Injectable, degradable, and mechanically adaptive hydrogel induced by L-serine and allyl-functionalized chitosan with platelet-rich plasma for treating intrauterine adhesions.

The integration of barrier materials with pharmacological therapy is a promising strategy to treat intrauterine adhesions (IUAs). However, most of these materials are surgically implanted in a fixed shape and incongruence with the natural mechanical properties of the uterus, causing poor adaptability and significant discomfort to the patients. Herein, an injectable, biodegradable, and mechanically adaptive hydrogel loaded with platelet-rich plasma (PRP) is created by L­serine and allyl functionalized chitosan (ACS) to achieve efficient, comfortable, and minimally invasive treatment of IUAs. L­serine induces fast gelation and mechanical reinforcement of the hydrogel, while ACS introduces, imparting a good injectability and complaint yet strong feature to the hydrogel. This design enables the hydrogel to adapt to the complex geometry and match the mechanical properties of the uterine. Moreover, the hydrogel exhibits proper degradability, sustained growth factors (GFs) of PRP release ability, and good biocompatibility. Consequently, the hydrogel shows promising therapeutic efficacy by reducing collagen fiber deposition and facilitating endometrium cell proliferation, thereby restoring the fertility function of the uterus in an IUAs model of rats. Accordingly, the combination of L­serine and ACS-induced hydrogel with such advantages holds great potential for treating IUAs. STATEMENT OF SIGNIFICANCE: This research introduces a breakthrough in the treatment of intrauterine adhesions (IUAs) with an injectable, biodegradable and mechanically adaptive hydrogel using L­serine and allyl functionalized chitosan (ACS). Unlike traditional surgical treatments, this hydrogel uniquely conforms to the uterus's geometry and mechanical properties, offering a minimally invasive, comfortable, and more effective solution. The hydrogel is designed to release growth factors from platelet-rich plasma (PRP) sustainably, promoting tissue regeneration by enhancing collagen fiber deposition and endometrium cell proliferation. Demonstrated efficacy in a rat model of IUAs indicates its great potential to significantly improve fertility restoration treatments. This advancement represents a significant leap in reproductive medicine, promising to transform IUAs treatment with its innovative approach to achieving efficient, comfortable, and minimally invasive therapy.

Injectable, stable, and biodegradable hydrogel with platelet-rich plasma induced by l-serine and sodium alginate for effective treatment of intrauterine adhesions.

The combination of pharmacological and physical barrier therapy is a highly promising strategy for treating intrauterine adhesions (IUAs), but there lacks a suitable scaffold that integrates good injectability, proper mechanical stability and degradability, excellent biocompatibility, and non-toxic, non-rejection therapeutic agents. To address this, a novel injectable, degradable hydrogel composed of poly(ethylene glycol) diacrylate (PEGDA), sodium alginate (SA), and l-serine, and loaded with platelet-rich plasma (PRP) (referred to as PSL-PRP) is developed for treating IUAs. l-Serine induces rapid gelation within 1 min and enhances the mechanical properties of the hydrogel, while degradable SA provides the hydrogel with strength, toughness, and appropriate degradation capabilities. As a result, the hydrogel exhibits an excellent scaffold for sustained release of growth factors in PRP and serves as an effective physical barrier. In vivo testing using a rat model of IUAs demonstrates that in situ injection of the PSL-PRP hydrogel significantly reduces fibrosis and promotes endometrial regeneration, ultimately leading to fertility restoration. The combined advantages make the PSL-PRP hydrogel very promising in IUAs therapy and in preventing adhesions in other internal tissue wounds.

Amino acid-induced rapid gelation and mechanical reinforcement of hydrogels with low-hysteresis and self-recoverable and fatigue-resistant properties.

Hydrogels with rapid gelation ability and robust mechanical properties are highly desirable for nascent applications in biomedical, wearable electronic, industrial and agricultural fields. However, current rapid-gelation hydrogels are compromised by poor mechanical properties, complex design of precursor molecular structures and limited precursor species. Herein, we propose a facile and universal strategy to achieve rapid gelation, strengthening and toughening of free-radical polymerized hydrogels by introducing cheap and accessible amino acids. Amino acids not only activate persulfate to quickly produce free radicals and thus induce fast free radical polymerization, but also can form strong hydrogen bonds with the network chains to strengthen and toughen the hydrogels. For example, with the presence of L-serine, the acrylamide (AM) monomer shows rapid gelation within tens of seconds, and moreover the resulting hydrogel reaches a tensile strength of 0.45 MPa and a breaking strain of 2060%. More importantly, owing to the extremely dynamic feature of the hydrogen bonds between L-serine molecules and network chains, the hydrogel possesses the advantages of low hysteresis, rapid self-recovery capability and outstanding fatigue resistance. Furthermore, this strategy is general to a wide range of amino acids and monomers. We also demonstrate that this rapid, controllable and universal strategy for the fabrication of mechanically robust hydrogels holds tremendous potential for diverse practical applications, such as flexible electronic sensors and ultraviolet (UV)-blocking artificial skins.

A mechanically robust and stable estradiol-loaded PHEMA-based hydrogel barrier for intrauterine adhesion treatment.

Estrogen combined with physical barrier therapy may be a prospective method to repair a damaged endometrium and prevent postsurgical re-adhesion in the treatment of intrauterine adhesions (IUAs), but there lacks a suitable scaffold with good biocompatibility, appropriate mechanical properties, and drug-releasing kinetics. Herein, a mechanically robust and stable barrier based on the poly(hydroxyethyl methacrylate) (PHEMA) hydrogel combined with estradiol-loaded mesoporous silica is designed. The network is formed by covalent bonds and noncovalent coordination bonds, which endow the hydrogel with superior mechanical properties to most reported PHEMA-based hydrogels. Meanwhile, the covalent bonds impart excellent stability to the hydrogel, which maintains its structure and mechanical properties in a simulated uterine fluid for 30 days. The excellent mechanical properties and stability are comparable to those of a typical barrier material intrauterine device (IUD), enabling the hydrogel to be retained in the uterus and removed intact like an IUD. In vitro and in vivo experiments show that the hydrogel possesses good biocompatibility similar to pure PHEMA hydrogels. In addition, the hydrogel releases estradiol continuously and stably, and exhibits a good therapeutic effect in promoting the proliferation of endometrial cells and inhibiting the progression of fibrosis. Therefore, the combinational advantages make the present hydrogel very promising in IUA treatment.

Compliant, Tough, Anti-Fatigue, Self-Recovery, and Biocompatible PHEMA-Based Hydrogels for Breast Tissue Replacement Enabled by Hydrogen Bonding Enhancement and Suppressed Phase Separation.

Although hydrogel is a promising prosthesis implantation material for breast reconstruction, there is no suitable hydrogel with proper mechanical properties and good biocompatibility. Here, we report a series of compliant and tough poly (hydroxyethyl methacrylate) (PHEMA)-based hydrogels based on hydrogen bond-reinforcing interactions and phase separation inhibition by introducing maleic acid (MA) units. As a result, the tensile strength, fracture strain, tensile modulus, and toughness are up to 420 kPa, 293.4%, 770 kPa, and 0.86 MJ/m3, respectively. Moreover, the hydrogels possess good compliance, where the compression modulus is comparable to that of the silicone breast prosthesis (~23 kPa). Meanwhile, the hydrogels have an excellent self-recovery ability and fatigue resistance: the dissipative energy and elastic modulus recover almost completely after waiting for 2 min under cyclic compression, and the maximum strength remains essentially unchanged after 1000 cyclic compressions. More importantly, in vitro cellular experiments and in vivo animal experiments demonstrate that the hydrogels have good biocompatibility and stability. The biocompatible hydrogels with breast tissue-like mechanical properties hold great potential as an alternative implant material for reconstructing breasts.