Existing biomedical devices based on polymer gels face three major limitations: mechanical mismatch with surrounding tissue leading to complications like capsular contracture and implant fracture; chemical leaching from gels posing long-term health risks; and invasive implantation procedures causing scarring and inflammation. This study aims to address these limitations by developing minimally invasive, solvent-free, injectable implants that do not leach harmful chemicals and precisely mimic the mechanical properties of soft biological tissues. Biological tissues exhibit a unique combination of softness (low initial modulus) and firmness (significant stiffening under deformation). Traditional gels struggle to replicate this due to the inherent flexibility of their linear network strands. While swelling can reduce crosslink density for softness, it hinders the ability to mimic the strong strain-stiffening response. This study leverages the brush-like polymer architecture, where densely grafted side-chains simultaneously dilute and stiffen network strands, creating elastomers with both enhanced softness and firmness. This approach allows independent control of these mechanical characteristics without solvents, enabling the precise replication of the stress-strain response of various tissues. However, current brush elastomer synthesis typically involves solvents and hazardous crosslinking methods. This research overcomes these challenges by utilizing the compact molecular conformation of bottlebrushes for low melt viscosity and the abundance of chain ends for facile functionalization, enabling solvent-free in vivo injection of reactive bottlebrush melts.

The authors review existing literature on polymer gels for biomedical applications, highlighting the limitations of current technologies. They discuss the mechanical mismatch between gels and tissues, leading to problems like capsular contracture and implant failure. The significant issue of chemical leaching from gels, especially organogels used in plastic surgery, is emphasized, along with the associated long-term health risks. Finally, the drawbacks of invasive implantation procedures are described, including post-operative scarring and inflammation. This review sets the stage for the introduction of the new injectable elastomer technology, which aims to solve these problems.

The researchers designed a dual-syringe formulation consisting of a bottlebrush polymer melt with functionalized side chains and a fully conjugated network to prevent uncontrolled reactions with surrounding tissue and polymerization-induced shrinkage. Gelation time was controlled by varying crosslinking chemistries (isocyanate/hydroxyl, isocyanate/amine, aldehyde/amine, alkyne/azide, and diene/dienophile), primarily focusing on isocyanate:hydroxyl (NCO:OH) and isocyanate:amine (NCO:NH2) couplings. Gelation time was further tuned by adjusting the fraction of functionalized chain ends, temperature, and catalyst concentration. Bottlebrushes were synthesized via atom transfer radical polymerization (ATRP) of polydimethylsiloxane-methacrylate (PDMSMA) macromonomers with controlled fractions of polyethyleneglycol-methacrylate (PEGMA) macromonomers, capped with hydroxyl (OH-) or azide (N3-) ends. ATRP ensured a random distribution of macromonomers, verified by time-resolved 1H-NMR. AFM imaging confirmed successful brush synthesis. Rheology was used to monitor gelation, defined by the crossover of storage (G') and loss (G'') moduli at 37 °C. Mechanical properties were assessed by uniaxial tensile tests using an equation of state to determine Young's modulus (E0) and firmness parameter (β). The effects of varying crosslinker concentration and side chain length on E0 and β were investigated. Leachability was evaluated by aqueous extraction and H-NMR. Cytotoxicity was assessed using ISO 10993-5 standards with NIH/3T3 fibroblasts and HUVECs. Cell proliferation was assessed by measuring DNA content. In vivo studies involved subcutaneous and intramuscular implantation in rats, with histological analysis to assess inflammatory response and capsular thickness. Long-term stability was assessed by re-evaluating mechanical properties after in vivo implantation and incubation in PBS at 70 °C. Texture profile analysis (TPA) was conducted to characterize the mechanical properties further.

The study successfully synthesized injectable, solvent-free elastomers with tunable gelation times ranging from minutes to hours, achieved by manipulating crosslinking chemistry, stoichiometry, temperature, and catalyst concentration. The bottlebrush architecture allowed for independent control of softness (Young's modulus) and firmness (strain-stiffening parameter), closely mimicking the mechanical properties of various biological tissues. The elastomers exhibited non-leaching properties, unlike commercial silicone gels, demonstrated by a paper-based test and time-resolved H-NMR. In vitro cytotoxicity and cell proliferation assays showed excellent biocompatibility, with NIH/3T3 fibroblast viability above 90% and minimal stimulation of fibroblast proliferation. In vivo studies in rats showed excellent biocompatibility with minimal inflammatory response and significantly thinner capsular thickness compared to commercial silicone gels. The injectable elastomers maintained their mechanical properties after in vivo implantation and incubation in PBS at 70°C. Texture profile analysis showed favorable comparison with commercial silicone gel implants.

The developed injectable, non-leaching elastomers successfully address the limitations of current biomedical implant materials by combining tissue-mimetic mechanics, minimal invasiveness, and excellent biocompatibility. The tunable gelation time allows for adaptation to diverse surgical procedures. The non-leaching property significantly reduces long-term health risks associated with conventional gels. The in vivo results demonstrate the biocompatibility and long-term stability of the implants, paving the way for a new generation of minimally invasive reconstructive surgery. This technology offers improved patient comfort, reduced costs, faster recovery, and minimal surgical and post-surgical complications compared to existing approaches.

This research presents a novel platform for minimally invasive reconstructive surgery using injectable, non-leaching tissue-mimetic elastomers. The unique bottlebrush architecture enables independent tuning of mechanical properties and gelation time, leading to materials that closely mimic the behavior of biological tissues. The excellent biocompatibility demonstrated both in vitro and in vivo suggests significant potential for a wide range of biomedical applications. Future work could explore a broader range of crosslinking chemistries and architectural parameters to further refine the elastomers' properties and expand their applicability.

While the study demonstrates promising results, further research is needed to validate the long-term efficacy and safety of these elastomers in humans. The current in vivo studies are limited to rat models, and larger-scale animal studies are required before clinical trials. The long-term biodegradation and potential for adverse reactions in human tissues need to be carefully evaluated. The effect of different injection techniques and volumes on the implant's performance should also be investigated.