Innovations In Biomaterials Research Articles

3D-Printed PCL-Based Scaffolds with High Nanosized Synthetic Smectic Clay Content: Fabrication, Mechanical Properties, and Biological Evaluation for Bone Tissue Engineering.

The 3D printing of macro- and mesoporous biomimetic grafts composed of polycaprolactone (PCL) infused with nanosized synthetic smectic clay is a promising innovation in biomaterials for bone tissue engineering (BTE). The main challenge lies in achieving a uniform distribution of nanoceramics across low to high concentrations within the polymer matrix while preserving mechanical properties and biological performance essential for successful osseointegration. This study utilized 3D printing to fabricate PCL scaffolds enriched with nanosized synthetic smectic clay (LAP) to evaluate its effects on structural, chemical, thermal, mechanical, and degradative properties, with a focus on in vitro biological performance and non-toxicity. Scaffolds were created with varying proportions of PCL and LAP. Comprehensive characterization included scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), mechanical testing, swelling analysis, and degradation studies. Biological performance was assessed through MTT assays (cell viability), alkaline phosphatase activity, histological analysis, and Raman spectroscopy, highlighting the scaffolds' biocompatibility and potential applications in regenerative medicine. The developed inks demonstrated excellent injectability, and the 3D-printed PCL/LAP scaffolds exhibited a microporous and rough structure, good structural fidelity, low degradability, thermal stability, and sufficient mechanical strength across all formulations. Intrinsic properties of the scaffolds revealed no cytotoxicity while enhancing bioactivity and promoting in vitro mineralization when cultured with mesenchymal stem cells in all analyzed groups. Notably, the high concentration of LAP within the PCL matrices did not induce in vitro cytotoxicity but rather stimulated in vitro mineralization and differentiation. This study demonstrated the feasibility of 3D printing PCL/LAP scaffolds with high concentrations of nanoceramics. Both in vitro and in vivo assays validated the regenerative potential of these scaffolds, emphasizing their efficacy as a promising approach for developing advanced biomimetic grafts.

Spatial dimension cues derived from fibrous scaffolds trigger mechanical activation to potentiate the paracrine and regenerative functions of MSCs via the FAK-PI3K/AKT axis

Secretomes from mesenchymal stem cells (MSCs) have significant therapeutic potential and could be the basis for future MSCs treatments. Innovative design of the topology of biomaterials, which mechanically regulate cell behavior and function, can tremendously improve the efficacy of stem cell therapy. However, how spatial dimension cues derived from specific topology command cell mechanotransduction to regulate the paracrine function of MSCs remains unknown. In this study, the three-dimensional (3D) fibrous constructs with box-like pores and precise strand spacing from 150 µm down to only 40 µm were manufactured using melt electrowriting (MEW), which were used to systematically investigate the spatial dimension cues-triggered mechanotransduction of adipose-derived mesenchymal stem cells (Ad-MSCs) and their impact on the paracrine and regeneration function of Ad-MSCs. The results demonstrated that spatial instructions from the 3D fibrous constructs could influence the spatial reorganization of the cytoskeleton, resulting in cell elongation and augmented immunomodulatory and angiogenic paracrine effects of Ad-MSCs, which was most pronounced at a minimum strand spacing of 40 µm. Besides, mechanical activation of the FAK-PI3K/AKT axis significantly enhanced the paracrine function of Ad-MSCs. In vivo experiments demonstrated that the Ad-MSCs trained using well-defined 3D fibrous constructs with a strand spacing of 40 µm significantly promoted skin regeneration via paracrine signals. In conclusion, this study provides a new horizon for deciphering space dimension insights into the interactional mechanisms of mechanotransduction in regulating cell function, which has inspired innovations in biomaterials for improving tissue regeneration. Statement of significanceThis study emphasized that designing cell-scale spatial dimension cues to command mechanical activation via the FAK-PI3K/AKT axis could significantly enhance the paracrine and regenerative functions of Ad-MSCs. Paracrine signals of Ad-MSCs triggered by mechanical activation promoted skin repair and regeneration via the immunomodulation and angiogenesis. The proposed mechanobiological signal transduction triggered by spatial dimensional cues, which potentiates the paracrine and regenerative functions of Ad-MSCs, is a promising engineering strategy and is expected to provide new inspirations for the development of biomaterials based on biophysical signals for cellular behavior modulation.

Finite element modeling of stress distribution and safety factors in a Ti-27Nb alloy hip implant under real-world physiological loading scenarios.

Total hip arthroplasty (THA) is one of the most successful orthopaedic interventions globally, with over 450,000 procedures annually in the U.S. alone. However, issues like aseptic loosening, dislocation, infection and stress shielding persist, necessitating complex, costly revision surgeries. This highlights the need for continued biomaterials innovation to enhance primary implant integrity and longevity. Implant materials play a pivotal role in determining long-term outcomes, with titanium alloys being the prominent choice. However, emerging evidence indicates scope for optimized materials. The nickel-free β titanium alloy Ti-27Nb shows promise with excellent biocompatibility and mechanical properties. Using finite element analysis (FEA), this study investigated the biomechanical performance and safety factors of a hip bone implant made of nickel-free titanium alloy (Ti-27Nb) under actual loading during routine day life activities for different body weights. The FEA modelled physiological loads during walking, jogging, stair ascent/descent, knee bend, standing up, sitting down and cycling for 75 kg and 100 kg body weights. Comparative analyses were conducted between untreated versus 816-hour simulated body fluid (SBF) treated implant conditions to determine in vivo degradation effects. The FEA predicted elevated von Mises stresses in the implant neck for all activities, especially stair climbing, due to its smaller cross-section. Stresses increased substantially with a higher 100 kg body weight compared to 75 kg, implying risks for heavier patients. Safety factors were reduced by up to 58% between body weights, although remaining above the desired minimum value of 1. Negligible variations were observed between untreated and SBF-treated responses, attributed to Ti-27Nb's excellent biocorrosion resistance. This comprehensive FEA provided clinically relevant insights into the biomechanical behaviour and integrity of the Ti-27Nb hip implant under complex loading scenarios. The results can guide shape and material optimization to improve robustness against repetitive stresses over long-term use. Identifying damage accumulation and failure risks is crucial for hip implants encountering real-world variable conditions. The negligible SBF effects validate Ti-27Nb's resistance to physiological degradation. Overall, the study significantly advances understanding of Ti-27Nb's suitability for reliable, durable hip arthroplasties with low revision rates.

Enhanced fibrocartilage regeneration at the tendon-bone interface injury through extracellular matrix hydrogel laden with bFGF-overexpressing human urine-derived stem cells

The tendon-bone interface (TBI) is crucial in the transfer of mechanical loads; however, it is susceptible to injuries that frequently result in healing via fibrous scar tissue formation. Consequently, regeneration of the fibrocartilaginous zone has become a pivotal area subject. At present, the use of stem cells represents a notably promising approach for TBI treatment. Especially, human urine-derived stem cells (hUSCs) present a practical option for cell-based therapies. Nevertheless, the chondrogenic differentiation potential of hUSCs is limited. To address this, basic fibroblast growth factor (bFGF) was transinfected into hUSCs to bolster their differentiation capacity and facilitate the formation of fibrocartilage in the target area. Additionally, the local immune microenvironment dramatically influences TBI healing, with macrophages playing a vital role. Effective healing relies on the phenotype transition of macrophages, with an imbalance often leading to insufficient regeneration and scar tissue formation. Innovations in biomaterials have provided new avenues for TBI repair, such as the porcine small intestinal submucosa (SIS) hydrogel developed in our prior research. In addition to serving as a carrier for stem cell delivery, the hydrogel’s bioactive components support tissue repair and immune regulation. In the present study, SIS hydrogel loaded with hUSCs that overexpress bFGF was used for the treatment of TBI injury, which is expected to correct inflammatory response imbalances, and promote macrophage polarization towards healing phenotypes, creating a favorable immune microenvironment. The combined effects of bFGF and the optimized immune setting are anticipated to enhance hUSCs’ chondrogenic potential, aiding in the functional restoration of TBI injuries.

Engineered heart tissue: Design considerations and the state of the art.

Originally developed more than 20 years ago, engineered heart tissue (EHT) has become an important tool in cardiovascular research for applications such as disease modeling and drug screening. Innovations in biomaterials, stem cell biology, and bioengineering, among other fields, have enabled EHT technologies to recapitulate many aspects of cardiac physiology and pathophysiology. While initial EHT designs were inspired by the isolated-trabecula culture system, current designs encompass a variety of formats, each of which have unique strengths and limitations. In this review, we describe the most common EHT formats, and then systematically evaluate each aspect of their design, emphasizing the rational selection of components for each application.

The future of cell-instructive biomaterials for tissue regeneration–a perspective from early career clinician-scientists

Cell-instructive biomaterials are an essential component in tissue engineering and regenerative medicine. In the past three decades since the term “Tissue Engineering” was coined, researchers have made significant progress towards regenerating disease or damage tissues and organs by combining innovations in biomaterials, signaling molecules and cell therapies. However, challenges persist including limitations in properties of cell-instructive biomaterials, lack of advanced manufacturing technologies for precise spatiotemporal control of key players in tissue engineering, and hurdles in clinical translation and regulatory process. In this perspective article, we briefly review the current state of the field including the evolution in our understanding of the role biomaterial mechanics and scaffolding architecture, development of self-healing and modular biomaterials, and progress in advanced manufacturing technologies such as 3D bioprinting. In addition, we discuss about how innovation in research technologies including multi-omics and spatial biology, and advanced imaging modalities may pave the way for enhancing our understanding about cell-biomaterial interactions. Finally, we present our perspective as early career clinicians and researchers on the key role and potential impact that clinician-scientists can generate in the development, validation, clinical translation and adoption of the next-generation of cell-instructive biomaterials for application in engineering tissues and organs to impact human health.

Editorial: Innovations in biomaterials to reduce environmental impact

Editorial: Innovations in biomaterials to reduce environmental impact

The Innovative Biomaterials and Technologies for Developing Corneal Endothelium Tissue Engineering Scaffolds: A Review and Prospect.

Corneal transplantation is the only treatment for corneal endothelial blindness. However, there is an urgent need to find substitutes for corneal endothelium grafts due to the global shortage of donor corneas. An emerging research field focuses on the construction of scaffold-based corneal endothelium tissue engineering (CETE). Long-term success in CETE transplantation may be achieved by selecting the appropriate biomaterials as scaffolds of corneal endothelial cells and adding bioactive materials to promote cell activity. This article reviews the research progress of CETE biomaterials in the past 20 years, describes the key characteristics required for corneal endothelial scaffolds, and summarizes the types of materials that have been reported. Based on these, we list feasible improvement strategies for biomaterials innovation. In addition, we describe the improved techniques for the scaffolds' surface topography and drug delivery system. Some promising technologies for constructing CETE are proposed. However, some questions have not been answered yet, and clinical trials and industrialization should be carried out with caution.

Frontier Review of the Molecular Mechanisms and Current Approaches of Stem Cell-Derived Exosomes

Exosomes are effective therapeutic vehicles that may transport their substances across cells. They are shown to possess the capacity to affect cell proliferation, migration, anti-apoptosis, anti-scarring, and angiogenesis, via the action of transporting molecular components. Possessing immense potential in regenerative medicine, exosomes, especially stem cell-derived exosomes, have the advantages of low immunogenicity, minimal invasiveness, and broad clinical applicability. Exosome biodistribution and pharmacokinetics may be altered, in response to recent advancements in technology, for the purpose of treating particular illnesses. Yet, prior to clinical application, it is crucial to ascertain the ideal dose and any potential negative consequences of an exosome. This review focuses on the therapeutic potential of stem cell-derived exosomes and further illustrates the molecular mechanisms that underpin their potential in musculoskeletal regeneration, wound healing, female infertility, cardiac recovery, immunomodulation, neurological disease, and metabolic regulation. In addition, we provide a summary of the currently effective techniques for isolating exosomes, and describe the innovations in biomaterials that improve the efficacy of exosome-based treatments. Overall, this paper provides an updated overview of the biological factors found in stem cell-derived exosomes, as well as potential targets for future cell-free therapeutic applications.

Recent Advances in Enzyme‐Based Biomaterials Toward Diabetic Wound Healing

Diabetic wound, also known as diabetic foot ulcer (DFU), is a form of chronic lesion that disrupts the patient's lifestyle and, in severe cases, may be fatal. Recent endeavors utilizing enzymes, particularly nanozymes in conjunction with other materials, have revealed the potential to treat diabetic wounds. Herein, the rational structural design of enzyme‐based biomaterials is summarized after presenting the types and processes of enzymes employed in diabetic wound healing, with the goal of better understanding the interaction between enzymes and other biological materials. The importance of enzyme catalytic activity, coupled with new therapeutic treatment strategies, is emphasized in the use of enzyme‐based biomaterials for diabetic wound healing. This review represents the most recent development in enzyme‐based biomaterials innovation for diabetic wound healing applications, and it can be used as a reference to guide other regenerative biomedicines from nanoenzyme biomaterials.

Spider Silks: An Overview of Their Component Proteins for Hydrophobicity and Biomedical Applications.

Spider silks have received extensive attention from scientists and industries around the world because of their remarkable mechanical properties, which include high tensile strength and extensibility. It is a leading-edge biomaterial resource, with a wide range of potential applications. Spider silks are composed of silk proteins, which are usually very large molecules, yet many silk proteins still remain largely underexplored. While there are numerous reviews on spider silks from diverse perspectives, here we provide a most up-to-date overview of the spider silk component protein family in terms of its molecular structure, evolution, hydrophobicity, and biomedical applications. Given the confusion regarding spidroin naming, we emphasize the need for coherent and consistent nomenclature for spidroins and provide recommendations for pre-existing spidroin names that are inconsistent with nomenclature. We then review recent advances in the components, identification, and structures of spidroin genes. We next discuss the hydrophobicity of spidroins, with particular attention on the unique aquatic spider silks. Aquatic spider silks are less known but may inspire innovation in biomaterials. Furthermore, we provide new insights into antimicrobial peptides from spider silk glands. Finally, we present possibilities for future uses of spider silks.

Biomaterials innovation for next generation exvivo immune tissue engineering.

Primary and secondary lymphoid organs are tissues that facilitate differentiation of B and T cells, leading to the induction of adaptive immune responses. These organs are present in the body from birth and are also recognized as locations where self-reactive B and T cells can be eliminated during the natural selection process. Many insights into the mechanisms that control the process of immune cell development and maturation in response to infection come from the analysis of various gene-deficient mice that lack some or all hallmark features of lymphoid tissues. The complexity of such animal models limits our ability to modulate the parameters that control the process of immune cell development, differentiation, and immunomodulation. Engineering functional, living immune tissues using biomaterials can grant researchers the ability to reproduce immunological events with tunable parameters for more rapid development of immunotherapeutics, cell-based therapy, and enhancing our understanding of fundamental biology as well as improving efforts in regenerative medicine. Here the author provides his review and perspective on the bioengineering of primary and secondary lymphoid tissues, and biomaterials innovation needed for the construction of these immune organs in tissue culture plates and on-chip.

Biomaterials innovation: a savior for a healthcare system under strain?

Renowned futurist Ray Kurzweil has made some eye-popping predictions about the future of human longevity. For example, by 2030 he predicts average lifespans will grow by one annum per annum. This progress will accelerate rapidly and not too long after, the average person can expect to live for 1000 years. Now, if having a swarm of nanobots floating around your body repairing cells and damaged DNA seems a little far-fetched, it may be comforting to learn that in the meantime, biomaterials innovators have some tricks up their sleeve to help our aging population better heal from disease, trauma, and wear-and-tear.

Progressing innovation in biomaterials. From the bench to the bed of patients.

A Translational Research Symposium was organized at the 2014 annual meeting of the European society for biomaterials. This brought together leading Tier one companies in clinical biomaterials and medical device markets, small and medium enterprises and entrepreneurial academics who shared their experiences on taking biomaterials technologies to commercial endpoints, in the clinics. The symposium focused on "Progressing Innovation in Biomaterials. From the Bench to the Bed of Patients". The aim of the present document is to illustrate the content of the symposium and to highlight the key lessons from selected lectures.

Innovations in Biomaterials: Achievements and Opportunities

AbstractThis article is an edited transcript based on a presentation given by Rebecca M. Bergman (Medtronic Inc.) as part of Symposium X—Frontiers of Materials Research on November 30, 2004, at the Materials Research Society Fall Meeting in Boston. Materials innovations have been at the heart of many important advances in implantable medical devices. Miniaturization, improved durability and longevity, enhanced biocompatibility, and controlled delivery are several areas where materials innovations have been important in advancing medical products and therapies. The demands on materials used in the physiological environment are stringent and include requirements related to materials properties as well as safety, quality, and reliability. Looking ahead, materials will undoubtedly continue to be an enabling technology for future innovations in medicine, including novel therapies such as tissue engineering, cell therapy, and gene therapy.

Design of new titanium alloys for orthopaedic applications.

Parallel to the biofunctionalisation of existing materials, innovation in biomaterials engineering has led to the specific design of titanium alloys for medical applications. Studies of the biological behaviour of metallic elements have shown that the composition and structure of the material should be carefully tailored to minimise adverse body reactions and to enhance implant longevity, respectively. Consequently, interest has focused on a new family of titanium alloys: Ti-6Mo-3Fe-5Ta, Ti-4Mo-2Fe-5Ta and Ti-6Mo-3Fe-5Zr-5Hf alloys. The non-toxicity of the specially designed titanium alloys compared with osteoblastic cells has been ascertained using MTT and RN tests. In addition, phase transformations upon thermal processing have been investigated, with comparison with a well-defined beta titanium alloy. Optimum thermal processing windows (above 550 degrees C) have been designed to generate a stable and nanostructured alpha phase from the isothermal omega phase that precipitates in a low temperature range (150-350 degrees C). The generation of such nanostructured microstructures should provide a promising opportunity to investigate tissue-biomaterial interactions at the scale of biomolecules such as proteins.

Biomaterials innovation: it's a long road to the operating room

An innovative process for forming a wide variety of porous biomaterials was conceived of and developed over several years at a University and later by a company that licensed the early patents. The family of patents formed the basis for several promising innovative biomaterials devices. However, only one commercial product has been realized. That product is the very successfull coralline hydroxyapatite (HA) now widely used in orthopaedic surgery, oral and maxillofacial bone repair and plastic surgery. This paper challenges the equation of discovery with a genuine innovation which reaches the marketplace. The paper reviews several aspects of the innovation and development history with an emphasis on the challenges of bringing any new biomaterial through all the conceptual, developmental, business and regulatory hurdles. New class three medical devices require huge investments of time and money typically requiring a minimum of eight years and 15–20 million dollars per new device to take it from concept to an approved product. These hurdles are so high that most research innovations in biomaterials never get put into the developmental pipeline. This paper is presented from an anecdotal perspective of an innovator who has had a continuous research and development involvement in the technology but has no significant management involvement beyond the early startup activities. It differs from predecessors is that it deals not only with the initial step of discovery but in the very difficult steps that follow on the road to a real innovation. Several strategies that may help other R&D groups outside the bio- medical industry shorten the development cycle and increase the probability that a given biomaterials innovation can be seen through to approved product are discussed. Guidelines are suggested for culling out ideas that are technically sound but that likely won't lead to successful products.