File Download
Supplementary

postgraduate thesis: Detection of biomaterial in vivo microenvironment pH (μe-pH) and its effect on bone defect regeneration under unbalanced bone remodling condition

TitleDetection of biomaterial in vivo microenvironment pH (μe-pH) and its effect on bone defect regeneration under unbalanced bone remodling condition
Authors
Issue Date2016
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Liu, W. [刘文龙]. (2016). Detection of biomaterial in vivo microenvironment pH (μe-pH) and its effect on bone defect regeneration under unbalanced bone remodling condition. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5760941
AbstractIn scenario of osteoporotic fracture, significantly higher activity of osteoclasts than osteoblasts may lead to continuous loss of bone in fracture/defect site. The impaired bone regeneration efficiency is the major barrier that influences endosseous implants to get a better performance, and this substantially increases the risk of a second fracture, non-union and aseptic implant loosening. Currently, there are no clinically approved biomaterials specifically tailored for applications in osteoporotic bones, and it is a challenging topic for material scientists to design proper orthopaedic biomaterials with biological functions for osteoporotic patients. The key issue for developing such biomaterials is to re-establish normal bone regeneration at the fracture site. According to the literatures, acid-base equilibrium is one of the most important factors that influence behaviours of bone cells. Therefore, microenvironment pH (μe-pH), which is influenced by implants biodegradation, may play a crucial role in guiding the localized bone regeneration. We then propose to reconstruct the regeneration balance by controlling the μe-pH through the application of biodegradable materials. The aims of this study include: 1. Establish a method for in vivo μe-pH detection; 2. Evaluate the effect of μe-pH on early-stage bone regeneration process; 3. Reveal the mechanisms by examining osteoclasts behavior in response to the change of μe-pH. The measurement of in vivo μe-pH was realized by using the pH microelectrode. Alkaline biodegradable materials generated an in vivo μe-pH which was higher than the normal physiological value, in particular, at the initial stage. The preliminary results indicated that osteoclasts may play important roles in the early-stage of defect healing process. Therefore, in order to further study the osteoclasts behaviors in response to the elevated μe-pH in a bone marrow microenvironment, a boneimplant interaction mouse model and a borosilicate glass system (with μe-pH gradient) with same type of ions and similar composition were developed. Based on our in vitro data, osteoclasts differentiation and pit-formation activity were significantly suppressed when RANKL-stimulated RAW264.7 cells were cultured in different glasses extracts which were adjusted to higher pH conditions (pH 7.59-8.02). Furthermore, the abnormal osteoclastogenesis potential of bone marrow cells in mouse after hindlimb unloading treatment could also be balanced by the elevated culture media pH (pH 7.62-7.84). In vivo, significantly suppressed osteoclasts activity together with a thicker new bone on materials surface were observed for glasses with higher e-pHs. Further assessments by using RT-PCR and immunostaining indicated that the decreased activity of matrix-degrading proteases (e.g. cathepsin K) may be one of the reasons for the suppressed osteoclasts activity under higher μe-pH conditions. In conclusion, the impaired regeneration process under osteoporotic or immobilized conditions may be ameliorated by adjusting the materials to generate a weakly-alkaline microenvironment. And the e-pH is an important and accessible factor which should be taken into consideration in the development of orthopaedic biomaterials, in particular for repair of osteoporotic bone fracture /defect.
DegreeDoctor of Philosophy
SubjectBiomedical materials
Bone regeneration
Dept/ProgramOrthopaedics and Traumatology
Persistent Identifierhttp://hdl.handle.net/10722/226785

 

DC FieldValueLanguage
dc.contributor.authorLiu, Wenlong-
dc.contributor.author刘文龙-
dc.date.accessioned2016-06-30T04:24:10Z-
dc.date.available2016-06-30T04:24:10Z-
dc.date.issued2016-
dc.identifier.citationLiu, W. [刘文龙]. (2016). Detection of biomaterial in vivo microenvironment pH (μe-pH) and its effect on bone defect regeneration under unbalanced bone remodling condition. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5760941-
dc.identifier.urihttp://hdl.handle.net/10722/226785-
dc.description.abstractIn scenario of osteoporotic fracture, significantly higher activity of osteoclasts than osteoblasts may lead to continuous loss of bone in fracture/defect site. The impaired bone regeneration efficiency is the major barrier that influences endosseous implants to get a better performance, and this substantially increases the risk of a second fracture, non-union and aseptic implant loosening. Currently, there are no clinically approved biomaterials specifically tailored for applications in osteoporotic bones, and it is a challenging topic for material scientists to design proper orthopaedic biomaterials with biological functions for osteoporotic patients. The key issue for developing such biomaterials is to re-establish normal bone regeneration at the fracture site. According to the literatures, acid-base equilibrium is one of the most important factors that influence behaviours of bone cells. Therefore, microenvironment pH (μe-pH), which is influenced by implants biodegradation, may play a crucial role in guiding the localized bone regeneration. We then propose to reconstruct the regeneration balance by controlling the μe-pH through the application of biodegradable materials. The aims of this study include: 1. Establish a method for in vivo μe-pH detection; 2. Evaluate the effect of μe-pH on early-stage bone regeneration process; 3. Reveal the mechanisms by examining osteoclasts behavior in response to the change of μe-pH. The measurement of in vivo μe-pH was realized by using the pH microelectrode. Alkaline biodegradable materials generated an in vivo μe-pH which was higher than the normal physiological value, in particular, at the initial stage. The preliminary results indicated that osteoclasts may play important roles in the early-stage of defect healing process. Therefore, in order to further study the osteoclasts behaviors in response to the elevated μe-pH in a bone marrow microenvironment, a boneimplant interaction mouse model and a borosilicate glass system (with μe-pH gradient) with same type of ions and similar composition were developed. Based on our in vitro data, osteoclasts differentiation and pit-formation activity were significantly suppressed when RANKL-stimulated RAW264.7 cells were cultured in different glasses extracts which were adjusted to higher pH conditions (pH 7.59-8.02). Furthermore, the abnormal osteoclastogenesis potential of bone marrow cells in mouse after hindlimb unloading treatment could also be balanced by the elevated culture media pH (pH 7.62-7.84). In vivo, significantly suppressed osteoclasts activity together with a thicker new bone on materials surface were observed for glasses with higher e-pHs. Further assessments by using RT-PCR and immunostaining indicated that the decreased activity of matrix-degrading proteases (e.g. cathepsin K) may be one of the reasons for the suppressed osteoclasts activity under higher μe-pH conditions. In conclusion, the impaired regeneration process under osteoporotic or immobilized conditions may be ameliorated by adjusting the materials to generate a weakly-alkaline microenvironment. And the e-pH is an important and accessible factor which should be taken into consideration in the development of orthopaedic biomaterials, in particular for repair of osteoporotic bone fracture /defect.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.lcshBiomedical materials-
dc.subject.lcshBone regeneration-
dc.titleDetection of biomaterial in vivo microenvironment pH (μe-pH) and its effect on bone defect regeneration under unbalanced bone remodling condition-
dc.typePG_Thesis-
dc.identifier.hkulb5760941-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineOrthopaedics and Traumatology-
dc.description.naturepublished_or_final_version-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats