Tissue engineering faces a critical need for improved materials and techniques for soft tissue repair, particularly in cases like post-breast cancer treatment. While porous materials offer mechanical support for tissue infiltration, existing materials often suffer from limitations in pore morphology, biocompatibility, and processability. 3D printing offers a solution to overcome processing limitations, but suitable biocompatible and processable materials remain scarce. The authors introduce the concept of 4D materials—3D-printed structures that change shape over time—as a potential solution. Shape-changing polymers can facilitate minimally invasive implantation, reducing surgical trauma. However, challenges exist with current minimally invasive biomaterials like foams which show uneven pore distribution and limited material choices. This research aims to develop and characterize 4D-printable resin inks based on aliphatic polycarbonates, offering a combination of biocompatibility, shape memory, and surface erosion for effective soft tissue regeneration. These materials aim to overcome the limitations of current approaches, resulting in a minimally invasive 4D structure that improves healing and patient recovery.

The literature review highlights the limitations of current tissue engineering scaffolds for soft tissue repair, including issues with pore morphology, post-processing requirements, biocompatibility, and processability. The focus is on the limitations of commonly used materials such as acrylates, epoxides, and PLLA. The authors discuss the emerging field of 4D printing and its potential to create minimally invasive medical devices and scaffolds, but note the scarcity of examples using clinically relevant materials. Existing shape-memory polymers are often limited by uneven pore distribution and the availability of biocompatible options. The paper emphasizes the need for a biomaterial that combines minimally invasive behavior with nutrient/waste diffusion and support for tissue regrowth while degrading to non-toxic byproducts.

Aliphatic polycarbonates were synthesized via organocatalytic ring-opening polymerization (ROP) of cyclic carbonates, using 2-allyloxymethyl-2-ethyltrimethylene carbonate (TMPAC) and 2-norbornene-5,5-bis(hydroxymethyl) trimethylene carbonate (NTC) monomers. The resulting homo- and co-oligocarbonates (M_n ~2 kDa, Đ_M = 1.1) were characterized using ¹H NMR, FT-IR, and SEC. To create printable resins, the oligomers were diluted and solubilized in pentaerythritol tetrakis(mercaptopropanoic acid) (PETMP), along with a photoinitiator and photoinhibitor. Digital light processing (DLP) 3D printing was employed to fabricate porous scaffolds with various pore sizes and geometries. Cytocompatibility was assessed using 2D and 3D cell cultures with various cell types including fibroblasts, adipocytes, and macrophages. Thermomechanical properties were evaluated using dynamic mechanical analysis (DMA), uniaxial tensile testing, and cyclic compression testing. The shape memory behavior of the scaffolds was quantified through DMA, optical measurements, and expansion behavior in alginate hydrogels. Hydrolytic degradation was studied using both static and dynamic methods. In vivo studies involved subcutaneous implantation in mice, assessing material degradation, tissue infiltration, and capsule formation through histological analysis. Specific details regarding reagents, equipment, and analytical techniques are provided in the Materials and Methods section.

The authors successfully synthesized and characterized aliphatic polycarbonate oligomers with tunable properties. These oligomers were formulated into printable resins that underwent rapid photopolymerization upon irradiation. DLP 3D printing enabled the fabrication of porous scaffolds with precisely controlled pore sizes and geometries. In vitro studies showed excellent cytocompatibility with various cell types, and cells were able to proliferate throughout the 3D scaffolds. Thermomechanical testing revealed tunable stiffness and shape memory properties by varying the monomer composition. Scaffolds displayed impressive compression without catastrophic failure and shape recovery. Alginate gel experiments demonstrated the ability of the scaffolds to conform to irregular voids with minimal expansion forces. In vivo studies over 4 months in murine subcutaneous implants showed significant adipocyte infiltration and lobule formation within the porous scaffolds. Neovascularization was observed, and capsule formation was minimal. Material degradation occurred primarily through surface erosion, with sufficient mechanical support lasting for at least one year. Histological analysis confirmed the biocompatibility of the scaffolds, showing minimal inflammation and favorable integration with the surrounding tissue. The degradation rate, swelling, and gel fraction were also assessed. Detailed thermomechanical properties of various compositions (glass transition temperature, compressive modulus, elastic modulus, strain at break, ultimate tensile strength, and toughness) are presented in Table 1. Pathological scoring of the implants is given in Table 2.

The findings demonstrate that the developed 4D-printable aliphatic polycarbonate scaffolds offer a promising solution for soft tissue engineering applications. The unique combination of biocompatibility, shape memory, surface erosion, and tunable mechanical properties addresses the limitations of existing materials. The ability of the scaffolds to conform to irregular tissue voids in a minimally invasive manner, coupled with their bioresorbable nature and excellent tissue integration, represents a significant advancement in the field. The results show strong potential for use in various applications requiring soft tissue repair.

This research successfully demonstrates the synthesis and application of 4D-printable aliphatic polycarbonate scaffolds for soft tissue repair. The materials exhibit excellent biocompatibility, tunable mechanical properties, shape memory capabilities, and surface-erosion degradation. The in vivo results showcasing successful tissue infiltration and minimal inflammation indicate the potential for clinical translation. Future work could focus on exploring various applications and tailoring material properties for specific tissue types.

While the study provides compelling evidence of the potential of these scaffolds, limitations include the relatively small sample size in the in vivo studies and the use of a murine model. Further investigation in larger animal models and clinical trials are needed to fully validate the efficacy and safety of these materials. The long-term effects of degradation products also warrant further investigation.