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      Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg 2+/curcumin from injectable self-healing hydrogels

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          Abstract

          Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing.

          Methods: In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg 2+ and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated in vitro and in vivo. Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests.

          Results: The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg 2+ promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing.

          Conclusions: The composite hydrogel mediated sustained in situ release of curcumin and Mg 2+ to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.

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          Bioavailability of curcumin: problems and promises.

          Preetha Anand, Ajaikumar Kunnumakkara, Robert A. Newman … (2007)
          Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.
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            Antibacterial adhesive injectable hydrogels with rapid self-healing, extensibility and compressibility as wound dressing for joints skin wound healing

            Tianlong Zhang, Jin Qu, Xin Zhao … (2018)
            Designing wound dressing materials with outstanding therapeutic effects, self-healing, adhesiveness and suitable mechanical property has great practical significance in healthcare, especially for joints skin wound healing. Here, we designed a kind of self-healing injectable micelle/hydrogel composites with multi-functions as wound dressing for joint skin damage. By combining the dynamic Schiff base and copolymer micelle cross-linking in one system, a series of hydrogels were prepared by mixing quaternized chitosan (QCS) and benzaldehyde-terminated Pluronic®F127 (PF127-CHO) under physiological conditions. The inherent antibacterial property, pH-dependent biodegradation and release behavior were investigated to confirm multi-functions of wound dressing. The hydrogel dressings showed suitable stretchable and compressive property, comparable modulus with human skin, good adhesiveness and fast self-healing ability to bear deformation. The hydrogels exhibited efficient hemostatic performance and biocompatibility. Moreover, the curcumin loaded hydrogel showed good antioxidant ability and pH responsive release profiles. In vivo experiments indicated that curcumin loaded hydrogels significantly accelerated wound healing rate with higher granulation tissue thickness and collagen disposition and upregulated vascular endothelial growth factor (VEGF) in a full-thickness skin defect model. Taken together, the antibacterial adhesive hydrogels with self-healing and good mechanical property offer significant promise as dressing materials for joints skin wound healing.
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              Prevalence and risk factors of a rotator cuff tear in the general population.

              Atsushi Yamamoto, Kenji Takagishi, Toshihisa Osawa … (2010)
              Little information is available about the epidemiology of rotator cuff tears in a population-based study. The purpose of this study was to elucidate the true prevalence of rotator cuff tears regardless of the presence or absence of symptoms in the general population and to assess the relationship between tears and their backgrounds. A medical check-up was conducted for residents of a mountain village in Japan. The subjects consisted of 683 people (total of 1,366 shoulders), including 229 males and 454 females with a mean age of 57.9 years (range, 22-87). We examined their background factors, physical examinations and ultrasonographic examinations on both shoulders. Rotator cuff tears were present in 20.7% and the prevalence increased with age. Thirty-six percent of the subjects with current symptoms had rotator cuff tears, while 16.9% of the subjects without symptoms also had rotator cuff tears. Rotator cuff tears in the general population were most commonly associated with elderly patients, males, affected the dominant arm, engaged in heavy labor, having a history of trauma, positive for impingement sign, showed lesser active forward elevation and weaker muscle strength in abduction and external rotation. A logistic regression analysis revealed the risk factors for a rotator cuff tear to be a history of trauma, dominant arm and age. 20.7% of 1,366 shoulders had full-thickness rotator cuff tears in the general population. The risk factors for rotator cuff tear included a history of trauma, dominant arm and age. Level 3.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Theranostics
                Journal ID (iso-abbrev): Theranostics
                Journal ID (publisher-id): thno
                Title: Theranostics
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1838-7640
                Publication date Collection: 2021
                Publication date (Electronic): 3 April 2021
                Volume: 11
                Issue: 12
                Pages: 5911-5925
                Affiliations
                [1 ]Department of Orthopaedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
                [2 ]Frontier Institute of Science and Technology, and State Key Laboratory for Mechanical Behavior of Materials, and Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710049, China.
                [3 ]Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. School of Medicine, Northwest University, 229 Taibai North Road, Xi'an 710069, China.
                Author notes
                ✉ Corresponding authors: E-mail: baoling@ 123456mail.xjtu.edu.cn (B. Guo), zhanhai.yin@ 123456mail.xjtu.edu.cn (Z. Yin).

                *These authors contributed equally to this work.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                Publisher ID: thnov11p5911
                DOI: 10.7150/thno.56266
                PMC ID: 8058719
                PubMed ID: 33897889
                SO-VID: 34e4a059-d3dc-40dc-ad18-7c13dc6aadfa
                Copyright © © The author(s)
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                Date received : 22 November 2020
                Date accepted : 18 March 2021
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Molecular medicine
                Keywords: anti-inflammation,pro-chondrogenesis,hydrogels,tendon-to-bone healing,rotator cuff,synergistic effects
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: anti-inflammation, pro-chondrogenesis, hydrogels, tendon-to-bone healing, rotator cuff, synergistic effects

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