Porous Heat-Treated Polyacrylonitrile Scaffolds for Bone Tissue Engineering

Guided bone regeneration (GBR) is a promising technique in bone tissue engineering that aims to replace lost or injured bone using resorbable scaffolds. The promotion of osteoblast adhesion, migration, and proliferation is greatly aided by GBR materials, and surface changes are critical in imitating the natural bone structure to improve cellular responses. Moreover, the interactions between bioresponsive scaffolds, growth factors (GFs), immune cells, and stromal progenitor cells are essential in promoting bone regeneration. This literature review comprehensively discusses various aspects of resorbable scaffolds in bone tissue engineering, encompassing scaffold design, materials, fabrication techniques, and advanced manufacturing methods, including three-dimensional printing. In addition, this review explores surface modifications to replicate native bone structures and their impact on cellular responses. Moreover, the mechanisms of bone regeneration are described, providing information on how immune cells, GFs, and bioresponsive scaffolds orchestrate tissue healing. Practical applications in clinical settings are presented to underscore the importance of these principles in promoting tissue integration, healing, and regeneration. Furthermore, this literature review delves into emerging areas of metamaterials and artificial intelligence applications in tissue engineering and regenerative medicine. These interdisciplinary approaches hold immense promise for furthering bone tissue engineering and improving therapeutic outcomes, leading to enhanced patient well-being. The potential of combining material science, advanced manufacturing, and cellular biology is showcased as a pathway to advance bone tissue engineering, addressing a variety of clinical needs and challenges. By providing this comprehensive narrative, a detailed, up-to-date account of resorbable scaffolds' role in bone tissue engineering and their transformative potential is offered.

The effects of collagen concentration and crosslink density on the biological, structural and mechanical properties of collagen-GAG scaffolds for bone tissue engineering

Electrospinning is a promising and versatile technique that is used to fabricate polymeric nanofibrous scaffolds for bone tissue engineering. Ideal scaffolds should be biocompatible and bioactive with appropriate surface chemistry, good mechanical properties and should mimic the natural extracellular matrix (ECM) of bone. Selection of the most appropriate material to produce a scaffold is an important step towards the construction of a tissue engineered product. Bone tissue engineering is an interdisciplinary field, where the principles of engineering are applied on bone-related biochemical reactions. Scaffolds, cells, growth factors, and their interrelation in microenvironment are the major concerns in bone tissue engineering. This review covers the latest development of biomimetic electrospun polymeric biomaterials for bone tissue engineering. It includes the brief details to bone tissue engineering along with bone structure and ideal bone scaffolds requirements. Details about various engineered materials and methodologies used for bone scaffolds development were discussed. Description of electrospinning technique and its parameters relating their fabrication, advantages, and applications in bone tissue engineering were also presented. The use of synthetic and natural polymers based electrospun nanofibrous scaffolds for bone tissue engineering and their biomineralization processes were discussed and reviewed comprehensively. Finally, we give conclusion along with perspectives and challenges of biomimetic scaffolds for bone tissue engineering based on electrospun nanofibers.

Tissue engineering (TE) is a modern approach to improve or restore tissues that has been diseased or damaged by combining the factors in growth signaling and appropriate cells to form compatible biomaterial scaffold. Bone repair has been a major global health challenge in recent decades. Bone transplantation is widely used as an effective clinical treatment for this purpose. However, there are several serious issues with transplantation, including a shortage of autologous bone, immune rejection, the risk of virus transmission with allogeneic bone, and postoperative complications. In recent years, scaffolds for bone tissue engineering have emerged as a promising alternative for bone repair. These scaffolds have porous structures that mimic the extracellular matrix, which can enhance the migration, proliferation, and differentiation of osteoblasts. This process accelerates the repair of bone defects.The usage of bioactive materials has become important tool in tissue engineering and regenerative medicine application as they are to mimic tissues mechanically, chemically, and physically. Polymeric scaffold provides numerous advantageous for tissue engineering since the physicochemical properties such as porosity, pore size, solubility and biocompatibility can be controlled. Therefore, research works were carried out to explore the potential of various materials in producing bone scaffolds in tissue engineering technology. As for both newcomers and experts, this review paper will help them to find information on various types of biomaterials in imparting or enhancing their biological properties such as biocompatibility, bacterial inhibition, tissue regeneration and cell growth, bio inertness, bioactive and resorbability for bone scaffold tissue engineering application.

Mineralized polymer scaffolds have proven to be effective biomaterials for inducing osteoinductivity in bone tissue engineering. Sequential mineralization is a promising technique for depositing minerals in three-dimensional (3D) scaffolds. Paper, which is made of cellulose fibers, can be used as a tissue scaffold due to its highly porous structure and flexibility, as well as its excellent ability to wick fluids and support the growth of bone cells. In this study, paper-based, mineralized scaffolds were fabricated using sequential mineralization. We conducted experiments with two groups of scaffolds based on different incubation times in the mineralization solutions (30 min and 24 h). Ten cycles of mineralization were performed for each group. We found that the mineral content increased as the cycle number increased and that the 24-h group scaffolds consistently had more mineralization than did the 30-min group scaffolds when measured at the same cycle number. A quantitative reverse transcription-polymerase chain reaction was performed for two osteogenic differentiation markers of the preosteoblasts that were grown on the mineralized paper scaffolds. The gene expression results for bone-specific markers revealed that the mineralized scaffolds were osteoinductive. Subcutaneous implantation of the scaffolds in rats demonstrated favorable biocompatibility, high vascularization, and non-immunogenicity in vivo. The overall results suggest that the sequentially mineralized paper scaffolds are promising materials for use in bone tissue engineering.

Currently available bone grafts present certain limitations such as donor-site morbidity for autografts and risk of disease transmission for allografts. These limitations suggest a need for alternative strategies. The use of polymer/ceramic composites as scaffolds for trabecular bone tissue engineering capitalizes on the benefits of both materials. Polymers are easily formed and shaped and add structural rigidity while calcium phosphates impart osteoconductivity and osteointegration. We have developed a biodegradable, microsphere-based scaffold for bone tissue engineering based on poly(lactide-co-glycolide)/calcium phosphate composite microspheres in which a nanocrystalline hydroxyapatite is synthesized within the forming microspheres.

Macroporous calcium phosphate-chitosan composite scaffolds were fabricated and evaluated for use in bone tissue engineering. Human osteoblast-like MG63 cells were cultured on the composite scaffolds, and their response to the materials was studied. Cell morphology, total protein content, and expression of classic markers for osteoblast differentiation were characterized. MG63 cells on the hydroxyapatite scaffolds nesting chitosan sponges (HC1) showed significantly higher alkaline phosphatase (ALP) level and osteocalcin (OC) production during the 11-day culture period, compared with the control culture on tissue culture plates. Cells on the chitosan scaffolds incorporated with hydroxyapatite powders (HC2) exhibited lower ALP activity during the 11-day culture period and OC secretion during the first 7 days, in comparison with that on HC1. The addition of calcium phosphate glass as in HC3 scaffolds increased the ALP and OC levels of MG63 cells. Our study indicated that the hydroxyapatite-matrix composite scaffolds might enhance the phenotype expression of MG63 cells, in comparison with chitosan-matrix scaffolds. Soluble calcium phosphate glasses should be added to the scaffolds to prevent chitosan from fast degradation that may affect the differentiation of osteoblast cells.

Bioengineering scaffolds have been improved to achieve efficient regeneration of various damaged tissues. In this study, we attempted to fabricate mechanically and biologically activated 3D printed scaffold in which porous gelatin/hydroxyapatite (G/H) as a matrix material provided outstanding mechanical properties with recoverable behavior, and human placental extracts (hPE) embedded in the scaffold were used as bioactive components.Methods: Various cell types (human adipose-derived stem cells; hASCs, pre-osteoblast; MC3T3-E1, human endothelial cell line; EA.hy926, and human dermal fibroblast; hDFs) were used to assess the effect of the hPE on cellular responses. High weight fraction (~ 70 wt%) of hydroxyapatite (HA) in a gelatin solution supplemented with glycerol was used for the G/H scaffold fabrication, and the scaffolds were immersed in hPE for the embedding (G/H/hPE scaffold). The osteogenic abilities of the scaffolds were investigated in cultured cells (hASCs) assaying for ALP activity and expression of osteogenic genes. For the in vivo test, the G/H and G/H/hPE scaffolds were implanted in the rat mastoid obliteration model.Results: The G/H/hPE scaffold presented unique elastic recoverable properties, which are important for efficient usage of implantable scaffolds. The effects of G/H and G/H/hPE scaffold on various in vitro cell-activities including non-toxicity, biocompatibility, and cell proliferation were investigated. The in vitro results indicated that proliferation (G/H = 351.1 ± 13.3%, G/H/hPE = 430.9 ± 8.7% at day 14) and expression of osteogenic markers (ALP: 3.4-fold, Runx2: 3.9-fold, BMP2: 1.7-fold, OPN: 2.4-fold, and OCN: 4.8-fold at day 21) of hASCs grown in the G/H/hPE scaffold were significantly enhanced compared with that in cells grown in the G/H scaffold. In addition, bone formation was also observed in an in vivo model using rat mastoid obliteration.Conclusion: In vitro and in vivo results suggested that the G/H/hPE scaffold is a potential candidate for use in bone tissue engineering.

Over the past few decades, the engineering of helical, spring, curled, and hierarchically structured nano/microfibers has attracted considerable attention due to their unique characteristics and potential applications in tissue engineering and various industrial fields. Understanding the parameters and processes involved in the fabrication of these fibers is essential. This comprehensive review outlines recent advancements in research on helical nano/microfibers, focusing on processing techniques, fiber structure, and property characterization, and their applications in fields such as tissue engineering and regenerative medicine. The study also investigates the mechanical and hydrodynamic parameters that influence the fabrication of helical fibers using contemporary techniques. It highlights that helical structures form when electric and elastic forces are balanced due to non-uniform electric fields. The coaxial electrospinning technique, along with the use of polymers with varying elastic and conductive properties, plays a crucial role in producing these structures. The distinctive properties of helical nanofibers, such as their mechanical strength, high porosity, biocompatibility, and ability to promote cellular activities, make them promising candidates for developing scaffolds in bone tissue engineering.

Development and assessment of modified-honeycomb-structure scaffold for bone tissue engineering

Decellularized periosteum as a potential biologic scaffold for bone tissue engineering

Bone-like apatite formation in biocompatible phosphate-crosslinked bacterial cellulose-based hydrogels for bone tissue engineering applications

Small intestinal submucosa (SIS) membranes as a decellularized tissue are known to be a natural nanofibrous biomaterial mainly made of type I collagen fibers and containing some growth factors (fibroblast growth factor 2 and transforming growth factor β) desired in tissue engineering. Here we show that the SIS membranes can promote the formation of bone mineral hydroxylapatite (HAP) crystals along the collagen fibers constituting the membranes from a HAP-supersaturated solution. The resultant biomineralized HAP-SIS scaffolds were found to promote the attachment, growth and osteogenic differentiation of mesenchymal stem cells (MSCs) in both basal and osteogenic media by the evaluation of osteogenic marker formation. More importantly, the HAP-SIS scaffolds could induce the osteogenic differentiation in the basal media without osteogenic supplements due to the presence of HAP crystals in the scaffolds. Histological characterization of the MSC-seeded scaffolds showed that HAP-SIS scaffolds are biocompatible and promote the formation of new tissue in vitro. The biomineralized SIS membranes mimic some aspects of natural bone in terms of the composition and nanostructures and can find potential use in bone tissue engineering.

Poly(DL-lactide) (PDLLA) foams and bioactive glass (Bioglass) particles were used to form bioresorbable and bioactive composite scaffolds for applications in bone tissue engineering. A thermally induced phase separation process was applied to prepare highly porous PDLLA foams filled with 10 wt % Bioglass particles. Stable and homogeneous layers of Bioglass particles on the surface of the PDLLA/Bioglass composite foams as well as infiltration of Bioglass particles throughout the porous network were achieved using a slurry-dipping technique. The quality of the bioactive glass coatings was reproducible in terms of thickness and microstructure. In vitro studies in simulated body fluid (SBF) were performed to study the formation of hydroxyapatite (HA) on the surface of the PDLLA/Bioglass composites, as an indication of the bioactivity of the materials. Formation of the HA layer after immersion in SBF was confirmed by X-ray diffraction and Raman spectroscopy measurements. The rate of HA formation in Bioglass-coated samples was higher than that observed in non-coated samples. SEM analysis showed that the HA layer thickness rapidly increased with increasing time in SBF in the Bioglass-coated samples. The high bioactivity of the developed composites suggests that the materials are attractive for use as bioactive, resorbable scaffolds in bone tissue engineering.

The long-term nonunion of bone defects remains a significant challenge in the field of orthopedics. Poly(L-lactic acid) (PLLA), widely used in bone tissue engineering, offers hope for addressing this issue. In our previous study, we aimed to enhance the poor toughness and slow degradation of PLLA by introducing flexible p-dioxanone (PDO) and highly reactive glycolide (GA) units into the molecular chain of PLLA to prepare PLLA-ran-PDO-ran-GA (PLPG) scaffolds, effectively mitigating the limitations of PLLA. However, the crystallization capacity of PLPG copolymers was weakened, resulting in insufficient mechanical properties. Therefore, in this study, poly(D-lactic acid) (PDLA) was introduced into PLPG via solution blending to enhance its crystallization properties through the in situ generation of stereocomplex poly(lactic acid) (SC-PLA). Subsequently, PLPG/PDLA scaffolds were prepared using 3D printing technology. The results demonstrated that PLPG/PDLA composites exhibited good machinability, while the scaffolds showed satisfactory mechanical and degradation properties. Additionally, cell experiments indicated that PLPG/PDLA scaffolds possess biocompatibility, allowing for cell growth and proliferation on their surfaces. We believe that PLPG/PDLA scaffolds have significant potential for application in bone tissue engineering, effectively addressing the issue of long-term non-healing bone defects.