Cell-scaffold interactions in the bone tissue engineering triad (original) (raw)
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Porosity of 3D biomaterial scaffolds and osteogenesis
Biomaterials, 2005
Porosity and pore size of biomaterial scaffolds play a critical role in bone formation in vitro and in vivo. This review explores the state of knowledge regarding the relationship between porosity and pore size of biomaterials used for bone regeneration. The effect of these morphological features on osteogenesis in vitro and in vivo, as well as relationships to mechanical properties of the scaffolds, are addressed. In vitro, lower porosity stimulates osteogenesis by suppressing cell proliferation and forcing cell aggregation. In contrast, in vivo, higher porosity and pore size result in greater bone ingrowth, a conclusion that is supported by the absence of reports that show enhanced osteogenic outcomes for scaffolds with low void volumes. However, this trend results in diminished mechanical properties, thereby setting an upper functional limit for pore size and porosity. Thus, a balance must be reached depending on the repair, rate of remodeling and rate of degradation of the scaffold material. Based on early studies, the minimum requirement for pore size is considered to be $100 mm due to cell size, migration requirements and transport. However, pore sizes 4300 mm are recommended, due to enhanced new bone formation and the formation of capillaries. Because of vasculariziation, pore size has been shown to affect the progression of osteogenesis. Small pores favored hypoxic conditions and induced osteochondral formation before osteogenesis, while large pores, that are well-vascularized, lead to direct osteogenesis (without preceding cartilage formation). Gradients in pore sizes are recommended for future studies focused on the formation of multiple tissues and tissue interfaces. New fabrication techniques, such as solid-free form fabrication, can potentially be used to generate scaffolds with morphological and mechanical properties more selectively designed to meet the specificity of bonerepair needs. r
Scaffold Structural Microenvironmental Cues to Guide Tissue Regeneration in Bone Tissue Applications
Nanomaterials, 2018
In the process of bone regeneration, new bone formation is largely affected by physico-chemical cues in the surrounding microenvironment. Tissue cells reside in a complex scaffold physiological microenvironment. The scaffold should provide certain circumstance full of structural cues to enhance multipotent mesenchymal stem cell (MSC) differentiation, osteoblast growth, extracellular matrix (ECM) deposition, and subsequent new bone formation. This article reviewed advances in fabrication technology that enable the creation of biomaterials with well-defined pore structure and surface topography, which can be sensed by host tissue cells (esp., stem cells) and subsequently determine cell fates during differentiation. Three important cues, including scaffold pore structure (i.e., porosity and pore size), grain size, and surface topography were studied. These findings improve our understanding of how the mechanism scaffold microenvironmental cues guide bone tissue regeneration.
Biomaterials, 2010
In the literature there are conflicting reports on the optimal scaffold mean pore sizerequired for successful bone tissue engineering. This study set out to investigate the effectof mean pore size, in a series of collagen- glycosaminoglycan (CG) scaffolds with meanpore sizes ranging from 85 µm – 325 µm, on osteoblast adhesion and early stageproliferation up to 7 days post seeding. The results show that cell number was highest inscaffolds with the largest pore size of 325 µm. However, an early additional peak in cellnumber was also seen in scaffolds with a mean pore size of 120 µm at time points up to48 hours post-seeding. This is consistent with previous studies from our laboratory whichsuggest that scaffold specific surface area plays an important role on initial cell adhesion.This early peak disappears following cell proliferation indicating that while specificsurface area may be important for initial cell adhesion, improved cell migration providedby scaffolds with pores above 300 µm overcomes this effect. An added advantage of thelarger pores is a reduction in cell aggregations that develop along the edges of thescaffolds. Ultimately scaffolds with a mean pore size of 325 µm were deemed optimal forbone tissue engineering
Porous scaffolds for bone regeneration
Journal of Science: Advanced Materials and Devices, 2020
Globally, bone fractures due to osteoporosis occur every 20 s in people aged over 50 years. The significant healthcare costs required to manage this problem are further exacerbated by the long healing times experienced with current treatment practices. Novel treatment approaches such as tissue engineering, is using biomaterial scaffolds to stimulate and guide the regeneration of damaged tissue that cannot heal spontaneously. Scaffolds provide a three-dimensional network that mimics the extra cellular microenvironment supporting the viability, attachment, growth and migration of cells whilst maintaining the structure of the regenerated tissue in vivo. The osteogenic capability of the scaffold is influenced by the interconnections between the scaffold pores which facilitate cell distribution, integration with the host tissue and capillary ingrowth. Hence, the preparation of bone scaffolds with applicable pore size and interconnectivity is a significant issue in bone tissue engineering. To be effective however in vivo, the scaffold must also cope with the requirements for physiological mechanical loading. This review focuses on the relationship between the porosity and pore size of scaffolds and subsequent osteogenesis, vascularisation and scaffold degradation during bone regeneration.
Porous scaffold architecture guides tissue formation
Journal of Bone and Mineral Research, 2012
Critical-sized bone defect regeneration is a remaining clinical concern. Numerous scaffold-based strategies are currently being investigated to enable in vivo bone defect healing. However, a deeper understanding of how a scaffold influences the tissue formation process and how this compares to endogenous bone formation or to regular fracture healing is missing. It is hypothesized that the porous scaffold architecture can serve as a guiding substrate to enable the formation of a structured fibrous network as a prerequirement for later bone formation. An ovine, tibial, 30-mm critical-sized defect is used as a model system to better understand the effect of the scaffold architecture on cell organization, fibrous tissue, and mineralized tissue formation mechanisms in vivo. Tissue regeneration patterns within two geometrically distinct macroscopic regions of a specific scaffold design, the scaffold wall and the endosteal cavity, are compared with tissue formation in an empty defect (negative control) and with cortical bone (positive control). Histology, backscattered electron imaging, scanning small-angle X-ray scattering, and nanoindentation are used to assess the morphology of fibrous and mineralized tissue, to measure the average mineral particle thickness and the degree of alignment, and to map the local elastic indentation modulus. The scaffold proves to function as a guiding substrate to the tissue formation process. It enables the arrangement of a structured fibrous tissue across the entire defect, which acts as a secondary supporting network for cells. Mineralization can then initiate along the fibrous network, resulting in bone ingrowth into a critical-sized defect, although not in complete bridging of the defect. The fibrous network morphology, which in turn is guided by the scaffold architecture, influences the microstructure of the newly formed bone. These results allow a deeper understanding of the mode of mineral tissue formation and the way this is influenced by the scaffold architecture. ß
Tissue engineering of bone: search for a better scaffold
Orthodontics and Craniofacial Research, 2005
Structured Abstract Authors -Mastrogiacomo M, Muraglia A, Komlev V, Peyrin F, Rustichelli F, Crovace A, Cancedda R Background -Large bone defects still represent a major problem in orthopedics. Traditional bone-repair treatments can be divided into two groups: the bone transport (Ilizarov technology) and the graft transplant (autologous or allogeneic bone grafts). Thus far, none of these strategies have proven to be always resolving. As an alternative, a tissue engineering approach has been proposed where osteogenic cells, bioceramic scaffolds, growth factors and physical forces concur to the bone defect repair. Different sources of osteoprogenitor cells have been suggested, bone marrow stromal cells (BMSC) being in most cases the first choice. Methods and Results -In association with mineral tridimensional scaffolds, BMSC form a primary bone tissue which is highly vascularized and colonized by host hemopoietic marrow. The chemical composition of the scaffold is crucial for the osteoconductive properties and the resorbability of the material. In addition, scaffolds should have an internal structure permissive for vascular invasion. Porous bioceramics [hydroxyapatite (HA) and tricalcium phosphate] are osteoconductive and are particularly advantageous for bone tissue engineering application as they induce neither an immune nor an inflammatory response in the implanted host.
Osteoblast Behavior on Novel Porous Polymeric Scaffolds
Journal of Biomaterials and Tissue Engineering, 2011
Current efforts in bone tissue engineering have as one focus the search for a scaffold material that supports osteoblast proliferation, matrix mineralization, and, ultimately, bone formation. Electrospraying of polymer solutions has enabled the engineering of porous materials to meet current challenges in bone replacement therapies. Porous scaffolds of poly(-caprolactone)/poly(diisopropyl fumarate) compatibilized blend for bone tissue engineering were obtained by electrospraying technique in order to create a better osteophilic environment for the growth and differentiation of osteoblasts. Non-porous films having smooth surface were obtained by casting and used for comparison purposes. Studies on cell-scaffold interaction were carried out by culturing two osteoblastlike cell lines, MC3T3E1 and UMR106, on three-dimensional scaffolds and two-dimensional films. Growth, proliferation, and differentiation (alkaline phosphatase activity) of osteoblasts, were assessed. Scaffolds displayed a highly porous structure with interconnected pores formed by polymer microparticles, and higher hydrophobicity than the observed in non-porous films. The adhesion, proliferation and alkaline phosphatase activity of cells grown on the porous scaffolds increased significantly in comparison to those observed on flat films. The rough surface morphology of this novel scaffold enhances osteoblast response. These results suggest that electrosprayed porous scaffolds may be potentially used as tissue engineering scaffolds with high bone regenerative efficacy.
Biomaterials as Scaffold for Bone Tissue Engineering
European Journal of Trauma, 2006
Almost 20 years after the invention of tissue engineering, autogenous bone grafting has remained the favored strategy for the treatment of bone defects. As an alternative, a vast variety of bone substitutes has been developed and is available for clinical use. The ongoing search for bone substitutes, however, reflects the limitations imposed to both autogenous and allogenous bone grafts as well as to bone substitute materials. The concept of tissue engineering holds great promise for the future treatment of osseous defects. Research in this interdisciplinary field is carried out to find a way of producing biologic substitutes as functional tissue replacement. For this, functionally active cells are applied on supporting scaffolds under controlled stimulation with growth factors. Scaffolds are temporary matrices for bone growth and provide a specific environment and architecture for tissue development. Ideally, scaffolds favor cellular attachment, growth and differentiation in vitro and in vivo. Especially ceramics and biodegradable polymers are widely used and have been tested in various animal studies. Yet, to allow for precise production of specific custom-made scaffolds, rapid prototyping (RP) techniques have recently drawn a lot of attention. Using these methods scaffolds with a predefined, well-controlled internal and external architecture mimicking the structure of natural bone can be generated. Although biocompatibility of the materials used in the process and the structural resolution that can be technically achieved so far limit the range of use, rapid manufacturing techniques do offer great opportunities to generate suitable scaffolds for bone tissue engineering in the near future.