ABSTRACT
Postoperative tissue adhesion and poor tendon healing are major clinical problems associated with tendon surgery. To avoid postoperative adhesion and promote tendon healing, we developed and synthesized a membrane to wrap the surgical site after tendon suturing. The bilayer-structured porous membrane comprised an outer layer [1,4-butanediol diglycidyl ether cross-linked with carboxymethyl cellulose (CX)] and an inner layer [1,4-butanediol diglycidyl ether cross-linked with Bletilla striata polysaccharides and carboxymethyl cellulose (CXB)]. The morphology, chemical functional groups, and membrane structure were determined. In vitro experiments revealed that the CX/CXB membrane demonstrated good biosafety and biodegradability, promoted tenocyte proliferation and migration, and exhibited low cell attachment and anti-inflammatory effects. Furthermore, in in vivo animal study, the CX/CXB membrane effectively reduced postoperative tendon-peripheral tissue adhesion and improved tendon repair, downregulating inflammatory cytokines in the tendon tissue at the surgical site, which ultimately increased tendon strength by 54% after 4 weeks.
ABSTRACT
Herpes simplex virus type 1 (HSV-1), a neurotropic DNA virus, establishes latency in neural tissues, with reactivation causing severe consequences like encephalitis. Emerging evidence links HSV-1 infection to chronic neuroinflammation and neurodegenerative diseases. Microglia, the central nervous system's (CNS) immune sentinels, express diverse receptors, including α7 nicotinic acetylcholine receptors (α7 nAChRs), critical for immune regulation. Recent studies suggest α7 nAChR activation protects against viral infections. Here, we show that α7 nAChR agonists, choline and PNU-282987, significantly inhibit HSV-1 replication in microglial BV2 cells. Notably, this inhibition is independent of the traditional ionotropic nAChR signaling pathway. mRNA profiling revealed that choline stimulates the expression of antiviral factors, IL-1ß and Nos2, and down-regulates the apoptosis genes and type A Lamins in BV2 cells. These findings suggest a novel mechanism by which microglial α7 nAChRs restrict viral infections by regulating innate immune responses.
Subject(s)
Choline , Herpesvirus 1, Human , Microglia , Virus Replication , alpha7 Nicotinic Acetylcholine Receptor , alpha7 Nicotinic Acetylcholine Receptor/metabolism , alpha7 Nicotinic Acetylcholine Receptor/genetics , Microglia/virology , Microglia/drug effects , Microglia/metabolism , Herpesvirus 1, Human/physiology , Herpesvirus 1, Human/drug effects , Animals , Cell Line , Mice , Virus Replication/drug effects , Choline/pharmacology , Choline/metabolism , Bridged Bicyclo Compounds/pharmacology , Benzamides/pharmacology , Immunity, Innate , Herpes Simplex/virology , Herpes Simplex/metabolism , Interleukin-1beta/metabolism , Signal Transduction/drug effects , Apoptosis/drug effects , Antiviral Agents/pharmacology , Nicotinic Agonists/pharmacology , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type II/geneticsABSTRACT
BACKGROUND: Speech restoration is important for communication and social activities after pharyngolaryngectomy in head and neck cancer or corrosive injury. Several techniques of voice restoration have been developed to improve life quality. The aim of this paper was to focus on the microsurgical transfer of ileocolon flap and outcome of further voice rehabilitation. PATIENTS AND METHODS: From 2010 to 2022, 69 patients had ileocolon flap at our hospital with postoperative speech training and regular follow-up for over 1 year. The patients received deglutition training first, followed by voice rehabilitation. Voice outcomes were evaluated at an interval of 3 months and finally at 12 months of voice training rehabilitation. Among other examinations, the speech function was evaluated using a 4-point Likert scale and senior surgeon (H-c.C.) scoring system. RESULTS: The results showed that speech function reached 13.1% of excellent voice, 65.1% of good voice, 13.1% of fair result, and 8.7% of poor result by Likert scales. Meanwhile, the senior surgeon (H-c.C.) score showed 17.4% of excellent, 63.8% of moderate, and 18.8% of poor results. About voice laboratory results, maximal phonation time was 11.0 seconds, and the average number counted in one breath was 15. Loudness and frequency showed 56.0 dB and 105.0 Hz, respectively. CONCLUSION: The study showed that after voice reconstruction with ileocolon flap followed by the voice rehabilitation program, the patients would have a better understanding of the altered anatomical structures and practice in a more efficient way. Adequate recommendation by the therapists to plastic surgeons for revision surgeries optimized voice function of the patients.
ABSTRACT
Current synthetic grafts for ligament rupture repair often fail to integrate well with the surrounding biological tissue, leading to complications such as graft wear, fatigue, and subsequent re-rupture. To address this medical challenge, this study aims at advancing the development of a biological ligament through the integration of physiologically-inspired principles and tissue engineering strategies. In this study, interfacial polyelectrolyte complexation (IPC) spinning technique, along with a custom-designed collection system, to fabricate a hierarchical scaffold mimicking native ligament structure, is utilized. To emulate the bone-ligament interface and alleviate stress concentration, a hydroxyapatite (HAp) mineral gradient is strategically introduced near both ends of the scaffold to enhance interface integration and diminish the risk of avulsion rupture. Biomimetic viscoelasticity is successfully displayed to provide similar mechanical support to native ligamentous tissue under physiological conditions. By introducing the connective tissue growth factor (CTGF) and conducting mesenchymal stem cells transplantation, the regenerative potential of the synthetic ligament is significantly amplified. This pioneering study offers a multifaceted solution combining biomimetic materials, regenerative therapies, and advanced techniques to potentially transform ligament rupture treatment.
Subject(s)
Biomimetic Materials , Ligaments , Polyelectrolytes , Regeneration , Tissue Scaffolds , Ligaments/chemistry , Ligaments/physiology , Tissue Scaffolds/chemistry , Polyelectrolytes/chemistry , Biomimetic Materials/chemistry , Animals , Durapatite/chemistry , Tissue Engineering/methods , Mesenchymal Stem Cells/cytology , HumansABSTRACT
BACKGROUND: High ulnar nerve injuries result in intrinsic muscle weakness and are inconvenient for patients. Moreover, conventional surgical techniques often fail to achieve satisfactory motor recovery. A potential reconstructive solution in the form of the supercharge end-to-side (SETS) anterior interosseous nerve (AIN) transfer method has emerged. Therefore, this study aims to compare surgical outcomes of patients with transected and in-continuity high ulnar nerve lesions following SETS AIN transfer. METHODS: Between June 2015 and May 2023, patients with high ulnar palsy in the form of transection injuries or lesion-in-continuity were recruited. The assessment encompassed several objective results, including grip strength, key pinch strength, compound muscle action potential, sensory nerve action potential, and two-point discrimination tests. The muscle power of finger abduction and adduction was also recorded. Additionally, subjective questionnaires were utilized to collect data on patient-reported outcomes. Overall, the patients were followed up for up to 2 years. RESULTS: Patients with transected high ulnar nerve lesions exhibited worse baseline performance than those with lesion-in-continuity, including motor and sensory functions. However, they experienced greater motor improvement but less sensory recovery, resulting in comparable final motor outcomes in both groups. In contrast, the transection group showed worse sensory outcomes. CONCLUSIONS: Our findings suggest that SETS AIN transfer benefits patients with high ulnar nerve palsy, regardless of the lesion type. Nonetheless, improvements may be more pronounced in patients with transected lesions.
Subject(s)
Nerve Transfer , Recovery of Function , Ulnar Nerve , Humans , Male , Nerve Transfer/methods , Female , Adult , Ulnar Nerve/injuries , Ulnar Nerve/surgery , Middle Aged , Treatment Outcome , Young Adult , Hand Strength/physiology , Ulnar Neuropathies/surgery , Ulnar Neuropathies/etiology , Follow-Up Studies , AdolescentABSTRACT
The prognosis for postinjury peripheral nerve regeneration remains suboptimal. Although transplantation of exogenous Schwann cells (SCs) has been considered a promising treatment to promote nerve repair, this strategy has been hampered in practice by the limited availability of SC sources and an insufficient postengraftment cell retention rate. In this study, to address these challenges, SCs were aggregated into spheroids before being delivered to an injured rat sciatic nerve. We found that the three-dimensional aggregation of SCs induced their acquisition of a repair phenotype, as indicated by enhanced levels of c-Jun expression/activation and decreased expression of myelin sheath protein. Furthermore, our in vitro results demonstrated the superior potential of the SC spheroid-derived secretome in promoting neurite outgrowth of dorsal root ganglion neurons, enhancing the proliferation and migration of endogenous SCs, and recruiting macrophages. Moreover, transplantation of SC spheroids into rats after sciatic nerve transection effectively increased the postinjury nerve structure restoration and motor functional recovery rates, demonstrating the therapeutic potential of SC spheroids. In summary, transplantation of preassembled SC spheroids may hold great potential for enhancing the cell delivery efficiency and the resultant therapeutic outcome, thereby improving SC-based transplantation approaches for promoting peripheral nerve regeneration.
ABSTRACT
Lower limb trauma often results in mangled extremities, and in some cases, complete amputation may be necessary. However, limiting the extent of amputation and preserving the major knee joint are crucial to enhance mobility and overall functionality. By providing painless soft tissue coverage on the stump, early prosthesis use and the initiation of physiotherapy become more feasible. Soft tissue transfers hold the potential to benefit patients in two essential aspects: first, resolving soft tissue deficiencies without causing bone shortening, and second, preparing the stump to enhance overall functionality. A retrospective study conducted at Chang Gung Memorial Hospital (2009-2016) focused on lower limb amputation patients who underwent soft tissue transfers at different time periods compared to those without stump reconstruction. Out of the 2391 cases of lower limb injuries treated operatively, 117 amputations were performed in 110 patients (44 above the knee and 73 below the knee). Among them, 12 patients received soft tissue transfers for limb salvage and soft tissue deficiency after amputations. It was observed that patients in this group were typically younger, predominantly female, had longer hospital stays, and underwent a greater number of surgical procedures (p < 0.05). Through the use of soft tissue transfers, successfully preserved tibial bone length and functional knee joint in selected patients was achieved. This approach effectively resolved soft tissue deficiencies following lower limb amputations, optimizing physiotherapy and facilitating functional rehabilitation.
ABSTRACT
BACKGROUND: Sleep assessment in the intensive care unit (ICU) is difficult and often unreliable. The most commonly used questionnaire for assessing ICU sleep, the Richards-Campbell Sleep Scale (RCSQ), has not been tested for reliability and construct validity in the Mandarin-Taiwanese speaking population. OBJECTIVE: The objective of this study was to test the construct validity and criterion validity of the traditional Chinese version of RCSQ (TC-RCSQ) in critically ill patients without physical restraint. METHODS: We adopted a cross-sectional study design. Adults aged 20 years and above were recruited from a plastic surgery ICU of a medical center. The Cronbach's alpha was used to test internal consistency; the validity testing included content validity, criterion validity, and construct validity. Criterion validity was analysed by testing the association of TC-RCSQ with the Chinese version of Verran and Snyder-Halpern Sleep Questionnaire and sleep parameter of actigraphy using the Pearson correlation coefficient; construct validity was analysed using exploratory factor analysis. RESULTS: A total of 100 patients were included with a mean age of 49.78 years. Internal consistency reliability suggested Cronbach's alpha of 0.93. Moderate to strong correlations of TC-RCSQ with Verran-Snyder-Halpern Sleep Questionnaire were identified (r = 0.36 to 0.80, P < 0.05). We found significant correlations of actigraphic sleep efficiency with difficulty of falling sleep, awakening times, sleep quality, and total score of the TC-RCSQ (r = 0.23, 0.23, 0.20, and 0.23, P < 0.05). One factor (named as overall sleep quality) was extracted by exploratory factor analysis with a total variance explained of 78.40 %, which had good construction validity. CONCLUSIONS: The TC-RCSQ yields satisfactory reliability and validity in critically ill patients. Actigraphic sleep efficiency may be a single index for objectively sleep assessment of sleep quality in patients without physical restraint. Both the TC-RCSQ and actigraphy can aid nurses to evaluate the sleep quality in critically ill patients without physical restraint.
Subject(s)
Intensive Care Units , Psychometrics , Humans , Male , Middle Aged , Female , Surveys and Questionnaires/standards , Cross-Sectional Studies , Reproducibility of Results , Taiwan , Critical Illness , Adult , Restraint, Physical , AgedABSTRACT
BACKGROUND: Tendons have limited regenerative potential, so healing of ruptured tendon tissue requires a prolonged period, and the prognosis is suboptimal. Although stem cell transplantation-based approaches show promise for accelerating tendon repair, the resultant therapeutic efficacy remains unsatisfactory. HYPOTHESIS: The transplantation of stem cells preassembled as 3-dimensional spheroids achieves a superior therapeutic outcome compared with the transplantation of single-cell suspensions. STUDY DESIGN: Controlled laboratory study. METHODS: Adipose-derived stem cells (ADSCs) were assembled as spheroids using a methylcellulose hydrogel system. The secretome of ADSC suspensions or spheroids was collected and utilized to treat tenocytes and macrophages to evaluate their therapeutic potential and investigate the mechanisms underlying their effects. RNA sequencing was performed to investigate the global difference in gene expression between ADSC suspensions and spheroids in an in vitro inflammatory microenvironment. For the in vivo experiment, rabbits that underwent Achilles tendon transection, followed by stump suturing, were randomly assigned to 1 of 3 groups: intratendinous injection of saline, rabbit ADSCs as conventional single-cell suspensions, or preassembled ADSC spheroids. The tendons were harvested for biomechanical testing and histological analysis at 4 weeks postoperatively. RESULTS: Our in vitro results demonstrated that the secretome of ADSCs assembled as spheroids exhibited enhanced modulatory activity in (1) tenocyte proliferation (P = .015) and migration (P = .001) by activating extracellular signal-regulated kinase (ERK) signaling and (2) the suppression of the secretion of interleukin-6 (P = .005) and interleukin-1α (P = .042) by M1 macrophages via the COX-2/PGE2/EP4 signaling axis. Gene expression profiling of cells exposed to an inflammatory milieu revealed significantly enriched terms that were associated with the immune response, cytokines, and tissue remodeling in preassembled ADSC spheroids. Ex vivo fluorescence imaging revealed that the engraftment efficiency of ADSCs in the form of spheroids was higher than that of ADSCs in single-cell suspensions (P = .003). Furthermore, the transplantation of ADSC spheroids showed superior therapeutic effects in promoting the healing of sutured stumps, as evidenced by improvements in the tensile strength (P = .019) and fiber alignment (P < .001) of the repaired tendons. CONCLUSION: The assembly of ADSCs as spheroids significantly advanced their potential to harness tenocytes and macrophages. As a proof of concept, this study clearly demonstrates the effectiveness of using ADSC spheroids to promote tendon regeneration. CLINICAL RELEVANCE: The present study lays a foundation for future clinical applications of stem cell spheroid-based therapy for the management of tendon injuries.