Progenitor-like cells contributing to cellular heterogeneity in the nucleus pulposus are lost in intervertebral disc degeneration.

The nucleus pulposus (NP) in the intervertebral disc (IVD) arises from embryonic notochord. Loss of notochordal-like cells in humans correlates with onset of IVD degeneration, suggesting that they are critical for healthy NP homeostasis and function. Comparative transcriptomic analyses identified expression of progenitor-associated genes (GREM1, KRT18, and TAGLN) in the young mouse and non-degenerated human NP, with TAGLN expression reducing with aging. Lineage tracing using Tagln-CreERt2 mice identified peripherally located proliferative NP (PeriNP) cells in developing and postnatal NP that provide a continuous supply of cells to the entire NP. PeriNP cells were diminished in aged mice and absent in puncture-induced degenerated discs. Single-cell transcriptomes of postnatal Tagln-CreERt2 IVD cells indicate enrichment for TGF-ß signaling in Tagln descendant NP sub-populations. Notochord-specific removal of TGF-ß/BMP mediator Smad4 results in loss of Tagln+ cells and abnormal NP morphologies. We propose Tagln+ PeriNP cells are potential progenitors crucial for NP homeostasis.

Elasticity and cross-sectional thickness of paraspinal muscles in progressive adolescent idiopathic scoliosis.

Objectives: (1) Compare the cross-sectional thickness (CST) and shear wave speed (SWS) of paraspinal muscles (PSM) in adolescent idiopathic scoliosis (AIS) with and without curve progression; (2) investigate the relationship between CST/SWS and radiographic characteristics in AIS with curve progression; (3) compare the CST/SWS between AIS and non-scoliosis controls. Methods: This cross-sectional study analyzed the CST and SWS of PSM in 48 AIS with mild to moderate curvature and 24 non-scoliosis participants. Participants with scoliosis greater than 45° of Cobb angles were excluded. The Change of Cobb angles within the last 6-months was retrieved to allocate AIS into progression and non-progression groups. The SWS and CST of multifidus; longissimus and iliocostalis of the major curve were measured using B-mode ultrasound image with an elastography mode. Discrepancies of the SWS (SWS-ratio: SWS on the convex side divided by SWS on the concave side) and CST (CST-ratio: CST on the convex side divided by CST on the concave side) at the upper/lower end and apical vertebrae were studied. Results: A higher SWS at the apical vertebrae on the concave side of the major curve (multifidus: 3.9 ± 1.0 m/s vs. 3.1 ± 0.6 m/s; p < 0.01, longissimus: 3.3 ± 1.0 m/s vs. 3.0 ± 0.9 m/s; p < 0.01, iliocostalis: 2.8 ± 1.0 m/s vs. 2.5 ± 0.8 m/s; p < 0.01) was observed in AIS with curve progression. A lower SWS-ratio at apical vertebrae was detected with a greater vertebral rotation in participants with curve progression (multifidus [grade II]: 0.7 ± 0.1 vs. grade I: 0.9 ± 0.2; p = 0.03, longissimus [grade II]: 0.8 ± 0.2 vs. grade I: 1.1 ± 0.2; p < 0.01). CST was not different among the progressive, non-progressive AIS and non-scoliosis controls. Conclusions: Increased SWS of PSM without change of CST was observed on the concave side of the major curve in participants with progressive AIS.

Assessment of reliability and validity of a handheld surface spine scanner for measuring trunk rotation in adolescent idiopathic scoliosis.

PURPOSE: To assess the reliability and validity of a handheld scanner (SpineScan3D) for trunk rotation measurement in adolescent idiopathic scoliosis (AIS) subjects, as compared with Scoliometer. METHODS: This was a cross-sectional study with AIS subjects recruited. Biplanar spine radiographs were performed using an EOS imaging system with coronal Cobb angle (CCA) determined. The angle of trunk rotation (ATR) was measured using Scoliometer. SpineScan3D was employed to assess the axial rotation of subjects' back at forward bending, recorded as surface tilt angle (STA). Intra- and inter-examiner repeats were conducted to evaluate the reliability of SpineScan3D. RESULTS: 97 AIS patients were recruited. Intra- and inter-examiner reliability of STA measures were good to excellent in major thoracic and lumbar curves (p < 0.001). A strong correlation was found between STA and ATR measures in both curve types (p < 0.001) with a standard error of the ATR estimate of between 1 and 2 degrees from linear regression models (R squared: 0.8-0.9, p < 0.001). A similar correlation with CCA was found for STA and ATR measures (r: 0.5-0.6, p < 0.002), which also demonstrated a similar sensitivity (72%-74%) and specificity (62%-77%) for diagnosing moderate to severe curves. CONCLUSION: SpineScan3D is a handheld surface scanner with a potential of wide applications in subjects with AIS. The current study indicated that SpineScan3D is reliable and valid for measuring trunk rotation in AIS subjects, comparable to Scoliometer. Further studies are planned to investigate its measurements in coronal and sagittal planes and the potential of this device as a screening and monitoring tool. TRIAL REGISTRATION NUMBER (DATE OF REGISTRATION): HKUCTR-2288 (06 Dec 2017). LEVEL OF EVIDENCE: Level III.

Fibro-Gel: An All-Aqueous Hydrogel Consisting of Microfibers with Tunable Release Profile and its Application in Wound Healing.

Injectable hydrogels are valuable tools in tissue engineering and regenerative medicine due to their unique advantages of injectability with minimal invasiveness and usability for irregularly shaped sites. However, it remains challenging to achieve scalable manufacturing together with matching physicochemical properties and on-demand drug release for a high level of control over biophysical and biomedical cues to direct endogenous cells. Here, the use of an injectable fibro-gel is demonstrated, a water-filled network of entangled hydrogel microfibers, whose physicochemical properties and drug release profiles can be tailored to overcome these shortcomings. This fibro-gel exhibits favorable in vitro biocompatibility and the capability to aid vascularization. The potential use of the fibro-gel for advancing tissue regeneration is explored with a mice excision skin model. Preliminary in vivo tests indicate that the fibro-gel promotes wound healing and new healthy tissue regeneration at a faster rate than a commercial gel. Moreover, it is demonstrated that the release of distinct drugs at different rates can further accelerate wound healing with higher efficiency, by using a two-layer fibro-gel model. The combination of injectability and tailorable properties of this fibro-gel offers a promising approach in biomedical fields such as therapeutic delivery, medical dressings, and 3D tissue scaffolds for tissue engineering.

Quality of Surgery and Patient Selection Are Keys to Success in Hip Stabilization Surgery in Cerebral Palsy.

BACKGROUND: Cerebral palsy patients are at risk of hip instability, to which various soft tissue and bony surgeries are performed should conservative management fail. We aim to identify factors associated with treatment failure to guide surgical management. METHODS: Cerebral palsy patients treated at 2 university-affiliated tertiary pediatric orthopaedic referral centers with hip stabilization surgery performed for subluxation in 1998 to 2015 with minimum of 5 years follow-up were reviewed. Failure was defined as reoperation to the same hip because of recurrent subluxation. Age, sex, Gross Motor Function Classification System level, tone abnormality, operation type, Reimer's migration index (RMI), and acetabular index (AI) were assessed. Cut-off values were identified through Youden index on receiver operating characteristic curve. RESULTS: Eighty-nine hips from 55 patients with mean follow-up of 12.4 years were analyzed. Revision surgery was performed in 14 hips. Postoperative hip subluxation (P<0.001) and acetabular dysplasia (P=0.001) were predictive of failure, with postoperative RMI conferring an adjusted hazard ratio of 1.13 (95% confidence interval: 1.08-1.19, P<0.001) on multivariable survival analysis. Achieving a postoperative RMI of <27.5% predicts success with 92.9% sensitivity and 72% specificity with area under curve of 0.916 (P<0.001), while postoperative AI of <23.1 degrees predicts success with 92.3% sensitivity and 62.2% specificity with area under curve of 0.796 (P=0.001). In subgroup analysis of soft-tissue-only procedures, RMI >44% preoperative and >32% postoperative were associated with reoperation. In femur-only osteotomies, preoperative RMI >48% and postoperative RMI >28% were associated with failure. In pelvic and combined osteotomies, postoperative RMI >32% and AI >30 degrees were associated with failure. Other factors analyzed were not associated with reoperation. CONCLUSIONS: Patient selection and quality of surgery in terms of residual postoperative hip subluxation and acetabular dysplasia are associated with need for remedial surgery. Soft-tissue-only procedures should aim to correct RMI to <32%. Bony surgery should be considered when preoperative RMI >44%, and pelvic osteotomies if RMI >48%. Pelvic osteotomies should target postoperative RMI <32% and AI <30 degrees. LEVEL OF EVIDENCE: Level II-prognostic study.

Does curve pattern impact on the effects of physiotherapeutic scoliosis specific exercises on Cobb angles of participants with adolescent idiopathic scoliosis: A prospective clinical trial with two years follow-up.

BACKGROUND: Current clinical evidence suggests that a well-planned physiotherapeutic scoliosis specific exercise (PSSE) program is effective for scoliosis regression. OBJECTIVES: We investigated the effect of curve patterns on Cobb angles with PSSE. METHODS: This was a non-randomized prospective clinical trial that recruited participants with adolescent idiopathic scoliosis between January and June 2017. Participants were grouped by curve pattern into major thoracic and major lumbar groups. An outpatient-based PSSE program was conducted with the following schedule of intensive exercise: ≥ 1 session of supervised PSSE per month and > 30min of home exercise 5 days/week in the first 6 months, after which exercise frequency was reduced to 1 session of supervised PSSE every three months and > 30min of home exercise 5 days/week until 2 years after study initiation. Radiographic Cobb angle progressions were identified at the 1, 1.5 and 2-year follow-ups. A mixed model analysis of variance (ANOVA) was performed to examine the differences in Cobb angles between groups at four testing time points. The two-tailed significance level was set to 0.05. RESULTS: In total, 40 participants were recruited, including 22 with major thoracic curves (5 males and 17 females; mean age 13.5±1.8 years; Cobb angle 18-45 degrees) and 18 with major lumbar curves (7 males and 11 females; mean age 12.7±1.7 years; Cobb angle 15-48 degrees). Curve regressions, namely the reduction of Cobb angles between 7 to 10 degrees were noted in 9.1% of participants in the major thoracic group; reductions of 6 to 13 degrees were noted in 33.3% of participants in the major lumbar group at the 2-year follow-up. Repeated measurements revealed a significant time effect (F2.2,79.8 = 4.1, p = 0.02), but no group (F2.2,79.8 = 2.3, p = 0.1) or time × group (F1,37 = 0.97, p = 0.3) effects in reducing Cobb angles after 2 years of PSSE. A logistic regression analysis revealed that no correlation was observed between curve pattern and curve regression or stabilization (OR: 0.2, 95% CI: 0.31-1.1, p = 0.068) at the 2-year follow-up. CONCLUSION: This was the first study to investigate the long-term effects of PSSE in reducing Cobb angles on the basis of major curve location. No significant differences in correction were observed between major thoracic and major lumbar curves. A regression effect and no curve deterioration were noted in both groups at the 2-year follow-up. TRIAL REGISTRATION: ChiCTR1900028073.

Development of novel implants with self-antibacterial performance through in-situ growth of 1D ZnO nanowire.

To prevent the attachment of bacteria to implant surfaces, the 1D zinc oxide nanowire-coating has been successfully developed on material surfaces by using a custom-made hydrothermal approach. The chemical nature, surface topography and wettability of spike-like 1D ZnO nanowire-coating are comprehensively investigated. The anti-adhesive and antimicrobial properties of 1D nanowire-coating are tested against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli by using in vitro live/dead staining and scanning electron microscopy. We find that the adhesion of bacteria can be reduced via the special spike-like topography and that the release of Zn(2+) ions can help suppress the growth of attached bacteria. Furthermore, the antimicrobial effect is also evaluated under in vivo conditions by using a rat model infected with bioluminescent S. aureus. The amount of live bacteria in the rat implanted with a nanowire-coated sample is less than that of the control at various time points. Hence, it is believed that the nanowire-coated material is promising for application in orthopaedic implantation after the long-term animal studies have been completed.

Interfacial Fast Release Layer in Monodisperse Poly (lactic-co-glycolic acid) Microspheres Accelerates the Drug Release.

Understanding microstructural evolutions of drug delivery devices during drug release process is essential for revealing the drug release mechanisms and controlling the drug release profiles. In this study, monodisperse poly (lactic-co-glycolic acid) microspheres in different diameters were fabricated by microfluidics in order to find out the relationships between the microstructural evolutions and the drug release profiles. It was found that poly (lactic-co-glycolic acid) microspheres underwent significant size expansion which took place from the periphery to the center, resulting in the formation of interfacial fast release layers. At the same time, inner pores were created and the diffusion rate was increased so that the early stage drug release was accelerated. Due to the different expansion rates, small poly (lactic-co-glycolic acid) microspheres tendered to follow homogeneous drug release while large poly (lactic-co-glycolic acid) microspheres tendered to follow heterogeneous drug release. This study suggests that the size expansion and the occurrence of interfacial fast release layer were important mechanisms for early stage drug release of poly (lactic-co-glycolic acid) microspheres.

Silver nanoparticles alter proteoglycan expression in the promotion of tendon repair.

This study demonstrates a novel method of using silver nanoparticles for Achilles tendon injury healing. In vitro results indicated a stimulatory effect on cell proliferation and collagen synthesis with silver nanoparticles. Biomechanical test on the 42-day post operation Achilles tendon sample exhibited a significant improvement in tensile modulus when compared to the untreated group. Histology suggested that silver nanoparticles promoted cell alignment and proteoglycan synthesis. The collagen deposition was also improved. An alleviation of tumor necrosis factor α, and an increase in fibromodulin and proliferating cell nuclear antigen expression were seen in silver nanoparticles group by immunohistochemistry. This study further corroborates the finding of our previous study that silver nanoparticles help to restore the functionality of injured connective tissues. We believe that the anti-inflammatory nature of silver nanoparticles has an important role in accelerating the healing process and reducing scarring, leading to better functional outcome. From the clinical editor: Tendon healing after surgeries remains a slow and tedious process, typically requiring several weeks of recovery time and gradual introduction of physical therapy. There are no currently utilized methods that could promote tendon healing. In this study, silver nanoparticles are reported to facilitate Achilles tendon repair in a model system, through increased proteoglycan and collagen synthesis, paving the way to potential clinical applications in the future.

Screening for developmental dysplasia of the hip in Hong Kong.

PURPOSE: To review records of children referred to our hospital for developmental dysplasia of the hip (DDH) and evaluate the effectiveness of hip screening in Hong Kong. METHODS: Records of children suspected of DDH and referred to our hospital between 1 January 2005 and 31 March 2010 were reviewed. The diagnosis was based on static and dynamic ultrasonography of the hips and/or radiographic features of hip subluxation, dislocation, and pelvic dysplasia. The age of the children at presentation was recorded. Late diagnoses were those presenting after the age of 6 months. Late presentations were those presenting after the walking age. RESULTS: Of 213 referred children, 33 were diagnosed to have DDH. Their mean age at presentation was 90.8 (range, 9-559) days. The female-to-male ratio was 2.9:1, and the mean follow-up duration was 25.1 (range, 4.2-50.3) months. 30 of the DDH infants were diagnosed before the age of 6 months, one at 8 months, and 2 were late presenters. Hence, the failure rate of the hip screening was 0.09 per 1000 live births. The remaining 180 were confirmed to be normal and followed up until the walking age. The point prevalence of DDH on Hong Kong Island was 0.87/1000 live births. CONCLUSION: In light of the low point prevalence of DDH in Hong Kong born children, the protocol of universal clinical assessment and selective ultrasonographic screening of suspected cases is justified.

Modulation of collagen alignment by silver nanoparticles results in better mechanical properties in wound healing.

Our previous study has revealed that silver nanoparticles (AgNPs) have potential to promote wound healing by accelerated re-epithelization and enhanced differentiation of fibroblasts. However, the effect of AgNPs on the functionality of repaired skin is unknown. The aim of this study was to explore the tensile properties of healed skin after treatment with AgNPs. Immunohistochemical staining, quantitative assay and scanning electron microscopy (SEM) were used to detect and compare collagen deposition, and the morphology and distribution of collagen fibers. Our results showed that AgNPs improved tensile properties and led to better fibril alignments in repaired skin, with a close resemblance to normal skin. Based on our findings, we concluded that AgNPs were predominantly responsible for regulating deposition of collagen and their use resulted in excellent alignment in the wound healing process. The exact signaling pathway by which AgNPs affect collagen regeneration is yet to be investigated. FROM THE CLINICAL EDITOR: The aim of this study was to explore the tensile properties of healed skin after treatment with AgNPs. These nanoparticles improved tensile properties and led to better fibril alignments in repaired skin, with a close resemblance to normal skin. The exact signaling pathway by which AgNPs affect collagen regeneration is yet to be investigated.