An Elastomer with In Situ Generated Pure Zwitterionic Surfaces for Fibrosis-resistant Implants.

Polymeric elastomers are widely utilized in implantable biomedical devices. Nevertheless, the implantation of these elastomers can provoke a robust foreign body response (FBR), leading to the rejection of foreign implants and consequently reducing their effectiveness in vivo. Building effective anti-FBR coatings on those implants remains challenging. Herein, we introduce a coating-free elastomer with superior immunocompatibility. A super-hydrophilic anti-fouling zwitterionic layer can be generated in situ on the surface of the elastomer through a simple chemical trigger. This elastomer can repel the adsorption of proteins, as well as the adhesion of cells, platelets, and diverse microbes. The elastomer elicited negligible inflammatory responses after subcutaneous implantation in rodents for 2 weeks. No apparent fibrotic capsule formation was observed surrounding the elastomer after 6 months in rodents. Continuous subcutaneous insulin infusion (CSII) catheters constructed from the elastomer demonstrated prolonged longevity and performance compared to commercial catheters, indicating its great potential for enhancing and extending the performance of various implantable biomedical devices by effectively attenuating local immune responses. STATEMENT OF SIGNIFICANCE: The foreign body response remains a significant challenge for implants. Complicated coating procedures are usually needed to construct anti-fibrotic coatings on implantable elastomers. Herein, a coating-free elastomer with superior immunocompatibility was achieved using a zwitterionic monomer derivative. A pure zwitterionic layer can be generated on the elastomer surface through a simple chemical trigger. This elastomer significantly reduces protein adsorption, cell and bacterial adhesion, and platelet activation, leading to minimal fibrotic capsule formation even after six months of subcutaneous implantation in rodents. CSII catheters constructed from the PQCBE-H elastomer demonstrated prolonged longevity and performance compared to commercial catheters, highlighting the significant potential of PQCBE-H elastomers for enhancing and extending the performance of various implantable biomedical devices.

Poly(Glutamic Acid-Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non-Human Primates.

The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long-term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.

Covalently grafted human serum albumin coating mitigates the foreign body response against silicone implants in mice.

Implantable biomaterials and biosensors are integral components of modern medical systems but often encounter hindrances due to the foreign body response (FBR). Herein, we report an albumin coating strategy aimed at addressing this challenge. Using a facile and scalable silane coupling strategy, human serum albumin (HSA) is covalently grafted to the surface of polydimethylsiloxane (PDMS) implants. This covalently grafted albumin coating remains stable and resistant to displacement by other proteins. Notably, the PDMS with covalently grafted HSA strongly resists the fibrotic capsule formation following a 180-day subcutaneous implantation in C57BL/6 mice. Furthermore, the albumin coating led to reduced recruitment of macrophages and triggered a mild immune activation pattern. Exploration of albumin coatings sourced from various mammalian species has shown that only HSA exhibited a promising anti-FBR effect. The albumin coating method reported here holds the potential to improve and extend the function of silicone-based implants by mitigating the host responses to subcutaneously implanted biomaterials.

Fibrous capsule-resistant, controllably degradable and functionalizable zwitterion-albumin hybrid hydrogels.

Foreign body response (FBR) represents an immune-mediated cascade reaction capable of inducing the rejection of foreign implants, thereby compromising their in vivo performance. Pure zwitterionic hydrogels have demonstrated the ability to resist long-term FBR, owing to their outstanding antifouling capabilities. However, achieving such a robust anti-FBR effect necessitates stringent requirements concerning the purity of zwitterionic materials, which constrains their broader functional applications. Herein, we present a biocompatible, controllably degradable, and functionalizable zwitterion-albumin hybrid hydrogel. The zwitterionic hydrogel crosslinked with serum albumin exhibits controllable degradation and excels in preventing the adsorption of various proteins and adhesion of cells and bacteria. Moreover, the hydrogel significantly alleviates the host's FBR compared with PEG hydrogels and particularly outperforms PEG-based cross-linker crosslinked zwitterionic hydrogels in reducing collagen encapsulation when subcutaneously implanted into mice. The zwitterion-albumin hybrid hydrogel shows potential as a functionalizable anti-FBR material in the context of implantable materials and biomedical devices.

[Triple-strong stimulation therapy at Dazhui (GV 14) in prevention and treatment of children allergic rhinitis: a randomized controlled trial].

OBJECTIVE: To evaluate the short-term efficacy and long-term preventive effect on recurrence in prevention and treatment of children allergic rhinitis treated with the multiple therapy at Dazhui (GV 14) as the main acupoint and acupoint plaster therapy. METHODS: One hundred and twenty cases of children allergic rhinitis were randomized into a triple-strong stimulation therapy group and an acupoint plaster therapy group, 60 cases in each one. In the triple-strong stimulation therapy group, Dazhui (GV 14) was the main acupoint, combined with one of Feishu (BL 13), Zhiyang (GV 9) and Shenshu (BL 23) accordingly. The heavy needling technique was adopted with the three-edged needle, followed by heavy cupping and heavy moxibustion. The treatment was given once every 3 days, continuously for 10 times. In the acupoint plaster therapy group, the acupoints selected were same as the triple-strong stimulation therapy group. The self-prepared Chinese herbal plaster was used, 4 h to 8 h each one time, once every 3 days, continuously for 10 times. The changes in the symptom and physical sign scores were observed before treatment, after treatment and in 6 months follow-up visit after treatment in the two groups. The clinical efficacy was compared between the two groups. RESULTS: After treatment and in 6 months follow-up visit after treatment, the symptom scores, physical sign scores and symptom scores of each item were different signi ficantly as compared with those before treatment in the triple-strong stimulation therapy group (P<0.01, P<0.05), and the results in the triple-strong stimulation therapy group were better than those in the acupoint plaster therapy group (all P<0.01). In 6 months follow-up visit, the total effective rate was 94.6% (53/56) in the triple-strong stimulation therapy group and was 25.9% (15/58) in the acupoint plaster therapy group, indicating the significant difference (P<0.001). CONCLUSION: The triple-strong stimulation therapy at Dazhui (GV 14) achieves the superior effect on the prevention and treatment of children allergic rhinitis as compared with the acupoint plas ter therapy and has good long-term effect of the prevention from recurrence.

[Allergic rhinitis treated with acupuncture and the triple-strong stimulation therapy at dazhui (GV 14): a randomized controlled trial].

OBJECTIVE: To evaluate the impacts on the short-term efficacy and the long-term prevention of recurrence of allergic rhinitis treated with the triple-strong stimulation at Dazhui (GV 14) so as to provide the convenient and long-term effective therapy of acupuncture and moxibustion for allergic rhinitis. METHODS: One hundred and twenty cases of allergic rhinitis were randomized into an acupuncture group, an acupuncture + medication group and a triple-strong stimulation group, 40 cases in each one. In the acupuncture group, acupuncture was applied at Dazhui (GV 14), Fengchi (GB 20), Baihui (GV 20), Yintang (GV 29) and the others, stimulating with reinforcing manipulation for the deficiency and reducing manipulation for the excess, once every day. In the acupuncture + medication group, on the basis of acupuncture therapy, claritin (loratadine tablets) was supplemented for oral administration, 10 mg, once every two days, continuously for 30 days. In the triple-strong stimulation group, on the basis of acupuncture therapy, the strong needling, strong cupping and strong moxibustion were applied at Dazhui (GV 14). This combined therapy was given once every day in the first 3 days and once every two days afterwards. The 10 day treatment made one session, at the interval of 3 days between the sessions and totally 3 sessions were required in the three groups. Separately, before treatment, after treatment and in 6 months after treatment, the changes of symptom and physical sign score and value of single item symptom including nasal itching, nasal blockage, sneezing and rhinorrhea were observed in the patients of the three groups. And the long-term clinical efficacy was compared among the three groups. RESULTS: The symptom and physical sign score and the value of single item symptom were all reduced in the three groups after treatment and in 6 months after treatment (P < 0.001, P < 0.01, P < 0.05). The results in the triple-strong stimulation group were superior to the other two groups (all P < 0.05). In the triple-strong stimulation group, the total effective rate was 92.5% (36/40) in the follow-up of 6 months after treatment, which was better than 60.5% (23/38) in the acupuncture group and 69.2% (27/39) in the acupuncture + medication group (both P < 0.01). CONCLUSION: The combined therapy of acupuncture and the triple-strong stimulation at Dazhui (GV 14) achieves the reliable and effective result in the clinical treatment of allergic rhinitis and displays the good role on the prevention from long-term recurrence.

[Children peripheral facial palsy treated with three therapies of strong stimulation: a randomized controlled trial].

OBJECTIVE: To evaluate the clinical efficacy and safety of the three therapies of strong stimulation for children peripheral facial palsy so as to deal with the problem on the inactive acceptance of acupuncture in children. METHODS: Eighty cases of children peripheral facial palsy were randomized into a moxa stick group (group A) and a group with three therapies of strong stimulation (group B). Baihui (GV 20), Sibai (ST 2), Dicang (ST 4), Jiache (ST 6) and the other acupoints were selected in the two groups and stimulated with half-needling technique. In the group A, 3 moxa sticks were bunched together for surrounding moxibustion over one of Dazhui (GV 14), Yangbai (GB 14), Xiaguan (ST 7) and Jiache (ST 6) in each treatment. In the group B, the strong pricking therapy, strong cupping therapy and strong moxibustion were adopted at the same acupoints as the group A. The treatment was given twice every day in the first 5 days. Afterwards, the clinical efficacy was analyzed statistically. The treatment was kept on for the effective case. Those with failed effect were transferred to the other group. Since the 6th day, the treatment was given once every day. In 15 days, the clinical efficacy was compared between the two groups and House-Brackmann (H-B) facial nerve function grade was compared before and after treatment. RESULTS: In 5 days of treatment, the total effective rate was 94.7% (36/38) in the group B, which was better than 52.4% (22/42) in the group A, (P < 0.001). In 15 days of treatment, the cured rate and the total effective rate in the group B were 67.3% (35/52) and 96.2% (50/52), which were better than 9.5% (2/21) and 85.7% (18/21) in the group A, respectively (P < 0. 001, P < 0.05). Additionally, the result of H-B facial nerve function grade in the group B was superior to the group A (P < 0.001). CONCLUSION: The half-needling technique and the three therapies of strong stimulation in combination achieve the superior efficacy on children peripheral facial palsy as compared with the half-needling technique combined with moxa stick therapy. And the obvious adverse reaction has not been found.