Covalently Grafted Biomimetic Matrix Reconstructs the Regenerative Microenvironment of the Porous Gradient Polycaprolactone Scaffold to Accelerate Bone Remodeling.

Integrating a biomimetic extracellular matrix to improve the microenvironment of 3D printing scaffolds is an emerging strategy for bone substitute design. Here, a "soft-hard" bone implant (BM-g-DPCL) consisting of a bioactive matrix chemically integrated on a polydopamine (PDA)-coated porous gradient scaffold by polyphenol groups is constructed. The PDA-coated "hard" scaffolds promoted Ca2+ chelation and mineral deposition; the "soft" bioactive matrix is beneficial to the migration, proliferation, and osteogenic differentiation of stem cells in vitro, accelerated endogenous stem cell recruitment, and initiated rapid angiogenesis in vivo. The results of the rabbit cranial defect model (Φ = 10 mm) confirmed that BM-g-DPCL promoted the integration between bone tissue and implant and induced the deposition of bone matrix. Proteomics confirmed that cytokine adhesion, biomineralization, rapid vascularization, and extracellular matrix formation are major factors that accelerate bone defect healing. This strategy of highly chemically bonded soft-hard components guided the construction of the bioactive regenerative scaffold.

Gradient nanocomposite hydrogels for interface tissue engineering.

Two-dimensional (2D) nanomaterials are an emerging class of materials with unique physical and chemical properties due to their high surface area and disc-like shape. Recently, these 2D nanomaterials have been investigated for a range of biomedical applications including tissue engineering, therapeutic delivery and bioimaging, due to their ability to physically reinforce polymeric networks. Here, we present a facile fabrication of a gradient scaffold with two natural polymers (gelatin methacryloyl (GelMA) and methacrylated kappa carrageenan (MκCA)) reinforced with 2D nanosilicates to mimic the native tissue interface. The addition of nanosilicates results in shear-thinning characteristics of prepolymer solution and increases the mechanical stiffness of crosslinked gradient structure. A gradient in mechanical properties, microstructures and cell adhesion characteristics was obtained using a microengineered flow channel. The gradient structure can be used to understand cell-matrix interactions and to design gradient scaffolds for mimicking tissue interfaces.

Mechanisms and Microenvironment Investigation of Cellularized High Density Gradient Collagen Matrices via Densification.

Biological tissues and biomaterials are often defined by unique spatial gradients in physical properties that impart specialized function over hierarchical scales. The structure and organization of these materials forms continuous transitional gradients and discrete local microenvironments between adjacent (or within) tissues, and across matrix-cell boundaries, which can be difficult to replicate with common scaffold systems. Here, we studied the matrix densification of collagen leading to gradients in density, mechanical properties, and fibril morphology. High-density regions formed via a fluid pore pressure and flow-driven mechanism, with increased relative fibril density (10×), mechanical properties (20×, to 94.40±18.74kPa), and maximum fibril thickness (1.9×, to >1µm) compared to low-density regions, while maintaining porosity and fluid/mass transport to support viability of encapsulated cells. Similar to the organization of the articular cartilage zonal structure, we found that high-density collagen regions induced cell and nuclear alignment of primary chondrocytes. Chondrocyte gene expression was maintained in collagen matrices, and no phenotypic changes were observed as a result of densification. Densification of collagen matrices provides a unique, tunable platform for the creation of gradient systems to study complex cell-matrix interactions. These methods are easily generalized to compression and boundary condition modalities useful to mimic a broad range of tissues.

Dual cross-linked COL1/HAp bionic gradient scaffolds containing human amniotic mesenchymal stem cells promote rotator cuff tendon-bone interface healing.

The tendon-bone interface heals through scar tissue, while the lack of a natural interface gradient structure and collagen fibre alignment leads to the occurrence of retearing. Therefore, the promotion of tendon healing has become the focus of regenerative medicine. The purpose of this study was to develop a gradient COL1/ hydroxyapatite (HAp) biomaterial loaded with human amniotic mesenchymal stem cells (hAMSCs). The performance of common cross-linking agents, Genipin, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), and dual cross-linked materials were compared to select the best cross-linking mechanism to optimize the biological and mechanical properties of the scaffold. The optimal COL1/HAp-loaded with hAMSCs were implanted into the tendon-bone rotator cuff interfaces in rats and the effect on the tendon-bone healing was assessed by micro-CT, histological analysis, and biomechanical properties. The results showed that Genipin and EDC/NHS dual cross-linked COL1/HAp had good biological activity and mechanical properties and promoted the proliferation and differentiation of hAMSCs. Animal experiments showed that the group using a scaffold loaded with hAMSCs had excellent continuity and orientation of collagen fibers, increased fibrocartilage and bone formation, and significantly higher biomechanical functions than the control group at the interface at 12 weeks post operation. This study demonstrated that dual cross-linked gradient COL1/HAp-loaded hAMSCs could promote interface healing, thereby providing a feasible strategy for tendon-bone interface regeneration.

Fabrication of Helix aspersa Extract Loaded Gradient Scaffold with an Integrated Architecture for Osteochondral Tissue Regeneration: Morphology, Structure, and In Vitro Bioactivity.

Regeneration of osteochondral tissue with its layered complex structure and limited self-repair capacity has come into prominence as an application area for biomaterial design. Thus, literature studies have aimed to design multilayered scaffolds using natural polymers to mimic its unique structure. In this study, fabricated scaffolds are composed of transition layers both chemically and morphologically to mimic the gradient structure of osteochondral tissue. The aim of this study is to produce gradient chitosan (CHI) scaffolds with bioactive snail (Helix aspersa) mucus (M) and slime (S) extract and investigate the structures regarding their physicochemical, mechanical, and morphological characteristics as well as in vitro cytocompatibility and bioactivity. Gradient scaffolds (CHI-M and CHI-S) were fabricated via a layer-by-layer freezing and lyophilization technique. Highly porous and continuous 3D structures were obtained and observed with SEM analysis. In addition, scaffolds were physically characterized with water uptake test, micro-CT, mechanical analysis (compression tests), and XRD analysis. In vitro bioactivity of scaffolds was investigated by co-culturing Saos-2 and SW1353 cells on each compartment of gradient scaffolds. Osteogenic activity of Saos-2 cells on extract loaded gradient scaffolds was investigated in terms of ALP secretion, osteocalcin (OC) production, and biomineralization. Chondrogenic bioactivity of SW1353 cells was investigated regarding COMP and GAG production and observed with Alcian Blue staining. Both mucus and slime incorporation in the chitosan matrix increased the osteogenic differentiation of Saos-2 and SW1353 cells in comparison to the pristine matrix. In addition, histological and immunohistological staining was performed to investigate ECM formation on gradient scaffolds. Both characterization and in vitro bioactivity results indicated that CHI-M and CHI-S scaffolds show potential for osteochondral tissue regeneration, mimicking the structure as well as enhancing physical characteristics and bioactivity.

Preparation and Characterization of Biomimetic Functional Scaffold with Gradient Structure for Osteochondral Defect Repair.

Osteochondral (OC) defects cannot adequately repair themselves due to their sophisticated layered structure and lack of blood supply in cartilage. Although therapeutic interventions are reaching an advanced stage, current clinical therapies to repair defects are in their infancy. Among the possible therapies, OC tissue engineering has shown considerable promise, and multiple approaches utilizing scaffolds, cells, and bioactive factors have been pursued. The most recent trend in OC tissue engineering has been to design gradient scaffolds using different materials and construction strategies (such as bi-layered, multi-layered, and continuous gradient structures) to mimic the physiological and mechanical properties of OC tissues while further enabling OC repair. This review focuses specifically on design and construction strategies for gradient scaffolds and their role in the successful engineering of OC tissues. The current dilemmas in the field of OC defect repair and the efforts of tissue engineering to address these challenges were reviewed. In addition, the advantages and limitations of the typical fabrication techniques for gradient scaffolds were discussed, with examples of recent studies summarizing the future prospects for integrated gradient scaffold construction. This updated and enlightening review could provide insights into our current understanding of gradient scaffolds in OC tissue engineering.

Mechanical properties and failure mechanisms of polyamide 12 gradient scaffolds developed with selective laser sintering.

Developing a functional gradient scaffold compatible with the fantastic biological and mechanical properties of natural bone tissue is imperative in bone tissue engineering. In this work, the stretch-dominated (cubical and circular) and bending-dominant (diamond and gyroid) pore styles were employed to design custom-graded scaffolds based on the curve interference method and then were fabricated by selective laser sintering (SLS) using polyamide 12 (PA12) powder. Subsequently, the mechanical behavior, failure mechanism, and energy absorption performance of porous structures were investigated via compression experiments and finite element (FE) simulation. The results indicated that the stretch-dominated radial gradient structures entire exhibited transverse shear failure and the bending-dominant radial gradient structures whole exhibited progressive destruction, while all of the axial gradient scaffolds suffered a predictable layer-by-layer fracture. Among them, the bending-dominated radial gradient structure of gyroid had been proven to sustain stronger deformability and energy absorption capacity. Meanwhile, the FE method powerfully predicted the mechanical behavior of the scaffold, and this research thereby possessed significant implications for the development of bone tissue engineering.

Bioinspired gradient scaffolds for osteochondral tissue engineering.

Repairing articular osteochondral defects present considerable challenges in self-repair due to the complex tissue structure and low proliferation of chondrocytes. Conventional clinical therapies have not shown significant efficacy, including microfracture, autologous/allograft osteochondral transplantation, and cell-based techniques. Therefore, tissue engineering has been widely explored in repairing osteochondral defects by leveraging the natural regenerative potential of biomaterials to control cell functions. However, osteochondral tissue is a gradient structure with a smooth transition from the cartilage to subchondral bone, involving changes in chondrocyte morphologies and phenotypes, extracellular matrix components, collagen type and orientation, and cytokines. Bioinspired scaffolds have been developed by simulating gradient characteristics in heterogeneous tissues, such as the pores, components, and osteochondrogenesis-inducing factors, to satisfy the anisotropic features of osteochondral matrices. Bioinspired gradient scaffolds repair osteochondral defects by altering the microenvironments of cell growth to induce osteochondrogenesis and promote the formation of osteochondral interfaces compared with homogeneous scaffolds. This review outlines the meaningful strategies for repairing osteochondral defects by tissue engineering based on gradient scaffolds and predicts the pros and cons of prospective translation into clinical practice.

Design and performance analysis of 3D-printed stiffness gradient femoral scaffold.

Studies on 3D-printed porous bone scaffolds mostly focus on materials or structural parameters, while the repair of large femoral defects needs to select appropriate structural parameters according to the needs of different parts. In this paper, a kind of stiffness gradient scaffold design idea is proposed. Different structures are selected according to the different functions of different parts of the scaffold. At the same time, an integrated fixation device is designed to fix the scaffold. Finite element method was used to analyze the stress and strain of homogeneous scaffolds and the stiffness gradient scaffolds, and the relative displacement and stress between stiffness gradient scaffolds and bone in the case of integrated fixation and steel plate fixation. The results showed that the stress distribution of the stiffness gradient scaffolds was more uniform, and the strain of host bone tissue was changed greatly, which was beneficial to the growth of bone tissue. The integrated fixation method is more stable, less stress and evenly distributed. Therefore, the integrated fixation device combined with the design of stiffness gradient can repair the large femoral bone defect well.

Multimaterial and multiscale scaffold for engineering enthesis organ.

Tendon and ligament injuries are relevant clinical problems in modern society, and the current medical approaches do not guarantee complete recovery of the physiological functionalities. Moreover, they present a non-negligible failure rate after surgery. Failures often occur at the enthesis, which is the area of tendons and ligaments insertion to bones. This area is highly anisotropic and composed of four distinct zones: tendon or ligament, non-mineralized fibrocartilage, mineralized fibrocartilage, and bone. The organization of these regions provides a gradient in mechanical properties, biochemical composition, cellular phenotype, and extracellular matrix organization. Tissue engineering represents an alternative to traditional medical approaches. This work presents a novel biofabrication approach for engineering the enthesis. Gradient-based scaffolds were fabricated by exploiting the combination of electrospinning and three-dimensional (3D) bioprinting technologies. Studies were conducted to evaluate scaffold biocompatibility by seeding bone marrow-derived mesenchymal stem cells (BM-MSCs). Then, the scaffold's ability to promote cellular adhesion, growth, proliferation, and differentiation in both tenogenic and osteogenic phenotypes was evaluated. Fabricated scaffolds were also morphologically and mechanically characterized, showing optimal properties comparable to literature data. The versatility and potentiality of this novel biofabrication approach were demonstrated by fabricating clinical-size 3D enthesis scaffolds. The mechanical characterization highlighted their behavior during a tensile test was comparable to tendons and ligaments in vivo.

[Application of microcarrier technology in cartilage repairing: a review].

Cartilage has poor self-recovery because of its characteristics of no blood vessels and high extracellular matrix. In clinical treatment, physical therapy or drug therapy is usually used for mild cartilage defects, and surgical treatment is needed for severe ones. In recent years, cartilage tissue engineering technology provides a new way for the treatment of cartilage defects. Compared with the traditional surgical treatment, cartilage tissue engineering technology has the advantages of small wound and good recovery. The application of microcarrier technology in the design of tissue engineering scaffolds further expands the function of scaffolds and promotes cartilage regeneration. This review summarized the main preparation methods and development of microcarrier technology in recent years. Subsequently, the properties and specific application scenarios of microcarriers with different materials and functions were introduced according to the materials and functions of microcarriers used in cartilage repair. Based on our research on osteochondral integrated layered scaffolds, we proposed an idea of optimizing the performance of layered scaffolds through microcarriers, which is expected to prepare bionic scaffolds that are more suitable for the structural characteristics of natural cartilage.

A hydrogel/particle composite with a gradient of oxygen releasing microparticle for concurrent osteogenic and chondrogenic differentiation in a single scaffold.

In the present study, a hydrogel/particle scaffold with a gradient of the oxygen releasing microparticles was developed. Hydrogel component was composed of the oxidized pectin and silk fibroin, whereas the microparticles were constituted from polylactic acid (PLA) and calcium peroxide (CPO). A controlled mixing of the suspensions with different content of the PLA/CPO microparticles conferred a gradient of microparticles in scaffold thickness in a manner that the microparticle content increased with moving from lower to upper face of the composite. Measurement of the scaffold mechanical properties corroborated that with moving from lower to upper face, the compressive modulus increased by 78 %. The measurement of the oxygen and calcium release from the successive sections of the composite revealed that the gradient of microparticle concentration resulted in the gradient of the released oxygen and calcium. MTT analysis proved that the gradient oxygen releasing composite did not induce any toxic effect on human adipose-derived mesenchymal stem cells (hAd-MSCs). Moreover, the cell culture on successive sections of the gradient composite confirmed that oxygen releasing composite substantially improved the cell viability and density comparing the pristine hydrogel and the non-oxygen releasing counterpart. The increase in microparticle content conferred a positive impact on the number of viable cells. The study of osteogenic (ALP, OCN and OPN) and chondrogenic (SOX9, AGG and COL ⅠⅠ) gene expression proved that the gradient composite parts with high microparticle content promoted osteogenesis, whereas the parts with low microparticle content encouraged chondrogenesis of mesenchymal stem cells.

Articular cartilage and osteochondral tissue engineering techniques: Recent advances and challenges.

In spite of the considerable achievements in the field of regenerative medicine in the past several decades, osteochondral defect regeneration remains a challenging issue among diseases in the musculoskeletal system because of the spatial complexity of osteochondral units in composition, structure and functions. In order to repair the hierarchical tissue involving different layers of articular cartilage, cartilage-bone interface and subchondral bone, traditional clinical treatments including palliative and reparative methods have showed certain improvement in pain relief and defect filling. It is the development of tissue engineering that has provided more promising results in regenerating neo-tissues with comparable compositional, structural and functional characteristics to the native osteochondral tissues. Here in this review, some basic knowledge of the osteochondral units including the anatomical structure and composition, the defect classification and clinical treatments will be first introduced. Then we will highlight the recent progress in osteochondral tissue engineering from perspectives of scaffold design, cell encapsulation and signaling factor incorporation including bioreactor application. Clinical products for osteochondral defect repair will be analyzed and summarized later. Moreover, we will discuss the current obstacles and future directions to regenerate the damaged osteochondral tissues.

Directed differentiation of BMSCs on structural/compositional gradient nanofibrous scaffolds for ligament-bone osteointegration.

Nanofibrous scaffolds with structural and compositional gradients exhibit great potential to modulate zonal differentiation of stem cells for the regeneration of soft-to-hard tissue interface. Here, the response of bone marrow stem cells (BMSCs) to electrospun gradient nanofibrous scaffolds was investigated to demonstrate their potential capabilities for interfacial tissue regeneration. The electrospun scaffolds showed gradient distribution of BMP-2/nanoHA contents and the fiber orientations gradually changed from random to align. Biomimetic mineralization demonstrated that calcium and phosphorus elements can deposit onto the surface of the nanofibers in a gradient manner similar to nanoHA content. BMSCs cultured on the gradient nanofibrous scaffolds exhibited high cell viability and cell morphology gradually changed from disorder to highly align similar to the underlying fiber orientation. BMP-2/nanoHA content gradients in the nanofibrous scaffolds were found to effectively promote the zonal expression of bone-specific genes like osteocalcin (OCN), Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). Immunofluorescent staining of osteopontin (OPN) and OCN further confirmed osteoblastic phenotypic maturation on the regions of the scaffolds with a higher level of nanoHA and BMP-2 contents after cultured 28 days. These results indicated that the gradient nanofibrous scaffolds enable to guide zonal differentiation of BMSCs in vitro, which might be useful to realize multitissue regeneration in one construct for the regeneration of soft-to-hard tissue interface.

Regeneration of the rotator cuff tendon-to-bone interface using umbilical cord-derived mesenchymal stem cells and gradient extracellular matrix scaffolds from adipose tissue in a rat model.

Regeneration of the gradient structure of the tendon-to-bone interface (TBI) is a crucial goal after rotator cuff repair. The purpose of this study was to investigate the efficacy of a biomimetic hydroxyapatite-gradient scaffold (HA-G scaffold) isolated from adipose tissue (AD) with umbilical cord derived mesenchymal stem cells (UC MSCs) on the regeneration of the structure of the TBI by analyzing the histological and biomechanical changes in a rat repair model. As a result, the HA-G scaffold had progressively increased numbers of hydroxyapatite (HA) particles from the tendon to the bone phase. After seeding UC MSCs to the scaffold, specific matrices, such as collagen, glycoaminoglycan, and calcium, were synthesized with respect to the HA density. In a rat repair model, compared to the repair group, the UC MSCs seeded HA-G scaffold group had improved collagen organization and cartilage formation by 52% at 8 weeks and 262.96% at 4 weeks respectively. Moreover, ultimate failure load also increased by 30.71% at 4 weeks in the UC MSCs seeded HA-G scaffold group compared to the repair group. Especially, the improved values were comparable to values in normal tissue. This study demonstrated that HA-G scaffold isolated from AD induced UC MSCs to form tendon, cartilage and bone matrices similar to the TBI structure according to the HA density. Furthermore, UC MSC-seeded HA-G scaffold regenerated the TBI of the rotator cuff in a rat repair model in terms of histological and biomechanical properties similar to the normal TBI. Statement of Significance We found specific extracellular matrix (ECM) formation in the biomimetic-hydroxyapatite-gradient-scaffold (HA-G-scaffold) in vitro as well as improved histological and biomechanical results of repaired rotator cuff after the scaffold implantation in a rat model. This study has four strengths; An ECM scaffold derived from human adipose tissue; only one-layer used for a gradient scaffold not a multilayer used to mimic the unique structure of the gradient tendon-to-bone-interface (TBI) of the rotator cuff; UC-MSCs as a new cell source for TBI regeneration; and the UC-MSCs synthesized specific matrices with respect to the HA density without any other stimuli. This study suggested that the UC-MSC seeded HA-G-scaffold could be used as a promising strategy for the regeneration of rotator cuff tears.

Preparation and properties of dopamine-modified alginate/chitosan-hydroxyapatite scaffolds with gradient structure for bone tissue engineering.

Three-dimensional (3D) homogenous scaffolds composed of natural biopolymers have been reported as superior candidates for bone tissue engineering. There are still remaining challenges in fabricating the functional scaffolds with gradient structures to similar with natural bone tissues, as well as high mechanical properties and excellent affinity to surround tissues. Herein, inspired by the natural bone structure, a gradient-structural scaffold composed of functional biopolymers was designed to provide an optimized 3D environment for promoting cell growth. To increase the interactions among the scaffolds, dopamine (DA) was employed to modify alginate (Alg) and needle-like nano-hydroxyapatite (HA) was prepared with quaternized chitosan as template. The obtained dopamine-modified alginate (Alg-DA) and quaternized chitosan-templated hydroxyapatite (QCHA) were then used to fabricate the porous gradient scaffold by "iterative layering" freeze-drying technique with further crosslinking by calcium ions (Ca2+ ). The as-prepared Alg-DA/QCHA gradient scaffolds were possessed seamlessly integrated layer structures and high levels of porosity at around 77.5%. Moreover, the scaffolds showed higher compression modules (1.7 MPa) than many other biopolyermic scaffolds. The gradient scaffolds showed appropriate degradation rate to satisfy with the time of the bone regeneration. Both human chondrocytes and fibroblasts could adhesive and growth well on the scaffolds in vitro. Furthermore, an excellent osteogenetic activity of the gradient scaffold can effectively promote the regeneration of the bone tissue and accelerate the repair of the bone defects in vivo, compared with that of the scaffold with the homogenous structure. The novel multilayered scaffold with gradient structure provided an interesting option for bone tissue engineering. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1615-1627, 2019.

Three-Dimensional Printing of Tissue Engineering Scaffolds with Horizontal Pore and Composition Gradients.

IMPACT STATEMENT: In this study, we report the development of a novel multimaterial segmented three-dimensional printing methodology to fabricate porous scaffolds containing discrete horizontal gradients of composition and porosity. This methodology is particularly beneficial to preparing porous scaffolds with intricate structures and graded compositions for the regeneration of complex tissues. The technique presented is compatible with many commercially available bioprinters commonly used in biofabrication, and can be adapted to better replicate the architectural and compositional requirements of individual tissues compared with traditional scaffold printing methods.

Hybrid polycaprolactone/hydrogel scaffold fabrication and in-process plasma treatment using PABS.

A challenge for tissue engineering is to produce synthetic scaffolds of adequate chemical, physical, and biological cues effectively. Due to the hydrophobicity of the commonly used synthetic polymers, the printed scaffolds are limited in cell-seeding and proliferation efficiency. Furthermore, non-uniform cell distribution along the scaffolds with rare cell attachment in the core region is a common problem. There are no available commercial systems able to produce multi-type material and gradient scaffolds which could mimic the nature tissues. This paper describes a plasma-assisted bio-extrusion system (PABS) to overcome the above limitations and capable of producing functional-gradient scaffolds; it comprises pressure-assisted and screw-assisted extruders and plasma jets. A hybrid scaffold consisting of synthetic biopolymer and natural hybrid hydrogel alginate-gelatin (Alg-Gel) methacrylate anhydride, and full-layer N2 plasma modification scaffolds were produced using PABS. Water contact angle and in vitro biological tests confirm that the plasma modification alters the hydrophilicity properties of synthetic polymers and promotes proliferation of cells, leading to homogeneous cell colonization. The results confirm the printing capability for soft hard material integration of PABS and suggest that it is promising for producing functional gradient scaffolds of biomaterials.

A biomimetic cartilage gradient hybrid scaffold for functional tissue engineering of cartilage.

Osteochondral tissue has a complex layered structure that is not self-repairing after a cartilage defect. Therefore, constructing a biomimetic gradient scaffold that meets the specific structural requirements of osteochondral tissue is a major challenge in the field of cartilage tissue engineering. In this study, chitosan/Sodium ß-glycerophosphate/Gelatin (Cs/GP/Gel) biomimetic gradient scaffolds were prepared by regulating the mass ratio of single layer raw materials. The same ratio of Cs/GP/Gel hybrid scaffold material was used as the control. Physical properties such as water absorption, porosity and the degradation rate of the material were compared to optimize the proportion of scaffold materials. P3 Bone Mesenchymal Stem Cells (BMSCs) were inoculated on the gradient and the control scaffolds to investigate its biocompatibility. Scanning electron microscopy (SEM) results show that 3:1:2, 6:1:3.5, 9:1:5, 12:1:6.5, 15:1:8 Cs/GP/Gel gradient scaffolds had excellent three-dimensional porous structures. Channels were also shown to have been interconnected, and the walls of the pores were folded. In the longitudinal dimension, gradient scaffolds had an obvious stratified structure and pore gradient gradualism, that effectively simulated the natural physiological stratified structure of real cartilage. The diameter of the pores in the control scaffold was uniform and without any pore gradient. Gradient scaffolds had good water absorption (584.24 ± 3.79˜677.47 ± 1.70%), porosity (86.34 ± 5.10˜95.20 ± 2.86%) and degradation (86.09 ± 2.46˜92.48 ± 3.86%). After considering the physical properties assessed, the Cs/GP/Gel gradient scaffold with a ratio of 9:1:5 was found to be the most suitable material to support osteochondral tissue. BMSCs were subsequently inoculated on the proportional gradient and hybrid scaffolds culture. These cells survived, distributed and extended well on the gradient and hybrid scaffold material. The biomimetic gradient scaffold designed and prepared in this study provides an important foundation for the development of new gradient composite biomedical materials for osteochondral repair.

Application of microcarrier technology in cartilage repairing: a review / 生物工程学报

Cartilage has poor self-recovery because of its characteristics of no blood vessels and high extracellular matrix. In clinical treatment, physical therapy or drug therapy is usually used for mild cartilage defects, and surgical treatment is needed for severe ones. In recent years, cartilage tissue engineering technology provides a new way for the treatment of cartilage defects. Compared with the traditional surgical treatment, cartilage tissue engineering technology has the advantages of small wound and good recovery. The application of microcarrier technology in the design of tissue engineering scaffolds further expands the function of scaffolds and promotes cartilage regeneration. This review summarized the main preparation methods and development of microcarrier technology in recent years. Subsequently, the properties and specific application scenarios of microcarriers with different materials and functions were introduced according to the materials and functions of microcarriers used in cartilage repair. Based on our research on osteochondral integrated layered scaffolds, we proposed an idea of optimizing the performance of layered scaffolds through microcarriers, which is expected to prepare bionic scaffolds that are more suitable for the structural characteristics of natural cartilage.