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Background Alveolar Bone loss occurs frequently during the first six months after tooth extraction. Various studies have proposed different methods to reduce as much as possible the atrophy of the alveolar ridge after tooth extraction. Filling the socket with biomaterials after extraction can reduce the resorption of the alveolar ridge. We compared the height of the alveolar process at the mesial and distal aspects of the extraction site and the resorption rate was calculated after the application of HA/β-TCP or synthetic co-polymer polyglycolic - polylactic acid PLGA mixed with blood to prevent socket resorption immediately and after tooth extraction. Methods The study was conducted on 24 extraction sockets of impacted mandibular third molars bilaterally, vertically, and completely covered, with a thin bony layer. HA/β-TCP was inserted into 12 of the dental sockets immediately after extraction, and the synthetic polymer PLGA was inserted into 12 of the dental sockets. All sockets were covered completely with a full-thickness envelope flap. Follow-up was performed for one year after extraction, using radiographs and stents for the vertical alveolar ridge measurements. Results The mean resorption rate in the HA/β-TCP and PLGA groups was ± 1.23 mm and ± 0.1 mm, respectively. A minimal alveolar bone height reduction of HA/β-TCP was observed after 9 months, the reduction showed a slight decrease to 0.93 mm, while this rate was 0.04 mm after 9 months in the PLGA group. Moreover, the bone height was maintained after three months, indicating a good HA/β-TCP graft performance in preserving alveolar bone (1.04 mm) while this rate was (0.04 mm) for PLGA. Conclusion The PLGA graft demonstrated adequate safety and efficacy in dental socket preservation following tooth extraction. However, HA/β-TCP causes greater resorption at augmented sites than PLGA, which clinicians should consider during treatment planning.

Radiofrequency ablation (RFA) is clinically adopted to destruct solid tumors, but is often incapable of completely ablating large tumors and those with multiple metastatic sites. Here we develop a CaCO 3 -assisted double emulsion method to encapsulate lipoxidase and hemin with poly(lactic-co-glycolic acid) (PLGA) to enhance RFA. We show the HLCaP nanoreactors (NRs) with pH-dependent catalytic capacity can continuously produce cytotoxic lipid radicals via the lipid peroxidation chain reaction using cancer cell debris as the fuel. Upon being fixed inside the residual tumors post RFA, HLCaP NRs exhibit a suppression effect on residual tumors in mice and rabbits by triggering ferroptosis. Moreover, treatment with HLCaP NRs post RFA can prime antitumor immunity to effectively suppress the growth of both residual and metastatic tumors, also in combination with immune checkpoint blockade. This work highlights that tumor-debris-fueled nanoreactors can benefit RFA by inhibiting tumor recurrence and preventing tumor metastasis. Radiofrequency ablation (RFA) is a minimally invasive tumor ablation method, however incomplete ablation and the induction of an immunosuppressive microenvironment limit its efficacy in the clinic. Here the authors design a pH-responsive lipoxidase-loaded nanoreactor, that by triggering ferroptosis and anti-tumor immunity, amplify the therapeutic benefits of RFA in preclinical models.

Cisplatin (CDDP) is a potent chemotherapeutic drug, but its severe side-effects often prohibit its use. Combined treatment with CDDP plus Farnesol (FAR) and their co-encapsulated nano form were investigated in in vitro to examine if synergistic cytotoxicity of this combination could reduce unwanted side-effects of CDDP chemotherapy and potentiate CDDP anticancer activity against hepatocellular carcinoma (HCC) cells. After finding combination therapy of CDDP and FAR successfully combat HCC we formulated co-encapsulation of CDDP and FAR within poly(lactic-co-glycolic acid) copolymer (NCDDPFAR) by following the standardized solvent displacement method. NCDDPFAR treatment caused faster drug mobility, sustained particle release, site-specific action and higher percentage of apoptotic death compared with single drug treatment even at relatively low concentrations. Co-encapsulation of two drugs exhibited additive effects against HCC; FAR reduced CDDP-induced glutathione level by increasing expression of CYP2E1 while CDDP directly interacted with DNA; FAR up-regulated the expression of TopII, thereby promoting DNA breaks and escaping DNA repair machinery. Expression pattern of apoptotic genes like p53, Bax, cytochrome c and caspase-3 suggested that NCDDPFAR induced HCC cell death through mitochondrial intrinsic pathway. Administration of NCDDPFAR had better ability of drug carriage and enhanced anticancer potentials against HCC cells.

Background and Objectives: Implant-associated complications, including foreign-body responses and infection risk, remain major concerns in reconstructive and aesthetic breast surgery. Antimicrobial polymer coatings have been proposed as potential preventive strategies, but early-stage development requires simple and ethically refined in vivo models. This pilot study aimed to (i) establish a practical workflow for applying PLGA–vancomycin coatings onto PTFE substrates used as experimental analogs for smooth silicone implants, and (ii) develop a small-animal implantation protocol for short-term evaluation of surgical feasibility and local tissue tolerability. Materials and Methods: PLGA microparticles and PLGA–vancomycin microparticles were prepared using a double-emulsion solvent-evaporation method and applied onto PTFE discs. Particle size and polydispersity were assessed based on dynamic light scattering (DLS), and surface charge was measured via zeta potential. A bilateral subcutaneous implantation model was used in four Wistar rats, each receiving a PTFE disc coated with PLGA-only on one side and a disc coated with PLGA–vancomycin on the other. Animals were monitored for postoperative recovery, wound appearance, and general condition. After four weeks, implants and surrounding tissues were harvested for macroscopic and preliminary histological evaluation. Results: Both PLGA-only and PLGA–vancomycin microparticles showed submicron mean hydrodynamic diameters and moderately polydisperse distributions typical for double-emulsion formulations. All animals recovered normally, maintained stable body weight, and exhibited no macroscopic signs of adverse reactions. Preliminary histology showed early fibrous capsule formation with mild inflammatory infiltrate around both types of coated implants, without qualitative differences observed in this pilot setting. Conclusions: This preliminary study demonstrates the feasibility of applying PLGA-only and PLGA–vancomycin coatings onto PTFE implant analogs and establishes a reproducible, minimal-use rat model for short-term evaluation of local tissue tolerability. The protocol provides a practical foundation for future work on coating stability, drug-release kinetics, antibacterial activity, and long-term tissue responses on medical-grade silicone substrates.

Pseudomonas aeruginosa is the major infectious agent of concern for cystic fibrosis (CF) patients. Therefore, it is necessary to develop appropriate strategies for preventing colonization by this bacterium and/or neutralizing virulence factors. In this study, we formulated the encapsulation of exotoxin A into PLGA nanoparticles. The biological activities of the nanovaccine candidate were also characterized. Based on the results, ETA-PLGA can act as a suitable immunogen to stimulate the humoral and cellular immune response. The antibodies raised against ETA-PLGA significantly decreased bacterial titer in the spleens of the immunized mice after challenge with PAO1 strain, compared to the control groups. The encapsulation of PLGA into ETA led to a significantly higher production of INF-γ, TNF-α, IL-4, and IL-17A cytokine responses compared to the ETA group. ETA-PLGA enhanced IgG responses in immunized mice compared to ETA antigen. We concluded that encapsulation of Pseudomonas aeruginosa ETA to PLGA nanoparticles can increase its functional activity by decreasing the bacterial dissemination.

The main development process of periodontitis involves periodontal pathogenic bacteria as the initiating factor causing the onset of destructive inflammation, which in turn stimulates the destruction of periodontal tissue. It is difficult to achieve the eradication of periodontitis due to the complex interaction among antibacterial, anti-inflammatory, and bone restoration. Herein, we propose an antibacterial-anti-inflammatory-bone restoration procedural treatment strategy with minocycline (MIN) for the efficient treatment of periodontitis. In brief, MIN was prepared into PLGA microspheres with tunable release behavior using different species of PLGA, respectively. The optimally selected PLGA microspheres (LA:GA with 50:50, 10 kDa, and carboxyl group) had a drug loading of 16.91%, an in vitro release of approximately 30 days, which also had a particle size of approximately 11.8 µm with a smooth appearance and a rounded morphology. The DSC and XRD results showed that the MIN was completely encapsulated in the microspheres as an amorphous state. Cytotoxicity tests demonstrated the safety and biocompatibility of the microspheres (cell viabilities at a concentration of 1–200 μg/mL were greater than 97%), and in vitro bacterial inhibition tests showed that the selected microspheres could achieve effective bacterial inhibition at the initial stage after administration. The favorable anti-inflammatory (low TNF-α and IL-10 levels) and bone restoration effects (BV/TV: 71.8869%; BMD: 0.9782 g/cm 3 ; TB.Th: 0.1366 mm; Tb.N: 6.9318 mm −1 ; Tb.Sp: 0.0735 mm) were achieved in a SD rat periodontitis model after administering once a week for four weeks. The MIN-loaded PLGA microspheres were proved to be an efficient and safe treatment for periodontitis by procedural antibacterial, anti-inflammatory, and bone restoration. Graphical Abstract

Surgery of the chest wall is potentially required to cover large defects after  removal of malignant tumours. Usually, inert and non-degradable Gore-Tex serves to replace the missing tissue. However, novel biodegradable materials combined with stem cells are available that stimulate the healing. Based on poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/aCaP) and pure PLGA, a dual layer biodegradable hybrid nanocomposite was generated. Mouse adipose-derived stem cells were cultered on electrospun disks (ASCs of C57BL/6), and biomechanical tests were performed. The cell-seeded scaffolds were engrafted in C57BL/LY5.1 mice to serve as a chest wall substitute. Cell invasion into the bi-layered material, extent of CD45 + cells, inflammatory response, neo-vascularization and ECM composition were determined at 1 and 2 months post-surgery, respectively. The bi-layered hybrid nanocomposite was stable after a 2-week in vitro culture, in contrast to PLGA/aCaP without a PLGA layer. There was a complete biointegration and good vascularization in vivo . The presence of ASCs attracted more CD45 + cells (hematopoietic origin) compared to cell-free scaffolds. Inflammatory reaction was similar for both groups (±ASCs) at 8 weeks. A bi-layered hybrid nanocomposite fabricated of electrospun PLGA/aCaP and a reinforcing layer of pristine PLGA is an ideal scaffold for chest wall reconstruction. It is stable and allows a proper host tissue integration. If ASCs are seeded, they attract more CD45 + cells, supporting the regeneration process.

Purpose The aim of this study is to follow morphological imaging characteristics and osteointegration of TruFit® bone graft substitute (BGS) plugs in cases of chondral and osteochondral defects of the articular surface of the knee joint, using high-quality cartilage-sensitive 3-T magnetic resonance imaging (MRI), linked to clinical outcomes.MethodsThe MRI was used to assess osteointegration and biological evolution of the TruFit® BGS plugs in cases with minimum 5-year follow-up: The TruFit® plug was used in 46 patients for a total of 47 cases with mean age of 57.89 (range 32–80). In this study, we reviewed only the cases with minimum follow-up of 5 years: 5 patients with mean age 64.4 years (minimum 38, maximum 80). The mean follow-up was 71 months (range 63–77). Patients were evaluated clinically, with Lysholm Knee Scoring Scale and MOCART Scale.Results3-T MRI, which is preferable to 1.5 T for the better signal-to-noise ratio, contrast and the ability to acquire morphological images at higher spatial resolution, shows a satisfactory integration of bone scaffolds in studied cases for more than 5 years and a satisfactory restoration of the articular cartilage, with the exception of a case of which we still have to consider the factors age, type of lesion and the relationship between the plugs implanted.ConclusionClinical and radiological results significantly improve in a longer follow-up time.

Developing new strategies to reduce the output power of microwave (MW) ablation while keeping anti-tumor effect are highly desirable for the simultaneous achievement of effective tumor killing and avoidance of complications. We find that mild MW irradiation can significantly increase intracellular Ca concentration in the presence of doxorubicin hydrochloride (DOX) and thus induce massive tumor cell apoptosis. Herein, we designed a synergistic nanoplatform that not only amplifies the intracellular Ca concentration and induce cell death under mild MW irradiation but also avoids the side effect of thermal ablation and chemotherapy. The as-made NaCl-DOX@PLGA nanoplatform selectively elevates the temperature of tumor tissue distributed with nanoparticles under low-output MW, which further prompts the release of DOX from the PLGA nanoparticles and tumor cellular uptake of DOX. More importantly, its synergistic effect not only combines thermal ablation and chemotherapy, but also obviously increases the intracellular Ca concentration. Changes of Ca broke the homeostasis of tumor cells, decreased the mitochondrial inner membrane potential and finally induced the cascade of apoptosis under nonlethal temperature. As such, the NaCl-DOX@PLGA efficiently suppressed the tumor cell progression in vivo and in vitro under mild MW irradiation for the triple synergic effect. This work provides a biocompatible and biodegradable nanoplatform with triple functions to realize the effective tumor killing in unlethal temperature. Those findings provide reliable solution to solve the bottleneck problem bothering clinics about the balance of thermal efficiency and normal tissue protection.

Triamcinolone acetonide extended-release (ER) 32 mg (Zilretta ® ) is approved in the USA for the management of osteoarthritis (OA) pain of the knee and is administered as a single, 5 mL intra-articular (IA) injection. Although the therapeutic effects from IA corticosteroids are typically short-lived, triamcinolone acetonide ER is formulated in poly (lactic-co-glycolic acid) (PLGA) microspheres that slowly release triamcinolone acetonide in the synovium, enabling their prolonged presence in the joint. This reduces systemic exposure and lessens corticosteroid-related systemic adverse reactions, such as blood glucose elevations. In a 24-week, randomized, phase III clinical trial, triamcinolone acetonide ER 32 mg significantly improved mean average daily pain intensity in patients with knee OA relative to placebo, and pain, stiffness and physical function (according to WOMAC criteria) relative to placebo and triamcinolone acetonide crystalline suspension (CS). Triamcinolone acetonide ER was generally well tolerated, with a tolerability profile similar to that of triamcinolone acetonide CS and placebo. Findings from a single-arm phase IIIb study indicated that a repeat administration of triamcinolone acetonide ER may be similarly efficacious to an initial injection without having deleterious effects on cartilage or other aspects of joint structure. Thus, triamcinolone acetonide ER expands the treatment options available for the management of OA pain of the knee.