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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 9 - 9
17 Apr 2023
Mortimer J Tamaddon M Liu C
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Rotator cuff tears are common, with failure rates of up to 94% for large and massive tears1. For such tears, reattachment of the musculotendinous unit back to bone is problematic, and any possible tendon-bone repair heals through scar tissue rather than the specially adapted native enthesis. We aim to develop and characterise a novel soft-hard tissue connector device, specific to repairing/bridging the tendon-bone injury in significant rotator cuff tears, employing decellularised animal bone partially demineralised at one end for soft tissue continuation.

Optimisation samples of 15×10×5mm3, trialled as separate cancellous and cortical bone samples, were cut from porcine femoral condyles and shafts, respectively. Samples underwent 1-week progressive stepwise decellularisation and a partial demineralisation process of half wax embedding and acid bathing. Characterisations were performed histologically for the presence/absence of cellular staining in both peripheral and central tissue areas (n=3 for each cortical/cancellous, test/PBS control and peripheral/central group), and with BioDent reference point indentation (RPI) for pre- and post-processing mechanical properties.

Histology revealed absent cellular staining in peripheral and central cancellous samples, whilst reduced in cortical samples compared to controls. Cancellous samples decreased in wet mass after decellularisation by 45.3% (p<0.001). RPI measurements associated with toughness (total indentation depth, indentation depth increase) and elasticity (1st cycle unloading slope) showed no consistent changes after decellularisation. X-rays confirmed half wax embedding provided predictable control of the mineralised-demineralised interface position.

Initial optimisation trials show proof-of-concept of a soft-hard hybrid scaffold as an immune compatible xenograft for irreparable rotator cuff tears. Decellularisation did not appreciably affect mechanical properties, and further biological, structural and chemical characterisations are underway to assess validity before in vivo animal trials and potential clinical translation.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 89 - 89
4 Apr 2023
Cui C Long Y Liu C Wong R Chow S Cheung W
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Sarcopenia is an age-related geriatric syndrome which is associated with subsequent disability and morbidity. Currently there is no promising therapy approved for the treatment of sarcopenia. The receptor activator of nuclear factor NF-κB ligand (RANKL) and its receptor (RANK) are expressed in bone and skeletal muscle. Activation of the NF-κB pathway mainly inhibits myogenic differentiation, which leads to skeletal muscle dysfunction and loss. LYVE1 and CD206 positive macrophage has been reported to be associated with progressive impairment of skeletal muscle function with aging. The study aims to investigate the effects of an anti-RANKL treatment on sarcopenic skeletal muscle and explore the related mechanisms on muscle inflammation and the polarization status of macrophages.

Sarcopenic senescence-accelerated mouse P8 (SAMP8) mice at month 8 were treated intraperitoneally with 5mg/kg anti-RANKL (IK22/5) or isotype control (2A3; Bio X Cell) antibody every 4 weeks and harvested at month 10. Senescence accelerated mouse resistant-1 (SAMR1) were collected at month 10 as the age-matched non-sarcopenic group. Ex-vivo functional assessment, grip strength and immunostaining of C/EBPa, CD206, F4/80, LYVE1 and PAX7 were performed. Data analysis was done with one-way ANOVA, and the significant level was set at p≤0.05.

At month 10, tetanic force/specific tetanic force, twitch force/specific twitch force in anti-RANKL group were significantly higher than control group (all p<0.01). The mice in the anti-RANKL treatment group also showed significantly higher grip strength than Con group (p<0.001). The SAMP8 mice at month 10 expressed significantly more C/EBPa, CD206 and LYVE1 positive area than in SAMR1, while anti-RANKL treatment significantly decreased C/EBPa, CD206 and LYVE1 positive area.

The anti-RANKL treatment protected against skeletal muscle dysfunctions through suppressing muscle inflammation and modulating M2 macrophages, which may represent a novel therapeutic approach for sarcopenia.

Acknowledgment: Collaborative Research Fund (CRF, Ref: C4032-21GF)


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 102 - 102
1 Dec 2022
Bhattacharjee S Seidel H Liu A Liu C Strelzow J
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The use of cannabis is increasingly medically relevant as it is legalized and gains acceptance more broadly. However, the effects of marijuana use on postoperative outcomes following orthopedic surgery have not been well-characterized. This study seeks to illuminate the relationship between marijuana use and the incidence postoperative complications including: DVT, PE, nonunion, and infection following common orthopedic procedures.

This study was conducted using a national orthopaedic claims insurance database. We identified all patients undergoing knee arthroscopy, shoulder arthroscopy, operatively managed long bone fractures (humerus, femur, tibia and/or fibula, and radius and/or ulna), and single-level lumbar fusion. The proportion of patients within each surgery cohort who had a diagnostic code for marijuana dependence was assessed. The rates of DVT, PE, and infection within 90 days were assessed for all patients. The rate of nonunion was assessed for the long bone fracture and lumbar fusion cohorts. Univariate analyses of marijuana dependence on all outcomes were performed, followed by a multivariate logistic regression analysis controlling for known patient comorbidities.

We identified 1,113,944 knee arthroscopy, 747,938 shoulder arthroscopy, 88,891 lumbar fusion, and 37,163 long bone fracture patients. Out of the 1,987,936 patients, 24,404 patients had a diagnostic code for marijuana dependence. Within all four surgical subgroups, the marijuana dependence cohort experienced increased rates of infection, PE, and DVT, as well as increased rates of nonunion in the lumbar fusion and long bone fracture populations. In the multivariate analyses controlling for a variety of patient risk factors including tobacco use, marijuana dependence was identified as an independent risk factor for infection within all four surgical subgroups (Knee: OR 1.85, p < 0.001; Shoulder: OR 1.65, p < 0.001; Spine: OR 1.45, p < 0.001; Long bone: OR 1.28, p < 0.001), and for nonunion in the lumbar fusion (OR 1.38, p < 0.001) and long bone fracture (OR 1.31, p < 0.001) subgroups.

Our data suggests that marijuana dependence may be associated with increased rates of infection and nonunion following a variety of orthopaedic procedures. During preoperative evaluation, surgeons may consider marijuana use as a potential risk factor for postoperative complications, especially within the context of marijuana legalization. Future research into this relationship is necessary.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 807 - 819
1 Dec 2021
Wong RMY Wong PY Liu C Chung YL Wong KC Tso CY Chow SK Cheung W Yung PS Chui CS Law SW

Aims

The use of 3D printing has become increasingly popular and has been widely used in orthopaedic surgery. There has been a trend towards an increasing number of publications in this field, but existing literature incorporates limited high-quality studies, and there is a lack of reports on outcomes. The aim of this study was to perform a scoping review with Level I evidence on the application and effectiveness of 3D printing.

Methods

A literature search was performed in PubMed, Embase, and Web of Science databases. The keywords used for the search criteria were ((3d print*) OR (rapid prototyp*) OR (additive manufactur*)) AND (orthopaedic). The inclusion criteria were: 1) use of 3D printing in orthopaedics, 2) randomized controlled trials, and 3) studies with participants/patients. Risk of bias was assessed with Cochrane Collaboration Tool and PEDro Score. Pooled analysis was performed.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 61 - 61
1 Dec 2021
Naghavi SA Hua J Moazen M Taylor S Liu C
Full Access

Abstract

Objectives

Currently, total hip replacement surgery is an effective treatment for osteoarthritis, where the damaged hip joint is replaced with an artificial joint. Stress shielding is a mechanical phenomenon that refers to the reduction of bone density as a result of altered stresses acting on the host bone. Due to solid metallic nature and high stiffness of the current orthopaedic prostheses, surrounding bones undergo too much bone resorption secondary to stress shielding. With the use of 3D printing technology such as selective laser melting (SLM), it is now possible to produce porous graded microstructure hip stems to mimics the surrounding bone tissue properties.

Method

In this study we have compared the physical and mechanical properties of two triply periodic minimal surface (TPMS) lattice structure namely gyroid and diamond TPMS. Based on initial investigations, it was decided to design, and 3D print the gyroid and diamond scaffolds having pore size of 800 and 1100 um respectively. Scaffold of each type of structure were manufactured and were tested mechanically in compression (n=8), tension (n=5) and bending (n=1).


Bone & Joint Research
Vol. 10, Issue 10 | Pages 677 - 689
1 Oct 2021
Tamaddon M Blunn G Xu W Alemán Domínguez ME Monzón M Donaldson J Skinner J Arnett TR Wang L Liu C

Aims

Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone.

Methods

The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 411 - 424
14 Jul 2021
Zhao D Ren B Wang H Zhang X Yu M Cheng L Sang Y Cao S Thieringer FM Zhang D Wan Y Liu C

Aims

The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration.

Methods

IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively.


Bone & Joint Research
Vol. 10, Issue 1 | Pages 51 - 59
1 Jan 2021
Li J Ho WTP Liu C Chow SK Ip M Yu J Wong HS Cheung W Sung JJY Wong RMY

Aims

The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone.

Methods

Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted.


Bone & Joint Research
Vol. 8, Issue 11 | Pages 544 - 549
1 Nov 2019
Zheng W Liu C Lei M Han Y Zhou X Li C Sun S Ma X

Objectives

The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility.

Methods

Chinese patients with OP were recruited between March 2011 and December 2015 from our hospital. In this study, a total of 1267 post-menopausal female patients (631 OP patients and 636 control patients) were selected. The mean age of all subjects was 69.2 years (sd 15.8). A generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OP. For OP patient-control haplotype analyses, the SHEsis online haplotype analysis software (http://analysis.bio-x.cn/) was employed.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_2 | Pages 11 - 11
1 Jan 2019
Giusto E Pendegrass C Liu C Blunn G
Full Access

Intraosseous Transcutaneous Amputation Prosthesis (ITAP) is a new generation of limb replacements that can provide to amputees, an alternative solution to the main problems caused by the most common used external prosthesis such as pressure sores, infections and unnatural gait. ITAP is designed as one pylon osteointegrated into the bone and protruding through the skin, allowing both the mechanical forces to be directly transferred to the skeleton and the external skin being free from frictions and infections. The skin attachment to the implant is fundamental for the success of the ITAP, as it prevents the implant to move and consequently fail.

In this study we wanted to test if cell viability and attachment was improved using TiO2 nanotubes.

Human keratinocytes and human dermal fibroblasts were seeded for three days on TiO2 nanotubes with different sizes (18–30nm, 40–60nm and 60–110nm), compared with controls (smooth titanium) and tested for viability and attachment. A Mann-Whitney U test was used to compare groups where p values < 0.05 were considered significant. The results showed that the viability and cell attachment for keratinocytes were significantly higher after three days on controls comparing with all nanotubes (p=0.02), while attachment was higher on bigger nanotubes and controls. Cell viability for fibroblasts was significantly higher on nanotubes between 40 and 110nm comparing with smaller size and controls (p=0.03), while investigation of cell attachment is ongoing.

From these early results, we can say that TiO2 nanotubes can improve the soft tissue attachment on ITAP. Further in-vitro and ex-vivo experiments on cell attachment will be carried out.


Bone & Joint Research
Vol. 7, Issue 3 | Pages 213 - 222
1 Mar 2018
Tang X Teng S Petri M Krettek C Liu C Jagodzinski M

Objectives

The aims of this study were to determine whether the administration of anti-inflammatory and antifibrotic agents affect the proliferation, viability, and expression of markers involved in the fibrotic development of the fibroblasts obtained from arthrofibrotic tissue in vitro, and to evaluate the effect of the agents on arthrofibrosis prevention in vivo.

Methods

Dexamethasone, diclofenac, and decorin, in different concentrations, were employed to treat fibroblasts from arthrofibrotic tissue (AFib). Cell proliferation was measured by DNA quantitation, and viability was analyzed by Live/Dead staining. The levels of procollagen type I N-terminal propeptide (PINP) and procollagen type III N-terminal propeptide (PIIINP) were evaluated with enzyme-linked immunosorbent assay (ELISA) kits. In addition, the expressions of fibrotic markers were detected by real-time polymerase chain reaction (PCR). Fibroblasts isolated from healthy tissue (Fib) served as control. Further, a rabbit model of joint contracture was used to evaluate the antifibrotic effect of the three different agents.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 14 - 14
1 Nov 2016
Ma Y Dalmia S Gao P Young J Liu C You L
Full Access

Bone metastases are common and severe complications of cancers. It is estimated to occur in 65–75% of breast and prostate cancer patients and cause 80% of breast cancer-related deaths. Metastasised cancer cells have devastating impacts on bone due to their ability to alter bone remodeling by interacting with osteoblasts and osteoclasts. Exercise, often used as an intervention for cancer patients, regulates bone remodeling via osteocytes. Therefore, we hypothesise that bone mechanical loading may regulate bone metastases via osteocytes. This provides novel insights into the impact of exercises on bone metastases. It will assist in designing cancer intervention programs that lowers the risk for bone metastases. Investigating the mechanisms for the observed effects may also identify potential drug targets.

MLO-Y4 osteocyte-like cells (gift of Dr. Bonewald, University of Missouri-Kansas City) on glass slides were placed in flow chambers and subjected to oscillatory fluid flow (1Pa; 1Hz; 2 hours). Media were extracted (conditioned media; CM) post-flow. RAW264.7 osteoclast precursors were conditioned in MLO-Y4 CM for 7 days. Migration of MDA-MB-231 breast cancer cells and PC3 prostate cancer cells towards CM was assayed using Transwell. Viability, apoptosis, and proliferation of the cancer cells in the CM were measured with Fixable Viability Dye eFluor 450, APOPercentage, and BrDu, respectively. P-values were calculated using Student's t-test.

Significantly more MDA-MB-231 and PC3 cells migrated towards the CM from MLO-Y4 cells with exposure to flow in comparison to CM from MLO-Y4 cells not exposed to flow. The preferential migration is abolished with anti-VEGF antibodies. MDA-MB-231 cells apoptosis rate was slightly lower in CM from MLO-Y4 cells exposed to flow, while proliferation rate was slightly higher. The current data showed no difference in cancer cells viability and adhesion to collagen between any two groups. On the other hand, it was observed that less MDA-MB-231 cells migrated towards CM from RAW264.7 cells conditioned in CM from MLO-Y4 cells stimulated with flow in comparison to those conditioned in CM from MLO-Y4 cells not stimulated with flow. TRAP staining results confirmed that there were less differentiated osteoclasts when RAW264.7 cells were cultured in CM from MLO-Y4 cells exposed to flow.

Overall, this study suggests that when only osteocytes and cancer cells are involved, osteocytes subjected to mechanical loading can promote metastases due to the increased secretion of VEGF. However, with the incorporation of osteoclasts, mechanical loading on osteocytes seems to reduce MDA-MB-231 cell migration. This is likely because osteocytes reduce osteoclastogenesis in response to mechanical stimulation, and osteoclasts have been shown to support cancer cells. Animal studies will also be conducted to verify the pro- or anti-metastatic effect of mechanical loading that is observed in the in vitro part of this study.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_16 | Pages 10 - 10
1 Oct 2016
Albannaa R Kirkham J Burke J Liu C Yang X
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Poly-lactic acid (PLA) scaffolds are widely used in bone tissue engineering. The introduction of 3D printing has greatly increased the ability for tailoring different geometrical designs of these scaffolds for improved cellular attachment, growth and differentiation. This study aimed to investigate the effect of PLA fibre angle in 3D printed PLA scaffolds on hDPSC attachment and growth in vitro.

Two types of PLA scaffolds were prepared via 3D printing containing fibres angled at either 45° or 90°. hDPSCs (P4, 2*105 cells per scaffold) were statically seeded for 4 hours on to the scaffolds (7×3.5×3 mm3, n=3). Cellular attachment was checked using fluorescence microscopy and the number of unattached cells was counted using a haemocytometer (HCM). The cell-scaffold constructs were then cultured in osteogenic medium for up to 5 weeks. ALP staining and SEM were performed for one construct from each group at week 3. Cellular viability was determined using CMFDA/EHD1 live/dead labelling at week 4. After 5 weeks, constructs were processed for histology.

Fluorescence micrographs showed high numbers of hDPSCs attached to scaffold surfaces in both groups after seeding irrespective of fibre angle. However, HCM cell count revealed that the 45° angled PLA scaffolds had significantly greater cell attachment compared to the 90° angled PLA group (p<0.0001). After 3 weeks in osteogenic culture, both types of construct showed strong ALP staining. SEM showed that in the 45° angled PLA group, almost all macro-pores were fully closed with newly formed cell sheets. In comparison, in the 90° angled group, most of the macro-pores remained open although a limited amount of cellular bridging was present. SEM also detected crystal deposits in different areas within the cell sheets for both construct groups. Most hDPSCs were alive in both groups at week 4 of culture with few dead cells present. After 5 weeks, histology showed marked cellular growth and new matrix formation, with detectable Van Kossa +ve crystal deposits in different areas within all constructs irrespective of PLA fibre angle.

This study showed that 45° angled PLA 3D printed scaffolds enhanced hDPSC attachment and cellular bridging, which may help to rapidly close the macro-pores within the scaffold compared to the 90° angled group. This illustrates the potential of 45° angled 3D printed PLA scaffolds as good candidates for bone tissue engineering.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_16 | Pages 45 - 45
1 Oct 2016
Niu J Henckel J Hart A Liu* C
Full Access

Osteoarthritis (OA) affects bone cartilage and underlying bone. Mechanically, the underlying bone provides support to the healthy growth of the overlying cartilage. However, with the progress of OA, bone losses and cysts occur in the bone and these would alter the biomechanical behaviour of the joint, and further leading to bone remodelling adversely affect the overlying cartilage.

Human femoral head and femoral condyle were collected during hip or knee replacement operation due to the end stage of osteoarthritis (age 50–70), and the cartilage patches were graded and marked. A volunteer patient, with minor cartilage injury in his left knee while the right knee is intact, was used as control. Peripheral quantitative computed tomography (pQCT) was used to scan the bone and to determine the volumetric bone mineral density (vBMD) distribution.

The examination of retrieved tissue explants from osteoarthritic patients revealed that patches of cartilage were worn away from the articular surface, and patches of intact cartilage were left. The cysts, ranging from 1 to 10mm were existed in all osteoarthritic bones, and were located close to cartilage defects in the weight-bearing regions, and closely associated with the grade of cartilage defect as measured by pQCT. The bone mineral density (vBMD) distribution demonstrated that the bones around cysts had much higher vBMD than the trabecular bone away from the cysts. Compared to the subchondral bone under thicker cartilage, subchondral bone within cartilage defect has higher vBMD. This may result from the mechanical stimulation as a result of bone-bone direct contact with less protection of cartilage in cartilage defect regions.

This study showed an association between cartilage defect and subchondral bone mineral density distribution. Cysts were observed in all osteoarthritic samples and they are located close to cartilage defects in the weight-bearing regions. Cartilage defect altered the loading pattern of the joints, this leading to the bone remodelling and resultant bone structural changes as compared to the normal bone tissues.

This work was financially supported by The ARUK Proof of Concept Award (grant no: 21160).


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 97 - 97
1 Jul 2014
Wen C Wong K Liu C Yan C Lu W Chiu K
Full Access

Summary Statement

OA knee with subchondral cyst formation presented differential microstructure and mechanical competence of trabecular bone. This finding sheds light on the pivot role of subchondral cyst in OA bone pathophysiology.

Introduction

Subchondral bone cyst (SBC) is a major radiological finding in knee osteoarthritis (OA), together with joint space narrowing, osteophyte and sclerotic bone formation. There is mounting evidence showing that SBC originates in the same region as bone marrow lesions (BMLs). The presence of subchondral bone cyst (SBCs), in conjunction with BMLs, was associated with the severity of pain, and was able to predict tibial cartilage lolume loss and risk of joint replacement surgery in knee OA patient. It is speculated that the presence of SBCs might increase intraosseous pressure of subchondral bone, and trigger active remodeling and high turnover of surrounding trabecular bone. Yet the exact effect of SBC on the structural and mechanical properties trabecular bone, which provides the support to overlying articular cartilage, remains to be elucidated. Therefore, this study aimed to investiate the microstructure and mechanical competence of trabecular bone of knee OA in presence or absence of SBC.