Load-bearing Scaffolds Research Articles

Mechanical, Biological and In Vitro Degradation Investigation of Braided Scaffolds for Tendon and Ligament Tissue Engineering Based on Different Polycaprolactone Materials with Chitosan-Graft-PCL Surface Modification.

Injuries to tendons and ligaments are highly prevalent in the musculoskeletal system. Current treatments involve autologous transplants with limited availability and donor site morbidity. Tissue engineering offers a new approach through temporary load-bearing scaffolds. These scaffolds have to fulfill numerous requirements, the majority of which can be met using braiding combined with high-strength polycaprolactone (PCL) fibers. Considering regulatory requirements, several medical-grade PCL materials were assessed regarding their mechanical, degradational and cell biological properties. In the course of the investigation, an excellent fiber tensile strength of up to 850 MPa was achieved. The fibers were braided into multilayer scaffolds and scaled to match the human ACL. These were characterized regarding their morphology and their mechanical and degradational properties. Two strategies were followed to provide biological cues: (a) applying a chitosan-graft-PCL surface modification and (b) using non-circular fiber morphologies as topographical stimuli. Cell vitality assays showed generally positive cytocompatibility and no impairments due to the surface modification or material grade. The best cell vitality was achieved with a scaffold consisting of snowflake-shaped monofilaments combined with a 25° braiding angle. The surface modification equips the scaffold with a release platform for function molecules (as recently demonstrated) so that a holistic approach to addressing the numerous requirements is provided.

Development and Characterization of Heparin-Containing Hydrogel/3D-Printed Scaffold Composites for Craniofacial Reconstruction.

Regeneration of cartilage and bone tissues remains challenging in tissue engineering due to their complex structures, and the need for both mechanical support and delivery of biological repair stimuli. Therefore, the goal of this study was to develop a composite scaffold platform for anatomic chondral and osteochondral repair using heparin-based hydrogels to deliver small molecules within 3D-printed porous scaffolds that provide structure, stiffness, and controlled biologic delivery. We designed a mold-injection system to combine hydrolytically degradable hydrogels and 3D-printed scaffolds that could be employed rapidly (<30min) in operating room settings (~23°C). Micro-CT analysis demonstrated the effectiveness of our injection system through homogeneously distributed hydrogel within the pores of the scaffolds. Hydrogels and composite scaffolds exhibited efficient loading (~94%) of a small positively charged heparin-binding molecule (crystal violet) with sustained release over 14days and showed high viability of encapsulated porcine chondrocytes over 7days. Compression testing demonstrated nonlinear viscoelastic behavior where tangent stiffness decreased with scaffold porosity (porous scaffold tangent stiffness: 70%: 4.9MPa, 80%: 1.5MPa, and 90%: 0.20MPa) but relaxation was not affected. Lower-porosity scaffolds (70%) showed stiffness similar to lower ranges of trabecular bone (4-8MPa) while higher-porosity scaffolds (80% and 90%) showed stiffness similar to auricular cartilage (0.16-2MPa). Ultimately, this rapid composite scaffold fabrication method may be employed in the operating room and utilized to control biologic delivery within load-bearing scaffolds.

Preparation, properties and in vitro osteogensis of self-reinforcing injectable hydrogel

As an attractive biomaterial for bone reconstruction, injectable biomaterials have many prominent characteristics such as good biocompatibility and bone-filling ability. However, there are weak as load-bearing scaffolds. In this study, polyvinyl alcohol (PVA) and bioactive glass (BAG) were interpenetrated into sodium alginate (SA) network to obtain self-enhanced injectable hydrogel. The optimum ratio of PVA/SA/BAG hydrogel was determined based on injectability, gelation time and chemical characterization. Results showed that the selected ratio had the shortest gelation time of 3.5min, and the hydrogel had a rough surface and good coagulation property. The hydrogel was capable of carrying 1kg of weight by mineralization for 14 d The compressive strength, compressive modulus, and fracture energy of the hydrogel reached 0.12MPa, 0.376MPa and 17.750kJ m−2, respectively. Meanwhile, the hydrogel had high moisture content and dissolution rate, and it was sensitive to temperature and ionic strength. Hydroxyapatite was generated on the hydrogel surface, and the hydrogel pores increased, and the pore size enlarged. The biocompatibility of PVA/SA/BAG hydrogel was analyzed using hemolysis and cytotoxicity assays. Results revealed its good biocompatibility with low hemolysis rate and no cytotoxicity to MC3T3-E1 cells. The hydrogel was also found to promote the differentiation of MC3T3-E1 cells with significantly increased in ALP activity and expression of relevant differentiation factors. In vitro mineralization assay showed an increase in calcium nodules and calcification area, indicating the ability of hydrogel to promote mineralization MC3T3-E1 cells. These findings indicated that PVA/SA/BAG hydrogel had potential uses in the field of irregular bone-defect repair due to its injectability, cytocompatibility, and tailorable functionality.

In Vivo Evaluation of the Regenerative Capacity of a Nanofibrous, Prevascularized, Load-Bearing Scaffold for Bone Tissue Engineering

In Vivo Evaluation of the Regenerative Capacity of a Nanofibrous, Prevascularized, Load-Bearing Scaffold for Bone Tissue Engineering

Construction of Processable Ultrastiff Hydrogel for Periarticular Fracture Strutting and Healing.

Development of bioactive bone and joint implants that offer superior mechanical properties to facilitate personalized surgical procedures remains challenging in the field of biomedical materials. As for the hydrogel, mechanical property and processability are major obstructions hampering its application as load-bearing scaffolds in orthopedics. Herein, we constructed implantable composite hydrogels with appealing processability and ultrahigh stiffness. Central to our design is the incorporation of a thixotropic composite network into an elastic polymer network via dynamic interactions to synthesize a percolation-structured double-network (DN) hydrogel with plasticity, followed by in situ strengthening and self-strengthening mechanisms for fostering the DN structure to the cojoined-network structure and subsequently mineralized-composite-network structure to harvest excellent stiffness. The ultrastiff hydrogel is shapeable and can reach a compressive modulus of 80-200 MPa together with a fracture energy of 6-10 MJ/m3, comparable to the mechanical performance of cancellous bone. Moreover, the hydrogel is cytocompatible, osteogenic, and showed almost no volume shrinkage within 28 days in simulated body fluid or culture medium. Such characteristics enabled the utility of a hydrogel in the reduction and stabilization of periarticular fracture treatment on a distal femoral AO/OTA B1 fracture rabbit model and successfully avoided the recollapse of the articular surface.

Composite bone-implant engineered with magnesium and variable degradation for orthopaedics

Metallic biomaterials are suitable for load-bearing scaffolds, and magnesium (Mg) alloy is the most preferable because of its mechanical properties are comparable to those of hard tissue (bone). The most important characteristic of an implant is its biocompatibility and Mg fully satisfies this standard. Mg is also biodegradable, thereby avoiding the need for secondary surgery. An uncontrollable degradation rate is one of the most significant limitations of magnesium-based implants, which hinders their applications in bone tissue engineering. Hydroxyapatite (HAP), a bioactive material, was incorporated into a magnesium metal matrix as a catalyst for enhancing bone tissue regeneration. Porosity in the scaffold could serve as a conduit for nutrients and also aids in the scaffold's weight reduction. This study investigated the effect of selective alloying elements (Ca, Zn, and Fe) on the biodegradability of scaffolds. Powder metallurgy was used to produce the magnesium alloy scaffolds. A calculated quantity of porogen particles, carbamide (urea), was incorporated into the Mg-Ca-Zn-Fe matrix in order to achieve 30% and 50% porosity. Due to the formation of Mg-Ca-Zn-Fe intermetallic compounds, the current study establishes that Mg alloy-based samples exhibit favorable biodegradation behavior. After seven days of immersion, the pH of the immersion liquid had also been found to have stabilized. Consequently, the observations suggest that the biodegradation behavior of bone implants could be modified by developing composite porous magnesium alloy implants.

Rational design and fabrication of monophasic bioceramic microspheres with enhanced mechanical and biological performances in reconstruction of segmental bone defect.

Over the past decades, there has been extensive study on the design of porous bioceramic scaffolds with controlled bioactivity and biodegradation in bone tissue repair. A variety of suggestive models and concepts have been proposed with regard to the role of microstructure and composition of biomaterials which affect new bone tissue growth. However, it is a challenge to fabricate functional scaffolds with the desired physiological properties and osteogenic potentials that is comparable to the bone's natural healing time scale. We demonstrate a one-step versatile fabrication of a single-phase and homogenously mixed bioactive load-bearing scaffolds (Sr-CS, CaSiO3/Ca2SiO4, and CaP) with superior biological properties in a critical size bone defect (Ø ~ 6.0 × 8.0mm). In vivo study revealed the CaSiO3/Ca2SiO4 scaffold had the best amount of new bone growth and osteogenic repair. The Sr-CS exhibited an adequate pore network for rapid inorganic exchange and moderate mechanical stability; however, the CaSiO3/Ca2SiO4 saw over-fast resorption and mass loss compared to the Sr-CS and CaP. On the other hand, the CaP scaffold saw mechanically outstanding elastroplastine and stability but had limited biodegradation of its constructs which retarded new cancellous bone growth. The CaSiO3/Ca2SiO4 group saw superior acceleration and formation of mineralized new bone tissues in the defect. Moreover, the CaSiO3/Ca2SiO4 showed appreciable decay of the biomaterials beneficial for osteogenic cell activity. The dramatic stimulation of bone repair and angiogenesis with the CaSiO3/Ca2SiO4 suggests a promising application of this novel bioactive scaffold in the repair of skeletal defects. Systemic representation of the fabricated microspheres with in vivo and in vitro study analysis.

Shape optimization of orthopedic porous scaffolds to enhance mechanical performance

Polymeric bone scaffolds are supposed to temporarily bear the external mechanical forces applied to the injured area. The implanted scaffolds should satisfy both mechanical and cell-proliferation requirements. In this study, to design an optimum scaffold structure from mechanical and cell growth perspectives, a new scaffold structure named MFCC (Modified Face Centered Cubic) is introduced, which is based on the Face Centered Cubic (FCC) arrangement of spherical pores. The geometric parameters of the scaffold structure are optimized to increase the stiffness of the scaffolds with 70%, 75%, and 80% porosities. The optimized MFCC scaffolds satisfy the cell growth requirements and show greater elastic modulus compared to regular OCS (Orthogonal Cylindrical Struts) scaffolds. For validation, the designed scaffolds made by the finite element optimization process were 3D printed, tested and compared with the OCS scaffolds. The results show that the gradual cross-section variation of the spheres in the optimized scaffold reduces the stress concentration and distributes the applied mechanical loads more uniformly compared to OCS scaffolds. Moreover, from the cell growth perspective, a spherical pore with a concave surface provides a better surface for the proliferation of cells. The optimized MFCC scaffolds are stiffer in small strains and have a greater apparent yield stress compared to the OCS scaffolds at the same porosity. The enhancement in the stiffness of the scaffold is shape attributed and is independent of the material used. Therefore, the same percentage increase in the stiffness is achievable for a broad range of materials. The presented new design with improved stiffness helps to enhance the quality of load-bearing scaffolds.

Soft while strong mechanical shock tolerable e-skins

Soft while strong mechanical shock tolerable e-skins relied on non-Newtonian gel embedded within the load-bearing scaffold of conductive collagen fiber sponge spontaneously mimic the protection and sensing functions of natural skin.

Design procedure for triply periodic minimal surface based biomimetic scaffolds

Cellular additively manufactured metallic structures for load-bearing scaffolds in the context of bone tissue engineering (BTE) have emerged as promising candidates. Due to many advantages in terms of morphology, stiffness, strength and permeability compared to conventional truss structures, lattices based on triply periodic minimal surfaces (TPMS) have recently attracted increasing interest for this purpose. In addition, the finite element method (FEM) has been proven to be suitable for accurately predicting the deformation behavior as well as the mechanical properties of geometric structures after appropriate parameter validation based on experimental data. Numerous publications have examined many individual aspects, but conceptual design procedures that consider at least the essential requirements for cortical and trabecular bone simultaneously are still rare. Therefore, this paper presents a numerical approach to first determine the actual admissible design spaces for a choice of TPMS based lattices with respect to key parameters and then weight them with respect to further benefit parameters. The admissible design spaces are limited by pore size, strut size and volume fraction, and the subsequent weighting is based on Young’s modulus, cell size and surface area. Additively manufactured beta-Ti-42Nb with a strain stiffness of 60.5GPa is assumed as material. In total, the procedure considers twelve lattice types, consisting of six different TPMS, each as network solid and as sheet solid. The method is used for concrete prediction of suitable TPMS based lattices for cortical bone and trabecular bone. For cortical bone a lattice based on the Schwarz Primitive sheet solid with 67.572μm pore size, 0.5445 volume fraction and 18.758GPa Young’s modulus shows to be the best choice. For trabecular bone a lattice based on the Schoen Gyroid network solid with 401.39μm pore size, 0.3 volume fraction and 4.6835GPa Young’s modulus is the identified lattice. Finally, a model for a long bone scaffold is generated from these two lattices using functional grading methods in terms of volume fraction, cell size and TPMS type. In particular, the presented procedure allows an efficient estimation for a likely suitable biometric TPMS-based scaffolds. In addition to medical applications, however, the method can also be transferred to numerous other applications in mechanical, civil and electrical engineering.

3D printed multifunctional, load-bearing, low-frequency sound absorbers

Cellular porous materials are an attractive choice for lightweight structural design. However, though their open porous architecture is ideally suited for multifunctional applications, their use is typically limited by the pore sizes achievable by traditional as well as advanced fabrication processes. Here, we present an alternative route towards overcoming this pore size limitation by leveraging our recent success in printing fibrous structures. This is achieved by superimposing a fibrous network on a load-bearing, open-celled porous architecture. The multifunctional structure is 3D printed using a novel technique that enables us to simultaneously print a load-bearing scaffold and the necessary fibrous network. The acoustic properties of the printed structures are tested using a normal-incidence impedance tube method. Our results show that such structures can provide very high absorption at low frequencies while retaining the mechanical performance of the underlying architected structure.

Mechanical properties of chitin polymorphs: A computational study

Chitin-based bio-composites in nature such as the exoskeleton of crustaceans and squid pen usually exhibit hierarchical structures, where the chitin crystal is the most fundamental structural hierarchy as the load-bearing scaffold. Previous studies have unveiled the mechanical design of the structures at high hierarchies in these biomaterials, while the structure–property relationship remains unclear for the chitin crystal at the bottom hierarchy. In this paper, we investigate the mechanical properties of chitin crystals with $$\alpha$$ - and $$\beta$$ -polymorphic structures that mainly exist over the animal kingdom using the reactive force field molecular dynamics simulations. We first validate the force field parameters adopted from literature then study the mechanical behaviors of chitin polymorphs in response to the tensile and shear deformation. It is found that the mechanical performance of $$\alpha$$ -chitin crystal is comprehensively superior to that of $$\beta$$ -chitin crystal, such as the elastic modulus, work of fracture, shear modulus and strength. Different from the $$\beta$$ -chitin, yielding caused by the transformation of crystalline structure is observed in the $$\alpha$$ -chitin during uniaxial tension. Based on the mechanical properties obtained from simulations and theoretical analysis, we can deduce that the $$\alpha$$ -chitin shows higher wear resistance than the $$\beta$$ -chitin, implying better protection against the surface scratch that is one of the environmental threats to organisms. Our results shed light on the structure–property relationship of chitin crystals at the molecular level. The fundamental understanding of mechanical properties of chitin polymorphs is of great significance for the bottom-up modeling and design of chitin-based bio-composites.

Bacteria activated-macrophage membrane-coated tough nanocomposite hydrogel with targeted photothermal antibacterial ability for infected wound healing

A bacteria activated-macrophage membrane-coated tough nanocomposite hydrogel is fabricated by in situ polymerization of hydrogen bonding monomer N-acryloyl glycinamide loaded with polydopamine-modified gold nanorods (Au@PDA NRs), followed by coating bacteria-activated macrophage membrane (MM). The resultant E/SMM-PNAGA-Au@PDA NRs hydrogels exhibit high mechanical properties, excellent targeted photothermal antibacterial and wound healing capacity. • A macrophage membrane-coated hydrogel with a photothermal effect is fabricated. • The hydrogel can specifically recognize and capture the target bacteria. • The hydrogel enables healing of infected wound and harmless peeling. Antibacterial hydrogels have attracted extensive attention for preventing bacterial infection as wound dressing. However, development of broad-spectrum antibacterial hydrogel with a specific recognition ability and high strength remains challenging. In this work, a novel multifunctional nanocomposite antibacterial hydrogel with high strength and toughness is prepared by one-pot polymerization of hydrogen bonding monomer N-acryloyl glycinamide (NAGA) mixing with polydopamine-coated gold nanorods (Au@PDA NRs). The PNAGA-Au@PDA hydrogels are then coated with E. coli or S. aureus -pretreated macrophage membrane (termed as E/SMM-PNAGA-Au@PDA). Intriguingly, the resultant hydrogels can recognize specifically the source bacteria, and kill 98% bacteria in vitro under NIR irradiation for 5 min. Importantly, the SMM-PNAGA-Au@PDA hydrogel implanted on the dorsal area of rats can facilitate the infected wound healing and avoid secondary damage during peeling. This tough nanocomposite hydrogel coated with specific bacteria-activated macrophage membrane is promising to be developed as wound dressing, artificial skin and load-bearing scaffolds.

Single-Stage Autologous Chondrocyte-Based Treatment for the Repair of Knee Cartilage Lesions: Two-Year Follow-up of a Prospective Single-Arm Multicenter Study

Background: There is an unmet need for a single-stage cartilage repair treatment that is cost-effective and chondrocyte-based. Purpose: To evaluate the safety and preliminary efficacy of autologous freshly isolated primary chondrocytes and bone marrow mononucleated cells (MNCs) seeded into a PolyActive scaffold in patients with symptomatic cartilage lesions of the knee. Study Design: Case series; Level of evidence, 4. Methods: A total of 40 patients with symptomatic knee cartilage lesions were treated with freshly isolated autologous chondrocytes combined with bone marrow MNCs delivered in a biodegradable load-bearing scaffold. The treatment requires only 1 surgical intervention and is potentially a cost-effective alternative to autologous chondrocyte implantation. The primary chondrocytes and bone marrow MNCs were isolated, washed, counted, mixed, and seeded into a load-bearing scaffold in the operating room. Patients were followed up at 3, 6, 12, 18, and 24 months. Primary endpoints were treatment-related adverse events up to 3 months, adverse implant effects between 3 and 24 months, and the implant success rate at 3 months as measured by lesion filling. Results: Successful lesion filling (≥67% on magnetic resonance imaging) was found in 40 patients at 3 months and in 32 of the 32 patients analyzed at 24 months. Significant improvement over baseline was found for visual analog scale for pain from 3 months onward; Knee injury and Osteoarthritis Outcome Score (KOOS)-Pain and KOOS-Activities of Daily Living from 6 months onward; for KOOS-Symptoms and Stiffness, KOOS-Quality of Life and International Knee Documentation Committee from 12 months onward; and for KOOS-Sport and Recreation from 18 months onward. Hyaline-like repair tissue was found in 22 of 31 patients available for biopsy. Arthralgia and joint effusion were the most common adverse events. Scaffold delamination and adhesions led to removal of the implant in 2 patients. Conclusion: The treatment of knee cartilage lesions with autologous primary chondrocytes and bone marrow MNCs, both isolated and seeded into a load-bearing PolyActive scaffold within a single surgical intervention, is safe and clinically effective. Good lesion fill and sustained clinically important and statistically significant improvement in all patient-reported outcome scores were found throughout the 24-month study. Hyaline-like cartilage was observed on biopsy specimen in at least 22 of the 40 patients. Registration: NCT01041885 (ClinicalTrials.gov identifier)

An Injectable Strong Hydrogel for Bone Reconstruction.

For treating bone defects in periarticular fractures, there is a lack of biomaterial with injectable characteristics, tough structure, and osteogenic capacity for providing a whole-structure support and osteogenesis in the defect area. An injectable hydrogel is an ideal implant, however is weak as load-bearing scaffolds. Herein, a new strategy, i.e., an in situ formation of "active" composite double network (DN), is raised for the preparation of an injectable strong hydrogel particularly against compression. As a demonstration, 4-carboxyphenylboronic acid grafted poly(vinyl alcohol) (PVA) is crosslinked using calcium ions to provide a tough frame while bioactive glass (BG) microspheres are associated by poly(ethylene glycol) to obtain an interpenetrated inorganic network for reinforcement. The injected PVA/BG DN hydrogel gains compressive strength, modulus, and fracture energy of 34 MPa, 0.8 MPa, and 40 kJ m-2 , respectively. Then, the properties can be "autostrengthened" to 57 MPa, 2 MPa, and 65 kJ m-2 by mineralization in 14 days. In vivo experiments prove that the injected DN hydrogel is more efficient to treat femoral supracondylar bone defects than the implanted bulk DN gel. The work suggests a facile way to obtain a strong hydrogel with injectability, cytocompatibility, and tailorable functionality.

Biodegradable nanocomposite Fe–Ag load-bearing scaffolds for bone healing

Processing and properties of biodegradable load-bearing nanocomposite Fe–Ag scaffolds for bone ingrowth are reported. Fe–Ag nanocomposites were prepared employing high energy attrition milling of powders. Scaffolds with regular interconnected 300–400 μm pores and 60–75% porosity were prepared by cold sintering/high pressure consolidation of nanocomposite Fe–Ag granules, blended with porogen – highly water soluble sugar particles. The scaffolds' strength and permeability were found to be inversely related and to be strongly dependent on porosity. Presence of galvanic nanocouples in Fe5Ag and Fe10Ag resulted in desirable increase of degradation rate in saline solution as compared to pure Fe. The 70% and 75% macroporous Fe–Ag scaffolds possess high compressive strength (9.1–14.9 MPa) and permeability (1.0–3.5·10−10 m2) being in the range of trabecular/spongy bone. Method of estimation surface area of metal based macroporous scaffolds was proposed and successfully used.

Vegetable hierarchical structures as template for bone regeneration: New bio-ceramization process for the development of a bone scaffold applied to an experimental sheep model.

Long bone defects still represent a major clinical challenge in orthopedics, with the inherent loss of function considerably impairing the quality of life of the affected patients. Thus, the purpose of this study was to assess the safety and potential of bone regeneration offered by a load-bearing scaffold characterized by unique hierarchical architecture and high strength, with active surface facilitating new bone penetration and osseointegration in critical size bone defects. The results of this study showed the potential of bio-ceramization processes applied to vegetable hierarchical structures for the production of new wood-derived bone scaffolds, further improved by surface functionalization, with good biological and mechanical properties leading to successful treatment of critical size bone defects in the sheep model. Future studies are needed to evaluate if these scaffolds prototypes, as either biomaterial alone or in combination with augmentation strategies, may represent an optimal solution to enhance bone regeneration in humans.

Formulation of a covalently bonded hydroxyapatite and poly(ether ether ketone) composite

Spinal fusion devices can be fabricated from composites based on combining hydroxyapatite and poly(ether ether ketone) phases. These implants serve as load-bearing scaffolds for the formation of new bone tissue between adjacent vertebrae. In this work, we report a novel approach to covalently bond hydroxyapatite and poly(ether ether ketone) to produce a novel composite formulation with enhanced interfacial adhesion between phases. Compared to non-linked composites (HA_PEEK), covalently linked composites (HA_L_PEEK), loaded with 1.25 vol% hydroxyapatite, possessed a greater mean flexural strength (170 ± 5.4 vs 171.7 ± 14.8 MPa (mean ± SD)) and modulus (4.8 ± 0.2 vs 5.0 ± 0.3 GPa (mean ± SD)). Although the mechanical properties were not found to be significantly different (p > 0.05), PEEK_L_HA contained substantially larger hydroxyapatite inclusions (100–1000 µm) compared to HA_PEEK (50–200 µm), due to the inherently agglomerative nature of the covalently bonded hydroxyapatite and poly(ether ether ketone) additive. Larger inclusions would expectedly weaken the HA_L_PEEK composite; however, there is no significant difference between the flexural modulus of poly(ether ether ketone) with respect to HA_L_PEEK (p = 0.13). In addition, the flexural modulus of HA_PEEK is significantly lower compared to poly(ether ether ketone) (p = 0.03). Ultimately, covalent linking reduces hydroxyapatite particulate de-bonding from the polymeric matrix and inhibits micro-crack development, culminating in enhanced transfer of stiffness between hydroxyapatite and poly(ether ether ketone) under loading.

Bioglass® 45S5-based composites for bone tissue engineering and functional applications.

Bioglass® 45S5 (BG) has an outstanding ability to bond with bones and soft tissues, but its application as a load-bearing scaffold material is restricted due to its inherent brittleness. BG-based composites combine the amazing biological and bioactive characteristics of BG with structural and functional features of other materials. This article reviews the composites of Bioglass® in combination with metals, ceramics and polymers for a wide range of potential applications from bone scaffolds to nerve regeneration. Bioglass® also possesses angiogenic and antibacterial properties in addition to its very high bioactivity; hence, composite materials developed for these applications are also discussed. BG-based composites with polymer matrices have been developed for a wide variety of soft tissue engineering. This review focuses on the research that suggests the suitability of BG-based composites as a scaffold material for hard and soft tissues engineering. Composite production techniques have a direct influence on the bioactivity and mechanical behavior of scaffolds. A detailed discussion of the bioactivity, in vitro and in vivo biocompatibility and biodegradation is presented as a function of materials and its processing techniques. Finally, an outlook for future research is also proposed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3197-3223, 2017.

Influence of structural load-bearing scaffolds on mechanical load- and BMP-2-mediated bone regeneration

A common design constraint in functional tissue engineering is that scaffolds intended for use in load-bearing sites possess similar mechanical properties to the replaced tissue. Here, we tested the hypothesis that in vivo loading would enhance bone morphogenetic protein-2 (BMP-2)-mediated bone regeneration in the presence of a load-bearing PLDL scaffold, whose pores and central core were filled with BMP-2-releasing alginate hydrogel. First, we evaluated the effects of in vivo mechanical loading on bone regeneration in the structural scaffolds. Second, we compared scaffold-mediated bone regeneration, independent of mechanical loading, with alginate hydrogel constructs, without the structural scaffold, that have been shown previously to facilitate in vivo mechanical stimulation of bone formation.Contrary to our hypothesis, mechanical loading had no effect on bone formation, distribution, or biomechanical properties in structural scaffolds. Independent of loading, the structural scaffolds reduced bone formation compared to non-structural alginate, particularly in regions in which the scaffold was concentrated, resulting in impaired functional regeneration.This is attributable to a combination of stress shielding by the scaffold and inhibition of cellular infiltration and tissue ingrowth. Collectively, these data question the necessity of scaffold similarity to mature tissue at the time of implantation and emphasize development of an environment conducive to cellular activation of matrix production and ultimate functional regeneration.