Biodegradable implants are critical for regenerative orthopaedic procedures,but they may suffer from too fast corrosion in human-body environment.This necessitates the synthesis of a suitable coating that may improve ...Biodegradable implants are critical for regenerative orthopaedic procedures,but they may suffer from too fast corrosion in human-body environment.This necessitates the synthesis of a suitable coating that may improve the corrosion resistance of these implants without compromising their mechanical integrity.In this study,an AZ91 magnesium alloy,as a representative for a biodegradable Mg implant material,was modified with a thin reduced graphene oxide(RGO)-calcium carbonate(CaCO_(3))composite coating.Detailed analytical and in-vitro electrochemical characterization reveals that this coating significantly improves the corrosion resistance and mechanical integrity,and thus has the potential to greatly extend the related application field.展开更多
In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is ...In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone marrow.They are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling pathways.Successful fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune system.Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing.In this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely.The separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between them.Finally,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.展开更多
Intermittent injections of parathyroid hormone(iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone(PTH) primarily results in increased bone res...Intermittent injections of parathyroid hormone(iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone(PTH) primarily results in increased bone resorption. Here, we identified Calca,encoding the sepsis biomarker procalcitonin(ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH.展开更多
The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cel...The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cells present at the fracture site are poorly understood. In order to study the early events within a fracture hematoma, we established an in vitro fracture hematoma model: we cultured hematomas forming during an osteotomy (artificial bone fracture) of the femur during total hip arthroplasty (THA) in vitro under bioenergetically controlled conditions. This model allowed us to monitor immune cell populations, cell survival and cytokine expression during the early phase following a fracture. Moreover, this model enabled us to change the bioenergetical conditions in order to mimic the in vivo situation, which is assumed to be characterized by hypoxia and restricted amounts of nutrients. Using this model, we found that immune cells adapt to hypoxia via the expression of angiogenic factors, chemoattractants and pro-inflammatory molecules. In addition, combined restriction of oxygen and nutrient supply enhanced the selective survival of lymphocytes in comparison with that of myeloid derived cells (i.e., neutrophils). Of note, non-restricted bioenergetical conditions did not show any similar effects regarding cytokine expression and/or different survival rates of immune cell subsets. In conclusion, we found that the bioenergetical conditions are among the crucial factors inducing the initial inflammatory phase of fracture healing and are thus a critical step for influencing survival and function of immune cells in the early fracture hematoma.展开更多
Artificial prostheses for joint replacement are indispensable in orthopedic surgery.Unfortunately,the implanted surface is attractive to not only host cells but also bacteria.To enable better osteointegration,a mechan...Artificial prostheses for joint replacement are indispensable in orthopedic surgery.Unfortunately,the implanted surface is attractive to not only host cells but also bacteria.To enable better osteointegration,a mechanically stable porous structure was created on a titanium surface using laser treatment and metallic silver particles were embedded in a hydrophilic titanium oxide layer on top.The laser structuring resulted in unique amphora-shaped pores.Due to their hydrophilic surface conditions and capillary forces,the pores can be loaded preoperative with the antibiotic of choice/need,such as gentamicin.Cytotoxicity and differentiation assays with primary human osteoblast-like cells revealed no negative effect of the surface modification with or without gentamicin loading.An in vivo biocompatibility study showed significantly enhanced osteointegration as measured by push-out testing and histomorphometry 56 days after the implantation of the K-wires into rat femora.Using a S.aureus infection model,the porous,silver-coated K-wires slightly reduced the signs of bone destruction,while the wires were still colonized after 28 days.Loading the amphora-shaped pores with gentamicin significantly reduced the histopathological signs of bone destruction and no bacteria were detected on the wires.Taken together,this novel surface modification can be applied to new or established orthopedic implants.It enables preoperative loading with the antibiotic of choice/need without further equipment or post-coating,and supports osteointegration without a negative effect of the released dug,such as gentamicin.展开更多
Bioactive Materials is reporting about international events which may promote biomaterial research beyond national borders.In this regard,both countries,Germany and China have become global players in the field of hea...Bioactive Materials is reporting about international events which may promote biomaterial research beyond national borders.In this regard,both countries,Germany and China have become global players in the field of health economy in the last decades.A sino-german platform for life sciences has already been founded in the field of health economy that enables for more cooperative projects between both research and economy from both nations.Thus,many different research projects have already been conducted between both countries.However,cooperation between researchers,clinicians and industry of different disciplines and fields is especially essential for the progress in biomaterial research and related products.Chemists,material scientists,biologists and physicians amongst many others are participating in this research field and are ambitious to find mutual solutions for the regeneration of various tissues.This collaborative research and the markets for biomedical products become more and more global and,thus,programs to sustained established cooperative research are desirable.展开更多
文摘Biodegradable implants are critical for regenerative orthopaedic procedures,but they may suffer from too fast corrosion in human-body environment.This necessitates the synthesis of a suitable coating that may improve the corrosion resistance of these implants without compromising their mechanical integrity.In this study,an AZ91 magnesium alloy,as a representative for a biodegradable Mg implant material,was modified with a thin reduced graphene oxide(RGO)-calcium carbonate(CaCO_(3))composite coating.Detailed analytical and in-vitro electrochemical characterization reveals that this coating significantly improves the corrosion resistance and mechanical integrity,and thus has the potential to greatly extend the related application field.
基金Supported by German Research Foundation(DFG)focusing on“Interplay between mononuclear and osteogenic cells during fracture healing in type 2 diabetics”,No.EH 471/2(to Ehnert S)German Research Foundation within the context of the Collaborative Research Center(CRC)1149“Danger Response,Disturbance Factors and Regenerative Potential after Acute Trauma”,No.251293561,C01(to Ignatius A and Fischer V)+1 种基金DFG in context of the CRC 1149,No.251293561,A01 and No.251293561 Z02(to Huber-Lang M)and DFG in the context of the CRC 1149,No.251293561,C07(to Kalbitz M).
文摘In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone marrow.They are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling pathways.Successful fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune system.Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing.In this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely.The separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between them.Finally,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.
基金funded by grants from the Else-Kr?ner-Fresenius-Stiftung (EKFS 2017_A22)the German Research Foundation (DFG KE 2179/4-1)+3 种基金the Berlin Institute of Health to JKfrom the Hertie-Stiftung (Hertie Academy of Clinical Neuroscience)the German Research Foundation (DFGgrant numbers: DFG FOR 2879 [project LU 1924/1-]) to PL.
文摘Intermittent injections of parathyroid hormone(iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone(PTH) primarily results in increased bone resorption. Here, we identified Calca,encoding the sepsis biomarker procalcitonin(ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH.
文摘The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cells present at the fracture site are poorly understood. In order to study the early events within a fracture hematoma, we established an in vitro fracture hematoma model: we cultured hematomas forming during an osteotomy (artificial bone fracture) of the femur during total hip arthroplasty (THA) in vitro under bioenergetically controlled conditions. This model allowed us to monitor immune cell populations, cell survival and cytokine expression during the early phase following a fracture. Moreover, this model enabled us to change the bioenergetical conditions in order to mimic the in vivo situation, which is assumed to be characterized by hypoxia and restricted amounts of nutrients. Using this model, we found that immune cells adapt to hypoxia via the expression of angiogenic factors, chemoattractants and pro-inflammatory molecules. In addition, combined restriction of oxygen and nutrient supply enhanced the selective survival of lymphocytes in comparison with that of myeloid derived cells (i.e., neutrophils). Of note, non-restricted bioenergetical conditions did not show any similar effects regarding cytokine expression and/or different survival rates of immune cell subsets. In conclusion, we found that the bioenergetical conditions are among the crucial factors inducing the initial inflammatory phase of fracture healing and are thus a critical step for influencing survival and function of immune cells in the early fracture hematoma.
基金This work was funded by the Federal Ministry of Education and Research,Germany[grant numbers 03VP03681,03VP03682].
文摘Artificial prostheses for joint replacement are indispensable in orthopedic surgery.Unfortunately,the implanted surface is attractive to not only host cells but also bacteria.To enable better osteointegration,a mechanically stable porous structure was created on a titanium surface using laser treatment and metallic silver particles were embedded in a hydrophilic titanium oxide layer on top.The laser structuring resulted in unique amphora-shaped pores.Due to their hydrophilic surface conditions and capillary forces,the pores can be loaded preoperative with the antibiotic of choice/need,such as gentamicin.Cytotoxicity and differentiation assays with primary human osteoblast-like cells revealed no negative effect of the surface modification with or without gentamicin loading.An in vivo biocompatibility study showed significantly enhanced osteointegration as measured by push-out testing and histomorphometry 56 days after the implantation of the K-wires into rat femora.Using a S.aureus infection model,the porous,silver-coated K-wires slightly reduced the signs of bone destruction,while the wires were still colonized after 28 days.Loading the amphora-shaped pores with gentamicin significantly reduced the histopathological signs of bone destruction and no bacteria were detected on the wires.Taken together,this novel surface modification can be applied to new or established orthopedic implants.It enables preoperative loading with the antibiotic of choice/need without further equipment or post-coating,and supports osteointegration without a negative effect of the released dug,such as gentamicin.
文摘Bioactive Materials is reporting about international events which may promote biomaterial research beyond national borders.In this regard,both countries,Germany and China have become global players in the field of health economy in the last decades.A sino-german platform for life sciences has already been founded in the field of health economy that enables for more cooperative projects between both research and economy from both nations.Thus,many different research projects have already been conducted between both countries.However,cooperation between researchers,clinicians and industry of different disciplines and fields is especially essential for the progress in biomaterial research and related products.Chemists,material scientists,biologists and physicians amongst many others are participating in this research field and are ambitious to find mutual solutions for the regeneration of various tissues.This collaborative research and the markets for biomedical products become more and more global and,thus,programs to sustained established cooperative research are desirable.