Nanoparticle-Based Drug Delivery Systems for Enhancing Bone Regeneration.

The treatment of bone defects has been a long-standing challenge in clinical practice. Among the various bone tissue engineering approaches, there has been substantial progress in the development of drug delivery systems based on functional drugs and appropriate carrier materials owing to technological advances in recent years. A large number of materials based on functional nanocarriers have been developed and applied to improve the complex osteogenic microenvironment, including for promoting osteogenic activity, inhibiting osteoclast activity, and exerting certain antibacterial effects. This Review discusses the physicochemical properties, drug loading mechanisms, advantages and disadvantages of nanoparticles (NPs) used for constructing drug delivery systems. In addition, we provide an overview of the osteogenic microenvironment regulation mechanism of drug delivery systems based on nanoparticle (NP) carriers and the construction strategies of drug delivery systems. Finally, the advantages and disadvantages of NP carriers are summarized along with their prospects and future research trends in bone tissue engineering. This Review thus provides advanced strategies for the design and application of drug delivery systems based on NPs in the treatment of bone defects.

Dual-functional thermosensitive hydrogel for reducing infection and enhancing bone regeneration in infected bone defects.

The contamination of bone defects is a serious therapeutic problem. The treatment of infected bone defects involves rigorous infection control followed by bone reconstruction. Considering these two processes, the development of biomaterials possessing antibacterial and osteogenic properties offers a promising approach for the treatment of infected bone defects. In this study, a dual-functional, thermosensitive, and injectable hydrogel composed of chitosan (CS), quaternized CS (QCS), and nano-hydroxyapatite (nHA) was designed, and the ratio of CS to QCS in the hydrogel was optimized to enhance the antibacterial efficacy of CS while reducing the cytotoxicity of QCS. In vitro studies demonstrated that the hydrogel with an 85 %:15 % ratio of CS to QCS exhibited excellent biocompatibility and antibacterial properties while also possessing suitable mechanical characteristics and degradability. The incorporation of nHA into the hydrogel enhanced MC3T3-E1 proliferation and osteogenic differentiation. Moreover, this hydrogel demonstrated superior in vivo therapeutic effectiveness in a rabbit model of infected bone defect. In summary, this study provides a promising material design and a comprehensive one-step treatment strategy for infected bone defects.

Drug delivery systems based on polyethylene glycol hydrogels for enhanced bone regeneration.

Drug delivery systems composed of osteogenic substances and biological materials are of great significance in enhancing bone regeneration, and appropriate biological carriers are the cornerstone for their construction. Polyethylene glycol (PEG) is favored in bone tissue engineering due to its good biocompatibility and hydrophilicity. When combined with other substances, the physicochemical properties of PEG-based hydrogels fully meet the requirements of drug delivery carriers. Therefore, this paper reviews the application of PEG-based hydrogels in the treatment of bone defects. The advantages and disadvantages of PEG as a carrier are analyzed, and various modification methods of PEG hydrogels are summarized. On this basis, the application of PEG-based hydrogel drug delivery systems in promoting bone regeneration in recent years is summarized. Finally, the shortcomings and future developments of PEG-based hydrogel drug delivery systems are discussed. This review provides a theoretical basis and fabrication strategy for the application of PEG-based composite drug delivery systems in local bone defects.

Reverse-traction skin-stretching device for primary closure of large skin defects.

The tension in the skin margin of a wound is the major determinant for wound healing. The difficulty of primary closure for large skin defects due to excessive wound tension has long been a clinical challenge. In this study, we designed and fabricated a reverse-traction skin-stretching device (RT-SSD) to relieve the skin tension of a large skin defect and thereby allow primary wound closure. The novel RT-SSD designed in this study drives the fixing device fixed on the skin edge of the wound by rotating the pulling device, thus exerting a reverse tensile force on both sides of the wound, causing creep and stress relaxation, thus reducing the skin tension. Through the tension analyses; microcirculation detection; clinical scores; and a series of histological staining in vivo, it is verified that intraoperative application of RT-SSD can stretch and straighten collagen and fragment elastin, thus effectively reducing skin tension of large skin defect of miniature pigs. In addition, its special linear and planar traction protects the subcutaneous microcirculation of the wound site. The evaluation of wound healing confirmed that RT-SSD had negligible negative impact on wounds, reduced the incidence of complications, and promoted the healing of large skin defects. Therefore, this study provides a new safe and effective device for the primary closure of large skin defects.

Minimally invasive plate osteosynthesis for complex comminuted bone fractures in the Fraser's type II floating knee: a case report.

OBJECTIVE: Floating knee type IIC, according to Fraser's classification, is an uncommon severe injury that typically occurs in polytrauma. In such cases, intra-articular fracture and the high degree of comminution and deformity of the mid-distal femur make fixation challenging. The purpose of this study was to demonstrate that minimally invasive plate osteosynthesis (MIPO) technology can simplify these complex problems and improve patient prognosis. CASE PRESENTATION: A 38-year-old man injured his left leg in a car accident, causing pain, swelling, deformity, and limited mobility on his left knee and thigh, and two small open wounds were noted mainly of the anterior aspect of the mid-distal thigh. Physical examination and computed tomography angiography of the lower limb confirmed that there was no damage to the neurovascular system. The clinical diagnosis was closed intra-articular fracture of the proximal tibia, open intra-articular fracture of the distal femur with extension to the diaphysis, and a patellar fracture on the ipsilateral knee. The treatment strategy involved a locking plate system applying MIPO technology. Postoperative evaluation of the patient was satisfactory, with immediate functional exercise, full weight-bearing after three months, and return to daily activity without pain. Final follow-up taken 3 years after surgery showed good lower limb alignment and complete plasticity of the bone structure, by which time the patient showed good limb function. CONCLUSIONS: Minimally invasive techniques can provide a simple and effective treatment for some complex fractures.

TAT­fused IP3R­derived peptide enhances cisplatin sensitivity of ovarian cancer cells by increasing ER Ca2+ release.

Ovarian cancer is the most common gynecological malignancy. At present, cisplatin is used to treat ovarian cancer; however, the development of cisplatin resistance during therapy is a common obstacle to achieving favorable outcomes. Recently, the B­cell lymphoma 2 (Bcl­2) BH4 domain has been reported to mediate the prosurvival activity of Bcl­2 in cancer; however, the involvement of the BH4 domain of Bcl­2 in the cisplatin resistance of ovarian carcinoma cells is not entirely clear. In this study, we observed the cytoplasmic and mitochondrial levels of Ca2+ by confocal laser microscopy. We also detected cell apoptosis using western blot analysis and flow cytometry. The present study demonstrated that TAT­fused inositol 1,4,5­trisphosphate receptor­derived peptide (TAT­IDPS), which targets the BH4 domain of Bcl­2, increased cisplatin­induced Ca2+ flux from the endoplasmic reticulum (ER) into the cytosol and mitochondria. In addition, TAT­IDPS increased cisplatin­induced expression of mitochondrial apoptosis­associated proteins and ER stress­associated proteins. These results indicated that TAT­IDPS may enhance the cytotoxicity of cisplatin toward ovarian carcinoma cells by increasing ER Ca2+ release.