Tough bioadhesion has important implications in engineering and medicine but remains challenging to form and control. We report an ultrasound (US)–mediated strategy to achieve tough bioadhesion with controllability and fatigue resistance. Without chemical reaction, the US can amplify the adhesion energy and interfacial fatigue threshold between hydrogels and porcine skin by up to 100 and 10 times. Combined experiments and theoretical modeling suggest that the key mechanism is US-induced cavitation, which propels and immobilizes anchoring primers into tissues with mitigated barrier effects. Our strategy achieves spatial patterning of tough bioadhesion, on-demand detachment, and transdermal drug delivery. This work expands the material repertoire for tough bioadhesion and enables bioadhesive technologies with high-level controllability.

Sutures pervade surgeries, but their performance is limited by the mechanical mismatch with tissues and the lack of advanced functionality. Existing modification strategies result in either deterioration of suture’s bulk properties or a weak coating susceptible to rupture or delamination. Inspired by tendon endotenon sheath, we report a versatile strategy to functionalize fiber-based devices such as sutures. This strategy seamlessly unites surgical sutures, tough gel sheath, and various functional materials. Robust modification is demonstrated with strong interfacial adhesion (>2000 J m−2). The surface stiffness, friction, and drag of the suture when interfacing with tissues can be markedly reduced, without compromising the tensile strength. Versatile functionalization of the suture for infection prevention, wound monitoring, drug delivery, and near-infrared imaging is then presented. This platform technology is applicable to other fiber-based devices and foreseen to affect broad technological areas ranging from wound management to smart textiles.

Non-compressible hemorrhage is an unmet clinical challenge that accounts for high mortality in trauma. Rapid pressurized blood flows under hemorrhage impair the function and integrity of hemostatic agents and the adhesion of bioadhesive sealants. Here, we report the design and performance of bioinspired microstructured bioadhesives, formed with a macroporous tough xerogel infused with functional liquids. The xerogel can rapidly absorb interfacial fluids such as whole blood and promote blood clotting, while the infused liquids facilitate interfacial bonding, sealing, and antibacterial function. Their synergy enables the bioadhesives to form tough adhesion on ex vivo human and porcine tissues and diverse engineered surfaces without the need for compression, as well as on-demand instant removal and storage stability. We demonstrate a significantly improved hemostatic efficacy and biocompatibility in rats and pigs compared to non-structured counterparts and commercial products. This work opens new avenues for the development of bioadhesives and hemostatic sealants.

Objectives: This systematic review compared platelet concentrates (PCs) versus hyaluronic acid (HA) or saline/Ringer’s solution injections as treatments of temporomandibular osteoarthritis and disc displacement in terms of pain and maximum mouth opening (MMO). Methods: PubMed, Cochrane, and Scopus were searched up to March 6, 2020. Inclusion criteria were randomized clinical trials (RCTs). Exclusion criteria were case series, observational studies, animal studies, and reviews. The Effective Public Health Practice Project (EPHPP) quality assessment tool was used to assess the risk of bias in the included studies. The weighted mean difference was used to compare the results. Results: Nine RCTs were included with a total of 407 patients. The numbers of joints treated were 262, 112, and 112 in the PC, HA, and saline groups, respectively. The quality of studies was rated as strong in 4 studies, moderate in 4 studies, and weak in 1 study. The meta-analysis revealed that PCs decreased pain visual analogue scale (VAS) scores compared to HA by an average of −1.11 (CI, −1.62 to −0.60; P < 0.0001) and −0.57 (CI, −1.55 to 0.41; P = 0.26) at 3 and 12 mo follow-up respectively. Also, the average decrease in pain scores with PC compared to saline was −1.33 (CI, −2.61 to −0.06; P = 0.04), −2.07 (CI, −3.46 to −0.69; P = 0.003), and −2.71 (CI, −4.69 to −0.72; P = 0.008) at 3, 6, and 12 mo, respectively. Regarding MMO measurements, PC was comparable to HA, but it was significantly better than saline after 3 and 6 mo [2.9 mm (CI,1.47 to 4.3; P < 0.0001), and 1.69 mm (CI, 0.13 to 3.25; P = 0.03) respectively]. Conclusion: PC reduces pain VAS scores compared to HA during the first 3 m after treatment, and when compared to saline, it reduces pain and increases MMO for longer durations. However, due to differences between groups regarding PC preparation protocols and study heterogeneity, further standardized RCTs are required. Knowledge Transfer Statement: This study provides researchers and clinicians with quantitative and qualitative analyses of the current evidence regarding the clinical outcomes of platelet concentrate injections in the treatment of temporomandibular joint osteoarthritis and disc displacement in terms of pain control and maximum mouth opening.

Postoperative pain relief is crucial for full recovery. With the ongoing opioid epidemic and the insufficient effect of acetaminophen on severe pain; non-steroidal anti-inflammatory drugs (NSAIDs) are heavily used to alleviate this pain. However, NSAIDs are known to inhibit postoperative healing of connective tissues by inhibiting prostaglandin signaling. Pain intensity, inflammatory mediators associated with wound healing and the pharmacological action of NSAIDs vary throughout the day due to the circadian rhythm regulated by the clock genes. According to this rhythm, most of wound healing mediators and connective tissue formation occurs during the resting phase, while pain, inflammation and tissue resorption occur during the active period of the day. Here we show, in a murine tibia fracture surgical model, that NSAIDs are most effective in managing postoperative pain, healing and recovery when drug administration is limited to the active phase of the circadian rhythm. Limiting NSAID treatment to the active phase of the circadian rhythm resulted in overexpression of circadian clock genes, such as Period 2 (Per2) at the healing callus, and increased serum levels of anti-inflammatory cytokines interleukin-13 (IL-13), interleukin-4 (IL-4) and vascular endothelial growth factor. By contrast, NSAID administration during the resting phase resulted in severe bone healing impairment. open Scientific RepoRtS | (2020) 10:468 | https://doi.org/10.1038/s41598-019-57215-y www.nature.com/scientificreports www.nature.com/scientificreports/ and Table S2). For instance, macrophage activity, leukocyte recruitment, and pro-inflammatory mediators such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-12 (IL-12) increase at the beginning of daily activity. During this phase, the levels of Tol-Like Receptors TLR9 and TLR4 also increase, leading to the upregulation of CCL2, CXCL1, CCL5, and subsequent leukocyte recruitment and potential tissue damage in injured sites 12-15 ( Fig. 1). By contrast, anti-inflammatory mediators and other growth or angiogenesis factors, such as the vascular endothelial growth factor (VEGF), peak during the resting phase 13,16,17 ( Fig. 1 and Table S2).The circadian rhythm affects many aspects of connective tissue metabolism 18 . A 24-hour oscillation occurs in bone tissue during growth 19 , formation, resorption 20,21 , and in the endochondral ossification during bone fracture healing 21 . Bone formation occurs during the resting period, and resorption occurs mostly during the active period 21 . Experimental studies in rodents and humans reveal that the disruption of sleep and circadian rhythm impairs bone formation 22 . All bone cells such as osteoblasts, osteoclasts, and chondrocytes express clock genes, such as Per or Cry, that influence bone volume regulation 23,24 . Cry2 influences the osteoclastic activity and Per2 regulates osteoblast activity 25 . The circadian clock also affects pain, with sensitivity peaking during the active phase 26 . Part of the pain response oscillation could b...