Ting-Wu Qin

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (15)33.98 Total impact

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    ABSTRACT: We hereby report on a case in which a huge chest wall defect generated by resection of a massive aggressive tumor (desmoplastic fibroma) was repaired with osteogenic-induced mesenchymal stem cells embedded in a bone-derived biomaterial. In this case, there were three challenges to overcome: reconstruction of the soft tissue, repair of the skeletal defect of the thoracic wall and repair of the defect in the pleural cavity. The defects of soft tissue and pleural cavity were reconstructed, respectively, with an ipsilateral abdominal flap and a diaphragm muscular flap. The huge defect in the chest wall was successfully repaired with the tissue-engineered ribs, which was confirmed by long-term follow-up with computerized tomography and histological and immunohistochemical evaluations. In view of its effectiveness and safety, tissue-engineered bones may have a broad application for the repair of large skeletal defects and bone regeneration.
    Regenerative medicine. 07/2014; 9(4):431-436.
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    ABSTRACT: Although varieties of surgical repair techniques and materials have been used to repair rotator cuff defects, re-tearing frequently occurs. The purpose of this study is to evaluate the postoperative outcomes of rotator cuff repairs with a decellularized tendon slices (DTSs) graft in a rabbit model. Large defects in the infraspinatus tendons were created bilaterally in 21 rabbits. The graft group underwent reconstruction of the defects with the DTSs grafts, while the defect group did not undergo any treatment. The specimens underwent histological observation, biomechanical testing, and magnetic resonance imaging (MRI) detection at 4, 8, and 12 weeks after surgery. In addition, 2 rabbits that were not operated on were used for MRI detection as a normal reference. Histological analysis revealed that the graft promoted host cell ingrowth and tissue integration, and a tendon-like structure developed at 12 weeks. The ultimate tensile load had a significant difference between specimens at 4 and 12 weeks in the graft group, but there was no significant difference between the graft group and the defect group. In the graft group, the stiffness at 12 weeks was significantly greater than that at 4 or 8 weeks, and it was also greater than the stiffness in the defect group at 12 weeks. MRI demonstrated that the signal strength of the regenerative tissue from the graft group at 12 weeks was similar to that of normal infraspinatus tendon. The DTSs graft allowed for incorporation of host tendon and improved the biomechanical performance of the regenerative tendon. Therefore, the graft could be a promising bioscaffold to enhance the surgical repair of large rotator cuff defects and consequently improve the clinical outcome of rotator cuff tears.
    Knee Surgery Sports Traumatology Arthroscopy 03/2014; · 2.68 Impact Factor
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    ABSTRACT: The purpose of this study was to characterize the mechanical behavior of tendon slices with different thicknesses. Tendon slices of 100, 200, 300, 400, and 500 μm thickness were mechanically tested. The 300 μm slices were further tested for strength and modulus after 21,000-cycle fatigue testing under different applied strain levels (0, 1, 3, 5, 8, 10, and 12%). The tendon slice structure, morphology, and viability of bone marrow stromal cells (BMSCs) seeded onto the slices were also examined with histology, scanning electron microscopy, and vital cell labeling, respectively. Tendon slices 300 μm or more in thickness had similar ultimate tensile strength and Young's modulus to the intact tendon bundle. A strain of 5% or less did not cause any structural damage, nor did it change the mechanical properties of a 300 μm-thick tendon slice after 21,000-cycle fatigue testing. BMSCs were viable between and on the tendon slices after 2 weeks in tissue culture. This study demonstrated that, if tendon slices are used as a scaffold for tendon tissue engineering, slices 300 μm or more in thickness would be preferable from a mechanical strength point of view. If mechanical stimulation is performed for seeded-cell preparations, 5% strain or less would be appropriate.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 04/2012; 100(3):752-8. · 2.31 Impact Factor
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    ABSTRACT: To develop a naturally derived tendon tissue engineering scaffold with the preservation of the native ultrastructure, tensile strength, and biochemical composition of the tendon extracellular matrix (ECM), decellularized tendon slices (DTSs) were prepared using repetitive freeze/thaw of the intact Achilles tendons, frozen section, and nuclease treatment. The DTSs were characterized in the native ultrastructure, mechanical properties, biochemical composition, and cytocompatibility. Histological examination and DNA quantification analysis confirmed that cells were completely removed from tendon tissue by repetitive freeze/thaw in combination with nuclease treatment 12 h. The intrinsic ultrastructure of tendon tissue was well preserved based on scanning electron microscopy examination. The tensile strength of the DTSs was retained 85.62% of native tendon slice. More than 93% of proteoglycans (fibromodulin, biglycan) and growth factors (TGF-β1, IGF-1, VEGF, and CTGF) inherent in tendon ECM were preserved in the DTSs according to ELISA analysis. Furthermore, the DTSs facilitated attachment and repopulation of NIH-3T3 fibroblasts in vitro. Overall, the DTSs are sheet scaffolds with a combination of elemental mechanical strength and tendon ECM bioactive factors that may have many potential applications in tendon tissue engineering.
    Journal of Biomedical Materials Research Part A 02/2012; 100(6):1448-56. · 2.83 Impact Factor
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    ABSTRACT: Porcine small intestinal submucosa (SIS) has been widely used in repairing various tissues and organs. Despite this, some SIS products have the capacity to cause variable inflammatory responses after implantation resulting in severe adverse effects due to porcine cell existence. In this study, we described a multi-step method including mechanical disassociation, degrease, enzyme digestion, detergent treatment, freeze-drying and sterilization by irradiation for preparation of SIS. The efficacy of acellularization was evaluated by histological observation and the content of porcine immunoreceptor DAP12 gene. The change of growth factors contents within SIS accompanying with decellularization was quantitatively assessed by ELISA. Inflammatory reaction of SIS implanted subcutaneously in a rat was investigated. The histological examination revealed no remaining cells after enzyme digestion. Moreover, qPCR analysis demonstrated that the content of a porcine immunoreceptor gene DAP12 DNA in final SIS product (SISv) was only 1.05% of that in SIS samples (SISi) prepared by mechanical disassociation. Degrease with methanol/chloroform dramatically reduced the contents of VEGF, b-FGF, TGF-β, and TNF-α within SISii, but further treatment could not significantly reduced the contents of growth factors. SIS implanted into rats showed that inflammatory cells was more accumulated surrounded to SISi at 1, and 2 weeks, but reduced in SISv samples. The degree of inflammatory reaction for SISv was significantly less than that of SISi.
    Biomaterials 10/2010; 32(3):706-13. · 8.31 Impact Factor
  • Xiang-tao Mo, Zhi-ming Yang, Ting-wu W Qin
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    ABSTRACT: To enhance osteointegration with preservation of mechanical strength, a surface modification technique using 20% surface demineralization in a controlled manner was applied to custom-built cylindrical bio-derived compact bones (20% surface-demineralized cylindrical compact bio-derived bone scaffold: SDCBS); an undemineralized version was the control. The micro-surface topography of the two types of bone scaffolds was characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). 20% demineralization led to significant increases in surface roughness (38.19%, P=0.001) and surface area (15.1%, P=0.030), compared with the control group's, while the decrease in mechanical properties was not statistically significant. Results of orthotopic implantation for 9 months demonstrated that 20% surface demineralization caused significantly rapid and homogeneous bone remodeling at the interface compared to control and led to a significantly rapid osteointegration of SDCBS with the host bone at the early and intermediate stages of osteointegration. The study indicates the potential of SDCBS in repairing clinical bone defects, and would help direct the use of various processes of biomaterials to support defect repairs within osseous sites.
    Bone 05/2009; 45(2):301-8. · 4.46 Impact Factor
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    ABSTRACT: The effects of micropatterned surfaces coated with type I collagen (CNI) on the proliferation and morphology of rat tail tenocytes were investigated in this study. The micropatterned polydimethylsiloxane substrates were prepared by using the technique of microcontact printing and then coated with different concentrations of CNI by the microfluidic channels technology. After being seeded on the CNI-coated micropatterned substrates, the tenocytes were tested by MTT colorimetric assay at 1-, 3-, 5-, and 7-day time intervals to evaluate the proliferation of tenocytes on the substrates. The alignment and morphology of tenocytes on the CNI-coated substrates after incubation for 1 or 24 h were observed with SEM. The results showed tenocytes proliferated well with increase of CNI concentrations and identically aligned along the grooves of the CNI-coated micropatterned substrates. This could have a potential advantage in construction of engineered tendons in vitro.
    Applied Surface Science 11/2008; 255(2):368–370. · 2.54 Impact Factor
  • Xiang-Tao Mo, Zhi-Ming Yang, Ting-Wu Qin
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    ABSTRACT: To further improve surface characteristics of bio-derived compact bone scaffolds (BDCBS), 20% surface demineralization in a controlled manner was applied to the scaffolds. The surface configuration properties and roughness of the partially demineralized BDCBS and non-demineralized BDCBS (n = 12 in each group) were investigated with SEM and atomic force microscopy (AFM) in this study. The result demonstrated that the surface configuration of partially demineralized BDCBS exhibited specific porous micro-structure when compared to the compact structure of non-demineralized BDCBS. Furthermore, the result showed that the surface roughness of the partially demineralized BDCBS was significantly higher than that of BDCBS (P < 0.01). These results revealed that the partial demineralization could improve the surface configuration characteristics of BDCBS.
    Applied Surface Science 01/2008; · 2.54 Impact Factor
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    ABSTRACT: We report a direct measurement of the adhesion strength of human embryonic tenocytes (HETCs) and transformed human embryonic tenocytes (THETCs) to fibronectin (FN)- and type I collagen (CNI)- modified poly(DL-lactide-co-glycolide) (PLGA) substrates with a micropipette aspiration technique. PLGA substrates were first coated with poly-D-lysine (PDL), and then with various concentrations (1 microg/ml, 2 microg/ml, 5 microg/ml, and 10 microg/ml) of FN and CNI in serum-free F12 media. Anti-FN and Anti-CNI antibodies were used to inhibit attachment of tenocytes to FN- and CNI- modified substrates in a dilution range of 1:5000-1:500 and 1:1500-1:250, respectively. The substrates were employed for incubation of HETCs and THETCs for 30 min at 37 degrees C before the adhesion strength measurements. We found that the adhesion strengths showed a strong dependence on the seeding time and FN or CNI concentrations. Anti-FN and Anti-CNI antibodies significantly compromised adhesion of HETCs and THETCs to the corresponding modified substrates (P < 0.05). These findings show that FN- or CNI-modified polymer substrates offer significant advantages for tissue engineering tendon scaffolds concerning tenocyte adhesion. In addition, HETCs and THETCs bear similar biological behaviors in terms of adhesion, indicating the possibility of using THETCs in place of HETCs in tissue engineering construction of human tendons.
    Biomaterials 12/2005; 26(33):6635-42. · 8.31 Impact Factor
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    ABSTRACT: To investigate possibility of cartilage cultured in centrifuge tube as graft materials. Articular chondrocytes isolated from a 3-week-old rabbit formed cartilage after cultivation for 2 weeks. Articular cartilage of humeral head, growth plate of proximal tibia and meniscus were collected from a 6-week-old rabbit. The ultrastructure of chondrocytes and extracellular matrix in the three kinds of cartilages and cultured cartilage were observed by transmission electronic microscopy. Cartilage cultured in centrifuge tube possessed unique ultrastructure and was similar to articular cartilage and growth plate, but it was markedly different from meniscus. The four kinds of cartilages were characteristic of respectively different chondrocytes and extracellular matrix. Cultured cartilage showed typical apoptosis of chondrocytes and "dark chondrocytes" appeared in growth plate. Condrocyte apoptosis was not seen in articular cartilage and meniscus. Cartilage cultured in centrifuge tube has unique ultrastructure and may be used as graft materials for articular cartilage and growth plate.
    Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery 06/2003; 17(3):247-50.
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    ABSTRACT: To study the effect of mechanical stretch on the morphologic change of rat muscle satellite cell in the three-dimensional culture. Based on the apparatus for three-dimensional cell cultures under a cyclic mechanical strain, a specific stretch pattern (10% elongation, 10 stretches/min for 10 min of each hour 48 h total) was applied to cell-scaffolding composites. Under the stretch pattern, the shape of satellite cells changed to oblate and spread to the direction of the stretch. Furthermore, the myotube was observed. On the contrary, the satellite cells spread to the all direction, and the formation of the myotube was not been found in the control group. Cyclic mechanical stretch is helpful for the formation of the ideal directivity and these results are compatible with a significant role for the stretch in tissue-engineered muscle construction.
    Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA 03/2003; 23(2):141-3.
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    ABSTRACT: To study the ectopic osteogenesis of tissue engineered bone with recombinant human bone morphogenetic protein/transforming growth factor-beta (rhBMP/TGF-beta) or WO-1 slow-released factors. Partial demineralized freeze-dried bone (PDFDB) of pig was used as scaffold material. rhBMP/TGF-beta or WO-1 were pre-coated on the surface of material by means of vacuum negative pressure absorption, and then coated with polylactic acid (PLA) to make slow-released material. There were six group: PDFDB material (group A); PDFDB combined with osteoblasts (group B); PDFDB material with rhBMP/TGF-beta slow-released system (group C); PDFDB material combined with rhBMP/TGF-beta slow-released system osteoblasts (group D); PDFDB with WO-1 slow-released system (group E); PDFDB material combined with WO-1 slow-released system and osteoblasts (group F) were implanted in bilateral lower limbs of 36 Newzealand rabbits respectively (6 rabbits in each groups). Histological, histochemical and biochemical analysis were detected 2, 4, 6, 8 weeks after operation. Within the observation periods, no osteogenesis was observed in group A. The osteogenesis in group B, D, F were superior to that of group C and E (P < 0.05). The osteogenetic activity in group C and E was delayed. The quantity and quality of osteogenesis in group D and F were 2 weeks ahead of time compared with group B, and 4 weeks to that of group C and E. The newborn calcification content was superior to that of group A, C, and E (P < 0.05). The osteogenesis of PDFDB materials with BMP/TGF-beta or WO-1 is slower than that of which combined with osteoblasts. Simple material PDFDB has no ectopic osteogenesis.
    Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 02/2003; 25(1):2-6.
  • Zhi-ming Yang, Fu-guo Huang, Ting-wu Qin
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    ABSTRACT: To sum up the clinical results of bio-derived bone transplantation in orthopedics with tissue engineering technique. From January 2000 to May 2002, 52 cases with various types of bone defect were treated with tissue engineered bone, which was constructed in vitro by allogeneous osteoblasts from periosteum (1 x 10(6)/ml) with bio-derived bone scaffold following 3 to 7 days co-culture. Among them, there were 7 cases of bone cyst, 22 cases of non-union or malunion of old fracture, 15 cases of fresh comminuted fracture of bone defect, 4 cases of spinal fracture and posterior route spinal fusion, 3 cases of bone implant of alveolar bone, 1 case of fusion of tarsotarsal joint. The total weight of tissue engineered bone was 349 g in all the cases, averaged 6.7 g in each case. All the cases were followed up after operation, averaged in 18.5 months. The wound in all the case healed by first intention, but 1 case with second intention. Bone union was completed within 3 to 4.5 months in 50 cases, but 2 cases of delayed union. Six cases were performed analysis of CD3, CD4, CD8, ICAM-1 and VCAM-1 before and after operation, and no obvious abnormities were observed. Bio-derived tissue engineered bone has good osteogenesis. No obvious rejection and other complications are observed in the clinical application.
    Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery 10/2002; 16(5):311-4.
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    ABSTRACT: To investigate the feasibility of life span extension of transformed human embryonic tendon cells (THETC) by reconstitution of the telomerase activity. THETC were transfected by pGRN145 plasmid containing the human telomerase reverse transcriptase (hTERT) cNDA in vitro by molecular cloning technique. The biological characteristics of transfected cells were detected and compared by morphological observation, plate cloning efficiency, soft agar culture, growth curve of cells cultured in different conditions, immunohistochemistry, telomerase activity assay by telomeric repeat amplification protocol (TRAP). The THETC transfected by pGRN145 plasmid (telT) could express the telomerase activity with extension of life span. The telT maintained the original characteristics of temperature-dependant and serum-dependant, as well as secretion of type I collagen normally and without tendency of malignant transformation. The life span of THETC can be prolonged by reconstitution of telomerase activity, which provides the novel experimental methods to establish the standard cells line.
    Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 07/2002; 24(3):276-80.
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    ABSTRACT: INTRODUCTION The bio-scaffold and mechanical stimulation have been stressed in development of functional engineered tendons (Butler et al, 2008). We have developed a method for preparing an acellular tendon scaffold using chemical reagents to minimize host immune response. This study is designed to understand whether such bio-scaffold would provide an optimal micro-architecture to promote efficient tenocyte seeding, infiltration, and function under cyclic stretch. We investigated the effects of cyclic stretch on behavior of tenocytes seeded in the acellular tendon scaffold. We hypothesized that with cyclic mechanical stimulation, the tenocytes seeded in the acellular tendon scaffold would be accelerated in cell growth, infiltration, and function compared to those without cyclic stretch. METHODS AND PROCEDURES The flexor digitorum profundus (FDP) tendons were obtained from fresh cadavers. The acellular FDP tendon scaffold was prepared according to the following procedures. Briefly, dynamic treatment in a thermostatic water bath (37°C), defatting/decellularizing, and partly deproteining with chemical reagents were performed using a custom designed instrument. The scaffold was then freeze-dried and sterilized with ethylene oxide. Tenocytes were obtained from explant culture of rat tail tendons and cultivated in fresh F12 medium containing 10% FCS, 6mg/L penicillin, 0.1g/L streptomycin. Before seeded on the scaffolds at a density of 1×10 6 cell/scaffold, the 2-4 passages of tenocytes were digested from the culture flask with 0.25% trypsin (Gibico Co.). After 24h static culture, tenocyte-scaffold composites experienced a cyclic stretch culture (0.2Hz, 10% elongation, 15min/h) for 48h with a custom designed culture device. Then the composites were taken out for morphological observation, histological examination, and collagen assay. Sections were cut and stained with H&E. Collagen synthesis was quantified by measuring the hydroxyproline that was present in the composites using high performance liquid chromatography. Student's T-test was used for the statistical analysis. P<0.05 was considered significant.

Publication Stats

46 Citations
33.98 Total Impact Points

Institutions

  • 2012
    • Mayo Clinic - Rochester
      • Division of Orthopaedic Surgery
      Rochester, Minnesota, United States
  • 2002–2012
    • Sichuan University
      • • Laboratory of Stem Cell and Tissue Engineering
      • • State Key Laboratory of Biotherapy
      Hua-yang, Sichuan, China