2,952 research outputs found
Some Weighted Hardy-type Inequalities of Vector-Valued Functions
No full textBy adopting the C-technique of Cheung and Pečrić, we establish some interesting weighted Hardy-type inequalities of vector-valued functions. These generalize and improve some existing results of Cheung, Cheung-Hanjš-Pēcarić, Hanjš-Love-Pečarić, Levinson, and Pachpatte. [ABSTRACT FROM AUTHOR
Finite element modeling of bone cement for vertebroplasty
No full textpublished_or_final_versionOrthopaedic SurgeryMasterMaster of Philosoph
Recombinant adenovirus and adeno-associated virus mediated BMP2 and BMP4 gene therapy for new bone formation
No full textpublished_or_final_versionOrthopaedic SurgeryDoctoralDoctor of Philosoph
Construction of poly(octamethylene citrate)-based regenerative microenvironment to facilitate tenogenic and osteogenic differentiation of bone lineage cell
No full textIn the past decades, the investigation of musculoskeletal tissue has witnessed a revolution in tissue engineering, cell biology, and molecular biology. Among them, tissue engineering demonstrated a promising future as a discipline combining material science and cell biology. Since its invention in 2014, a click chemistry modified poly(octamethylene citrate) (POC) has exhibited strong potential for use in orthopaedics tissue engineering. However, the applications of this novel biomaterial still need to be further investigated. Hence, this study aims to investigate the feasibilities of applying a click chemistry modified POC to construct an artificial tendon tissue microenvironment (TME) and fabricate an osteo-inductive biomaterial for the purpose of extending the applications of this novel biodegradable biomaterial.
In the first study, the optimal cross-linking condition of POC was investigated by attempting nine groups of experimental parameters. A series of features were characterized, including thermophysical properties, hydrophilicity, acid release, dry/wet mechanical properties, and degradability. Next, the optimized cross-linking parameter of the click chemistry modified POC was adopted to construct a POC artificial tendon TME with Type I collagen coating. The tendon TME thus established was further examined in vitro to observe its tenogenic effects. The morphological behavior, cell attachment, cell proliferation, and tenogenic differentiation of bone marrow stem cells (BMSCs) on this POC artificial tendon TME were evaluated. Results suggested that POC artificial tendon TME efficiently induced the tenogenic differentiation of BMSCs and demonstrated excellent mechanical stability and suitable degradation rate.
To promote the hydrophilicity and increase the stability of the biochemical component, oxygen plasma treatment and C2 peptide conjugation were adopted to modify the surface of POC artificial tendon TME. Characterizations illustrated that oxygen plasma treatment significantly enhanced the material hydrophilicity and promoted cell adhesion without affecting the mechanical property. After the chemical conjugation of the C2 peptide, the resulting POC-C2 artificial tendon TME was used in the in vitro study. Results suggested that C2 peptide is feasible to substitute Type I collagen and effectively induce tenogenic differentiation of BMSC.
Finally, POC was applied to investigate the feasibility of fabricating an osteo-inductive biomaterial through the integration of oyster shell protein and POC. First, shell proteins from two species of oysters (Crassostrea Hong Kong genesis and Angulata) were extracted and purified. Then, these proteins were cultured with MC3T3-E1 (pre-osteoblast) to compare their osteogenic effect. In the next experiment, Hong Kong oyster shell proteins and Angulata shell proteins were covalently conjugated to the POC. The osteogenic effect of these osteo-inductive biomaterials was compared afterwards, and results suggested that shell proteins from both species of oysters demonstrated osteogenic effect, confirming that it was feasible to fabricate an osteo-inductive biomaterial through the integration of oyster shell proteins and POC. However, Hong Kong oyster shell protein exhibited superior osteogenic effect to Angulata shell protein. In terms of osteogenic effect, POC conjugated with Hong Kong oyster shell proteins demonstrated more potential for future clinical application.published_or_final_versionOrthopaedics and TraumatologyDoctoralDoctor of Philosoph
USES OF TRANSGENIC ANIMALS CONTAINING A TYPE X COLLAGEN MUTANT
No full textThis invention provides an isolated DNA comprising the sequence which codes for a mutated collagen X or a portion thereof wherein the expression of said DNA regulates bone growth. This invention provides a polypeptide encoded by the isolated DNA comprising the sequence which codes for a mutated collagen X or a portion thereof wherein the expression of said DNA regulates bone growth. This invention also provides a polypeptide which comprises the portion of the mutated collagen X capable of regulating bone growth. This invention further provides a transgenic animal comprising an isolated DNA comprising the sequence which codes for a mutated collagen X or a portion thereof wherein the expression of said DNA regulates bone growth.published_or_final_versio
In-vitro study of the cryopreserved intervertebral disc
No full textpublished_or_final_versionOrthopaedics and TraumatologyMasterMaster of Philosoph
Surface bioactivity enhancement of polyetheretherketone (PEEK) by plasma immersion ion implantation
No full textpublished_or_final_versionOrthopaedics and TraumatologyMasterMaster of Philosoph
Uses of transgenic animals containing a type X collagen mutant
No full textThis invention provides an isolated DNA comprising the sequence which codes for a mutated collagen X or a portion thereof wherein the expression of said DNA regulates bone growth. This invention provides a polypeptide encoded by the isolated DNA comprising the sequence which codes for a mutated collagen X or a portion thereof wherein the expression of said DNA regulates bone growth. This invention also provides a polypeptide which comprise the portion of the mutated collagen X capable of regulating bone growth. This invention further provides a transgenic animal comprising an isolated DNA comprising the sequence which codes for a mutated collagen X or a portion thereof wherein the expression of said DNA regulates bone growth.published_or_final_versio
Structure-activity relationship study of small molecule interfering proteoglycan catabolism in nucleus pulposus cells
No full textIntervertebral discs (IVDs) are semi-cartilaginous connective tissues
between vertebral bodies for spinal motion. Function of IVD relies on the integrity of the gelatinous core nucleus pulposus. IVD degeneration (IDD) is associated with low back pain. IDD is characterized by a reduction of
proteoglycans within the nucleus pulposus (NP) with a replacement of
fibrocartilaginous matrix, leading to a loss of mechanical strength and
shock-absorbing capacity of IVD. The reduction is linked to an enhanced
degradation of proteoglycans, which is mainly mediated by matrixdegrading
enzymes (e.g. metalloproteinases (MMPs)) under proinflammatory
cytokines (e.g. IL-1 and TNF) stimulation.
Through a high-throughput chemical screen, we previously identified a
small molecule termed CSG-1 that could interfere interleukin-1 alpha (IL-
1α)-driven proteoglycan catabolism in degenerative human NP cells. To
identify the functional motifs within CSG-1, we generated a series of
analogues, and conducted a small scale structure-activity relationship
(SAR) study. In this study, we firstly test the effects of bulk substitution
(methyl/ ether groups, or chlorobenzene ring) in an attempt to narrow
down the functional moiety. The performance of 28 analogues in
inhibiting IL-1 a-induced proteoglycan degradation was further assessed
using an alginate-bovine NP cell culture system. Data suggested that the
core structure/functional (position R1,R2 and R3 on GSG-1) motifs of CSG-
1 are essential to its biological activity. Interestingly, we identified an
analogue with a higher efficacy than CSG-1 in countering IL-1-induced proteoglycans degradation. Our findings may facilitate subsequent target
identification of CSG-1 in the future study and drug discovery for
modifying IVD degeneration as well as other degenerative disorders
associated with deregulated proteoglycan expression such as osteoarthritis.published_or_final_versionOrthopaedics and TraumatologyMasterMaster of Philosoph
Development of an rhBMP-2-binding PA carrier for spinal fusion : a porcine model
No full textLow back pain (LBP) is one of the most common musculoskeletal conditions and poses a huge health and socioeconomic burden worldwide. Spinal fusion surgery is often warranted for the treatment of LBP with neurological deficit or after treatment failure with nonsurgical methods. Despite well-established surgical procedures, postoperative pseudarthrosis still accounts for over 20% of revision spinal surgery. Since the discovery of bone morphogenetic proteins (BMPs), these osteogenetic growth factors, in particular, BMP-2 have been widely studied as a potential bone graft substitute to increase spinal fusion rates. Currently, only one BMP-2 bone graft substitute is approved for clinical use but its use was found to be associated with severe postoperative complications. This was attributed to the inefficacy of the collagen carrier which in turn requires supraphysiological doses of BMP-2 for successful bone fusion. Hence, the search for alternative carrier systems that reduces the amount of BMP-2 required ensues.
We have developed a novel self-assembling peptide amphiphile (PA) carrier system that forms nanofiber scaffolds for bone regeneration. These scaffolds are biomimetic of the extracellular matrix and display a high density of BMP-2 binding sequence on its surface, thereby increasing the affinity for both endogenous and exogenous BMP-2. Previous in vitro and in vivo testing with small animals showed that this PA carrier is able to elicit bone fusion at a greatly reduced rhBMP-2 dosage. As the next step to evaluate the translational potential of the carrier before human clinical trials, we aim to validate the efficacy of this new PA carrier in a higher order animal (porcine) model and to determine the optimal dose of rhBMP-2 needed for inducing bone fusion.
For this study, we conducted our experiments in three phases. Firstly, we sought to perform a proof-of-concept trial using miniature pigs but was met with postoperative wound complications and leakage of the PA carrier from the implant site. Hence, changes were proposed to increase the viscosity of the carrier, stabilize the spine with spinal instrumentation and to reduce the risk of surgical site infection (SSI). With these changes, our second phase of experiments showed successful spinal fusion in one out of four pigs using a 100-fold reduced dosage of rhBMP-2 in the absence of SSI. Still, subclinical SSI were observed in the other 3 pigs which prompted more aggressive prophylactic measures to eliminate risk of infection. Finally, in our last phase of experiments, no SSI was observed and solid bone fusion was formed in all spinal segments using a 200-fold reduction in rhBMP-2 concentration.
In summary, our findings showed that the rhBMP-2-binding PA carrier was able to elicit solid bone fusion in the porcine spinal fusion model at a dosage 100-fold and 200-fold lower than the currently available rhBMP-2 product. These encouraging results demonstrate the potential of the carrier as a bone graft substitute that can greatly reduce the dosage of BMP-2 needed for successful spinal fusion. Further studies will be needed to increase sample size and to establish the dose-dependent curve of rhBMP-2 using the PA carrier.
Abstract word count: 498 wordspublished_or_final_versionOrthopaedics and TraumatologyMasterMaster of Philosoph
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