3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with ß-tricalcium phosphate (ß-TCP) and constructed a bionic cancellous bone scaffolding system α/ß-tricalcium phosphate (α/ß-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/ß-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Efficacy and safety of glucagon-like peptide-1 receptor agonists in the elderly versus non-elderly patients with type 2 diabetes mellitus: insights from a systematic review.

This systematic review aimed to compare the influence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the efficacy and safety of elderly patients with type 2 diabetes and younger individuals. A comprehensive search of PubMed, Embase, and Web of Science databases was conducted up to September 2022. The summary standard means difference and odds ratios were calculated. Thirteen articles were included in the analysis. The incidence of adverse events (AEs) leading to discontinuation was higher in elderly patients (OR = 0.67, 95% CI 0.47 to 0.96, p = 0.028). However, no significant differences were observed in weight loss (SMD = 0.03, 95% CI -0.12 to 0.19, p = 0.686), HbA1c% (SMD = -0.02, 95% CI -0.11 to 0.08, p = 0.715), FBG levels (SMD = -0.03, 95% CI -0.11 to 0.06, p = 0.537), and the incidence of overall AEs (OR = 0.85, 95% CI 0.71 to 1.01, p = 0.072), serious AEs (OR = 0.68, 95% CI 0.45 to 1.04, p = 0.077), nausea (OR = 0.91, 95% CI 0.81 to 1.03, p = 0.140), vomiting (OR = 0.95, 95% CI 0.79 to 1.13, p = 0.532), diarrhea (OR = 0.86, 95% CI 0.72 to 1.02, p = 0.081), and hypoglycemia (OR = 1.22, 95% CI 0.90 to 1.65, p = 0.193). In conclusion, while certain AEs leading to discontinuation may be more prevalent in older patients, GLP-1RAs are effective for weight loss and lead to decreased glucose concentrations with a low rate of complications in elderly patients.

An Injectable Thermosensitive Hydrogel Containing Resveratrol and Dexamethasone-Loaded Carbonated Hydroxyapatite Microspheres for the Regeneration of Osteoporotic Bone Defects.

Bone defects in osteoporosis usually present excessive reactive oxygen species (ROS), abnormal inflammation levels, irregular shapes and impaired bone regeneration ability; therefore, osteoporotic bone defects are difficult to repair. In this study, an injectable thermosensitive hydrogel poly (D, L-lactide)-poly (ethylene glycol)- poly (D, L-lactide) (PLEL) system containing resveratrol (Res) and dexamethasone (DEX) is designed to create a microenvironment conducive to osteogenesis in osteoporotic bone defects. This PLEL hydrogel is injected and filled irregular defect areas and achieving a rapid sol-gel transition in situ. Res has a strong anti-inflammatory effects that can effectively remove excess free radicals at the damaged site, guide macrophage polarization to the M2 phenotype, and regulate immune responses. Additionally, DEX can promote osteogenic differentiation. In vitro experiments showed that the hydrogel effectively promoted osteogenic differentiation of mesenchymal stem cells, removed excess intracellular ROS, and regulated macrophage polarization to reduce inflammatory responses. In vivo experiments showed that the hydrogel promoted osteoporotic bone defect regeneration and modulated immune responses. Overall, this study confirmed that the hydrogel can treat osteoporotic bone defects by synergistically modulating bone damage microenvironment, alleviating inflammatory responses, and promoting osteogenesis; thus, it represents a promising drug delivery strategy to repair osteoporotic bone defects.

Cyclical endometrial repair and regeneration: Molecular mechanisms, diseases, and therapeutic interventions.

The endometrium is a unique human tissue with an extraordinary ability to undergo a hormone-regulated cycle encompassing shedding, bleeding, scarless repair, and regeneration throughout the female reproductive cycle. The cyclical repair and regeneration of the endometrium manifest as changes in endometrial epithelialization, glandular regeneration, and vascularization. The mechanisms encompass inflammation, coagulation, and fibrinolytic system balance. However, specific conditions such as endometriosis or TCRA treatment can disrupt the process of cyclical endometrial repair and regeneration. There is uncertainty about traditional clinical treatments' efficacy and side effects, and finding new therapeutic interventions is essential. Researchers have made substantial progress in the perspective of regenerative medicine toward maintaining cyclical endometrial repair and regeneration in recent years. Such progress encompasses the integration of biomaterials, tissue-engineered scaffolds, stem cell therapies, and 3D printing. This review analyzes the mechanisms, diseases, and interventions associated with cyclical endometrial repair and regeneration. The review discusses the advantages and disadvantages of the regenerative interventions currently employed in clinical practice. Additionally, it highlights the significant advantages of regenerative medicine in this domain. Finally, we review stem cells and biologics among the available interventions in regenerative medicine, providing insights into future therapeutic strategies.

Evaluation of polyetheretherketone composites modified by calcium silicate and carbon nanotubes for bone regeneration: mechanical properties, biomineralization and induction of osteoblasts.

Desired orthopedic implant materials must have a good biological activity and possess appropriate mechanical property that correspond to those of human bone. Although polyetheretherketone (PEEK) has displayed a promising application prospect in musculoskeletal and dentistry reconstruction thanks to its non-biodegradability and good biocompatibility in the body, the poor osseointegration and insufficient mechanical strength have significantly limited its application in the repair of load-bearing bones and surgical operations. In this study, carbon nanotubes (CNT)/calcium silicate (CS)/polyetheretherketone ternary composites were fabricated for the first time. The addition of CS was mainly aimed at improving biological activities and surface hydrophilicity, but it inevitably compromised the mechanical strength of PEEK. CNT can reinforce the composites even when brittle CS was introduced and further upgraded the biocompatibility of PEEK. The CNT/CS/PEEK composites exhibited higher mechanical strengths in tensile and bending tests, 64% and 90% higher than those of brittle CS/PEEK binary composites. Besides, after incorporation of CNT and CS into PEEK, the hydrophilicity, surface roughness and ability to induce apatite-layer deposition were significantly enhanced. More importantly, the adhesion, proliferation, and osteogenic differentiation of mouse embryo osteoblasts were effectively promoted on CNT/CS/PEEK composites. In contrast to PEEK, these composites exhibited a more satisfactory biocompatibility and osteoinductive activity. Overall, these results demonstrate that ternary CNT/CS/PEEK composites have the potential to serve as a feasible substitute to conventional metal alloys in musculoskeletal regeneration and orthopedic implantation.

Research progress of 3D printed poly (ether ether ketone) in the reconstruction of craniomaxillofacial bone defects.

The clinical challenge of bone defects in the craniomaxillofacial region, which can lead to significant physiological dysfunction and psychological distress, persists due to the complex and unique anatomy of craniomaxillofacial bones. These critical-sized defects require the use of bone grafts or substitutes for effective reconstruction. However, current biomaterials and methods have specific limitations in meeting the clinical demands for structural reinforcement, mechanical support, exceptional biological performance, and aesthetically pleasing reconstruction of the facial structure. These drawbacks have led to a growing need for novel materials and technologies. The growing development of 3D printing can offer significant advantages to address these issues, as demonstrated by the fabrication of patient-specific bioactive constructs with controlled structural design for complex bone defects in medical applications using this technology. Poly (ether ether ketone) (PEEK), among a number of materials used, is gaining recognition as a feasible substitute for a customized structure that closely resembles natural bone. It has proven to be an excellent, conformable, and 3D-printable material with the potential to replace traditional autografts and titanium implants. However, its biological inertness poses certain limitations. Therefore, this review summarizes the distinctive features of craniomaxillofacial bones and current methods for bone reconstruction, and then focuses on the increasingly applied 3D printed PEEK constructs in this field and an update on the advanced modifications for improved mechanical properties, biological performance, and antibacterial capacity. Exploring the potential of 3D printed PEEK is expected to lead to more cost-effective, biocompatible, and personalized treatment of craniomaxillofacial bone defects in clinical applications.

Progress in the application of 3D-printed sodium alginate-based hydrogel scaffolds in bone tissue repair.

In recent years, hydrogels have been widely used in the biomedical field as materials with excellent bionic structures and biological properties. Among them, the excellent comprehensive properties of natural polymer hydrogels represented by sodium alginate have attracted the great attention of researchers. At the same time, by physically blending sodium alginate with other materials, the problems of poor cell adhesion and mechanical properties of sodium alginate hydrogels were directly improved without chemical modification of sodium alginate. The composite blending of multiple materials can also improve the functionality of sodium alginate hydrogels, and the prepared composite hydrogel also has a larger application field. In addition, based on the adjustable viscosity of sodium alginate-based hydrogels, sodium alginate-based hydrogels can be loaded with cells to prepare biological ink, and the scaffold can be printed out by 3D printing technology for the repair of bone defects. This paper first summarizes the improvement of the properties of sodium alginate and other materials after physical blending. Then, it summarizes the application progress of sodium alginate-based hydrogel scaffolds for bone tissue repair based on 3D printing technology in recent years. Moreover, we provide relevant opinions and comments to provide a theoretical basis for follow-up research.

3D printed PCLA scaffold with nano-hydroxyapatite coating doped green tea EGCG promotes bone growth and inhibits multidrug-resistant bacteria colonization.

OBJECTIVES: 3D-printing scaffold with specifically customized and biomimetic structures gained significant recent attention in tissue engineering for the regeneration of damaged bone tissues. However, constructed scaffolds that simultaneously promote bone regeneration and in situ inhibit bacterial proliferation remains a great challenge. This study aimed to design a bone repair scaffold with in situ antibacterial functions. MATERIALS AND METHODS: Herein, a general strategy is developed by using epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, firmly anchored in the nano-hydroxyapatite (HA) and coating the 3D printed polymerization of caprolactone and lactide (PCLA) scaffold. Then, we evaluated the stability, mechanical properties, water absorption, biocompatibility, and in vitro antibacterial and osteocyte inductive ability of the scaffolds. RESULTS: The coated scaffold exhibit excellent activity in simultaneously stimulating osteogenic differentiation and in situ resisting methicillin-resistant Staphylococcus aureus colonization in a bone repair environment without antibiotics. Meanwhile, the prepared 3D scaffold has certain mechanical properties (39.3 ± 3.2 MPa), and the applied coating provides the scaffold with remarkable cell adhesion and osteogenic conductivity. CONCLUSION: This study demonstrates that EGCG self-assembled HA coating on PCLA surface could effectively enhance the scaffold's water absorption, osteogenic induction, and antibacterial properties in situ. It provides a new strategy to construct superior performance 3D printed scaffold to promote bone tissue regeneration and combat postoperative infection in situ.

3D-Printed Poly (P-Dioxanone) Stent for Endovascular Application: In Vitro Evaluations.

Rapid formation of innovative, inexpensive, personalized, and quickly reproducible artery bioresorbable stents (BRSs) is significantly important for treating dangerous and sometimes deadly cerebrovascular disorders. It is greatly challenging to give BRSs excellent mechanical properties, biocompatibility, and bioabsorbability. The current BRSs, which are mostly fabricated from poly-l-lactide (PLLA), are usually applied to coronary revascularization but may not be suitable for cerebrovascular revascularization. Here, novel 3D-printed BRSs for cerebrovascular disease enabling anti-stenosis and gradually disappearing after vessel endothelialization are designed and fabricated by combining biocompatible poly (p-dioxanone) (PPDO) and 3D printing technology for the first time. We can control the strut thickness and vessel coverage of BRSs by adjusting the printing parameters to make the size of BRSs suitable for small-diameter vascular use. We added bis-(2,6-diisopropylphenyl) carbodiimide (commercial name: stabaxol®-1) to PPDO to improve its hydrolytic stability without affecting its mechanical properties and biocompatibility. In vitro cell experiments confirmed that endothelial cells can be conveniently seeded and attached to the BRSs and subsequently demonstrated good proliferation ability. Owing to the excellent mechanical properties of the monofilaments fabricated by the PPDO, the 3D-printed BRSs with PPDO monofilaments support desirable flexibility, therefore offering a novel BRS application in the vascular disorders field.

Quantitative angiographic haemodynamic evaluation of bypasses for complex aneurysms: a preliminary study.

OBJECTIVE: Open microsurgery, often with bypass techniques, is indispensable for complex aneurysms. To date, it remains unknown whether arterial anatomy or quantitative blood flow measurements can predict insufficient flow-related stroke (IRS). The present study aimed to evaluate the risk factors for IRS in patients treated with open microsurgery with bypass procedures for complex internal carotid artery aneurysms. METHODS: Patients with complex aneurysms undergoing bypass surgery were retrospectively reviewed. The recipient/donor flow index (RDFI) was preoperatively evaluated using colour-coding angiography. RDFI was defined as the ratio of the cerebral blood volume of the recipient and donor arteries. The sizes of the recipient and donor arteries were measured. The recipient/donor diameter index (RDDI) was then calculated. IRS was defined as the presence of new postoperative neurological deficits and infarction on postoperative CT scans. We assessed the association between RDFI and other variables and the IRS. RESULTS: Twenty patients (38±12 years) were analysed. IRS was observed in 12 patients (60%). Patients with postoperative IRS had a higher RDFI than those without postoperative IRS (p<0.001). RDDI was not significantly different between patients with and without IRS (p=0.905). Patients with RDFI >2.3 were more likely to develop IRS (p<0.001). CONCLUSION: Quantitative digital subtraction angiography enables preoperative evaluation of cerebral blood volume. RDFI >2.3, rather than RDDI, was significantly associated with postoperative IRS. This preoperative evaluation allows appropriate decisions regarding the treatment strategy for preventing postoperative IRS.

Effect of sodium-glucose cotransporter protein-2 inhibitors on left ventricular hypertrophy in patients with type 2 diabetes: A systematic review and meta-analysis.

Objective: This systematic review and meta-analysis was performed to compare the effect of sodium-glucose cotransporter protein-2 inhibitors (SGLT-2i) and placebo on left ventricular hypertrophy (LVH) in patients with type 2 diabetes. Method: Randomized controlled trials (RCTs) comparing the LVH parameters of SGLT-2i to placebo in patients with type 2 diabetes were included. Our primary outcomes were the changes in left ventricular mass (LVM) and left ventricular mass index (LVMI) from baseline to the study endpoint. Secondary outcomes were the changes in left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early mitral inflow velocity to atrial inflow velocity (E/A). Summary odds ratios were estimated using a fixed-effect or random-effect model. Results: A total of 11 articles were included. Data were extracted from 11 original studies matching our inclusion criteria. In our meta-analysis, there were significant improvement in LVM (SMD -0.23, 95% CI -0.44 to -0.02, I 2 = 22.6%, p = 0.034), LVMI (SMD -0.25, 95% CI -0.38 to -0.12, I 2 = 0.0%, p = 0.000), LVEDV (SMD -0.19, 95% CI -0.36 to -0.01, I 2 = 62.3%, p = 0.035), and LVESV (SMD -0.21, 95% CI -0.39 to -0.04, I 2 = 32.9%, p = 0.017) in the SGLT-2i group compared with the placebo group. Furthermore, no significant differences were found in LVEF (SMD 0.13, 95% CI 0.00 to 0.26, I 2 = 0.0%, p = 0.050) and E/A (SMD -0.01, 95% CI -0.22 to 0.20, I 2 = 0%, p = 0.908) between the two groups. Conclusions: This meta-analysis confirmed the beneficial effects of SGLT-2i on reversal of left ventricular remodeling. The LVH regression was more pronounced in studies of type 2 diabetes patients receiving SGLT-2i than placebo.

The effectiveness and safety of prophylactic central neck dissection in clinically node-negative papillary thyroid carcinoma patients: A meta-analysis.

Objective: This meta-analysis was performed to evaluate the effectiveness and safety of prophylactic central neck dissection (PCND) in patients with clinically node-negative (cN0) papillary thyroid carcinoma. Materials and methods: A meta-analysis of the literature was performed using the key words "papillary thyroid carcinomas" and "lymph node ecisions" for searches of electronic databases. Complications such as transient hypocalcemia, permanent hypocalcemia, transient and permanent hypoparathyroidism, transient and permanent vocal cord paralysis, transient recurrent and permanent recurrent laryngeal nerve injury, and local recurrence were pooled by meta-analysis. Stata17.0 was used to carry out the meta-analysis. Results: Data were extracted from 15 studies. In the present review, the group of patients who had total thyroidectomy (TT) with PCND had a lower local recurrence than the group with TT alone (OR 0.22, 95% CI 0.10-0.45, P = 0.000), whereas the incidence of permanent hypocalcemia (OR 4.24, 95% CI 1.05-17.22, P = 0.043) and transient hypoparathyroidism (OR 2.14, 95% CI 1.34-3.42, P =0.001) were higher. No significant differences were recorded in the incidence of other complications: transient hypocalcemia (OR 2.24, 95% CI 0.77-6.51, P = 0.138), permanent hypoparathyroidism (OR 1.70, 95% CI 0.89-3.27, P = 0.111), transient vocal cord paralysis (OR 1.48, 95% CI 0.78-2.83, P = 0.231), permanent vocal cord paralysis (OR 1.44, 95% CI 0.53-3.94, P = 0.477), transient recurrent laryngeal nerve injury (OR 1.47, 95% CI 0.93-2.32, P = 0.102) and permanent recurrent laryngeal nerve injury (OR 1.24, 95% CI 0.56-2.74, P = 0.587) between the two groups. Conclusion: Compared with TT alone, TT with PCND was more effective in reducing local recurrence without increasing the risk of recurrent laryngeal nerve, thyroid and vocal cord, except for hypocalcemia and transient hypoparathyroidism. Therefore, we believe that TT with PCND should be recommended for patients with cN0 PTC. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD4202 2355078.

Biocompatible and biodegradable scaffold based on polytrimethylene carbonate-tricalcium phosphate microspheres for tissue engineering.

Biocompatible polymers and drug delivery vehicles have been driving development in bone regeneration. However, most bone scaffolds show poor degradation and proliferation. In this study, a composite microsphere scaffold was prepared using vancomycin hydrochloride(VH)-loaded polytrimethylene carbonate(PTMC) microsphere (PTMC-VH). Adopting a thermal technique, a three-dimensional oleic acid-modified tricalcium phosphate (PTMC-OA-TCP)/PTMC-VH microsphere scaffold was prepared. It had a porosity of 41-47 % and pore size of 129-154 µm. The highest drug loading and release efficiency were obtained with the scaffold produced using 2.4 % polymer concentration and 0.5 %polyvinyl alcohol. The scaffold with PTMC-VH microsphereshad enhancedmechanical properties, water absorption capacity, and degradation. In addition, the PTMC-OA-TCP scaffold had comparable performance with bone cement control in terms of bone regeneration in vivo. In summary, the prepared bioactive scaffolds, which had favorable mechanical properties and facilitated osteogenesis, could be a promising alternative for bone cement in bone tissue engineering.

Chitosan-coated hydroxyapatite and drug-loaded polytrimethylene carbonate/polylactic acid scaffold for enhancing bone regeneration.

Biocompatible polymers and drug-delivery scaffolds have driven development in bone regeneration. In this study, we fabricated a chitosan (CS)-coated polytrimethylene carbonate (PTMC)/polylactic acid (PLLA)/oleic acid-modified hydroxyapatite (OA-HA)/vancomycin hydrochloride (VH) microsphere scaffold for drug release with excellent biocompatibility. The incorporation of PLLA, OA-HA, and VH into PTMC microspheres not only slowed the biodegradability of the scaffold but also enhanced its mechanical properties and surface properties. Moreover, the CS coating stimulated extensive adhesion of osteoblasts before OA-HA incorporation, which facilitated the controlled release of OA-HA. The scaffolds were characterized via scanning electron microscopy, in vitro comprehensive performance testing, cell culturing, and microcomputer tomography scanning. The results indicated that the surface of the composite microsphere scaffold was suitable for osteoblast adhesion. Additionally, the release of OA-HA stimulated osteogenic proliferation. Our findings suggest that the CS-PTMC/PLLA/OA-HA/VH microsphere scaffold is promising for bone tissue engineering applications.

Biodegradable poly (lactic acid-co-trimethylene carbonate)/chitosan microsphere scaffold with shape-memory effect for bone tissue engineering.

Poly (lactic acid) (PLA), although extensively used as biomedical materials, has the distinct disadvantage of producing acidic byproducts which can lead to tissue inflammatory reactions and clinic failure. Here we presented a combination of Poly (lactic acid-co-trimethylene carbonate) and natural polymer chitosan, improving its compression resilience and reducing its acidic byproducts. In this case, we developed 3D scaffolds using solvent/nonsolvent technique sintered PLA-TMC and PLA-TMC/Chitosan microspheres with selected particle size (355-500 µm). By controlling the preparation methods and parameters, the porosity, pore size and mechanical properties of microsphere scaffolds can be designed and controlled. Strikingly, PLA-TMC/15 % Chitosan microsphere scaffolds possess shape-memory effect and rapidly recovered to initial shape when heated to 37℃ within 300 s. The microsphere scaffolds had a 3D porous architecture with pore size ranging from 105.67 ± 12.51 µm to 129.69 ± 11.39 µm. The mechanical and physicochemical properties of microspheres and scaffolds were characterized in details. Moreover, all microsphere scaffolds were qualified as their compressive modulus (120.36 MPa -195.32 MPa) matched the cancellous bone during 16 weeks degradation. Furthermore, CCK8 cell proliferation assay and ALP activity assay verified that the scaffolds were non-toxic and conductive to cell adhesion. The scaffolds are expected to be used in bone regeneration and bone repair field.