Reversible adhesives with controlled wrinkling patterns for programmable integration and discharging.

Switchable and minimally invasive tissue adhesives have great potential for medical applications. However, on-demand adherence to and detachment from tissue surfaces remain difficult. We fabricated a switchable hydrogel film adhesive by designing pattern-tunable wrinkles to control adhesion. When adhered to a substrate, the compressive stress generated from the bilayer system leads to self-similar wrinkling patterns at short and long wavelengths, regulating the interfacial adhesion. To verify the concept and explore its application, we established a random skin flap model, which is a crucial strategy for repairing severe or large-scale wounds. Our hydrogel adhesive provides sufficient adhesion for tissue sealing and promotes neovascularization at the first stage, and then gradually detaches from the tissue while a dynamic wrinkling pattern transition happens. The gel film can be progressively ejected out from the side margins after host-guest integration. Our findings provide insights into tunable bioadhesion by manipulating the wrinkling pattern transition.

Bioactive poly (methyl methacrylate) bone cement for the treatment of osteoporotic vertebral compression fractures.

Rationale: Poly (methyl methacrylate) (PMMA) bone cement is one of the most commonly used biomaterials for augmenting/stabilizing osteoporosis-induced vertebral compression fractures (OVCFs), such as percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP). However, its clinical applications are limited by its poor performance in high compressive modulus and weak bonding to bone. To address these issues, a bioactive composite bone cement was developed for the treatment of osteoporotic vertebral compression fractures, in which mineralized collagen (MC) was incorporated into the PMMA bone cement (MC-PMMA). Methods: The in vitro properties of PMMA and MC-PMMA composite bone cement were determined, including setting time, compressive modulus, adherence, proliferation, and osteogenic differentiation of rat bone mesenchymal stem cells. The in vivo properties of both cements were evaluated in an animal study (36 osteoporotic New Zealand female rabbits divided equally between the two bone cement groups; PVP at L5) and a small-scale and short-term clinical study (12 patients in each of the two bone cement groups; follow-up: 2 years). Results: In terms of value for PMMA bone cement, the handling properties of MC-PMMA bone cement were not significantly different. However, both compressive strength and compressive modulus were found to be significantly lower. In the rabbit model study, at 8 and 12 weeks post-surgery, bone regeneration was more significant in MC-PMMA bone cement (cortical bone thickness, osteoblast area, new bone area, and bone ingrowth %; each significantly higher). In the clinical study, at a follow-up of 2 years, both the Visual Analogue Score and Oswestry Disability Index were significantly reduced when MC-PMMA cement was used. Conclusions: MC-PMMA bone cement demonstrated good adaptive mechanical properties and biocompatibility and may be a promising alternative to commercial PMMA bone cements for the treatment of osteoporotic vertebral fractures in clinical settings. While the present results for MC-PMMA bone cement are encouraging, further study of this cement is needed to explore its viability as an ideal alternative for use in PVP and BKP.

Sustained release of dermal papilla-derived extracellular vesicles from injectable microgel promotes hair growth.

Hair regeneration has long captured researchers' attention because alopecia is a common condition and current therapeutic approaches have significant limitations. Dermal papilla (DP) cells serve as a signaling center in hair follicles and regulate hair formation and cycling by paracrine secretion. Secreted EVs are important signaling mediators for intercellular communication, and DP-derived extracellular vesicles (DP-EVs) may play an important role in hair regeneration. However, the instability of EVs in vivo and their low long-term retention after transplantation hinder their use in clinical applications. Methods: Human DP-EVs were encapsulated in partially oxidized sodium alginate (OSA) hydrogels, yielding OSA-encapsulated EVs (OSA-EVs), which act as a sustained-release system to increase the potential therapeutic effect of DP-EVs. The ability of the OSA-EVs to protect protein was assessed. The hair regeneration capacity of OSA-EVs, as well as the underlying mechanism, was explored in hair organ culture and a mouse model of depilation. Results: The OSA-EVs were approximately 100 µm in diameter, and as the hydrogel degraded, DP-EVs were gradually released. In addition, the hydrogel markedly increased the stability of vesicular proteins and increased the retention of EVs in vitro and in vivo. The OSA-EVs significantly facilitated proliferation of hair matrix cells, prolonged anagen phase in cultured human hairs, and accelerated the regrowth of back hair in mice after depilation. These effects may be due to upregulation of hair growth-promoting signaling molecules such as Wnt3a and ß-catenin, and downregulation of inhibitory molecule BMP2. Conclusion: This study demonstrated that OSA hydrogels promote the therapeutic effects of DP-EVs, and indicate that our novel OSA-EVs could be used to treat alopecia.