graft substitutes and fusion extenders was performed. All clinical studies reporting radiological and/or patient outcomes following the use of bone substitutes were reviewed under the broad categories of Allografts, Demineralized Bone Matrices (DBM), Ceramics, Bone Morphogenic proteins (BMPs), Autologous growth factors (AGFs), Stem cell products and Synthetic Peptides. These were further grouped depending on their application in lumbar and cervical spine surgeries, deformity correction or other miscellaneous procedures viz. trauma, infection or tumors; wherever data was forthcoming. Studies in animal populations and experimental in vitro studies were excluded. Primary endpoints were radiological fusion rates and successful clinical outcomes. RESULTS: A total of 181 clinical studies were found suitable to be included in the review. More than a third of the published articles (62 studies, 34.25%) focused on BMP. Ceramics (40 studies) and Allografts (39 studies) were the other two highly published groups of bone substitutes. Highest radiographic fusion rates were observed with BMPs, followed by allograft and DBM. There were no significant differences in the reported clinical outcomes across all classes of bone substitutes. CONCLUSIONS: There is a clear publication bias in the literature, mostly favoring BMP. Based on the available data, BMP is however associated with the highest radiographic fusion rate. Allograft is also very well corroborated in the literature. The use of DBM as a bone expander to augment autograft is supported, especially in the lumbar spine. Ceramics are also utilized as bone graft extenders and results are generally supportive, although limited. The use of autologous growth factors is not substantiated at this time. Cell matrix or stem cell-based products and the synthetic peptides have inadequate data. More comparative studies are needed to evaluate the efficacy of bone graft substitutes overall.

Demineralized bone matrix for alveolar cleft management.

The aim of this article is to describe the results of the use of demineralized bone matrix putty in alveolar cleft of patients with cleft lip and palate. We performed a prospective, descriptive case series study, in which we evaluated the results of the management of alveolar clefts with demineralized bone matrix. Surgery was performed in 10 patients aged between 7 and 26 years (mean 13 years), involving a total of 13 clefts in the 10 patients. A preoperative cone beam computed tomography (CBCT) was taken to the patients in whom the width of the cleft was measured from each edge of the cleft reporting values between 5.76 and 16.93 mm (average, 11.18 mm). The densities of the clefts were measured with a CBCT, 6 months postoperative to assess bone formation. The results showed a register of gray values of 1,148 to 1,396 (mean, 1,270). The follow-up was conducted for 15 to 33 months (mean, 28.2 months). The results did not show satisfactory bone formation in the cleft of patients with the use of demineralized bone matrix.

Stabilizing effects of a particulate demineralized bone matrix in the L4 interbody space with and without PEEK Cage: a literature review and preliminary results of a cadaveric biomechanical study / Estabilización de los efectos de una matriz osea desmineralizada Particulada en el espacio intersomático a nivel L4 con o sin cajetín PEEK: revisión de la literatura y resultados preliminares de un estudio biomecánico cadavérico

We reviewed the biological elements supporting the usefulness of a specifically designed particulate form of demineralized bone matrix (DBM) in spinal fusion, and report some limitations of its use described in the medical literature and in the interbody space using a cadaveric biomechanical model. A literature review and description of the techniques used to augment spinal fusion are presented, including a more thorough review of recent findings of cadaveric biomechanical flexibility studies using DBM alone at different percentage fills of the existing disc space and DBM with a polyetheretherketone (PEEK) interbody cage. The need for DBM was established by reviewing limitations of autografts and allografts in spinal fusion. Demineralized bone matrix used alone did not increase stability post discectomy at L4-L5, but was demonstrated to exhibit satisfactory stability when used with a PEEK interbody cage. There may be a future role for DBM that hardens and fills disc space more rigidly, overcoming this limitation to its use.

Examinamos los elementos biológicos que respaldan la utilidad de una forma particulada específicamente diseñada de matriz ósea desmineralizada (MOD) con fusión espinal. Asimismo reportamos algunas limitaciones de su uso en el espacio intersomático descritas en la literatura médica, mediante un modelo biomecánico cadavérico. Se presenta una revisión de la literatura, acompañada de una descripción de las técnicas utilizadas para aumentar la fusión espinal, incluyendo una revisión más exhaustiva de los hallazgos recientes de los estudios de flexibilidad biomecánico cadavérica, utilizando sólo MOD en diferentes rellenos de porcentajes del espacio discal existente, y MOD con cajetines intervertebrales de polieteretercetona (PEEK). La necesidad de MOD se estableció examinando las limitaciones de los autoinjertos y los aloinjertos en la fusión espinal. El uso de la matriz ósea desmineralizada sola, no aumentaba la estabilidad post-disectómica a nivel L4-L5, pero se demostró que presentaba una estabilidad satisfactoria cuando se utilizaba con un cajetín intervertebral PEEK. Puede haber un papel futuro para un MOD que se endurezca y rellene el espacio del disco más rígidamente, venciendo así esta limitación a su uso.

Matriz óssea homóloga desmineralizada associada à medula óssea autógena fresca na artrodese vertebral dorsolateral lombar em coelhos / Homologous demineralized bone matrix associated to autologous bone marrow in a rabbit dorsolateral lumbar vertebral fusion

Foi avaliada a matriz óssea homóloga desmineralizada (MOD), associada à medula óssea autógena fresca (MO), na artrodese vertebral dorsolateral lombar em 24 coelhos (grupo 1), depositada sobre os processos transversos de L5-L6 previamente descorticados. Em outros nove coelhos (grupo-controle), foi realizada apenas a descorticação dos processos transversos e nas diferentes avaliações, foi observada insignificante reação periosteal local, sem união óssea. No grupo 1, às cinco semanas de pós-operatório, 87,5 por cento dos animais apresentaram união (artrodese) à palpação, seguido por 75 e 100 por cento às sete e nove semanas, respectivamente. Os índices de artrodese aos RX foram de 50 por cento, 62 por cento e 75 por cento, no mesmo período de avaliação. Histologicamente, às cinco semanas havia características de osteointegração da MOD com os processos transversos descorticados, de onde partiram os vasos sangüíneos que penetraram a matriz, e presença de ilhas de cartilagem no centro do enxerto. Nas semanas seguintes, a ossificação endocondral evoluiu e a MOD foi quase totalmente substituída por tecido ósseo trabecular, formando uma ponte de osso maduro entre e sobre os processos transversos adjacentes, propiciando ao segmento operado maior resistência mecânica em comparação aos segmentos adjacentes. A associação da MOD com a MO mostrou-se uma opção exeqüível e de baixo custo na artrodese vertebral dorsolateral lombar em coelhos.(AU)

It was evaluated the homologous demineralized bone matrix (HDBM), associated with the fresh autogenous bone marrow (FABM), in the vertebral dorsolateral lumbar union in 24 rabbits (group 1), that was placed on the transverse processes of previously decorticated L5-L6 vertebrae. In other nine rabbits (control group), it was just accomplished the decortications of the transverse processes, which showed insignificant local periostial reaction, without bone union after different evaluations. In the group 1, after five weeks of postoperative interval, 87.5% of the animals presented union (arthrodesis), which was observed by palpation, followed by 75 and 100% after seven and nine weeks, respectively. The arthrodesis indexes to X rays were of 50%, 62% and 75%, in the same evaluation period. According to histological analysis, after five weeks, there were characteristics of osteointegration of HDBM with the decorticated transverse processes, from where the blood vessels that penetrated the bone matrix originated, and the presence of cartilage tissue in the center of the graft. In the following weeks, the endocondral ossification continued and HDBM was almost totally substituted by trabecular bone tissue, forming a bridge of ripe bone among and over the adjacent transverse processes, propitiating larger mechanical resistance to the operated segment in comparison to the adjacent segments. The association of HDBM with the FABM showed as a feasible option with low cost in the vertebral dorsolateral lumbar arthrodesis in rabbits.(AU)