Bifunctional tissue-engineered composite construct for bone regeneration: The role of copper and fibrin.

Bifunctional tissue engineering constructs promoting osteogenesis and angiogenesis are essential for bone regeneration. Metal ion-incorporated scaffolds and fibrin encapsulation attract much attention due to low cost, nontoxicity, and tunable control over ion and growth factor release. Herein, we investigated the effect of Cu.nHA/Cs/Gel scaffold and fibrin encapsulation on osteogenic and angiogenic differentiation of Wharton's jelly mesenchymal stem cells (WJMSCs) in vitro and in vivo. Cu-laden scaffolds were synthesized using salt leaching/freeze drying and were characterized using standard techniques. WJMSCs were isolated from the human umbilical cord and characterized. WJMSCs with or without encapsulating in fibrin were seeded onto scaffolds, followed by differentiating into the osteogenic lineage for 7 and 21 days. Osteogenic and angiogenic differentiation were evaluated using real-time polymerase chain reaction, western blot, and Alizarin red staining. Then, scaffolds were implanted into critical-sized calvarial bone defects in rats and histological assessments were performed using hematoxylin/eosin, Masson's trichrome, and CD31 immunohistochemical staining at 4 and 12 weeks. The scaffolds had good physicochemical and biological characteristics suitable for cell attachment and growth. Cu and fibrin increased the expression of ALP, RUNX2, OCN, COLI, VEGF, and HIF1α in differentiated WJMSCs. Implanted scaffolds were also biocompatible and were integrated well with the host tissue. Increased collagen condensation, mineralization, and blood vessel formation were observed in Cu-laden scaffolds. The fibrin-encapsulated groups showed the highest collagen and cell densities, immune cell infiltration, and bone trabeculae. CD31-positive cell population increased with fibrin encapsulation and seeding onto Cu-laden scaffolds. Adding Cu to scaffolds and encapsulating cells in fibrin are promising methods that guide osteogenesis and angiogenesis cellular signaling, leading to better bone regeneration.

The progressive trend of modeling and drug screening systems of breast cancer bone metastasis.

Bone metastasis is considered as a considerable challenge for breast cancer patients. Various in vitro and in vivo models have been developed to examine this occurrence. In vitro models are employed to simulate the intricate tumor microenvironment, investigate the interplay between cells and their adjacent microenvironment, and evaluate the effectiveness of therapeutic interventions for tumors. The endeavor to replicate the latency period of bone metastasis in animal models has presented a challenge, primarily due to the necessity of primary tumor removal and the presence of multiple potential metastatic sites.The utilization of novel bone metastasis models, including three-dimensional (3D) models, has been proposed as a promising approach to overcome the constraints associated with conventional 2D and animal models. However, existing 3D models are limited by various factors, such as irregular cellular proliferation, autofluorescence, and changes in genetic and epigenetic expression. The imperative for the advancement of future applications of 3D models lies in their standardization and automation. The utilization of artificial intelligence exhibits the capability to predict cellular behavior through the examination of substrate materials' chemical composition, geometry, and mechanical performance. The implementation of these algorithms possesses the capability to predict the progression and proliferation of cancer. This paper reviewed the mechanisms of bone metastasis following primary breast cancer. Current models of breast cancer bone metastasis, along with their challenges, as well as the future perspectives of using these models for translational drug development, were discussed.

Application of nano-radiosensitizers in combination cancer therapy.

Radiosensitizers are compounds or nanostructures, which can improve the efficiency of ionizing radiation to kill cells. Radiosensitization increases the susceptibility of cancer cells to radiation-induced killing, while simultaneously reducing the potentially damaging effect on the cellular structure and function of the surrounding healthy tissues. Therefore, radiosensitizers are therapeutic agents used to boost the effectiveness of radiation treatment. The complexity and heterogeneity of cancer, and the multifactorial nature of its pathophysiology has led to many approaches to treatment. The effectiveness of each approach has been proven to some extent, but no definitive treatment to eradicate cancer has been discovered. The current review discusses a broad range of nano-radiosensitizers, summarizing possible combinations of radiosensitizing NPs with several other types of cancer therapy options, focusing on the benefits and drawbacks, challenges, and future prospects.

Osteosarcoma, personalized medicine, and tissue engineering; an overview of overlapping fields of research.

INTRODUCTION: Osteosarcoma is a common bone malignancy in patients of all ages. Surgical and chemotherapy interventions fail to shrink tumor growth and metastasis. The development of efficient patient-specific therapeutic strategies for osteosarcoma is of great interest in tissue engineering and personalized medicine. The present manuscript aimed to review the advancements in tissue engineering and personalized medicine strategies to overcome osteosarcoma and the relevant biological aspects as well as the current tumor models in vitro and in vivo. RESULTS: Tissue engineering and personalized medicine contribute to gene/cell engineering and cell-based therapies specific to genomic and proteomic profiles of individual patients to improve the current treatment options. Also, tissue engineering scaffolds provide physical support to missing bones, could trap cancer cells and deliver immune cells. Taken together, these strategies suppress tumor growth, angiogenic potential, and the subsequent metastasis as well as elicit desirable immune responses against tumor mass. DISCUSSION: Advanced and high-throughput gene and protein identification technologies have facilitated the recognition of genomic and proteomic profiles of patients to design and develop patient-specific treatments. The pre-clinical studies showed promising outcomes to inhibit tumor growth and invasion but controversial results compared to clinical investigations make the importance of more clinical reports inevitable. The experimental tumor models assist the evolution of effective treatments by understanding the mechanisms of tumor progression. CONCLUSION: Tissue engineering and personalized medicine strategies seem encouraging alternatives to conventional therapies against osteosarcoma. Modeling the tumor microenvironment coupled with pre-clinical results give new intelligence into the translation of strategies into the clinic.

Recent advances in regenerative medicine strategies for cancer treatment.

Cancer stands as one of the most leading causes of death worldwide, while one of the most significant challenges in treating it is revealing novel alternatives to predict, diagnose, and eradicate tumor cell growth. Although various methods, such as surgery, chemotherapy, and radiation therapy, are used today to treat cancer, its mortality rate is still high due to the numerous shortcomings of each approach. Regenerative medicine field, including tissue engineering, cell therapy, gene therapy, participate in cancer treatment and development of cancer models to improve the understanding of cancer biology. The final intention is to convey fundamental and laboratory research to effective clinical treatments, from the bench to the bedside. Proper interpretation of research attempts helps to lessen the burden of treatment and illness for patients. The purpose of this review is to investigate the role of regenerative medicine in accelerating and improving cancer treatment. This study examines the capabilities of regenerative medicine in providing novel cancer treatments and the effectiveness of these treatments to clarify this path as much as possible and promote advanced future research in this field.

Mineralized Human Amniotic Membrane as a Biomimetic Scaffold for Hard Tissue Engineering Applications.

The human amniotic membrane (HAM) has been viewed as a potential regenerative material for a wide variety of injured tissues because of its collagen-rich content. High degradability of HAM limits its wide practical application in bone tissue engineering. In this study, the natural matrix of the decellularized amniotic membrane was developed by the double diffusion method. The results confirmed a reduction of the amniotic membrane's degradability because of the deposition of calcium and phosphate ions during the double diffusion process. Real-time PCR results showed a high expression of osteogenesis-related genes from adipose-derived mesenchymal stem cells (ADMSCs) cultured on the surface of the developed mineralized amniotic membrane (MAM). Further in vivo experiments were conducted using an MAM preseeded with ADMSCs and a critical-size rat calvarial defect model. Histopathological results confirmed that the MAM + cell sample has excellent potential in bone regeneration.