MSC-Exos: Important active factor of bone regeneration.

Bone defect and repair is a common but difficult problem in restorative and reconstructive surgery. Bone tissue defects of different sizes caused by different reasons bring functional limitations and cosmetic deformities to patients. Mesenchymal stem cells (MSC), a major hotspot in the field of regeneration in recent years, have been widely used in various studies on bone tissue regeneration. Numerous studies have shown that the bone regenerative effects of MSC can be achieved through exosome-delivered messages. Although its osteogenic mechanism is still unclear, it is clear that MSC-Exos can directly or indirectly support the action of bone regeneration. It can act directly on various cells associated with osteogenesis, or by carrying substances that affect cellular activators or the local internal environment in target cells, or it can achieve activation of the osteogenic framework by binding to materials. Therefore, this review aims to summarize the types and content of effective contents of MSC-Exos in bone regeneration, as well as recent advances in the currently commonly used methods to enable the binding of MSC-Exos to the framework and to conclude that MSC-Exos is effective in promoting osteogenesis.

Effect of composite biodegradable biomaterials on wound healing in diabetes.

The repair of diabetic wounds has always been a job that doctors could not tackle quickly in plastic surgery. To solve this problem, it has become an important direction to use biocompatible biodegradable biomaterials as scaffolds or dressing loaded with a variety of active substances or cells, to construct a wound repair system integrating materials, cells, and growth factors. In terms of wound healing, composite biodegradable biomaterials show strong biocompatibility and the ability to promote wound healing. This review describes the multifaceted integration of biomaterials with drugs, stem cells, and active agents. In wounds, stem cells and their secreted exosomes regulate immune responses and inflammation. They promote angiogenesis, accelerate skin cell proliferation and re-epithelialization, and regulate collagen remodeling that inhibits scar hyperplasia. In the process of continuous combination with new materials, a series of materials that can be well matched with active ingredients such as cells or drugs are derived for precise delivery and controlled release of drugs. The ultimate goal of material development is clinical transformation. At present, the types of materials for clinical application are still relatively single, and the bottleneck is that the functions of emerging materials have not yet reached a stable and effective degree. The development of biomaterials that can be further translated into clinical practice will become the focus of research.

Review of the Role of Mesenchymal Stem Cells and Exosomes Derived from Mesenchymal Stem Cells in the Treatment of Orthopedic Disease.

Exosomes can be derived from mesenchymal stem cells (MSCs) and have recently been used to treat defects in the tendons. They may also have applications in treating osteoporosis. MSC-derived exosomes communicate with mesenchymal and osteogenic cells through endocrine or paracrine mechanisms and contribute factors involved in physiological and pathological orthopedic conditions associated with hypoxia and bone tumors. Also, generalized medical conditions, such as obesity, hyperglycemia, and degenerative diseases, can inhibit the osteogenic effect of MSC-derived exosomes. This review aims to present an update on the roles of MSCs and exosomes derived from MSCs in treating orthopedic diseases, such as osteoporosis, and in the repair of cartilage, tendons, and bone fractures.

Factors Influencing Total Delay of Breast Cancer in Northeast of China.

Objectives: Delay in diagnosis and treatment, called total delay, could probably result in lower survival rates in breast cancer patients. This study aimed to investigate the factors associated with the comprehensive delay behaviors and to evaluate its effect on outcomes in patients with breast cancer in Dalian, a northeast city of China. Methods: A retrospective chart review was conducted using a cancer registry dataset including 298 patients. The Kaplan-Meier survival analysis was used to identify the threshold of total delay, dividing the patients into a group with significant uncertainty and a group without substantial delay. The factors associated with the significant total delay were investigated from the potential candidates, like income level and marital status, by using the chi-squared test. The difference of the clinicopathologic characteristics between the patients grouped by the significant total delay, like tumor size and lymph node metastasis, was also investigated to find out the effect of the total delay. Results: A total of 238 charts were used for analysis. The mean age was 57.3. The median of total delays was 3.75 months. Thirty days was identified as a threshold, more than which the total delay can lead to worse survival. Patients' marital status (p = 0.010), income levels (p = 0.003), smoking status (p = 0.031), initial visiting hospital level (p = 0.005), self-health care (p = 0.001), and self-concern about initial symptom (p ≈ 0.000) were identified as the independent predictors of the total delay. Metastasis (p ≈ 0.000) was identified as the significant result relating to the significant total delay. Conclusions: A total delay of more than 30 days predicts worse survival in breast cancer patients in Dalian. Several factors, like patients' marital status and income levels, can be considered to be relevant to the significant total delay. We recommend that these factors be used to predict the potential patients with the significant total delay in the clinical practice.

Corrigendum: Effect of composite biodegradable biomaterials on wound healing in diabetes.

[This corrects the article DOI: 10.3389/fbioe.2022.1060026.].

Nanodelivery of a self-assembling prodrug with exceptionally high drug loading potentiates chemotherapy efficacy.

Nanomedicines have achieved several successful clinical applications for cancer therapy over the past decades. To date, numerous nanomedicine formats and design rationales have been proposed to improve pharmaceutical delivery and treatment efficacy. Despite these advances, the achievement of high drug loading and loading efficiencies of drug payloads in nanocarriers remains a technical challenge. In addition, study of the correlation between therapeutic potential and drug loading has been ignored. Here, using a self-assembling dimeric cabazitaxel prodrug, we show that the prodrug can be quantitatively entrapped within clinically approved polymer matrices for intravenous injection and that the drug loading in the nanoparticles (NPs) is tunable. The engineered NPs (NPs1-4) with different drug loading values exhibit dissimilar morphologies, release kinetics, in vitro cytotoxic activity, pharmacokinetic properties, tissue distribution, and in vivo anticancer efficacy and safety profiles. Furthermore, the effect of drug loading on the treatment outcomes was explored through detailed in vitro and in vivo studies. Intriguingly, among the constructed NPs, those comprising poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PLA) copolymers showed substantially prolonged pharmacokinetic properties in the blood circulation, which further promoted their intratumoral delivery and accumulation. Furthermore, the PEG-PLA-composed NPs with high drug loading (~50%) demonstrated favorable efficacy and safety profile in animal models. These data provide convincing evidence that the in vivo performance of a given self-assembling drug is not compromised by high drug loading in nanoplatforms, which may potentially reduce concerns over excipient-associated side effects and immunotoxicities. Overall, our study provides new insight into the rationale for designing more effective and less toxic delivery systems.