Objective To introduce the related issues in the clinical translational application of adipose-derived stem cells (ASCs). Methods The latest papers were extensively reviewed, concerning the issues of ASCs production, management, transportation, use, and safety during clinical application. Results ASCs, as a new member of adult stem cells family, bring to wide application prospect in the field of regenerative medicine. Over 40 clinical trials using ASCs conducted in 15 countries have been registered on the website (http://www.clinicaltrials.gov) of the National Institutes of Health (NIH), suggesting that ASCs represents a promising approach to future cell-based therapies. In the clinical translational application, the related issues included the quality control standard that management and production should follow, the prevention measures of pathogenic microorganism pollution, the requirements of enzymes and related reagent in separation process, possible effect of donor site, age, and sex in sampling, low temperature storage, product transportation, and safety. Conclusion ASCs have the advantage of clinical translational application, much attention should be paid to these issues in clinical application to accelerate the clinical translation process.
Objective To review the regulating effects of estrogen on endothel ial cell functions, the involved endothel ial progenitor cells (EPCs), and the related VEGF, and explore the mechanism of estrogen participating in new vesselformation on wound basement and wound heal ing. Methods Recent l iterature about biological effects of estrogen oncapillary vessel formation was reviewed. Results The formation of new vessel in the wound’s granulation tissue contained vasculogenesis and vascularization, and the new vessels could transport the oxygen and nutrient for the metabol ism of the local heal ing tissue. The estrogen effected vascular endothel ial cells through its receptors. Peripheral vascular EPCs differentiated into endothel ial cells and participated into the formation of new vessels. Estradiol exerted influences on the dynamics of vascular EPCs and the neovascularization. VEGF was a key mediator in the processes of estradiol regulating angiogenesis. Conclusion Understanding the molecular mechanisms that regulate vessel formation in wound heal ing, especially how estrogen modulates its receptor and angiogenic factor, may provide new approaches for managing wound heal ing.
Objective To study the relationship between the adipose tissues and cutaneous morphogenesis on wound healing. Methods Adipose tissues’ participation in regulation of food intake, energy expenditure, fuel metabolism, and a variety of other physiological processes was reviewed in the latest literature. The wound healing was regulated by endocrine, paracrine, and adipocytederived molecules. Results Several factors secreted by adipose tissues (leptin, cytokines, growth factors, lipids, metallothioneins, ect) regulated wound healing. Conclusion Adipose tissues may play a vital role in the process of wound healing. Further understanding of the complex interaction between adipose cells and cutaneous morphogenesis is essential to explore the mechanism of wound healing.
Objective To review the current condition of growth factors and their application to clinical treatment of acute and chronic wounds. Methods Data from the literature and Medline were analyzed according to their different uses in acute and chronic wounds. Their potential side-effects were studied. Results All data showed that wound healing time in acute and chronic wounds was accelerated and wound healing quality was improved after treatment with growth factors. No sideeffect was observed. Conclusion The efficacy and safety of growth factors in improving wound healing were confirmed. However, some reconsideration aboutpotential problems of growth factors must be made to apply them clinically in the future.
ObjectiveTo investigate the technique of optimizing the location of femoral attachment in medial patellofemoral ligament (MPFL) reconstruction assisted with arthroscopy and evaluate the effectiveness.MethodsBetween January 2014 and September 2018, 35 patients with patellar dislocation were admitted. There were 14 males and 21 females with an average age of 22.6 years (range, 16-38 years). All patients had a history of knee sprain. The disease duration ranged from 1 to 7 days (mean, 2.8 days). Patellar dislocation occurred 2-4 times (mean, 2.5 times). The preoperative Lysholm score and Kujala score were 47.60±11.24 and 48.37±9.79, respectively. The patellar congruence angle was (31.40±6.81)°, the patellar tilt angle was (29.95±5.44)°, the lateral patellofemoral angle was (−11.46±5.18)°, and the tibial tubercle-trochlear groove distance was (16.66±1.28) mm. All patients were treated by MPFL reconstruction with the semitendinosus tendon under arthroscopy. During operation, the suture anchors were inserted into the midpoint and the 1/3 point of superomedial edge of the patella. Then, the femoral tunnels were created in medial femoral condyle through limited excision. For tendon fixation, the Kirschner wires were inserted into adductor tubercle, medial epicondyle of femur, and the midpoint between the two points, as well as the anteriorly and posteriorly. Afterwards, the changes of ligament length and tension, patellar tracking, and the relationship of patella and femoral trochlea were evaluated, thereby determining the optimized femoral attachment for MPFL reconstruction. Finally, the patellar congruence angle, patellar tilt angle, and lateral patellofemoral angle were measured by imaging to assess the relationship of patella and femoral trochlea. Moreover, Lysholm score and Kujala score were used to evaluate the knee joint function.ResultsAll incisions healed by first intention without infection. All patients were followed up 12-18 months (mean, 15.4 months). At 12 months, the Lysholm score was 94.40±3.99 and the Kujala score was 92.28±4.13, which were significant higher than those before operation (P<0.05). No patellar dislocation occurred during follow-up. At 12 months, the patellar congruence angle was (6.57±4.59)°, the patellar tilt angle was (9.73±2.82)°, the lateral patellofemoral angle was (7.14±4.63)°, which were superior to those before operation (P<0.05).ConclusionDuring the MPFL reconstruction under arthroscopy, a higher positioning accuracy for the femoral attachment and satisfactory effectiveness can be obtained by evaluating MPFL length and tension, patellofemoral joint kinematics, and patellar tracking.
Objective In vivo, the microenvironment of epidermal stem cells (ESCs) is complex, and estrogen might be involved in the micro environment. To investigate the biological effects of estrogen on the prol iferation and migration of ESCs in vitro. Methods hESCs were isolated from normal human foreskin and cultured. The second generation of hESCs were identified with flow cytometry after being marked with integrin β1, cytokeratin 19 (CK19), CK14, and CK10 antigens.hESCs of 2 × 106 cell density were cultured with ESCs special medium supplemented with 0.1 nmol/L Diethylstilbestrol in group A (estrogen group), with ESCs special medium supplemented with 10 nmol/L Raloxifene hydrochloride in group B (ER blocking agent group), and with ESCs special medium in group C (control group), respectively. The 100 μm “scratch” wounds were created by scraping confluent hESCs plated on Petri dishes with a sterile pipette tip in vitro. The migrating cells from the wound edge were quantified at 24, 48, and 72 hours after incubation. The rates of wound heal ing were calculated by SigmaScan Pro 5.0 software at 72 hours. The prol iferating effect of estrogen on hESCs was determined with MTT method at 24, 48, 72, 96, and 120 hours. Results Cultured primary hESCs could adhere to the wall showing ovoid in shape and grew into colonies. Flow cytometry showed the positive results for integrin β1, CK19, and CK14 (with positive rate of 96.63%, 95.47%, and 94.27%, respectively) and the negative result for CK10 (with positive rate of 1.32%). In group A, the number of cells crossing the wound edge was more than those of group B and group C at 24, 48, and 72 hours. The rates of wound heal ing were 69.00% ± 0.05% in group A, 35.00% ± 0.05% in group B, and 48.00% ± 0.06% in group C at 72 hours, showing significant differences among groups (P lt; 0.05). The prol iferating speed of hESCs was significantly higher in group A than in groups B and C (P lt; 0.01), and significantly higher in group C than in group B (P lt; 0.01) at 24, 48, 72, 96, and 120 hours. Conclusion The estrogen can promote the prol iferation and migration of hESCs in vitro. It may be involved in many biological activity of skin.
Objective To investigate the possible signaling mechanisms by which recombinant human plateletderived growth factor (rhPDGF) accelerated healingof cutaneous wound in diabetic rats. Methods Four full-thickness skin woundswere incised in the back of 26 male Wistar diabetic rats. The wounded rats were divided into 3 groups (7 or 8 rats each group). One group without treatmentwas used as a control, and the other 2 groups were treated with rhPDGF at a dose of 7.0 μg/cm2 wound or vehicle (DMSO/09% NaCl, vol/vol 1∶1) from 1 to14 days. The wound healing was evaluated by the measurements of the wound volume and area. Immunofluorescent and immunohistochemical staining were used to examine the phosphorylation of extracellular signalregulated kinase 1/2 (ERK1/2) andthe expression of proliferative cell nuclear antigen (PCNA), respectively. Results Granulation tissue appeared in the bed of wound after injury. The number of blood capillary buds and fibroblasts was greater in the rhPDGF-treated group than that in the other 2 groups. A lot of inflammatory cells infiltration and collagen deposition were observed in the wound. The wound-volume in the rhPDGF-treated group was smaller than that in control group (Plt;0.05). The reepithelialization rate in rhPDGF-treated group was higher than that inthe other 2 groups at 7 days after injury (Plt;0.05). The expression of PCNA in reparative cells was higher in rhPDGF-treated group than in control group or vehicle-treated group at 3,7 days after injury(Plt;0.05). The phosphorylation of ERK1/2 was ber in rhPDGF-treated group than that in control group or vehicle group at 7 and 14 days after injury(Plt;0.05). Conclusion These results suggest that rhPDGF accelerates wound healing and improves healing quality by increasingthe phosphorylation of ERK1/2.
ObjectiveTo assess the effect of microfracture and biomimetic hydrogel scaffold on tendon-to-bone healing in a rabbit rotator cuff tear model.MethodsGelatin and methacrylic anhydride were used to synthesize gelatin methacryloyl (GelMA). Then the GelMA were treated with ultraviolet rays and vacuum freeze-drying method to obtain a biomimetic hydrogel scaffold. The morphology of the scaffold was observed by gross observation and scanning electron microscope. Degradation of the scaffold was determined at different time points. Twenty-four adult New Zealand rabbits, weighting 2.8-3.5 kg and male or female, were surgically created the bilateral acute rotator cuff tear models. One shoulder was treated with microfractures on the footprint and transosseous suture (control group, n=24). The other shoulder was treated with the same way, except for putting the scaffold on the footprint before transosseous suture (experimental group, n=24). The general conditions of rabbits were observed postoperatively. Tendon-to-bone healing was evaluated by gross observation, Micro-CT, HE staining, and bio-mechanical testing at 4 and 8 weeks after operation.ResultsThe scaffold was white and has a porous structure with pore size of 31.7-89.9 μm, which degraded slowly in PBS solution. The degradation rate was about 95% at 18 days. All the rabbits survived to the completion of the experiment. Micro-CT showed that there was no obvious defect and re-tear at the tendon-to-bone interface in both groups. No difference was found in bone mineral density (BMD), tissue mineral density (TMD), and bone volume/total volume (BV/TV) between the two groups at 4 and 8 weeks postoperatively (P>0.05). HE staining showed that the fibrous scar tissue was the main component at the tendon-to-bone interface in the control group at 4 and 8 weeks postoperatively; the disorderly arranged mineralized cartilage and fibrocartilage formation were observed at the tendon-to-bone interface in the experimental group at 4 weeks, and the orderly arranged cartilage formation was observed at 8 weeks. Besides, the tendon maturation scores of the experimental group were significantly higher than those of the control group at 4 and 8 weeks (P<0.05). There was no significant difference in the ultimate load to failure and stiffness between the two groups at 4 weeks (P>0.05); the ultimate load to failure at 8 weeks was significantly higher in the experiment group than in the control group (t=4.162, P=0.009), and no significant difference was found in stiffness between the two groups at 8 weeks (t=2.286, P=0.071).ConclusionCompared with microfracture alone, microfracture combined with biomimetic hydrogel scaffold can enhance tendon-to-bone healing and improve the ultimate load to failure in rabbits.
Objective To identify the effect of β-endorphin in the development of paresthesia in hypertrophic scar by detecting the expression and content of β-endorphin in human normal skin and hypertrophic scar. Methods Hypertrophic scar samples were collected from 42 patients with hypertrophic scar for 1-20 years (mean, 4.5 years), including 15 males and27 females with an average age of 32.6 years (range, 16-50 years). According to the kind of paresthesia, they were divided into 3 gourps: non-pain-pruritus group (n=20), pruritus group (n=14), and pain-pruritus group (n=8). Normal skin samples (normal skin group) were harvested from 5 patients undergoing skin grafting surgery, including 3 males and 2 females with an average age of 24.6 years (range, 15-37 years). The immunofluorescence method was used to observe the expression of β-endorphin and ELISA method to detect the concentrations of β-endorphin in the tissues. Results The β-endorphin expressed in all samples, and it expressed around peri pheral nerve fibers in the dermis, fibroblasts, and monocytoid cells princi pally; and it expressed significantly ber in pruritus group and pain-pruritus group than in non-pain-pruritus group and normal skin group. The β-endorphin content was (617.401 ± 97.518) pg/mL in non-pain-pruritus group, (739.543 ± 94.149) pg/mL in pruritus group, (623.294 ± 149.613) pg/mL in pain-pruritus group, and (319.734 ± 85.301) pg/mL in normal skin group; it was significantly higher in non-pain-pruritus group, pruritus group, and pain-pruritus group than in normal skin group (P lt; 0.05); it was significantly higher in pruritus group than in non-pain-pruritus group and pain-pruritus group (P lt; 0.05); and there was no significant difference between non-pain-pruritus group and pain-pruritus group (P gt; 0.05). Conclusion The expression of β-endorphin is high in hypertrophic scar, it may paly an important role in process of pruritus in these patients.
Objective To explore the secondary surgical reconstruction for orbital bone deformities accompanied with canthus dislocation after trauma. Methods From June 1998 to July 2007, 37 patients with secondary orbital bone fracture deformity accompanied with medial or lateral canthal l igament dislocation posttraumatically were treated, among whom there were 22 males and 15 females, aged 13-46 years old (21 on average). There were 29 cases of traffic accident, 6 of boxinginjury and 2 of beating injury by sticks. The latest reconstruction was performed on these 37 cases during 3 months to 8 years after injuries. There were 11 cases of orbital maxillary zygoma (OMZ) fracture, 15 of naso-orbito-ethmoid (NOE) fracture, 8 of OMZ and NOE fracture and 3 of frontal fracture. There were 31 patients who were reconstructed for the first time and 6 for the second time. Typical bicoronal and subcill iary incisions and intro-oral approach were employed to expose all the fractured sites. According to the fractured position and the degree of deformity and dislocation, the orbito-zygomatic fracture was repositioned after osteotomy and rigid fixation, or the heaved fragments were trimmed with a burr and the depressed fragments were filled with autogenous bone such as il ium, cranial outer table or Medpor in order to reconstruct orbital wall framework; the orbital walls were repaired to correct the enophthalmos with autogeneous bone or Medpor after the herniated orbital contents were released. The medial canthal l igament was anchored superior-posteriorly to the lacrimal fossa with transnasal wires fixation or fixed with titanium mini plates and nails. Results The 36 patients’ incisions obtained heal ing by first intention after the operation, and 1 case failed because of wound infection from maxillary sinusitis. There were 24 patients who were cured successfully with facial appearance and function improved significantly. During the follow-up for 3-6 months, no compl ication was found such as dislocation of the implant, rejection and infection. Two patients still showed sl ight enophthalmos while 3 patients with canthus dislocation regained improved appearances but not satisfactory. At 6 months after operation, the CT scan conducted in 3 patients with autogenous bone and Medpor grafting showed all fractures were fixed rigidly. Conclusion Surgical reduction combined with bone grafting is a satisfactory method for the correction of secondary orbital bone deformity, and the repair of canthus dislocation and correction of enophthalmos should be considered at the same time. An ideal result could be achieved only through all-round consideration and comprehensive treatment.