Allicin-Loaded Hydroxyapatite: Enhanced Release, Cytocompatibility, and Antibacterial Properties for Bone Tissue Engineering Applications.

Allicin, the active compound of garlic extract, is a naturally sourced biomolecule, which promotes a vast range of health benefits. However, the limited stability of allicin restricts its applications in tissue engineering. Additionally, the detailed effects of allicin in bone health are yet to be explored. Our work reports on the fabrication of a novel allicin-loaded hydroxyapatite drug delivery system with enhanced biological properties. The fabricated system shows excellent antibacterial efficiency against S. aureus after 36 h of bacterial interaction with a sample. The allicin release kinetics are enhanced with polycaprolactone (PCL). The obtained results after 20 days of drug release study indicate that PCL coating leads to an increase in cumulative allicin release from ~ 35% to 70% at a physiological pH of 7.4. These scaffolds maintain stability during the whole period of drug release. Cytocompatibility of tested compositions with osteoblasts indicates enhanced cell viability and good filopodial attachment on the sample surface at day 7. These allicin-loaded antibacterial and cytocompatible scaffolds can find applications as localized delivery vehicles for bone tissue engineering.

3D printed ß-TCP bone tissue engineering scaffolds: Effects of chemistry on in vivo biological properties in a rabbit tibia model.

In this study the effects of 3D printed SiO2 and ZnO doped tricalcium phosphate (TCP) scaffolds with interconnected pores were evaluated on the in vivo bone formation and healing properties of a rabbit tibial defect model. Pure and doped TCP scaffolds were fabricated by a ceramic powder-based 3D printing technique and implanted into critical sized rabbit tibial defects for up to 4 months. In vivo bone regeneration was evaluated using chronological radiological examination, histological evaluations, SEM micrographs and fluorochrome labeling studies. Radiograph results showed that Si/Zn doped samples had slower degradation kinetics than the pure TCP samples. 3D printing of TCP scaffolds improved bone formation. The addition of dopants in the TCP scaffolds improved osteogenic capabilities when compared to the pure scaffolds. In summary, our findings indicate that addition of dopants to the TCP scaffolds enhanced bone formation and in turn leading to accelerated healing.

Calcium phosphate coated 3D printed porous titanium with nanoscale surface modification for orthopedic and dental applications.

This study aims to improve the interfacial bonding between the osseous host tissue and the implant surface through the application of doped calcium phosphate (CaP) coating on 3D printed porous titanium. Porous titanium (Ti) cylinders with 25% volume porosity were fabricated using Laser Engineered Net Shaping (LENS™), a commercial 3D Printing technique. The surface of these 3D printed cylinders was modified by growing TiO2 nanotubes first, followed by a coating of with Sr2+ and Si4+ doped bioactive CaP ceramic in simulated body fluid (SBF). Doped CaP coated implants were hypothesized to show enhanced early stage bone tissue integration. Biological properties of these implants were investigated in vivo using a rat distal femur model after 4 and 10 weeks. CaP coated porous Ti implants have enhanced tissue ingrowth as was evident from the CT scan analysis, push out test results, and the histological analysis compared to porous implants with or without surface modification via titania nanotubes. Increased osteoid-like new bone formation and accelerated mineralization was revealed inside the CaP coated porous implants. It is envisioned that such an approach of adding a bioactive doped CaP layer on porous Ti surface can reduce healing time by enhancing early stage osseointegration in vivo.

Bioengineering and Clinical Translation of Human Lung and its Components.

Clinical lung transplantation has rapidly established itself as the gold standard of treatment for end-stage lung diseases in a restricted group of patients since the first successful lung transplant occurred. Although significant progress has been made in lung transplantation, there are still numerous obstacles on the path to clinical success. The development of bioartificial lung grafts using patient-derived cells may serve as an alternative treatment modality; however, challenges include developing appropriate scaffold materials, advanced culture strategies for lung-specific multiple cell populations, and fully matured constructs to ensure increased transplant lifetime following implantation. This review highlights the development of tissue-engineered tracheal and lung equivalents over the past two decades, key problems in lung transplantation in a clinical environment, the advancements made in scaffolds, bioprinting technologies, bioreactors, organoids, and organ-on-a-chip technologies. The review aims to fill the lacuna in existing literature toward a holistic bioartificial lung tissue, including trachea, capillaries, airways, bifurcating bronchioles, lung disease models, and their clinical translation. Herein, the efforts are on bridging the application of lung tissue engineering methods in a clinical environment as it is thought that tissue engineering holds enormous promise for overcoming the challenges associated with the clinical translation of bioengineered human lung and its components.

Biofabrication of anin-vitrobone model for Gaucher disease.

Gaucher disease (GD), the most prevalent lysosomal disorder, is caused byGBA1gene mutations, leading to deficiency of glucocerebrosidase, and accumulation of glycosphingolipids in cells of the mononuclear phagocyte system. While skeletal diseases are the leading cause of morbidity and reduced quality of life in GD, the pathophysiology of bone involvement is not yet fully understood, partly due to lack of relevant human model systems. In this work, we present the first 3D human model of GD using aspiration-assisted freeform bioprinting, which enables a platform tool with a potential for decoding the cellular basis of the developmental bone abnormalities in GD. In this regard, human bone marrow-derived mesenchymal stem cells (obtained commercially) and peripheral blood mononuclear cells derived from a cohort of GD patients, at different severities, were co-cultured to form spheroids and differentiated into osteoblast and osteoclast lineages, respectively. Co-differentiated spheroids were then 3D bioprinted into rectangular tissue patches as a bone tissue model for GD. The results revealed positive alkaline phosphatase (ALP) and tartrate-resistant ALP activities, with multi-nucleated cells demonstrating the efficacy of the model, corroborating with gene expression studies. There were no significant changes in differentiation to osteogenic cells but pronounced morphological deformities in spheroid formation, more evident in the 'severe' cohort, were observed. Overall, the presented GD model has the potential to be adapted to personalized medicine not only for understanding the GD pathophysiology but also for personalized drug screening and development.

Ginger and Garlic Extracts Enhance Osteogenesis in 3D Printed Calcium Phosphate Bone Scaffolds with Bimodal Pore Distribution.

Natural medicines have long been used to treat physiological ailments where both ginger (gingerol) and garlic (allicin) are key players in immune system promotion, reduction in blood pressure, and lowering inflammation response. With their efficacy in bone healing, these compounds have great value as medicinal additives in bone scaffolds for localized treatment to support tissue formation, along with providing their natural therapeutic benefits. Utilization of 3D-printed (3DP) bone tissue engineering scaffolds as drug delivery vehicles for ginger and garlic extracts enables patient specificity in bone defect applications with enhanced osseointegration. Our objective is to understand their combined efficacy on osteogenesis when released from 3DP calcium phosphate bone scaffolds designed with a bimodal pore distribution. With a porous core and dense exterior, the resulting scaffolds have good mechanical integrity with 10 ± 1 MPa compressive strengths. Results show that ginger + garlic extracts released from bone scaffolds enhance their osteogenic potential through on site drug delivery. Both compounds exhibit exponential drug release profiles which fit Weibull distribution equations. The release of ginger extract also increases osteoblast proliferation by 59%. Both compounds show decreased osteoclast resorption activity, with a greater than 20% reduction in pit area on sample surfaces. Ginger + garlic extract induces a twofold increase in early osteoid tissue formation in vivo at week 4, in addition to a 30% increase in total bone area and a 90% increase in osteocytes with respect to control 3DP tricalcium phosphate scaffolds. Late-stage bone healing at week 10 reveals healthy angiogenic tissue, a twofold higher bone mineralization, and significant enhancement of type I collagen formation in the presence of ginger and garlic extracts. Naturally sourced ginger and garlic extracts provide osteogenic promotion and improved bone tissue in-growth in a patient-specific 3DP scaffold biomedical device for low load-bearing bone tissue engineering and dental applications.

Aspiration-assisted freeform bioprinting of mesenchymal stem cell spheroids within alginate microgels.

Aspiration-assisted freeform bioprinting (AAfB) has emerged as a promising technique for precise placement of tissue spheroids in three-dimensional (3D) space enabling tissue fabrication. To achieve success in embedded bioprinting using AAfB, an ideal support bath should possess shear-thinning behavior and yield-stress to facilitate tight fusion and assembly of bioprinted spheroids forming tissues. Several studies have demonstrated support baths for embedded bioprinting in the past few years, yet a majority of these materials poses challenges due to their low biocompatibility, opaqueness, complex and prolonged preparation procedures, and limited spheroid fusion efficacy. In this study, to circumvent the aforementioned limitations, we present the feasibility of AAfB of human mesenchymal stem cell (hMSC) spheroids in alginate microgels as a support bath. Alginate microgels were first prepared with different particle sizes modulated by blending time and concentration, followed by determination of the optimal bioprinting conditions by the assessment of rheological properties, bioprintability, and spheroid fusion efficiency. The bioprinted and consequently self-assembled tissue structures made of hMSC spheroids were osteogenically induced for bone tissue formation. Alongside, we investigated the effects of peripheral blood monocyte-derived osteoclast incorporation into the hMSC spheroids in heterotypic bone tissue formation. We demonstrated that alginate microgels enabled unprecedented positional accuracy (∼5%), transparency for visualization, and improved fusion efficiency (∼97%) of bioprinted hMSC spheroids for bone fabrication. This study demonstrates the potential of using alginate microgels as a support bath for many different applications including but not limited to freeform bioprinting of spheroids, cell-laden hydrogels, and fugitive inks to form viable tissue constructs.

Strategies for 3D bioprinting of spheroids: A comprehensive review.

Biofabricated tissues have found numerous applications in tissue engineering and regenerative medicine in addition to the promotion of disease modeling and drug development and screening. Although three-dimensional (3D) printing strategies for designing and developing customized tissue constructs have made significant progress, the complexity of innate multicellular tissues hinders the accurate evaluation of physiological responses in vitro. Cellular aggregates, such as spheroids, are 3D structures where multiple types of cells are co-cultured and organized with endogenously secreted extracellular matrix and are designed to recapitulate the key features of native tissues more realistically. 3D Bioprinting has emerged as a crucial tool for positioning of these spheroids to assemble and organize them into physiologically- and histologically-relevant tissues, mimicking their native counterparts. This has triggered the convergence of spheroid fabrication and bioprinting, leading to the investigation of novel engineering methods for successful assembly of spheroids while simultaneously enhancing tissue repair. This review provides an overview of the current state-of-the-art in spheroid bioprinting methods and elucidates the involved technologies, intensively discusses the recent tissue fabrication applications, outlines the crucial properties that influence the bioprinting of these spheroids and bioprinted tissue characteristics, and finally details the current challenges and future perspectives of spheroid bioprinting efforts in the growing field of biofabrication.

Natural medicine delivery from biomedical devices to treat bone disorders: A review.

With an increasing life expectancy and aging population, orthopedic defects and bone graft surgeries are increasing in global prevalence. Research to date has advanced the understanding of bone biology and defect repair mechanism, leading to a marked success in the development of synthetic bone substitutes. Yet, the quest for functionalized bone grafts prompted the researchers to find a viable alternative that regulates cellular activity and supports bone regeneration and healing process without causing serious side-effects. Recently, researchers have introduced natural medicinal compounds (NMCs) in bone scaffold that enables them to release at a desirable rate, maintains a sustained release allowing sufficient time for tissue in-growth, and guides bone regeneration process with minimized risk of tissue toxicity. According to World Health Organization (WHO), NMCs are gaining popularity in western countries for the last two decades and are being used by 80% of the population worldwide. Compared to synthetic drugs, NMCs have a broader range of safety window and thus suitable for prolonged localized delivery for bone regeneration. There is limited literature focusing on the integration of bone grafts and natural medicines that provides detailed scientific evidences on NMCs, their toxic limits and particular application in bone tissue engineering, which could guide the researchers to develop functionalized implants for various bone disorders. This review will discuss the emerging trend of NMC delivery from bone grafts, including 3D-printed structures and surface-modified implants, highlighting the significance and potential of NMCs for bone health, guiding future paths toward the development of an ideal bone tissue engineering scaffold. STATEMENT OF SIGNIFICANCE: To date, additive manufacturing technology provids us with many advanced patient specific or defect specific bone constructs exhibiting three-dimensional, well-defined microstructure with interconnected porous networks for defect-repair applications. However, an ideal scaffold should also be able to supply biological signals that actively guide tissue regeneration while simultaneously preventing post-implantation complications. Natural biomolecules are gaining popularity in tissue engineering since they possess a safer, effective approach compared to synthetic drugs. The integration of bone scaffolds and natural biomolecules exploits the advantages of customized, multi-functional bone implants to provide localized delivery of biochemical signals in a controlled manner. This review presents an overview of bone scaffolds as delivery systems for natural biomolecules, which may provide prominent advancement in bone development and improve defect-healing caused by various musculoskeletal disorders.

Influence of random and designed porosities on 3D printed tricalcium phosphate-bioactive glass scaffolds.

Calcium phosphate (CaP)-based ceramics are a popular choice for bone-graft applications due to their compositional similarities with bone. Similarly, Bioactive glass (BG) is also common for bone tissue engineering applications due to its excellent biocompatibility and bone binding ability. We report tricalcium phosphate (TCP)-BG (45S5 BG) composite scaffolds using conventional processing and binder jetting-based 3D printing (3DP) technique. We hypothesize that BG's addition in TCP will enhance densification via liquid phase sintering and improve mechanical properties. Further, BG addition to TCP should modulate the dissolution kinetics in vitro. This work's scientific objective is to understand the influence of random vs. designed porosity in TCP-BG ceramics towards variations in compressive strength and in vitro biocompatibility. Our findings indicate that a 5 wt % BG in TCP composite shows a compressive strength of 26.7 ± 2.7 MPa for random porosity structures having a total porosity of ~47.9%. The same composition in a designed porosity structure shows a compressive strength of 21.3 ± 2.9 MPa, having a total porosity of ~54.1%. Scaffolds are also tested for their dissolution kinetics and in vitro bone cell materials interaction, where TCP-BG compositions show favorable bone cell materials interactions. The addition of BG enhances a flaky hydroxycarbonate apatite (HCA) layer in 8 weeks in vitro. Our research shows that the porous TCP- BG scaffolds, fabricated via binder jetting method with enhanced mechanical properties and dissolution properties can be utilized in bone graft applications.

Recent advances in bioprinting technologies for engineering hepatic tissue.

In the sphere of liver tissue engineering (LTE), 3D bioprinting has emerged as an effective technology to mimic the complex in vivo hepatic microenvironment, enabling the development of functional 3D constructs with potential application in the healthcare and diagnostic sector. This review gears off with a note on the liver's microscopic 3D architecture and pathologies linked to liver injury. The write-up is then directed towards unmasking recent advancements and prospects of bioprinting for recapitulating 3D hepatic structure and function. The article further introduces available stem cell opportunities and different strategies for their directed differentiation towards various hepatic stem cell types, including hepatocytes, hepatic sinusoidal endothelial cells, stellate cells, and Kupffer cells. Another thrust of the article is on understanding the dynamic interplay of different hepatic cells with various microenvironmental cues, which is crucial for controlling differentiation, maturation, and maintenance of functional hepatic cell phenotype. On a concluding note, various critical issues and future research direction towards clinical translation of bioprinted hepatic constructs are discussed.

Network Topology of Biological Aging and Geroscience-Guided Approaches to COVID-19.

Aging has emerged as the greatest and most prevalent risk factor for the development of severe COVID-19 infection and death following exposure to the SARS-CoV-2 virus. The presence of multiple co-existing chronic diseases and conditions of aging further enhances this risk. Biological aging not only enhances the risk of chronic diseases, but the presence of such conditions further accelerates varied biological processes or "hallmarks" implicated in aging. Given growing evidence that it is possible to slow the rate of many biological aging processes using pharmacological compounds has led to the proposal that such geroscience-guided interventions may help enhance immune resilience and improve outcomes in the face of SARS-CoV-2 infection. Our review of the literature indicates that most, if not all, hallmarks of aging may contribute to the enhanced COVID-19 vulnerability seen in frail older adults. Moreover, varied biological mechanisms implicated in aging do not function in isolation from each other, and exhibit intricate effects on each other. With all of these considerations in mind, we highlight limitations of current strategies mostly focused on individual single mechanisms, and we propose an approach which is far more multidisciplinary and systems-based emphasizing network topology of biological aging and geroscience-guided approaches to COVID-19.

Aspiration-assisted bioprinting of co-cultured osteogenic spheroids for bone tissue engineering.

Conventional top-down approaches in tissue engineering involving cell seeding on scaffolds have been widely used in bone engineering applications. However, scaffold-based bone tissue constructs have had limited clinical translation due to constrains in supporting scaffolds, minimal flexibility in tuning scaffold degradation, and low achievable cell seeding density as compared with native bone tissue. Here, we demonstrate a pragmatic and scalable bottom-up method, inspired from embryonic developmental biology, to build three-dimensional (3D) scaffold-free constructs using spheroids as building blocks. Human umbilical vein endothelial cells (HUVECs) were introduced to human mesenchymal stem cells (hMSCs) (hMSC/HUVEC) and spheroids were fabricated by an aggregate culture system. Bone tissue was generated by induction of osteogenic differentiation in hMSC/HUVEC spheroids for 10 d, with enhanced osteogenic differentiation and cell viability in the core of the spheroids compared to hMSC-only spheroids. Aspiration-assisted bioprinting (AAB) is a new bioprinting technique which allows precise positioning of spheroids (11% with respect to the spheroid diameter) by employing aspiration to lift individual spheroids and bioprint them onto a hydrogel. AAB facilitated bioprinting of scaffold-free bone tissue constructs using the pre-differentiated hMSC/HUVEC spheroids. These constructs demonstrated negligible changes in their shape for two days after bioprinting owing to the reduced proliferative potential of differentiated stem cells. Bioprinted bone tissues showed interconnectivity with actin-filament formation and high expression of osteogenic and endothelial-specific gene factors. This study thus presents a viable approach for 3D bioprinting of complex-shaped geometries using spheroids as building blocks, which can be used for various applications including but not limited to, tissue engineering, organ-on-a-chip and microfluidic devices, drug screening and, disease modeling.

Aspiration-assisted freeform bioprinting of prefabricated tissue spheroids in a yield-stress gel.

Bioprinting of cellular aggregates, such as tissue spheroids, to form three-dimensional (3D) complex-shaped arrangements, has posed a major challenge due to lack of robust, reproducible and practical bioprinting techniques. Here, we demonstrate 3D aspiration-assisted freeform bioprinting of tissue spheroids by precisely positioning them in self-healing yield-stress gels, enabling the self-assembly of spheroids for fabrication of tissues. The presented approach enables the traverse of spheroids directly from the cell media to the gel and freeform positioning of the spheroids on demand. We study the underlying physical mechanism of the approach to elucidate the interactions between the aspirated spheroids and the gel's yield-stress during the transfer of spheroids from cell media to the gel. We further demonstrate the application of the proposed approach in the realization of various freeform shapes and self-assembly of human mesenchymal stem cell spheroids for the construction of cartilage and bone tissues.

Effects of Aloe Vera Gel Extract in Doped Hydroxyapatite-Coated Titanium Implants on in Vivo and in Vitro Biological Properties.

Hydroxyapatite-coated titanium alloys have been a popular choice as bone implants for load-bearing applications for the compositional similarity of hydroxyapatite to natural bone. The limited osteoinductive properties exhibited by the hydroxyapatite (HA) coatings have led to the incorporation of growth factor or dopants for improved osseointegration. This study aims to investigate the effects of a naturally occurring aloe vera gel extract, acemannan, in doped hydroxyapatite coatings on the in vitro osteoblast cell viability and in vivo new bone formation in a rat distal femur model. Silver oxide and silica-doped hydroxyapatite coatings were developed by the induction plasma spray coating method on Ti alloys to introduce antibacterial properties along with induction of angiogenic properties, respectively. The doped coating was further consecutively dip coated with acemannan to analyze its effects on the in vivo early stage osseointegration and chitosan to control the burst release of the acemannan from the calcium phosphate matrix. The results show controlled release of acemannan from the chitosan coatings, with enhanced osteoblast cell viability by the incorporation of acemannan in vitro. Improved osseointegration with a seamless implant interface and improved new bone formation was noted by the acemannan and chitosan coating in vivo, 5 weeks after implantation. Our results demonstrate the efficacy of a combination of natural medicine and naturally occurring polymer in a doped hydroxyapatite-coated titanium implant on the bone tissue regeneration for load-bearing orthopedic applications.

Comparative effects of controlled release of sodium bicarbonate and doxorubicin on osteoblast and osteosarcoma cell viability.

This study intends to analyze the effects of doxorubicin and sodium bicarbonate release with polycaprolactone (PCL) coating on calcium phosphate system which is a bone like material, on the cell viability and proliferation of osteosarcoma and osteoblast. Increased systematic pH concentrations locally by the release of sodium bicarbonate diminished acidosis and hence, alleviated malignancy. In our studies, we have shown that the same of dosage of doxorubicin inhibited both osteoblast and osteosarcoma cell attachment and viability whereas, sodium bicarbonate abated osteosarcoma cell proliferation. Sodium bicarbonate also inhibited osteoblast cell proliferation in the early time points, however, the cell viability increased after the initial burst release of the molecule. Polymer coating on calcium phosphate-based implants, as carriers of drug, can minimize chances of toxic effects of higher oral drug dosage in the body, and also help in delivering effective doses of drugs, locally to the target tissues, as compared to the oral drug delivery approach. A coating of PCL was thus incorporated to control the initial burst release of bicarbonate, which enhanced the osteoblast cell viability, but was capable of diminishing osteosarcoma cell proliferation. The novelty and clinical significance of this study lies in the understanding of unique delivery using encapsulated naturally occurring and more benign sodium bicarbonate, for usage after excision of the cancerous bone, without any adverse effects on normal bone cells.

In Vitro Characterizations of Si4+ and Zn2+ Doped Plasma Sprayed Hydroxyapatite Coatings Using Osteoblast and Osteoclast Coculture.

Osteoporosis is one of the most commonly identified bone disorders, which leads to an enhanced risk of bone fracture, especially for the older population. Hydroxyapatite (HA) coated titanium (Ti) alloys have been used widespread for load bearing applications like hip or knee replacements owing to their compositional similarity to natural bone; however, incorporation of osteoinductivity is still a challenge. The objective of this study is to evaluate the effects of SiO2 and ZnO as dopants in HA coated Ti alloys on cellular osteoporotic conditions mimicked by an in vitro osteoblast and osteoclast coculture model. HA, Si-HA, and Zn-HA coatings showed adhesive bond strengths of 25.7 ± 1.9 MPa, 23.8 ± 2.3 MPa, and 22.9 ± 3.5 MPa, respectively. To study the effects of doped HA coatings on the simulated osteoporotic cellular condition, human mesenchymal stem cells (hMSCs) and monocytes (THP-1) were seeded simultaneously in a ratio of 1:4, respectively. Gene expressions studies were carried out with marker genes showing that the presence of the dopants in the HA coating enhanced osteoblast proliferation along with diminishing cell growth of osteoclasts. This study demonstrates the promising effects of SiO2 and ZnO in plasma sprayed HA coatings on alleviating osteoporosis cellular conditions, which can potentially be used for load-bearing implants in aging patients whose bone resorption is more dominant than bone formation.

Effects of PCL, PEG and PLGA polymers on curcumin release from calcium phosphate matrix for in vitro and in vivo bone regeneration.

Calcium phosphate materials are widely used as bone-like scaffolds or coating for metallic hip and knee implants due to their excellent biocompatibility, compositional similarity to natural bone and controllable bioresorbability. Local delivery of drugs or osteogenic factors from scaffolds and implants are required over a desired period of time for an effectual treatment of various musculoskeletal disorders. Curcumin, an antioxidant and anti-inflammatory molecule, enhances osteoblastc activity in addition to its anti-osteoclastic activity. However, due to its poor solubility and high intestinal liver metabolism, it showed limited oral efficacy in various preclinical and clinical studies. To enhance its bioavailability and to provide higher release, we have used poly (ε-caprolactone) (PCL), poly ethylene glycol (PEG) and poly lactide co glycolide (PLGA) as the polymeric system to enable continuous release of curcumin from the hydroxyapatite matrix for 22 days. Additionally, curcumin was incorporated in plasma sprayed hydroxyapatite coated Ti6Al4V substrate to study in vitro cell material interaction using human fetal osteoblast (hFOB) cells for load bearing implants. MTT cell viability assay and morphological characterization by FESEM showed highest cell viability with samples coated with curcumin-PCL-PEG. Finally, 3D printed interconnected macro porous ß-TCP scaffolds were prepared and curcumin-PCL-PEG was loaded to assess the effects of curcumin on in vivo bone regeneration. The presence of curcumin in TCP results in enhanced bone formation after 6 weeks. Complete mineralized bone formation increased from 29.6 % to 44.9% in curcumin-coated scaffolds compared to pure TCP. Results show that local release of curcumin can be designed for both load bearing or non-load bearing implants with the aid of polymers, which can be considered an excellent candidate for wound healing and tissue regeneration applications in bone tissue engineering.

Enhanced In Vivo Bone and Blood Vessel Formation by Iron Oxide and Silica Doped 3D Printed Tricalcium Phosphate Scaffolds.

Calcium phosphate (CaP) ceramics show significant promise towards bone graft applications because of the compositional similarity to inorganic materials of bone. With 3D printing, it is possible to create ceramic implants that closely mimic the geometry of human bone and can be custom-designed for unusual injuries or anatomical sites. The objective of the study was to optimize the 3D-printing parameters for the fabrication of scaffolds, with complex geometry, made from synthesized tricalcium phosphate (TCP) powder. This study was also intended to elucidate the mechanical and biological effects of the addition of Fe+3 and Si+4 in TCP implants in a rat distal femur model for 4, 8, and 12 weeks. Doped with Fe+3 and Si+4 TCP scaffolds with 3D interconnected channels were fabricated to provide channels for micronutrients delivery and improved cell-material interactions through bioactive fixation. Addition of Fe+3 into TCP enhanced early-stage new bone formation by increasing type I collagen production. Neovascularization was observed in the Si+4 doped samples after 12 weeks. These findings emphasize that the additive manufacturing of scaffolds with complex geometry from synthesized ceramic powder with modified chemistry is feasible and may serve as a potential candidate to introduce angiogenic and osteogenic properties to CaPs, leading to accelerated bone defect healing.

In Vivo Response of Laser Processed Porous Titanium Implants for Load-Bearing Implants.

Applications of porous metallic implants to enhance osseointegration of load-bearing implants are increasing. In this work, porous titanium implants, with 25 vol.% porosity, were manufactured using Laser Engineered Net Shaping (LENS™) to measure the influence of porosity towards bone tissue integration in vivo. Surfaces of the LENS™ processed porous Ti implants were further modified with TiO2 nanotubes to improve cytocompatibility of these implants. We hypothesized that interconnected porosity created via additive manufacturing will enhance bone tissue integration in vivo. To test our hypothesis, in vivo experiments using a distal femur model of male Sprague-Dawley rats were performed for a period of 4 and 10 weeks. In vivo samples were characterized via micro-computed tomography (CT), histological imaging, scanning electron microscopy, and mechanical push-out tests. Our results indicate that porosity played an important role to establish early stage osseointegration forming strong interfacial bonding between the porous implants and the surrounding tissue, with or without surface modification, compared to dense Ti implants used as a control.