Search

The intervertebral disc contributes to motion, weight bearing, and flexibility of the spine, but is susceptible to damage and morphological changes that contribute to pathology with age and injury. Engineering strategies that rely upon synthetic materials or composite implants that do not interface with the biological components of the disc have not met with widespread use or desirable outcomes in the treatment of intervertebral disc pathology. Here we review bioengineering advances to treat disc disorders, using cell-supplemented materials, or acellular, biologically based materials, that provide opportunity for cell-material interactions and remodeling in the treatment of intervertebral disc disorders. While a field still in early development, bioengineering-based strategies employing novel biomaterials are emerging as promising alternatives for clinical treatment of intervertebral disc disorders.

Self-assembly is a prominent phenomenon observed in nature. Inspired by this thermodynamically favorable approach, several natural and synthetic materials have been investigated to develop functional systems for various biomedical applications, including drug delivery. Furthermore, layered self-assembled systems provide added advantages of tunability and multifunctionality which are crucial for controlled and targeted drug release. Layer-by-layer (LbL) deposition has emerged as one of the most popular, well-established techniques for tailoring such layered self-assemblies. This review aims to provide a brief overview of drug delivery applications using LbL deposition, along with a discussion of associated scalability challenges, technological innovations to overcome them, and prospects for commercial translation of this versatile technique. Additionally, alternative self-assembly techniques such as metal-phenolic networks (MPNs) and Liesegang rings are also reviewed in the context of their recent utilization for controlled drug delivery. Blending the sophistication of these self-assembly phenomena with material science and technological advances can provide a powerful tool to develop smart drug carriers in a scalable manner.

Human civilization has witnessed the use of materials-derived from biomolecules of plants and animal origin for biomedical applications since ancient era. In recent years, precision design principles have been adopted to develop novel biomaterials derived from biomolecules. The biomolecules-derived biomaterials fabrication is dependent on chemical, biochemical and mechanical parameters of biomolecules and their bulk materials. Thus, structural variations and weak noncovalent interactions present within the basic building blocks greatly influence the functional features and applications. This comprehensive review provides one-stop information on recent innovations of various biomaterial-types derived from a diverse class of biomolecules through selected and representative examples with potential biomedical applications ranging from diagnosis, biosensing, antimicrobial efficacy, anticancer therapeutics, drug delivery, bioprinting, bioimaging, tissue engineering and regenerative medicine. The discussion systematically follows the top-down approach in the order of molecular complexity viz., biomacromolecules, oligomers and monomers of all classes of biomolecules (proteins, nucleic acids, carbohydrates and lipids) including a special section on biohybrid materials derived from molecular systems integrated with more than one class of biomolecules. In addition to providing overview of impressive advancements in the area, synergistic integration of biomolecules with synthetic materials to develop smart biomaterials is emphasized to improve the chemical, mechanical, stimuli-responsiveness, immunogenicity and biocompatibility features.

Treatment of complex bone defects places a significant burden on the US health care system. Current strategies for treatment include grafting and stabilization using internal metal plates/screws, intramedullary rods, or external fixators. Here, we introduce the use of shape memory polymer (SMP) materials for grafting and adjunct stabilization of segmental defects. Self-deploying SMP grafts and SMP sleeves capable of expanding and contracting, respectively, under intraoperative conditions were developed and evaluated in a mouse segmental defect model in vivo. Integration between grafts/sleeves and native bone was assessed using x-ray radiography, microcomputed tomography, and torsional mechanical testing. We found that SMP grafts were able to integrate with the native bone after 12 weeks, maintain defect stability, and provide torsional mechanical properties comparable to an allograft alone treatment; however no gross de novo bone formation was observed. SMP sleeves did not inhibit bony bridging at the margins, and limbs treated with a sleeve/allograft combination had torsional mechanical properties comparable to limbs treated with an allograft alone. In vitro torsional and bending tests suggest sleeves may provide additional torsional stability to defects. Incorporation of shape memory into synthetic bone graft substitutes and adjunct stabilization devices is anticipated to enhance functionality of synthetic materials employed in both applications.

Heart valve tissue engineering based on decellularized xenogenic or allogenic starter matrices has shown promising first clinical results. However, the availability of healthy homologous donor valves is limited and xenogenic materials are associated with infectious and immunologic risks. To address such limitations, biodegradable synthetic materials have been successfully used for the creation of living autologous tissue-engineered heart valves (TEHVs) invitro. Since these classical tissue engineering technologies necessitate substantial infrastructure and logistics, we recently introduced decellularized TEHVs (dTEHVs), based on biodegradable synthetic materials and vascular-derived cells, and successfully created a potential off-the-shelf starter matrix for guided tissue regeneration. Here, we investigate the host repopulation capacity of such dTEHVs in a non-human primate model with up to 8 weeks follow-up. After minimally invasive delivery into the orthotopic pulmonary position, dTEHVs revealed mobile and thin leaflets after 8 weeks of follow-up. Furthermore, mild-moderate valvular insufficiency and relative leaflet shortening were detected. However, in comparison to the decellularized human native heart valve control - representing currently used homografts - dTEHVs showed remarkable rapid cellular repopulation. Given this substantial in situ remodeling capacity, these results suggest that human cell-derived bioengineered decellularized materials represent a promising and clinically relevant starter matrix for heart valve tissue engineering. These biomaterials may ultimately overcome the limitations of currently used valve replacements by providing homologous, non-immunogenic, off-the-shelf replacement constructs. © 2013 Elsevier Ltd.

Research on biomaterial nerve scaffolds has been carried out for 50 years. Only three materials (collagen, polycaprolactone and polyglycollic acid) have progressed to clinical use. Pre-clinical animal models are critical for testing nerve scaffolds prior to implementation in clinical practice. We have conducted a systematic review of 416 reports in which animal models were used for evaluation of nerve regeneration into synthetic conduits. A valid animal model of nerve regeneration requires it to reproduce the specific processes that take place in regeneration after human peripheral nerve injury. No distinct animal species meets all the requirements for an ideal animal model. Certain models are well suited for understanding regenerative neurobiology while others are better for pre-clinical evaluation of efficacy. The review identified that more than 70 synthetic materials were tested in eight species using 17 different nerves. Nerve gaps ranged from 1 to 90 mm. More than 20 types of assessment methodology were used with no standardization of methods between any of the publications. The review emphasizes the urgent need for standardization or rationalization of animal models and evaluation methods for studying nerve repair.

Decellularized xenogenic or allogenic heart valves have been used as starter matrix for tissue-engineering of valve replacements with (pre-)clinical promising results. However, xenografts are associated with the risk of immunogenic reactions or disease transmission and availability of homografts is limited. Alternatively, biodegradable synthetic materials have been used to successfully create tissue-engineered heart valves (TEHV). However, such TEHV are associated with substantial technological and logistical complexity and have not yet entered clinical use. Here, decellularized TEHV, based on biodegradable synthetic materials and homologous cells, are introduced as an alternative starter matrix for guided tissue regeneration. Decellularization of TEHV did not alter the collagen structure or tissue strength and favored valve performance when compared to their cell-populated counterparts. Storage of the decellularized TEHV up to 18 months did not alter valve tissue properties. Reseeding the decellularized valves with mesenchymal stem cells was demonstrated feasible with minimal damage to the reseeded valve when trans-apical valve delivery was simulated. In conclusion, decellularization of in-vitro grown TEHV provides largely available off-the-shelf homologous scaffolds suitable for reseeding with autologous cells and trans-apical valve delivery.

Experimental and theoretical studies have demonstrated that biological and synthetic hydroxyapatites display crystal structure similarities and differences that affect greatly the bioactivity of the synthetic materials. Recent developments in structure research of bioapatites report experimental values of the hydroxyl concentration in biological apatites in the range of 20-0% of the amount in synthetic hydroxyapatite. Theoretical calculations find the hexagonal space groups energetically unfavorable for hydroxyapatite crystallization. Different configurations are proposed for the carbonate substitution in B-type carbonate apatites.

The type of nanostructure referred to in biomineralization as a mineral bridge has been directly observed and measured in the organic matrix layers of nacre by transmission electron microscopy and scanning electron microscopy. Statistical analysis provides the geometric characteristics and a distribution law of the mineral bridges in the organic matrix layers. Experiments reveal that the nanostructures significantly influences the mechanical properties of the organic matrix layers. In addition, the mechanical analysis illustrates the effects of the nanostructures on the behaviors of the organic matrix layers, and the analytical results explain the corresponding experimental phenomena fairly well. The present study shows that the mineral bridges play a key role in the mechanical performances of the organic matrix layers of nacre. The results obtained provide a guide to the interfacial design of synthetic materials.

This study was designed to validate an in vivo model in rat to study cell-implant interactions. Pieces of Dacron and Goretex and polydimethylsiloxane (reference material) precoated or not were implanted in the peritoneal cavity. In some cases the peritoneal cells were stimulated before the implantation. Macrophage phagocytosis and fibrinocoagulolytic activities were investigated in parallel with morphological studies 6 h after implantation. A graded cell response related to the different situations was observed, providing a measure of the material's behaviour. Using this model, other investigations of macrophage/polymer can be conducted, especially to explain implant encapsulation.This study was designed to validate an in vivo model in rat to study cell-implant interactions. Pieces of Dacron and Goretex and polydimethylsiloxane (reference material) precoated or not were implanted in the peritoneal cavity. In some cases the peritoneal cells were stimulated before the implantation. Macrophage phagocytosis and fibrinocoagulolytic activities were investigated in parallel with morphological studies 6 h after implantation. A graded cell response related to the different situations was observed, providing a measure of the material's behaviour. Using this model, other investigations of macrophage/polymer can be conducted, especially to explain implant encapsulation.

The sandwich culture of hepatocytes, between double layers of extra-cellular matrix (ECM), is a well-established in vitro model for re-establishing hepatic polarity and maintaining differentiated functions. Applications of the ECM-based sandwich culture are limited by the mass transfer barriers induced by the top gelled ECM layer, complex molecular composition of ECM with batch-to-batch variation and uncontrollable coating of the ECM double layers. We have addressed these limitations of the ECM-based sandwich culture by developing an 'ECM-free' synthetic sandwich culture, which is constructed by sandwiching a 3D hepatocyte monolayer between a glycine-arginine-glycine-aspatic acid-serine (GRGDS)-modified polyethylene terephthalate (PET) track-etched membrane (top support) and a galactosylated PET film (bottom substratum). The bioactive top support and bottom substratum in the synthetic sandwich culture substituted for the functionalities of the ECM in the ECM-based sandwich culture with further improvement in mass transfer and optimal material properties. The 3D hepatocyte monolayer in the synthetic sandwich culture exhibited a similar process of hepatic polarity formation, better cell-cell interaction and improved differentiated functions over 14-day culture compared to the hepatocytes in collagen sandwich culture. The novel 3D hepatocyte monolayer sandwich culture using bioactive synthetic materials may readily replace the ECM-based sandwich culture for liver tissue engineering applications, such as drug metabolism/toxicity testing and hepatocyte-based bioreactors.

Collagenous tissue as a biomaterial possesses many favourable characteristics and advantages over synthetic materials. The resemblance to human tissue suggests that it has a performance advantage over alternative materials. This advantage has been exploited to produce clinical devices that have been implanted in patients for more than a quarter of a century. The method of treating collagenous tissue for bioprostheses has developed from crude exposure of tissue to chemicals to a sophisticated level of considering the biochemical, chemical, engineering and clinical aspects of the process. This review focuses on the various chemical and physical treatments that have made the bioprostheses possible, highlighting the chemical agents and the cross-linking mechanism involved.