Despite considerable advances in microsurgical techniques over the past decades, bone tissue remains a challenging arena to obtain a satisfying functional and structural restoration after damage. Through the production of substituting materials mimicking the physical and biological properties of the healthy tissue, tissue engineering strategies address an urgent clinical need for therapeutic alternatives to bone autografts. By virtue of their structural versatility, polymers have a predominant role in generating the biodegradable matrices that hold the cells in situ to sustain the growth of new tissue until integration into the transplantation area (i.e., scaffolds). As compared to synthetic ones, polymers of natural origin generally present superior biocompatibility and bioactivity. Their assembly and further engineering give rise to a wide plethora of advanced supporting materials, accounting for systems based on hydrogels or scaffolds with either fibrous or porous architecture. The present review offers an overview of the various types of natural polymers currently adopted in bone tissue engineering, describing their manufacturing techniques and procedures of functionalization with active biomolecules, and listing the advantages and disadvantages in their respective use in order to critically compare their actual applicability potential. Their combination to other classes of materials (such as micro and nanomaterials) and other innovative strategies to reproduce physiological bone microenvironments in a more faithful way are also illustrated. The regeneration outcomes achieved in vitro and in vivo when the scaffolds are enriched with different cell types, as well as the preliminary clinical applications are presented, before the prospects in this research field are finally discussed. The collection of studies herein considered confirms that advances in natural polymer research will be determinant in designing translatable materials for efficient tissue regeneration with forthcoming impact expected in the treatment of bone defects.

A familiar stranger: CD34 expression and putative functions in SVF cells of adipose tissue

Human malignant hematopoietic stem and progenitor cells (HSPCs) reside in bone marrow (BM) niches, which remain challenging to explore due to limited in vivo accessibility and constraints with humanized animal models. Several in vitro systems have been established to culture patient-derived HSPCs in specific microenvironments, but they do not fully recapitulate the complex features of native bone marrow. Our group previously reported that human osteoblastic BM niches (O-N), engineered by culturing mesenchymal stromal cells within three-dimensional (3D) porous scaffolds under perfusion flow in a bioreactor system, are capable of maintaining, expanding, and functionally regulating healthy human cord blood-derived HSPCs. Here, we first demonstrate that this 3D O-N can sustain malignant CD34⁺ cells from acute myeloid leukemia (AML) and myeloproliferative neoplasm patients for up to 3 wk. Human malignant cells distributed in the bioreactor system mimicking the spatial distribution found in native BM tissue, where most HSPCs remain linked to the niches and mature cells are released to the circulation. Using human adipose tissue-derived stromal vascular fraction cells, we then generated a stromal-vascular niche and demonstrated that O-N and stromal-vascular niche differentially regulate leukemic UCSD-AML1 cell expansion, immunophenotype, and response to chemotherapy. The developed system offers a unique platform to investigate human leukemogenesis and response to drugs in customized environments, mimicking defined features of native hematopoietic niches and compatible with the establishment of personalized settings. Significance Recapitulating human blood cancers in vitro remains challenging due to the limitations of current models to culture patient-derived malignant hematopoietic stem and progenitor cells in entirely human bone marrow microenvironments. We demonstrate that progenitor cells from patients with acute myeloid leukemia and myeloproliferative neoplasms can be cultured for at least 3 wk in fully human cell-based three-dimensional osteoblastic niches engineered in perfusion bioreactors, while exhibiting key features found in native bone marrow. Furthermore, the system can be customized to include a human vascular component within the engineered stromal microenvironment, which enables investigation of human leukemogenesis under designed settings. This platform can be used to test the effectiveness of chemotherapy compounds, toward application in patient-personalized medicine.