Polylactic acid/Hydroxyapatite (PLA/HA) composite was widely studied and applied in the field of biomaterials for its good processability, bioactivity, and mechanical properties. In addition to ...traditional preparation methods, additive manufacturing has also been adopted to prepare PLA/HA composites with customized geometries. This work combined the comprehensive optimized PLLA (L-polylactic acid)/nano-HA (nHA) composite with the low-cost and stable Fused deposition modeling (FDM) technology to successfully prepare PLLA/nHA porous bone repair scaffolds. The results showed that PLLA/nHA composite ink satisfied the smoothness of printing, and the accuracy also met the requirements of personalized bone repair application. The high loaded nHA scaffold had suitable compressive strength was significantly higher than those of pure HA ceramic scaffold and cancellous bone. Besides, in vitro bone-like apatite formation on the surface in the degradation process and in vivo evaluations further verified its good osteogenic property. Compared with other complex and cutting-edge 3D printing technologies, this study provides a low-cost, stable, simple and fast way to realize personalized printing of bone repair scaffolds, which is undoubtedly conductive to the improvement and rapid deployment of personalized biomaterials in clinical applications.
Display omitted
•Comprehensive optimized PLLA/nano-hydroxyapatite composite was made successfully for bone repair scaffold printing.•Bone-like apatite can form on the scaffold surface in vitro degradation experiments just in PBS, indicating the high bioactivity of scaffold.•The high loaded nano- hydroxyapatite scaffold has suitable compressive strength and good osteogenic property.•This study provides a low-cost, stable, simple and fast way to realize personalized printing of bone repair scaffolds.
Limited stem cells, poor stretchability and mismatched interface fusion have plagued the reconstruction of cranial defects by cell-free scaffolds. Here, we designed an instantly fixable and ...self-adaptive scaffold by dopamine-modified hyaluronic acid chelating Ca
of the microhydroxyapatite surface and bonding type I collagen to highly simulate the natural bony matrix. It presents a good mechanical match and interface integration by appropriate calcium chelation, and responds to external stress by flexible deformation. Meanwhile, the appropriate matrix microenvironment regulates macrophage M2 polarization and recruits endogenous stem cells. This scaffold promotes the proliferation and osteogenic differentiation of BMSCs in vitro, as well as significant ectopic mineralization and angiogenesis. Transcriptome analysis confirmed the upregulation of relevant genes and signalling pathways was associated with M2 macrophage activation, endogenous stem cell recruitment, angiogenesis and osteogenesis. Together, the scaffold realized 97 and 72% bone cover areas after 12 weeks in cranial defect models of rabbit (Φ = 9 mm) and beagle dog (Φ = 15 mm), respectively.
The Ti6Al4V alloy is one of the most commonly used in orthopedic surgery. Mechanical property of implant contributes important biological functions for load-bearing bone tissue reconstruction. There ...is a significant need for design and fabrication of porous scaffold with customized mechanical properties for bone tissue engineering. In this paper, bionic design and fabrication of porous implants were studied by using finite element analysis (FEA) and 3D printing techniques. Novel porous architectures were built up with diamond lattice pore structure arraying units. With finite element analysis, the structure weak points under pressure were simulated so that the mechanical properties of the implants were optimized. Porous implants with different porosities and mechanical properties were precisely fabricated by selected laser melting (SLM), one of powder bed fusion additive manufacturing techniques. The biocompatibility and repair effect were studied by in vivo experiments. Animal results indicated that the damaged load-bearing bones were well reconstructed. New generated bones embedded and fitted into the designed porous implants. The optimized design and precisely manufactured implants are conducive to bone tissue repair and reconstruction.
Display omitted
•Scaffolds showed biomimetic structure design and customized mechanical properties.•Scaffolds with 66.1%–79.5% porosity were biomimetic designed by using diamond lattice pore units array formation.•Scaffolds within a wide range of compressive strength from 36 to 140 MPa were successfully fabricated.•Animal results indicated that the damaged load-bearing bones were well reconstructed.
Abstract
The discovery of osteoinductivity of calcium phosphate (Ca-P) ceramics has set an enduring paradigm of conferring biological regenerative activity to materials with carefully designed ...structural characteristics. The unique phase composition and porous structural features of osteoinductive Ca-P ceramics allow it to interact with signaling molecules and extracellular matrices in the host system, creating a local environment conducive to new bone formation. Mounting evidence now indicate that the osteoinductive activity of Ca-P ceramics is linked to their physicochemical and three-dimensional structural properties. Inspired by this conceptual breakthrough, many laboratories have shown that other materials can be also enticed to join the rank of tissue-inducing biomaterials, and besides the bones, other tissues such as cartilage, nerves and blood vessels were also regenerated with the assistance of biomaterials. Here, we give a brief historical recount about the discovery of the osteoinductivity of Ca-P ceramics, summarize the underlying material factors and biological characteristics, and discuss the mechanism of osteoinduction concerning protein adsorption, and the interaction with different types of cells, and the involvement of the vascular and immune systems.
The host immune response is critical for in situ osteogenesis, but correlations between local inflammatory reactions and biomaterial osteoinduction are still poorly understood. This study used a ...murine intramuscular implantation model to demonstrate that calcium phosphate ceramics with different phase compositions exhibited divergent osteoinductivities. The osteoinductive potential of each ceramic was closely associated with the immunomodulatory capacity of the material, and especially with the regulation of macrophage polarization and functional status. Biphasic calcium phosphate (BCP) ceramics with superior osteoinductive potential enhanced the fraction of CD206+ M2 macrophages, up-regulated expression of M2 phenotypic markers in vitro, and increased the ARG+ M2 population in vivo. This suggested that BCP ceramics could ameliorate long-term inflammation and build a pro-osteogenic microenvironment. However, β-tricalcium phosphate (β-TCP) ceramics with no obvious osteoinductivity increased the fraction of CCR7+ M1 macrophages, promoted the secretion of M1 phenotypic markers in vitro, and maintained a high proportion of iNOS+ M1 macrophages in vivo. It indicated that β-TCP ceramics could exacerbate inflammation and inhibit ectopic bone formation. Hydroxyapatite ceramics with an intermediate osteoinductivity exhibited a moderate amount of both M1 and M2 macrophages. These findings highlight the critical role of macrophage polarization in biomaterial-dependent osteoinduction, which not only deepens our understanding of osteoinductive mechanisms but also provides a strategy to design bone substitutes by endowing materials with the proper immunomodulatory abilities to achieve the desired clinic performance.
Calcium phosphate (CaP) ceramics with osteoinductive capacities are able to induce ectopic bone formation in non-osseous sites. However, its underlying mechanism is largely unknown. Previous studies have demonstrated an indispensable role of macrophages in osteogenesis, inspiring us that local inflammatory reaction may affect material-dependent osteoinduction. This study indicated that CaP ceramics with different phase composition could present divergent osteoinductive capacities through modulating polarization and functional status of macrophages, as biphasic calcium phosphate with potent osteoinductivity ameliorated long-term inflammation and induced a healing-associated M2 phenotype to initiate bone formation. These findings not only get an insight into the mechanism of CaP-involved osteoinduction, but also help the design of tissue-inducing implants by endowing biomaterials with proper immunomodulatory ability.
Display omitted
Bioceramics, because of its excellent biocompatible and mechanical properties, has always been considered as the most promising materials for hard tissue repair. It is well know that an appropriate ...cellular response to bioceramics surfaces is essential for tissue regeneration and integration. As the in vivo implants, the implanted bioceramics are immediately coated with proteins from blood and body fluids, and it is through this coated layer that cells sense and respond to foreign implants. Hence, the adsorption of proteins is critical within the sequence of biological activities. However, the biological mechanisms of the interactions of bioceramics and proteins are still not well understood. In this review, we will recapitulate the recent studies on the bioceramic–protein interactions.
Display omitted
Viscoelasticity of living tissues plays a critical role in tissue homeostasis and regeneration, and its implication in disease development and progression is being recognized ...recently. In this review, we first explored the state of knowledge regarding the potential application of tissue viscoelasticity in disease diagnosis. In order to better characterize viscoelasticity with local resolution and non-invasiveness, emerging characterization methods have been developed with the potential to be supplemented to existing facilities. To understand cellular responses to matrix viscoelastic behaviors in vitro, hydrogels made of natural polymers have been developed and the relationships between their molecular structure and viscoelastic behaviors, are elucidated. Moreover, how cells perceive the viscoelastic microenvironment and cellular responses including cell attachment, spreading, proliferation, differentiation and matrix production, have been discussed. Finally, some future perspective on an integrated mechanobiological comprehension of the viscoelastic behaviors involved in tissue homeostasis, cellular responses and biomaterial design are highlighted.
Tissue- or organ-scale viscoelastic behavior is critical for homeostasis, and the molecular basis and cellular responses of viscoelastic materials at micro- or nano-scale are being recognized recently. We summarized the potential applications of viscoelasticity in disease diagnosis enabled by emerging non-invasive characterization technologies, and discussed the underlying mechanism of viscoelasticity of hydrogels and current understandings of cell regulatory functions of them. With a growing understanding of the molecular basis of hydrogel viscoelasticity and recognition of its regulatory functions on cell behaviors, it is important to bring the clinical insights on how these characterization technologies and engineered materials may contribute to disease diagnosis and treatment. This review explains the basics in characterizing viscoelasticity with our hope to bridge the gap between basic research and clinical applications.
As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass ...spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis.
Bone defect and osteoporosis are common in clinic which are seriously harmful for public health. Bionic bone tissue engineering scaffolds are very important for bone tissue repair and reconstruction. ...In this study, different bionic bone tissue engineering scaffolds were constructed by computer-aided design and fabricated by selected laser melting. Novel porous structures were designed by using parameterization modeling. The accurate models with key characteristics such as porosity and the mechanical property of scaffolds were studied. Compared with the designed model, the error of the selective laser melting (SLM) printed scaffold porosity was less than 2.73%. The mechanical properties of the prepared scaffold can be calculated by finite element analysis of 3D models, and the mechanical properties of the 3D printed samples were consistent with the model design. Through the design, manufacture, characterization and evaluation of the scaffold porous structures, the parametric modeling of porous titanium bone tissue engineering scaffold with good mechanical and biological properties was realized. Optimized design and precisely manufactured implants are very important for bone tissue repair and reconstruction.
The design and fabrication of porous scaffold remains a major challenge in bone tissue engineering. Hierarchical microporous and macroporous structures in scaffold contribute different biological ...functions to tissue regeneration. This study introduced an integrated manufacturing method to fabricate hierarchical porous polymer scaffolds. Firstly, polylactic acid (PLA) scaffolds with 100–800μm macropores were fabricated by applying fused deposition modeling (FDM) techniques. Then, 1–10μm micropores were generated in scaffolds through gas foaming. This combined technique avoids the disadvantages of pure 3DP or gas foaming technology and elicits positive cooperative effects to fabricate hierarchical porous scaffolds. The design of porosity in scaffold could offer innovative opportunities to control cell performance within 3D microenvironments.
Display omitted
•Hierarchical macro/microporous polymer scaffold was fabricated.•Scaffolds with 100–800μm macropores were initially fabricated by using FDM technique.•Scaffolds with 1–10μm micropores were then fabricated by using gas foaming.•The integrated manufacturing method can fabricate grotesque and large scaffolds for bone tissue engineering application.
PDF
