Bone‐conditioned medium modulates the osteoconductive properties of collagen membranes in a rat calvaria defect model

Küchler, Uwe; Rybaczek, Tina; Dobask, Toni; Heimel, Patrick; Tangl, Stefan; Klehm, Jessica; Menzel, Matthias; Gruber, Reinhard

doi:10.1111/clr.13133

Cited by 31 publications

(54 citation statements)

References 31 publications

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“…Previous immunohistochemical observations suggested that collagen membranes participate in the bone regenerative process, as indicated by the positive immunoreactivity for bone proteins (ALP, OP and OC) within the lower side of the membrane that interfaces with the underlying tibia bone defect (Figure ; Taguchi et al., ). The immunohistochemical observations are corroborated by recent histological and electron microscopy findings showing bone formation and mineralization within the lower porous part of a similar collagen membrane, covering calvarial bone defect, after 4 weeks of healing (Kuchler et al., ). Recently, the emerging hypothesis of a bioactive role of the GBR membrane has been addressed in vivo with a collagen membrane derived from the porcine small intestinal submucosa (Turri et al., ).…”

Section: Results Of the Literature Surveysupporting

confidence: 71%

Barrier membranes: More than the barrier effect?

Omar

Elgali

Dahlin

et al. 2019

J Clinic Periodontology

178

157

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Aim To review the knowledge on the mechanisms controlling membrane–host interactions in guided bone regeneration ( GBR ) and investigate the possible role of GBR membranes as bioactive compartments in addition to their established role as barriers. Materials and Methods A narrative review was utilized based on in vitro , in vivo and available clinical studies on the cellular and molecular mechanisms underlying GBR and the possible bioactive role of membranes. Results Emerging data demonstrate that the membrane contributes bioactively to the regeneration of underlying defects. The cellular and molecular activities in the membrane are intimately linked to the promoted bone regeneration in the underlying defect. Along with the native bioactivity of GBR membranes, incorporating growth factors and cells in membranes or with graft materials may augment the regenerative processes in underlying defects. Conclusion In parallel with its barrier function, the membrane plays an active role in hosting and modulating the molecular activities of the membrane‐associated cells during GBR . The biological events in the membrane are linked to the bone regenerative and remodelling processes in the underlying defect. Furthermore, the bone‐promoting environments in the two compartments can likely be boosted by strategies targeting both material aspects of the membrane and host tissue responses.

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Section: Results Of the Literature Surveysupporting

confidence: 71%

Barrier membranes: More than the barrier effect?

Omar

Elgali

Dahlin

et al. 2019

J Clinic Periodontology

178

157

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“…In support for the latter concept are our findings that ABL considerably reduced osteogenic differentiation of calvaria cells, similar to TGF-β 44 and bone BCM 17 in MC3T3E1. Moreover, BCM loaded onto a collagen membrane can reduce bone formation in rat calvaria defects 45 . Thus, the clinical relevance of the present data has to be interpreted with caution, particularly with respect to the role of TGF-β1 released from bone grafts during graft consolidation.…”

Section: Discussionmentioning

confidence: 99%

“…Even though the most strongly regulated genes in oral fibroblasts are the consequence of TGF-β signalling, the possible cellular response to other growth factors and bioactive molecules within the ABL remain to be discovered. Another interesting approach would be to perform bone transplantation using mouse models with an osteoblast-specific TGF-β knock out 50 . This research can provide the scientific basis to refine protocols aiming to maintain growth factors and their activity during the preparation of allografts.…”

Section: Discussionmentioning

confidence: 99%

Acid bone lysate activates TGFβ signalling in human oral fibroblasts

Strauß

Stähli

Beer

et al. 2018

Sci Rep

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Demineralized bone matrix is a widely used allograft from which not only the inorganic mineral but also embedded growth factors are removed by hydrochloric acid (HCl). The cellular response to the growth factors released during the preparation of demineralized bone matrix, however, has not been studied. Here we investigated the in vitro impact of acid bone lysate (ABL) prepared from porcine cortical bone chips on oral fibroblasts. Proteomic analysis of ABL revealed a large spectrum of bone-derived proteins including TGF-β1. Whole genome microarrays and RT-PCR together with the pharmacologic blocking of TGF-β receptor type I kinase with SB431542 showed that ABL activates the TGF-β target genes interleukin 11, proteoglycan 4, and NADPH oxidase 4. Interleukin 11 expression was confirmed at the protein level by ELISA. Immunofluorescence and Western blot showed the nuclear localization of Smad2/3 and increased phosphorylation of Smad3 with ABL, respectively. This effect was independent of whether ABL was prepared from mandible, calvaria or tibia. These results demonstrate that TGF-β is a major growth factor that is removed upon the preparation of demineralized bone matrix.

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“…The surgical procedures were performed as previously described (Kuchler et al, 2018). Briefly, all rats received ketamine (50 mg/kg i.p.)…”

Section: Methodsmentioning

confidence: 99%

“…Since TGF‐β adsorbs to collagen (Hempel et al, 2012) and thus to the classical collagen barrier membranes (Stahli et al, 2016), these membranes can be considered as suitable carriers to investigate ABLs on bone regeneration in vivo. Using this approach, we recently demonstrated that bone‐conditioned medium lyophilized onto collagen membranes slightly reduces bone formation in rat calvaria defects (Kuchler et al, 2018). Taking advantage of this established model, the aim of the present study was, therefore, to examine the impact of ABL adsorbed to collagen membranes on bone regeneration in rat calvaria defects.…”

Section: Introductionmentioning

confidence: 99%

Acid bone lysates reduce bone regeneration in rat calvaria defects

Strauß

Küchler

Kobatake

et al. 2020

J Biomedical Materials Res

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Acid bone lysates (ABLs) represent the growth factors and other molecules released during autologous graft resorption. However, the impact of these bone‐derived growth factors on the healing of bone defects has not yet been investigated. The aim of the present study was, therefore, to examine the impact of ABLs adsorbed to collagen membranes on bone regeneration. To this end, in 16 female Sprague Dawley rats, a standardized 5‐mm‐diameter critical size defect on the calvarial bone was created. The defects were covered with collagen membranes that had been soaked either in serum‐free media or ABLs followed by lyophilization. After a healing period of 4 weeks, micro‐computed tomography (μCT) and histological analyses by means of undecalcified thin ground sections were performed. μCT analysis of the inner 4 mm of the calvaria defect showed a greater bone defect coverage in the control group when compared to ABL group, 29.8% (confidence interval [CI]: 17.7–50.3) versus 5.6% (CI: 1.0–29.8, p = .03), respectively. Moreover, we found significantly more absolute bone volume (BV) in the control group when compared to ABL group, 0.59 mm3 (CI: 0.27–1.25) versus 0.07 mm3 (CI: 0.06–0.59, p = .04), respectively. Histomorphometry confirmed these findings with a relative BV in the central compartment of 14.1% (CI: 8.4–20.6) versus 5.6% (CI: 3.4–7.9, p = .004), respectively. These findings indicate that bone‐derived growth factors contained in ABLs are able to attenuate bone regeneration within collagen membranes.

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Bone‐conditioned medium modulates the osteoconductive properties of collagen membranes in a rat calvaria defect model

Abstract: These results demonstrate that the commercial collagen membrane holds an osteoconductive competence in a rat calvaria defect model. Soaking collagen membranes with BCM shifts bone formation toward the formation of bony islands rather than new bone connected to the host bone.

Cited by 31 publications

References 31 publications

Barrier membranes: More than the barrier effect?

Barrier membranes: More than the barrier effect?

Acid bone lysate activates TGFβ signalling in human oral fibroblasts

Acid bone lysates reduce bone regeneration in rat calvaria defects

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