Publications by authors named "Hongshuai Li"

28 Publications

  • Page 1 of 1

Tissue response, macrophage phenotype, and intrinsic calcification induced by cardiovascular biomaterials: Can clinical regenerative potential be predicted in a rat subcutaneous implant model?

J Biomed Mater Res A 2021 Jul 29. Epub 2021 Jul 29.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

The host immune response to an implanted biomaterial, particularly the phenotype of infiltrating macrophages, is a key determinant of biocompatibility and downstream remodeling outcome. The present study used a subcutaneous rat model to compare the tissue response, including macrophage phenotype, remodeling potential, and calcification propensity of a biologic scaffold composed of glutaraldehyde-fixed bovine pericardium (GF-BP), the standard of care for heart valve replacement, with those of an electrospun polycarbonate-based supramolecular polymer scaffold (ePC-UPy), urinary bladder extracellular matrix (UBM-ECM), and a polypropylene mesh (PP). The ePC-UPy and UBM-ECM materials induced infiltration of mononuclear cells throughout the thickness of the scaffold within 2 days and neovascularization at 14 days. GF-BP and PP elicited a balance of pro-inflammatory (M1-like) and anti-inflammatory (M2-like) macrophages, while UBM-ECM and ePC-UPy supported a dominant M2-like macrophage phenotype at all timepoints. Relative to GF-BP, ePC-UPy was markedly less susceptible to calcification for the 180 day duration of the study. UBM-ECM induced an archetypical constructive remodeling response dominated by M2-like macrophages and the PP caused a typical foreign body reaction dominated by M1-like macrophages. The results of this study highlight the divergent macrophage and host remodeling response to biomaterials with distinct physical and chemical properties and suggest that the rat subcutaneous implantation model can be used to predict in vivo biocompatibility and regenerative potential for clinical application of cardiovascular biomaterials.
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http://dx.doi.org/10.1002/jbm.a.37280DOI Listing
July 2021

Identification of prognostic alternative splicing events in sarcoma.

Sci Rep 2021 Jul 22;11(1):14949. Epub 2021 Jul 22.

Department of Emergency Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Sarcoma is a rare malignancy with unfavorable prognoses. Accumulating evidence indicates that aberrant alternative splicing (AS) events are generally involved in cancer pathogenesis. The aim of this study was to identify the prognostic value of AS-related survival genes as potential biomarkers, and highlight the functional roles of AS events in sarcoma. RNA-sequencing and AS-event datasets were downloaded from The Cancer Genome Atlas (TCGA) sarcoma cohort and TCGA SpliceSeq, respectively. Survival-related AS events were further assessed using a univariate analysis. A multivariate Cox regression analysis was also performed to establish a survival-gene signature to predict patient survival, and the area-under-the-curve method was used to evaluate prognostic reliability. KOBAS 3.0 and Cytoscape were used to functionally annotate AS-related genes and to assess their network interactions. We detected 9674 AS events in 40,184 genes from 236 sarcoma samples, and the 15 most significant genes were then used to construct a survival regression model. We further validated the involvement of ten potential survival-related genes (TUBB3, TRIM69, ZNFX1, VAV1, KCNN2, VGLL3, AK7, ARMC4, LRRC1, and CRIP1) in the occurrence and development of sarcoma. Multivariate survival model analyses were also performed, and validated that a model using these ten genes provided good classifications for predicting patient outcomes. The present study has increased our understanding of AS events in sarcoma, and the gene-based model using AS-related events may serve as a potential predictor to determine the survival of sarcoma patients.
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http://dx.doi.org/10.1038/s41598-021-94485-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298452PMC
July 2021

Improved Bone Quality and Bone Healing of Dystrophic Mice by Parabiosis.

Metabolites 2021 Apr 16;11(4). Epub 2021 Apr 16.

Steadman Philippon Research Institute, Vail, CO 81657, USA.

Duchenne muscular dystrophy (DMD) is a degenerative muscle disorder characterized by a lack of dystrophin expression in the sarcolemma of muscle fibers. DMD patients acquire bone abnormalities including osteopenia, fragility fractures, and scoliosis indicating a deficiency in skeletal homeostasis. The dKO (dystrophin/Utrophin double knockout) is a more severe mouse model of DMD than the mdx mouse (dystrophin deficient), and display numerous clinically-relevant manifestations, including a spectrum of degenerative changes outside skeletal muscle including bone, articular cartilage, and intervertebral discs. To examine the influence of systemic factors on the bone abnormalities and healing in DMD, parabiotic pairing between dKO mice and mdx mice was established. Notably, heterochronic parabiosis with young mdx mice significantly increased bone mass and improved bone micro-structure in old dKO-hetero mice, which showed progressive bone deterioration. Furthermore, heterochronic parabiosis with WT C56/10J mice significantly improved tibia bone defect healing in dKO-homo mice. These results suggest that systemic blood-borne factor(s) and/or progenitors from WT and young mdx mice can influence the bone deficiencies in dKO mice. Understanding these circulating factors or progenitor cells that are responsible to alleviate the bone abnormalities in dKO mice after heterochronic parabiosis might be useful for the management of poor bone health in DMD.
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http://dx.doi.org/10.3390/metabo11040247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073674PMC
April 2021

GILT in tumor cells improves T cell-mediated anti-tumor immune surveillance.

Immunol Lett 2021 Jun 7;234:1-12. Epub 2021 Apr 7.

Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, Tianjin Medical University, Tianjin, China. Electronic address:

The lysosomal thiol reductase GILT catalyzes the reduction of disulfide bonds of protein antigens, facilitating antigen-presenting cells (APCs) to present antigen to T cells. However, whether GILT expression in tumor cells can be associated with improved T cell-mediated anti-tumor responses remains unknown. Here, we identify that GILT is able to facilitate anti-tumor immune surveillance via promoting MHC class I mediated-antigen presentation in colon carcinoma. By using mice model bearing colon tumors, we find that GILT inhibites tumor growth in vivo with more leucocytes infiltration but has no effect on tumor cell development in vitro in terms of proliferation, cell cycle and migration. Furthermore, by using transgenic OT-I mice, we recognize the tumor-expressing OVA peptide, a surrogate tumor antigen, we find that GILT is capable of enhancing MHC class I mediated antigen presentation and improving specific CD8 T cell anti-tumor responses in murine colon carcinoma. These findings propose the boost of GILT-MHC-I axis in tumors as a viable option for immune system against cancer.
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http://dx.doi.org/10.1016/j.imlet.2021.04.001DOI Listing
June 2021

Skeletal Muscle and Bone - Emerging Targets of Fibroblast Growth Factor-21.

Front Physiol 2021 8;12:625287. Epub 2021 Mar 8.

Musculoskeletal Growth & Regeneration Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, United States.

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family, which functions as a powerful endocrine and paracrine regulator of glucose and lipid metabolism. In addition to liver and adipose tissue, recent studies have shown that FGF21 can also be produced in skeletal muscle. As the most abundant tissue in the human body, skeletal muscle has become increasingly recognized as a major site of metabolic activity and an important modulator of systemic metabolic homeostasis. The function and mechanism of action of muscle-derived FGF21 have recently gained attention due to the findings of considerably increased expression and secretion of FGF21 from skeletal muscle under certain pathological conditions. Recent reports regarding the ectopic expression of FGF21 from skeletal muscle and its potential effects on the musculoskeletal system unfolds a new chapter in the story of FGF21. In this review, we summarize the current knowledge base of muscle-derived FGF21 and the possible functions of FGF21 on homeostasis of the musculoskeletal system with a focus on skeletal muscle and bone.
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http://dx.doi.org/10.3389/fphys.2021.625287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982600PMC
March 2021

Oncoprotein SND1 hijacks nascent MHC-I heavy chain to ER-associated degradation, leading to impaired CD8 T cell response in tumor.

Sci Adv 2020 May 29;6(22). Epub 2020 May 29.

Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Cellular and Molecular Immunology, Excellent Talent Project, Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

SND1 is highly expressed in various cancers. Here, we identify oncoprotein SND1 as a previously unidentified endoplasmic reticulum (ER) membrane-associated protein. The amino-terminal peptide of SND1 predominantly associates with SEC61A, which anchors on ER membrane. The SN domain of SND1 catches and guides the nascent synthesized heavy chain (HC) of MHC-I to ER-associated degradation (ERAD), hindering the normal assembly of MHC-I in the ER lumen. In mice model bearing tumors, especially in transgenic OT-I mice, deletion of SND1 promotes the presentation of MHC-I in both B16F10 and MC38 cells, and the infiltration of CD8 T cells is notably increased in tumor tissue. It was further confirmed that SND1 impaired tumor antigen presentation to cytotoxic CD8 T cells both in vivo and in vitro. These findings reveal SND1 as a novel ER-associated protein facilitating immune evasion of tumor cells through redirecting HC to ERAD pathway that consequently interrupts antigen presentation.
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http://dx.doi.org/10.1126/sciadv.aba5412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259962PMC
May 2020

Design and evaluation of collagen-inspired mineral-hydrogel nanocomposites for bone regeneration.

Acta Biomater 2020 08 1;112:262-273. Epub 2020 Jun 1.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15219; McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15260; UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15260. Electronic address:

Bone loss due to trauma and tumors remains a serious clinical concern. Due to limited availability and disease transmission risk with autografts and allografts, calcium phosphate bone fillers and growth factor-based substitute bone grafts are currently used in the clinic. However, substitute grafts lack bone regeneration potential when used without growth factors. When used along with the added growth factors, they lead to unwanted side effects such as uncontrolled bone growth. Collagen-based hydrogel grafts available on the market fail to provide structural guidance to native cells due to high water-solubility and faster degradation. To overcome these limitations, we employed bioinspired material design and fabricated three different hydrogels with structural features similar to native collagen at multiple length-scales. These hydrogels fabricated using polyionic complexation of oppositely charged natural polysaccharides exhibited multi-scale architecture mimicking nanoscale banding pattern, and microscale fibrous structure of native collagen. All three hydrogels promoted biomimetic apatite-like mineral deposition in vitro elucidating crystalline structure on the surface while amorphous calcium phosphate inside the hydrogels resulting in mineral-hydrogel nanocomposites. When evaluated in a non-load bearing critical size mouse calvaria defect model, chitosan - kappa carrageenan mineral-hydrogel nanocomposites enhanced bone regeneration without added growth factors compared to empty defect as well as widely used marketed collagen scaffolds. Histological assessment of the regenerated bone revealed improved healing and tissue remodeling with mineral-hydrogel nanocomposites. Overall, these collagen-inspired mineral-hydrogel nanocomposites showed multi-scale hierarchical structure and can potentially serve as promising bioactive hydrogel to promote bone regeneration. STATEMENT OF SIGNIFICANCE: Hydrogels, especially collagen, are widely used in bone tissue engineering. Collagen fibrils play arguably the most important role during natural bone development. Its multi-scale hierarchical structure to form fibers from fibrils and electrostatic charges enable mineral sequestration, nucleation, and growth. However, bulk collagen hydrogels exhibit limited bone regeneration and are mostly used as carriers for highly potent growth factors such as bone morphogenic protein-2, which increase the risk of uncontrolled bone growth. Thus, there is an unmet clinical need for a collagen-inspired biomaterial that can recreate structural hierarchy, mineral sequestration ability, and stimulate recruitment of host progenitor cells to facilitate bone regeneration. Here, we propose collagen-inspired bioactive mineral-hydrogel nanocomposites as a growth factor-free approach to guide and enhance bone regeneration.
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http://dx.doi.org/10.1016/j.actbio.2020.05.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446305PMC
August 2020

ATM is a key driver of NF-κB-dependent DNA-damage-induced senescence, stem cell dysfunction and aging.

Aging (Albany NY) 2020 03 22;12(6):4688-4710. Epub 2020 Mar 22.

Department of Molecular Medicine and the Center on Aging, Scripps Research, Jupiter, FL 33458, USA.

NF-κB is a transcription factor activated in response to inflammatory, genotoxic and oxidative stress and important for driving senescence and aging. Ataxia-telangiectasia mutated (ATM) kinase, a core component of DNA damage response signaling, activates NF-κB in response to genotoxic and oxidative stress via post-translational modifications. Here we demonstrate that ATM is activated in senescent cells in culture and murine tissues from -deficient mouse models of accelerated aging, as well as naturally aged mice. Genetic and pharmacologic inhibition of ATM reduced activation of NF-κB and markers of senescence and the senescence-associated secretory phenotype (SASP) in senescent MEFs. mice heterozygous for have reduced NF-κB activity and cellular senescence, improved function of muscle-derived stem/progenetor cells (MDSPCs) and extended healthspan with reduced age-related pathology especially age-related bone and intervertebral disc pathologies. In addition, treatment of mice with the ATM inhibitor KU-55933 suppressed markers of senescence and SASP. Taken together, these results demonstrate that the ATM kinase is a major mediator of DNA damage-induced, NF-κB-mediated cellular senescence, stem cell dysfunction and aging and thus represents a therapeutic target to slow the progression of aging.
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http://dx.doi.org/10.18632/aging.102863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138542PMC
March 2020

Increased Expression of FGF-21 Negatively Affects Bone Homeostasis in Dystrophin/Utrophin Double Knockout Mice.

J Bone Miner Res 2020 04 30;35(4):738-752. Epub 2019 Dec 30.

Vascular Medicine Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy seen in children. In addition to skeletal muscle, DMD also has a significant impact on bone. The pathogenesis of bone abnormalities in DMD is still unknown. Recently, we have identified a novel bone-regulating cytokine, fibroblast growth factor-21 (FGF-21), which is dramatically upregulated in skeletal muscles from DMD animal models. We hypothesize that muscle-derived FGF-21 negatively affects bone homeostasis in DMD. Dystrophin/utrophin double-knockout (dKO) mice were used in this study. We found that the levels of circulating FGF-21 were significantly higher in dKO mice than in age-matched WT controls. Further tests on FGF-21 expressing tissues revealed that both FGF-21 mRNA and protein expression were dramatically upregulated in dystrophic skeletal muscles, whereas FGF-21 mRNA expression was downregulated in liver and white adipose tissue (WAT) compared to WT controls. Neutralization of circulating FGF-21 by i.p. injection of anti-FGF-21 antibody significantly alleviated progressive bone loss in weight-bearing (vertebra, femur, and tibia) and non-weight bearing bones (parietal bones) in dKO mice. We also found that FGF-21 directly promoted RANKL-induced osteoclastogenesis from bone marrow macrophages (BMMs), as well as promoted adipogenesis while concomitantly inhibiting osteogenesis of bone marrow mesenchymal stem cells (BMMSCs). Furthermore, fibroblast growth factor receptors (FGFRs) and co-receptor β-klotho (KLB) were expressed in bone cells (BMM-derived osteoclasts and BMMSCs) and bone tissues. KLB knockdown by small interfering RNAs (siRNAs) significantly inhibited the effects of FGF21 on osteoclast formation of BMMs and on adipogenic differentiation of BMMSCs, indicating that FGF-21 may directly affect dystrophic bone via the FGFRs-β-klotho complex. In conclusion, this study shows that dystrophic skeletal muscles express and secrete significant levels of FGF-21, which negatively regulates bone homeostasis and represents an important pathological factor for the development of bone abnormalities in DMD. The current study highlights the importance of muscle/bone cross-talk via muscle-derived factors (myokines) in the pathogenesis of bone abnormalities in DMD. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3932DOI Listing
April 2020

The impact of keto-adaptation on exercise performance and the role of metabolic-regulating cytokines.

Am J Clin Nutr 2019 09;110(3):562-573

Musculoskeletal Growth and Regeneration Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

The ketogenic diet (KD) is a normocaloric diet composed of high-fat, low-carbohydrate, and adequate protein that induces fasting-like effects and results in the production of ketone bodies. Initially used widely for children with refractory epilepsy, the KD gained popularity due to its beneficial effects on weight loss, diabetes, and cancer. In recent years, there has been a resurgence in interest surrounding the KD and exercise performance. This review provides new insights into the adaptation period necessary for enhancement in skeletal muscle fat and ketone oxidation after sustained nutritional ketosis. In addition, this review highlights metabolically active growth factors and cytokines, which may function as important regulators of keto-adaptation in the setting of exercise and the KD.
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http://dx.doi.org/10.1093/ajcn/nqz145DOI Listing
September 2019

SHIP1 inhibits cell growth, migration, and invasion in non‑small cell lung cancer through the PI3K/AKT pathway.

Oncol Rep 2019 Apr 30;41(4):2337-2350. Epub 2019 Jan 30.

Department of Cancer Biotherapy Center, Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan 650118, P.R. China.

Src homology 2‑containing inositol‑5'‑phosphatase 1 (SHIP1) serves a vital role in the occurrence and development of hematological tumors, but there is limited knowledge regarding the role of SHIP1 in various solid tumors, including lung cancer. In the present study, the aim was to investigate the expression and functional mechanisms of SHIP1 in non‑small cell lung cancer (NSCLC). The Gene Expression Omnibus database demonstrated that SHIP1 had low expression in NSCLC. Further studies using fresh tissues and cell lines also confirmed this observation. Biological function analyses revealed that SHIP1 overexpression notably suppressed cell growth, migration and invasion in vitro and in vivo in NSCLC. Mechanistic analyses indicated that SHIP1 inactivated the phosphoinositide 3‑kinase (PI3K)/AKT pathway to suppress signals associated with the cell cycle and epithelial‑mesenchymal transition. In clinical specimens, reduced SHIP1 is an unfavorable factor and is negatively associated with the T classification, N classification and clinical stage. Furthermore, patients with low SHIP1 levels exhibited reduced survival rate, compared with patients with high levels of the protein. Notably, the promoter of the SHIP1 gene lacks CpG islands, and the suppression of SHIP1 expression is not associated with epidermal growth factor receptor or Kirsten rat sarcoma mutations. Thus, the present study demonstrated that SHIP1 inhibits cell growth, migration and invasion in NSCLC through the PI3K/AKT pathway. Additionally, reduced SHIP1 expression may be an unfavorable factor for NSCLC.
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http://dx.doi.org/10.3892/or.2019.6990DOI Listing
April 2019

Altered bone-regulating myokine expression in skeletal muscle Of Duchenne muscular dystrophy mouse models.

Muscle Nerve 2018 10 3;58(4):573-582. Epub 2018 Sep 3.

Musculoskeletal Growth & Regeneration Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, 15219, USA.

Introduction: Duchenne muscular dystrophy (DMD) has been well characterized as a disease that affects both skeletal muscle and bone. The pathophysiology responsible for the deficits in bone tissue is still unclear.

Methods: Quantitative reverse-transcription polymerase chain reaction and Western blot analyses of known myokines from skeletal muscle were performed on dystrophic mouse models and wild-type (WT) controls to identify differentially expressed bone-regulating myokines.

Results: Twenty-four of 43 myokine genes demonstrated significantly different mRNA expression in the skeletal muscles of dystrophic mice when compared with muscles of WT mice. Several differently expressed bone-regulating myokine genes were identified, and their protein levels were also verified by Western blot.

Conclusions: Dystrophic skeletal muscle demonstrated a significantly altered myokine gene expression profile. mRNA and protein levels of several bone-regulating myokines were significantly altered in dystrophic skeletal muscle, which suggests pathological role of bone-regulating myokines on bone homeostasis in DMD. Muscle Nerve 58: 573-582, 2018.
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http://dx.doi.org/10.1002/mus.26195DOI Listing
October 2018

Significant Chondrocyte Viability Is Present in Acetabular Chondral Flaps Associated With Femoroacetabular Impingement.

Am J Sports Med 2018 01 12;46(1):149-152. Epub 2017 Oct 12.

Steadman Philippon Research Institute, Vail, Colorado, USA.

Background: Patients presenting with cam deformity of the femoral head and neck sustain repeated trauma to the articular cartilage of the superior acetabulum, with chondral delamination injuries found during hip arthroscopy. Two previous studies reveal conflicting chondrocyte viability data in these traumatic cartilage injuries. The full-thickness nature of flaps may suggest that chondrocytes residing in the cartilage flap matrix in the joint environment would remain viable despite shear trauma. Hypothesis/Purpose: The purpose of this study is to determine the in vivo tissue viability of acetabular chondral flaps in patients with femoroacetabular impingement (FAI) when samples are analyzed immediately after biopsy. We hypothesize that the majority of the tissue in acetabular chondral flaps is viable in the joint microenvironment.

Study Design: Descriptive laboratory study.

Methods: Partially detached cartilage flaps from 10 patients undergoing arthroscopic hip surgery for FAI were biopsied in a minimally traumatic manner before chondroplasty and microfracture. Samples were placed in cold Hank's Balanced Salt Solution without phenol red solution and immediately transported on ice to our laboratory. The edge of the samples was trimmed and further cut into 3 separate, 1-mm-thick sections. Sections were stained using a live/dead staining kit. Images were obtained with confocal microscopy, and the percentage of live cells was quantified.

Results: Patients averaged 36 ± 11 years (range, 18-48 years), and 2 patients were female. The mean body mass index was 28.9 ± 5.6 kg/m. The total proportion of live cells from all sections analyzed was 85.8%. The proportion of live cells per patient was 87% ± 10%.

Conclusion: We determined that acetabular chondral flaps are approximately 87% live cells when analyzed immediately after biopsy, with 6 of 10 patients having greater than 90% live cells. These data point to the importance of laboratory techniques in making viability judgments in biologic systems.

Clinical Relevance: Full-thickness cartilage loss is a difficult problem for all active people but particularly in the young population in whom joint preservation is key. We describe the viability of chondrocytes present in full-thickness acetabular-based chondral flaps encountered during hip arthroscopy. Identification of greater than 85% chondrocyte viability supports a foundation for evaluation and creation of novel clinical innovations for repair and replacement techniques using the flap as donor tissue, as alternatives to chondroplasty and microfracture.
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http://dx.doi.org/10.1177/0363546517732751DOI Listing
January 2018

The superior regenerative potential of muscle-derived stem cells for articular cartilage repair is attributed to high cell survival and chondrogenic potential.

Mol Ther Methods Clin Dev 2016 30;3:16065. Epub 2016 Nov 30.

Department of Orthopedic Surgery, Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Orthopedic Surgery, University of Texas Health Science Center at Houston, Houston, Texas, USA; Steadman Philippon Research Institute, Vail, Colorado, USA; Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston Medical School, Houston, Texas, USA.

Three populations of muscle-derived cells (PP1, PP3, and PP6) were isolated from mouse skeletal muscle using modified preplate technique and retrovirally transduced with BMP4/GFP.  , the PP1 cells (fibroblasts) proliferated significantly slower than the PP3 (myoblasts) and PP6 cells (muscle-derived stem cells); the PP1 and PP6 cells showed a superior rate of survival compared with PP3 cells under oxidative stress; and the PP6 cells showed significantly superior chondrogenic capabilities than PP1 and PP3 cells. , the PP6 cells promoted superior cartilage regeneration compared with the other muscle-derived cell populations. The cartilage defects in the PP6 group had significantly higher histological scores than those of the other muscle-derived cell groups, and GFP detection revealed that the transplanted PP6 cells showed superior cell survival and chondrogenic capabilities compared with the PP1 and PP3 cells. PP6 cells (muscle-derived stem cells) are superior to other primary muscle-derived cells for use as a cellular vehicle for BMP4-based gene therapy to heal full-thickness osteo-chondral defects. The superiority of the PP6/muscle-derived stem cells appears to be attributable to a combination of increased rate of survival and superior chondrogenic differentiation capacity.
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http://dx.doi.org/10.1038/mtm.2016.65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129874PMC
November 2016

Customized platelet-rich plasma with transforming growth factor β1 neutralization antibody to reduce fibrosis in skeletal muscle.

Biomaterials 2016 May 17;87:147-156. Epub 2016 Feb 17.

Steadman Philippon Research Institute, Vail, CO 81657, USA; Department of Orthopaedic Surgery, University of Texas Health Science Center at Houston, TX 77054, USA. Electronic address:

Unlabelled: The formation of fibrous tissue during the healing of skeletal muscle injuries leads to incomplete recovery of the injured muscle. Platelet-rich-plasma (PRP) contains beneficial growth factors for skeletal muscle repair; however, it also contains deleterious cytokines and growth factors, such as TGF-β1, that can cause fibrosis and inhibit optimal muscle healing.

Objective: To test if neutralizing TGF-β1's action within PRP, through neutralization antibodies, could improve PRP's beneficial effect on skeletal muscle repair.

Methods: PRP was isolated from in-bred Fisher rats. TGF-β1 neutralization antibody (Ab) was used to block the TGF-β1 within the PRP prior to injection. The effects of customized PRP (TGF-β1 neutralized PRP) on muscle healing was tested on a cardiotoxin (CTX) induced muscle injury model.

Results: A significant increase in the numbers of regenerative myofibers was observed in the PRP and customized PRP groups compared to the untreated control. A significant decrease in collagen deposition was observed in customized PRP groups when compared to the control and PRP groups. Significantly enhanced angiogenesis and more Pax-7 positive satellite cells were found in the PRP and customized PRP groups compared to the control group. Macrophage infiltration was increased in the customized PRP groups when compared with the PRP group. More M2 macrophages were recruited to the injury site in the customized PRP groups when compared with the PRP and control groups.

Conclusion: Neutralizing TGF-β1 within PRP significantly promotes muscle regeneration while significantly reducing fibrosis. Not only did the neutralization reduce fibrosis, it enhanced angiogenesis, prolonged satellite cell activation, and recruited a greater number of M2 macrophages to the injury site which also contributed to the efficacy that the customized PRP had on muscle healing.
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http://dx.doi.org/10.1016/j.biomaterials.2016.02.017DOI Listing
May 2016

α-2,8-Sialyltransferase Is Involved in the Development of Multidrug Resistance via PI3K/Akt Pathway in Human Chronic Myeloid Leukemia.

IUBMB Life 2015 Feb 9;67(2):77-87. Epub 2015 Apr 9.

Department of Medical Laboratory, College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning Province, China.

Cell surface sialylation is emerging as an important feature of cancer cell multidrug resistance (MDR). We have focused on the influence of 2,8-sialyltransferases in key steps of the development of MDR in chronic myeloid leukemia (CML). The expressional profiles of six α-2,8-sialyltransferases were generated in three pairs of CML cell lines and peripheral blood mononuclear cells (PBMC) of CML patients. Cellular MDR phenotype positively correlated with ST8SIA4 and ST8SIA6 levels. Furthermore, ST8SIA4 mediated the activity of phosphoinositide-3 kinase (PI3K)/Akt signal pathway and the expression of P-glycoprotein (P-gp). Targeting the PI3K/Akt pathway by its specific inhibitor LY294002, or by Akt RNA interfering reversed the MDR phenotype of K562/ADR cells. Inhibition of PI3K/Akt pathway also attenuated the effects caused by the overexpression of ST8SIA4 on MDR. Therefore this study indicated that α-2,8-sialyltransferases involved in the development of MDR of CML cells probably through ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp.
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http://dx.doi.org/10.1002/iub.1351DOI Listing
February 2015

Sustained release of bone morphogenetic protein 2 via coacervate improves the osteogenic potential of muscle-derived stem cells.

Stem Cells Transl Med 2013 Sep 24;2(9):667-77. Epub 2013 Jul 24.

Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Muscle-derived stem cells (MDSCs) isolated from mouse skeletal muscle by a modified preplate technique exhibit long-term proliferation, high self-renewal, and multipotent differentiation capabilities in vitro. MDSCs retrovirally transduced to express bone morphogenetic proteins (BMPs) can differentiate into osteocytes and chondrocytes and enhance bone and articular cartilage repair in vivo, a feature that is not observed with nontransduced MDSCs. These results emphasize that MDSCs require prolonged exposure to BMPs to undergo osteogenic and chondrogenic differentiation. A sustained BMP protein delivery approach provides a viable and potentially more clinically translatable alternative to genetic manipulation of the cells. A unique growth factor delivery platform comprised of native heparin and a synthetic polycation, poly(ethylene argininylaspartate diglyceride) (PEAD), was used to bind, protect, and sustain the release of bone morphogenetic protein-2 (BMP2) in a temporally and spatially controlled manner. Prolonged exposure to BMP2 released by the PEAD:heparin delivery system promoted the differentiation of MDSCs to an osteogenic lineage in vitro and induced the formation of viable bone at an ectopic site in vivo. This new strategy represents an alternative approach for bone repair mediated by MDSCs while bypassing the need for gene therapy.
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http://dx.doi.org/10.5966/sctm.2013-0027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754467PMC
September 2013

Platelet-rich plasma promotes the proliferation of human muscle derived progenitor cells and maintains their stemness.

PLoS One 2013 7;8(6):e64923. Epub 2013 Jun 7.

Department of Orthopedic Surgery, Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Human muscle-derived progenitor cells (hMDPCs) offer great promise for muscle cell-based regenerative medicine; however, prolonged ex-vivo expansion using animal sera is necessary to acquire sufficient cells for transplantation. Due to the risks associated with the use of animal sera, the development of a strategy for the ex vivo expansion of hMDPCs is required. The purpose of this study was to investigate the efficacy of using platelet-rich plasma (PRP) for the ex-vivo expansion of hMDPCs. Pre-plated MDPCs, myoendothelial cells, and pericytes are three populations of hMDPCs that we isolated by the modified pre-plate technique and Fluorescence Activated Cell Sorting (FACS), respectively. Pooled allogeneic human PRP was obtained from a local blood bank, and the effect that thrombin-activated PRP-releasate supplemented media had on the ex-vivo expansion of the hMDPCs was tested against FBS supplemented media, both in vitro and in vivo. PRP significantly enhanced short and long-term cell proliferation, with or without FBS supplementation. Antibody-neutralization of PDGF significantly blocked the mitogenic/proliferative effects that PRP had on the hMDPCs. A more stable and sustained expression of markers associated with stemness, and a decreased expression of lineage specific markers was observed in the PRP-expanded cells when compared with the FBS-expanded cells. The in vitro osteogenic, chondrogenic, and myogenic differentiation capacities of the hMDPCs were not altered when expanded in media supplemented with PRP. All populations of hMDPCs that were expanded in PRP supplemented media retained their ability to regenerate myofibers in vivo. Our data demonstrated that PRP promoted the proliferation and maintained the multi-differentiation capacities of the hMDPCs during ex-vivo expansion by maintaining the cells in an undifferentiated state. Moreover, PDGF appears to be a key contributing factor to the beneficial effect that PRP has on the proliferation of hMDPCs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064923PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676442PMC
January 2014

PRP as a new approach to prevent infection: preparation and in vitro antimicrobial properties of PRP.

J Vis Exp 2013 Apr 9(74). Epub 2013 Apr 9.

Department of Orthopaedics, School of Medicine, West Virginia University, USA.

Implant-associated infection is becoming more and more challenging to the healthcare industry worldwide due to increasing antibiotic resistance, transmission of antibiotic resistant bacteria between animals and humans, and the high cost of treating infections. In this study, we disclose a new strategy that may be effective in preventing implant-associated infection based on the potential antimicrobial properties of platelet-rich plasma (PRP). Due to its well-studied properties for promoting healing, PRP (a biological product) has been increasingly used for clinical applications including orthopaedic surgeries, periodontal and oral surgeries, maxillofacial surgeries, plastic surgeries, sports medicine, etc. PRP could be an advanced alternative to conventional antibiotic treatments in preventing implant-associated infections. The use of PRP may be advantageous compared to conventional antibiotic treatments since PRP is less likely to induce antibiotic resistance and PRP's antimicrobial and healing-promoting properties may have a synergistic effect on infection prevention. It is well known that pathogens and human cells are racing for implant surfaces, and PRP's properties of promoting healing could improve human cell attachment thereby reducing the odds for infection. In addition, PRP is inherently biocompatible, and safe and free from the risk of transmissible diseases. For our study, we have selected several clinical bacterial strains that are commonly found in orthopaedic infections and examined whether PRP has in vitro antimicrobial properties against these bacteria. We have prepared PRP using a twice centrifugation approach which allows the same platelet concentration to be obtained for all samples. We have achieved consistent antimicrobial findings and found that PRP has strong in vitro antimicrobial properties against bacteria like methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Group A Streptococcus, and Neisseria gonorrhoeae. Therefore, the use of PRP may have the potential to prevent infection and to reduce the need for costly post-operative treatment of implant-associated infections.
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http://dx.doi.org/10.3791/50351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653398PMC
April 2013

Unique antimicrobial effects of platelet-rich plasma and its efficacy as a prophylaxis to prevent implant-associated spinal infection.

Adv Healthc Mater 2013 Sep 27;2(9):1277-84. Epub 2013 Feb 27.

Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506, USA; Department of Orthopaedics, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.

Platelet-rich-plasma (PRP) has attracted great attention and has been increasingly used for a variety of clinical applications including orthopedic surgeries, periodontal and oral surgeries, maxillofacial surgeries, plastic surgeries, and sports medicine. However, very little is known about the antimicrobial activities of PRP. PRP is found to have antimicrobial properties both in vitro and in vivo. In vitro, the antimicrobial properties of PRP are bacterial-strain-specific and time-specific: PRP significantly (80-100 fold reduction in colony-forming units) inhibits the growth of methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Group A streptococcus, and Neisseria gonorrhoeae within the first few hours but it has no significant antimicrobial properties against E. coli and Pseudomonas. The antimicrobial properties of PRP also depend on the concentration of thrombin. In vivo, an implant-associated spinal infection rabbit model is established and used to evaluate the antimicrobial and wound-healing properties of PRP. Compared to the infection controls, PRP treatment results in significant reduction in bacterial colonies in bone samples at all time points studied (i.e. 1, 2, and 3 weeks) and significant increase in mineralized tissues (thereby better bone healing) at postoperative weeks 2 and 3. PRP therefore may be a useful adjunct strategy against postoperative implant-associated infections.
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http://dx.doi.org/10.1002/adhm.201200465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774283PMC
September 2013

BMP2 is superior to BMP4 for promoting human muscle-derived stem cell-mediated bone regeneration in a critical-sized calvarial defect model.

Cell Transplant 2013 1;22(12):2393-408. Epub 2012 Nov 1.

Stem Cell Research Center, Growth and Developmental Laboratory, Department of Orthopaedic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Muscle-derived cells have been successfully isolated using a variety of different methods and have been shown to possess multilineage differentiation capacities, including an ability to differentiate into articular cartilage and bone in vivo; however, the characterization of human muscle-derived stem cells (hMDSCs) and their bone regenerative capacities have not been fully investigated. Genetic modification of these cells may enhance their osteogenic capacity, which could potentially be applied to bone regenerative therapies. We found that hMDSCs, isolated by the preplate technique, consistently expressed the myogenic marker CD56, the pericyte/endothelial cell marker CD146, and the mesenchymal stem cell markers CD73, CD90, CD105, and CD44 but did not express the hematopoietic stem cell marker CD45, and they could undergo osteogenic, chondrogenic, adipogenic, and myogenic differentiation in vitro. In order to investigate the osteoinductive potential of hMDSCs, we constructed a retroviral vector expressing BMP4 and GFP and a lentiviral vector expressing BMP2. The BMP4-expressing hMDSCs were able to undergo osteogenic differentiation in vitro and exhibited enhanced mineralization compared to nontransduced cells; however, when transplanted into a calvarial defect, they failed to regenerate bone. Local administration of BMP4 protein and cell pretreatment with N-acetylcysteine (NAC), which improves cell survival, did not enhance the osteogenic capacity of the retro-BMP4-transduced cells. In contrast, lenti-BMP2-transduced hMDSCs not only exhibited enhanced in vitro osteogenic differentiation but also induced robust bone formation and nearly completely healed a critical-sized calvarial defect in CD-1 nude mice 6 weeks following transplantation. Herovici's staining of the regenerated bone demonstrated that the bone matrix contained a large amount of type I collagen. Our findings indicated that the hMDSCs are likely mesenchymal stem cells of muscle origin and that BMP2 is more efficient than BMP4 in promoting the bone regenerative capacity of the hMDSCs in vivo.
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http://dx.doi.org/10.3727/096368912X658854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361002PMC
August 2014

Dystrophin and utrophin "double knockout" dystrophic mice exhibit a spectrum of degenerative musculoskeletal abnormalities.

J Orthop Res 2013 Mar 23;31(3):343-9. Epub 2012 Oct 23.

Stem Cell Research Center, Bridgeside Point II, 450 Technology Dr, Suite 206, Pittsburgh, Pennsylvania 15219, USA.

Duchenne muscular dystrophy (DMD) is a degenerative muscle disorder characterized by the lack of dystrophin expression at the sarcolemma of muscle fibers. In addition, DMD patients acquire osteopenia, fragility fractures, and scoliosis indicating that a deficiency in skeletal homeostasis coexists but little is known about the effects of DMD on bone and other connective tissues within the musculoskeletal system. Recent evidence has emerged implicating adult stem cell dysfunction in DMD myopathogenesis. Given the common mesenchymal origin of muscle and bone, we sought to investigate bone and other musculoskeletal tissues in a DMD mouse model. Here, we report that dystrophin-utrophin double knockout (dko) mice exhibit a spectrum of degenerative changes, outside skeletal muscle, in bone, articular cartilage, and intervertebral discs, in addition to reduced lifespan, muscle degeneration, spinal deformity, and cardiomyopathy previously reported. We also report these mice to have a reduced capacity for bone healing and exhibit spontaneous heterotopic ossification in the hind limb muscles. Therefore, we propose the dko mouse as a model for premature musculoskeletal aging and posit that a similar phenomenon may occur in patients with DMD.
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http://dx.doi.org/10.1002/jor.22236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108902PMC
March 2013

Nanoencapsulating living biological cells using electrostatic layer-by-layer self-assembly: platelets as a model.

J Mater Res 2011 Jan;26(2):347-351

Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.

In the literature, a few biological cells have been used as templates to form microcapsules of a variety of shapes and sizes. In this study, we proved the concept that living cells like platelets can be encapsulated with polyelectrolytes using electrostatic layer-by-layer self-assembly (LBL), and, most importantly, the encapsulation process did not induce activation of the platelets. Glycol-chitosan and poly-L-glutamic acid were electrostatically deposited onto platelets, and the encapsulation was confirmed using confocal laser scanning microscopy and scanning electron microscopy. Transmission electron microscopy observation further confirmed that the encapsulation process was mild and the activation of platelets was negligible. The encapsulation of living biological cells like platelets can serve as a model system in a wide range of biomedical applications including local and sustained drug delivery, immune protection of artificial tissues, and versatile artificial blood.
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http://dx.doi.org/10.1557/jmr.2010.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045201PMC
January 2011

Cefazolin embedded biodegradable polypeptide nanofilms promising for infection prevention: a preliminary study on cell responses.

J Orthop Res 2010 Aug;28(8):992-9

Biomaterials, Bioengineering & Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, West Virginia 26506-9196, USA.

Implant-associated infection is a serious complication in orthopedic surgery, and endowing implant surfaces with antibacterial properties could be one of the most promising approaches for preventing such infection. In this study, we developed cefazolin loaded biodegradable polypeptide multilayer nanofilms on orthopedic implants. We found that the amount of cefazolin released could be tuned. A high local concentration of cefazolin was achieved within the first a few hours and therefore may inhibit bacterial colonization in the critical postimplantation period. The developed cefazolin loaded nanofilms showed their in vitro efficacy against Staphylococcus aureus; the more antibiotics loaded, the longer the nanocoated implant had antibacterial properties. More interestingly, antibiotic-loaded polypeptide multilayer nanofilms also improved osteoblast bioactivity including cell viability and proliferation. These findings suggested that biodegradable polypeptide multilayer nanofilms as antibiotic carriers at the implant/tissue interface are compatible with human cells such as osteoblasts and bactericidal to bacteria such as S. aureus. These characteristics could be promising for preventing implant-associated infection and potentially improving bone healing.
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http://dx.doi.org/10.1002/jor.21115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699871PMC
August 2010

[Changes in bone micro-architecture and bone mineral density following experimental osteonecrosis of femoral head by local injection of ethanol in canines].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2008 Mar;22(3):281-9

Department of Orthopaedics, 6th People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, 200233, P. R. China.

Objective: To measure the changes of bone mineral density and bone micro-architecture of the femoral head that harvested from the three-foot bearing ethanol destroyed canine model for osteonecrosis of femoral head, and discuss the influences of local injection of ethanol and biomechanical loading to the structural properties of the femoral head.

Methods: Twenty-four Beagles were divided randomly into four-foot bearing canines and three-foot bearing canines. One fore-limb was fixed randomly in three-foot bearing canines. Osteonecrosis was induced in all experimental animals by local injection of 5 mL pure ethanol into one side of the femoral head. The hind limbs injected with NS were acted as control group, that of three-foot canines injected with ethanol were acted as three-foot canine group, and that of four-foot canines injected with ethanol were acted as four-foot canine group. The contralateral femoral head was injected into equal amount of NS. Animals were sacrificed at the time intervals of 1, 3, 6, and 12 weeks after the injection of ethanol. Quantitative microcomputed tomography was used to characterize changes in bone micro-architecture and bone mineral density of femoral head.

Results: The clear three-dimensional model of trabecular bone of necrotic femoral head were obtained. There were no significant differences among 3 groups according to the time line by 1 week after ethanol injection(P > 0.05). At 3 weeks after injection of ethanol, in three-foot canine group and four-foot canine group, the volume of BMC, BMD, BVF, and BS/BV increased gradually as the distance to the drilling canal increased. There were significant differences between 3 regions (P < 0.05). At 6 weeks, in three-foot canine group and four-foot canine group, the volume of BMC, BMD,BVF, and Tb.N of region I and II decreased significantly compared with region III (P < 0.05). At 12 weeks, there are no differences among 3 groups (P > 0.05). There were significant decreases in BMD values, BVF, BS/BV, Tb.N, Tb.Sp and Tb.Th after the injection of pure ethanol. And, the changes were more and more obvious by the time line. These changes were differentiable at 3 weeks after injection of ethanol, and became obvious at 6 weeks. These changes were more obvious at the part that near the injection canal. The changes in three-foot canine group were more obvious than that in four-foot canine group.

Conclusion: Resorption of necrotic compact bone trabecular may weaken the structural properties of the femoral head. Moreover, remodeling and repairing process of necrotic bone trabecular may be hampered by constant biomechanical loading that presented in three-foot bearing canines, and thereby further weaken the structural properties of the femoral head. Biomechanical loading may be one of the critical reasons that lead to the collapse of femoral head.
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March 2008

[Kinetic changes of canine's hindlimbs after fixation of one forelimb].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2008 Jan;22(1):66-9

Department of Orthopaedics, 6th People's Hospital, Affiliated to Shanghai Jiaotong University, Shanghai, 200233, P. R. China.

Objective: To establish a three-foot weight-bearing canine model to imitate the biomechanical loading environment of the human's hip joint. To observe and compare the kinetic changes of hind limbs between normal and three-foot weight bearing canines.

Methods: Using 10 beagles, three-foot weight-bearing canine models were made by fixing unilateral wrist joints at 90 epsilon flexionally. The changes of ground reaction forces and the time of standing phases (Ts) of the hind limbs were compared by 3-D gait analysis pre- and postoperatively.

Results: Canines could walk well with three limbs after the fixation of one fore limb. However, the gait pattern changed tremendously. The canine walked jumpily by raising its head and neck, and the bilateral hind limbs kept contacting ground alternately. Ts of ipsilateral hind limb was (0.48+/-0.04)s, and Ts of contralateral hind limb was (0.46+/-0.06)s. Although, the time durations were increased a little, but there were no significant differences when compared with that of normal canines (0.43+/-0.05)s (P > 0.05). The vertical ground reaction force (Fz) of ipsilateral hind limb was (4.63+/-0.85) body weight, and the Fz of contralateral hind limb was (4.78+/-0.49) body weight. There were significant increases when compared with the Fz of normal canines (3.26+/-0.48) body weight (P < 0.05). The peak acceleration force of the ipsilateral hind limb was (0.80+/-0.30) body weight. There was significant increase compared with that of normal canines (0.72+/-0.13) body weight (P < 0.05). The peak acceleration force of the contralateral hind limbs was (0.68+/-0.22) body weight, there was no difference compared with that of normal canines (P > 0.05). The peak deceleration forces of the ipsilateral and contralateral hind limbs were--(0.26+/-0.14) body weight and--(0.13+/-0.05) body weight separately. They decreased significantly when compared with that of normal canines--(0.43+/-0.13) body weight (P < 0.05). In normal canines, the upper limbs were main load bearing limbs, they could bear 62.8%+/-2.4% of body weight. However, the hind limbs could bear only 37.2%+/-1.8% of body weight. On the contrary, in three-foot weight-bearing canines, the hind limbs became the main load bearing limbs, they could bear 59.1%+/-6.7% of body weight.

Conclusion: Three-foot weight-bearing canine model can be used as a candidate animal model to research the effects of biomechanical loading on the progression of hip joint diseases.
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January 2008

[Progress of joint-preserving procedures for treatment of avascular necrosis of femoral head].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2006 Jun;20(6):655-8

Department of Orthopedics, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, 200233, PR China.

Objective: To review the researches on the joint-preserving procedures for the treatment of the avascular necrosis (AVN) of the femoral head.

Methods: The latest original literatures about the joint-preserving procedures for the treatment of AVN of the femoral head were extensively reviewed.

Results: There were many surgical joint-preserving procedures to treat AVN of the femoral head, such as core decompression, bone grafting, and osteotomy. Most researchers achieved excellent clinical results by using the joint-preserving procedures to treat the early stages of AVN of the femoral head.

Conclusion: Treating AVN of the femoral head by the joint-preserving procedures, especially the free vascularized fibula grafting, can achieve an excellent long-term clinical outcome.
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June 2006

[Surgical technique of modified free vascularized fibular grafting for treatment of osteonecrosis of the femoral head].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2005 Sep;19(9):692-6

Department of Orthopedics, Shanghai No. 6 People's Hospital, Shanghai Jiaotong University, Shanghai, 200233, P. R. China

Objective: To evaluate the surgical technique, clinical results, and the complications of modified free vascularized fibular grafting for the treatment of osteonecrosis of the femoral head.

Methods: From October 2000 to August 2004, 124 patients (139 hips) with osteonecrosis of the femoral head were treated with modified free vascularized fibular grafting. There were 83 males(93 hips) and 41 females (46 hips), with a mean age of 36.4 years (16-57). The disease was caused by trauma in 49 cases(54 hips), use of steroids in 29 cases (32 hips), consumption of alcohol in 19 cases (21 hips) and idiopathic condition in 27 cases (32 hips). Of 139 hips, 50 were classified as stage II ; 71 as stage II, 18 as stage IV according to Steinberg system; the Harris hip scores were 79.3, 69.3 and 58.4, respectively. At the operation, modified technique of the fibular osteotomy was adopted. A front-hip operative approach was designed and a modified technique of removing the necrotic bone in femoral head was applied. During operation, the duration of operation, the bleeding volume, and the length of incisions were recorded. The follow-up items included the results of X-ray examination, the Harris score of the hip, and the evaluation of the complications.

Results: The duration of the fibular osteotomy was 10 to 30 min (15 min on average). The duration of the total operation was 80 to 120 min (90 min on average). The length of incision at the hip was 6 to 12 cm (8 cm on average). The bleeding volume was 100 to 300 ml (200 ml on average). The average hospitalization days was 7 days. After operation, Harris hip scores in most cases were improved. According to postoperative X-ray, 62 hips (79.5%) were improved to different extents and 14 hips (17.9%) had no significant changes. Deterioration occurred in 2 hips (2.6%).

Conclusion: The modified free vascularized fibular grafting has lots of virtues, such as less bleeding volume, more clear anatomic structure, more convenience for operation, less damage, less complications, and better results of function recovery. It is an effective method for treating osteonecrosis of the femoral head.
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September 2005
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