Design And Mechanical Properties Of 4D Printed Shape Memory Polymer Tissue Engineering Scaffolds

At present,although metal implantable tissue engineering scaffolds have been widely used in clinic,there are still many deficiencies.For example,an occluder used to close a congenital heart defect.Ideally,it only provides a “temporary bridge” for the self-repair of the heart,while the metal occluder has many problems such as nondegradability,displacement,embolism,corrosion,and nickel allergy.In addition,the mismatch in size between the occluder and defect,as well as the huge difference in mechanical properties between the occluder metal frame and human tissue will lead to tissue wear and even erosion of the aorta.Another typical example is metal intestinal stents,which also have similar problems such as perforation caused by metal stents eroding the intestinal wall.Specifically,when used for benign intestinal obstruction,secondary endoscopic removal is required due to the non-degradability of metal stents,which increases the pain and economic burden of patients;when used for malignant intestinal obstruction,bare metal stents tend to cause tumor tissue to grow into the lumen of the stents,resulting in re-obstruction.Covered metal stents play a part in preventing the tumor from growing inward but at the expense of significantly increasing the risk of stent migration.In view of the problems of the above two types of typical metal tissue engineering scaffolds,novel occluders and intestinal stents were designed and prepared based on bioinspired structures and four-dimensional(4D)printed technology.First,a variety of 4D printed biocomposite filaments with controllability and functionality were designed and prepared;then,biodegradable personalized occluders were designed and prepared based on the developed biocomposite filaments and two-dimensional bioinspired structures;finally,the two-dimensional bioinspired structures were extended to three-dimensional structures,and personalized intestinal stents for benign and malignant intestinal obstruction were designed and prepared.(1)With shape memory polylactic acid(PLA)as the matrix,4D printed biocomposite filaments were prepared by melt blending.Molecular dynamics simulation and the establishment of micro-mechanical models of particle reinforced shape memory polymer(SMP)composites provided theoretical support for material preparation and performance prediction.The plasticizer polyethylene glycol was introduced into the PLA matrix to prepare the biocomposite filaments that can be triggered the shape memory process at near body temperature(42.5 ℃-43.1 ℃),avoiding the influence of excessive temperature required to trigger SMP on the tissue.By introducing the photothermal agent graphene oxide and ferroferric oxide magnetic nanoparticles,light actuated and magnetic actuated biocomposite filaments were prepared to realize the remote,accurate and controllable deployment of tissue engineering scaffolds.In addition,antibacterial gentamycin sulfate and radiopaque barium sulfate were introduced into the matrix to obtain biocomposite filaments with drug loading and radiopaque capabilities to achieve the antibacterial and overall radiopaque properties of the tissue engineering scaffolds.The mechanical properties,degradation behaviors,and shape memory properties of the filaments were systematically characterized to verify their feasibility as printing consumables for tissue engineering scaffolds.(2)Given the problems of current metal occluders,4D printed remotely controllable,personalized,and biodegradable atrial septal defect occluders were designed and prepared based on the wavy structure.Magnetic-actuated biocomposites enabled the remote-controllable deployment of the occluder.4D printing ensured that the occluder possessed a patient-customized geometric configuration,which can effectively avoid the risk of tissue wear and displacement caused by size mismatch.The unique ligament structure design combined with excellent shape memory performance enabled a large volume ratio before and after deformation,facilitating interventional delivery and treatment.The occluder exhibited excellent biocompatibility and promoted tissue adhesion and growth,which helped prevent complications such as nickel allergy and corrosion caused by metal occluders.Animal implantation experiments verified the biodegradability of the occluder,which can avoid serious problems such as displacement and embolism of the permanent metal occluder.Subsequently,to solve the wear caused by the significant mismatch between the metal occluder and the surrounding tissue in terms of mechanical properties,the wavy bioinspired structure was further optimized,and left atrial appendage occluders with customizable mechanical properties were designed and prepared.By iterative optimization and adjustment of geometric parameters,a bioinspired structure with“J”-shaped stress-strain behavior similar to that of left atrial appendage tissue was obtained,which can realize cooperative deformation with the surrounding tissue.Based on the optimized bioinspired structure,single-layer and double-layer left atrial appendage occluders were designed and prepared,and the compression behavior,biocompatibility,and thermal-/magnetic-actuated 4D transformation behavior of the occluders were systematically evaluated.Then,the occluders with wavy bioinspired structures were further used to occlude more complex ventricular septal defects,and multi-shape ventricular septal defect occluders(e.g.,thin waist-large disc occluders and eccentric occluders)were designed.The prepared occluders were overall radiopaque under X-rays,which can effectively solve the inaccurate positioning caused by only a few radiopaque points of the current metal occluders.The overall radiopacity of occluders can achieve accurate positioning,which was helpful to further improve the success rate of occluding and facilitated postoperative follow-up monitoring.(3)To solve the problems of tissue hyperplasia,high risk of restenosis,and secondary endoscopic removal of metal colorectal stents,4D printed biodegradable intestinal stents with negative Poisson’s ratio structures were designed and prepared.To further improve the flexibility of the stent and reduce the damage to the intestinal wall,biodegradable intestinal stents with wavy network structures were developed.The mechanical properties,shape recovery properties,and functionality of the two intestinal stents were studied.Subsequently,to address the problems of lack of sustained anti-tumor ability and high displacement risk of metal colorectal stents for malignant obstruction,bioinspired personalized colorectal stents integrating antidisplacement,anti-tumor,and drug loading ability were designed and prepared.The introduction of the microstructures of imitating tree frog toe pads,octopus suckers,and gecko feet on the surface of the stents significantly improved the antidisplacement ability of the stents(up to 470%).The photothermal functionalized stents can not only prevent tumors from growing into the lumen through their fully covered configurations but also ablate tumors through prominent photothermal performance.In addition,the mechanical properties,anti-displacement ability,drugloading ability,and ability to dilate the obstructed intestine of the stents were evaluated.