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The repair of irregular bone tissue suffers severe clinical problems due to the scarcity of an appropriate therapeutic carrier that can match dynamic and complex bone damage. Fortunately, stimuli-responsive in situ hydrogel systems that are triggered by a special microenvironment could be an ideal method of regenerating bone tissue because of the injectability, in situ gelatin, and spatiotemporally tunable drug release. Herein, we introduce the two main stimulus-response approaches, exogenous and endogenous, to forming in situ hydrogels in bone tissue engineering. First, we summarize specific and distinct responses to an extensive range of external stimuli (e.g., ultraviolet, near-infrared, ultrasound, etc.) to form in situ hydrogels created from biocompatible materials modified by various functional groups or hybrid functional nanoparticles. Furthermore, "smart" hydrogels, which respond to endogenous physiological or environmental stimuli (e.g., temperature, pH, enzyme, etc.), can achieve in situ gelation by one injection in vivo without additional intervention. Moreover, the mild chemistry response-mediated in situ hydrogel systems also offer fascinating prospects in bone tissue engineering, such as a Diels-Alder, Michael addition, thiol-Michael addition, and Schiff reactions, etc. The recent developments and challenges of various smart in situ hydrogels and their application to drug administration and bone tissue engineering are discussed in this review. It is anticipated that advanced strategies and innovative ideas of in situ hydrogels will be exploited in the clinical field and increase the quality of life for patients with bone damage.
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Objective To evaluate the effect of minocycline hydrochloride (MH)-loaded in-situ hydrogels on periodontitis of rats. Methods Ligation, high sugar diet, local vaccination of Porphyromonas gingivalis and intramusclar injection of acetic predniso-lone were combined to establish the periodontitis of rats. Whether periodontitis was established successfully or not was determined according to clinical examination and pathology after 4 weeks. 28 periodontitis rats were divided into the model group, the positive controll (MH ointment), the blank in-situ hydrogels (ISG) and MH-loaded ISG groups. The detection index included gingival index, bleeding index, bleeding on probing, and probing depth before treatment and 4 weeks after treatment, respectively. Results The inflame-matory and destruction degrees of periodontal tissues in the positive and MH ISG groups were better than those of the model and the blank groups. Conclusion The curative effect of MH-loaded ISG on periodontitis is obvious. It is expected to become a novel formulation to treat periodontitis in future.
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Objective To investigate the therapeutic effect of curcumin in situ hydrogels for treatment of vaginal candidiasis. Methods In situ hydrogels were prepared using poloxamer 407 and 188 as the gel matrix.Gelation temperature,gelation time and rheological characteristics were determined.Mice models with vaginal candidiasis were established.The animals were divided into six groups:the healthy mice group,the model group,the positive control group(ketoconazole cream),curcumin-loaded in situ hydrogels of 0.025,0.10 and 0.20 g/ml.Before treatment and after the fourth and eighth treatments,the vaginal smears were collected and Gram-stained.The vagina washings fluid of mice were collected to determine DNA of Lactobacillus.On 8thday,the mice were sacrificed and the vaginal tissues were excised for pathological detection.Results The gelation temperature and time of in situ hydrogels were 29℃and 2′30″,respectively.Rheological profiles demonstrated that it showed good retention effect in vivo.Compared with the model group, curcumin hydrogels of 0.025,0.10 and 0.20 g/ml could inhibit the growth of Candida albicans,inhibit vaginal mucosal edema,inflam?matory hyperplasia,and decrease the expression of inflammatory factors including TNF-α(P<0.01)and IL-1β(P<0.01).Howev?er,curcumin hydrogels could not influence the growth of lactobacillus in the vagina.It indicated that curcumin hydrogels did not de?pend on lactobacillus to treat fungal vaginitis.Conclusion Curcumin in situ hydrogels could inhibit candidiasis growth,decrease ede?ma of vaginal mucosa and inflammatory hyperplasia,and reduce the expression of inflammatory factors.It provides a novel choice for the treatment of clinical vaginal candidiasis.
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Objective To prepare thermosensitive in situ hydrogels (ISG) of gabexate mesilate and establish quality control method.Methods ISGs were prepared using PF127 and PF68 as matrix, evaluated by gelling temperature , gelling time, gelling ca-pacity in vitro, and determinated by HPLC.Results The gelling time of ISG was (1.8 ±0.2)min, with gelling temperature at 31℃. When the gel temperature rose to 31℃, the viscosity of ISG increased dramatically .The linear range of HPLC determination curve was 10-350 μg/ml, with an average recovery of 99.63%( RSD=0.88%) .Conclusion Preparation of the gel with controllable quality is simple and easy .The determination method is reliable for gabexate mesilate thermosensitive in situ hydrogels .
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Objective To prepare thermosensitive in sitt hydrogels (ISG) of gabexate mesilate and establish quality control method. Methods ISGs were prepared using PF127 and PF68 as matrix, evaluated by gelling temperature, gelling time, gelling capacity in vitro, and determinated by HPLC. Results The gelling time of ISG was (1. 8 ±0. 2) min, with gelling temperature at 317. When the gel temperature rose to 31 7, the viscosity of ISG increased dramatically. The linear range of HPLC determination curve was 10 -350 μg/ml, with an average recovery of 99. 63% (RSD =0. 88%). Conclusion Preparation of the gel with controllable quality is simple and easy. The determination method is reliable for gabexate mesilate thermosensitive m sitt hydrogels.