(1) Background: Cerium silicate (CeSi) nanoparticles (NPs) have potential as a restorative filler particle with multifunctional properties to improve longevity. To increase the biological activity, these nanoparticles can be fabricated with ultrasmall pores (mesoporous) (MPCeSi-NP) that can be loaded with a polyphosphate inhibitor, such as gallein. (2) Methods: MPCeSi-NPs were custom-synthesized with a microemulsion method, using cetyltrimethylammonium bromide (CTAB) as a template for self-assembly. Biocompatibility with oral keratinocytes/fibroblasts was tested, with the addition of examining the biomineralization potential with human bone-marrow-derived mesenchymal stromal cells (BM-MSCs). MPCeSi-NP, loaded with gallein, was tested against Rothia dentocariosa (Rd). MPCeSi-NP was added to a resin matrix of triethylene glycol dimethacrylate (TEGDMA) and Bisphenol A-glycidyl methacrylate (BisGMA) with subsequent mechanical properties evaluation. (3) Results: MPCeSi-NPs had high biocompatibility with oral keratinocytes and fibroblasts, especially at concentrations below 300 µg/mL. MPCeSi-NPs induced the biomineralization of BM-MSCs. Higher cerium levels increased mineralization. MPCeSi-NP had weak antimicrobial activity against Rd. At 1% wt, MPCeSi-NPs did not reduce the polymerization potential and mechanical properties of a TEGDMA:BisGMA polymer material, with controlled release of gallein in a simulated degradation model. (4) Conclusions: MPCeSi-NPs are highly biocompatible and bioinductive and have the potential to improve the biological response of current restorative materials.

OBJECTIVES:Sympathomimetic nasal solutions (SNS), containing oxymetazoline or phenylephrine, may be used directly onto dental pulp tissue and initiate hemostasis via activation of alpha-receptors that innervate arteriole smooth muscles. The aim of this study was to assess these SNS's biocompatibility with human dental pulp stem cells (hDPSCs) and ability to kill a deep caries-associated pathogen, Rothia dentocariosa. MATERIALS AND METHODS:A Kirby-Bauer disk diffusion susceptibility test assessed SNS zones of inhibition (ZOI) toward R. dentocariosa growth on agar plates. Over-the-counter (OTC) SNS containing 0.025% and 0.05% oxymetazoline (NS-OXY-kids, NS-OXY-original) and 1% phenylephrine (NS-PHE) were tested along with ingredients found in these nasal solutions: 0.025%, 0.05% oxymetazoline; 0.0125%, 0.025% benzalkonium chloride; and 0.2%, 1% phenylephrine (PHE). A second antimicrobial broth inhibition assay examined effects on R. dentocariosa planktonic growth. A 24-h recovery biocompatibility assay with resazurin (alamarBlue) was performed on hDPSC that were exposed to pure respective compound solutions, NS-OXY-kids, NS-PHE, and 1% PHE for 10 min. RESULTS:NS-OXY-kids, NS-OXY-original, NS-PHE, and 0.025% BKC were bactericidal toward R. dentocariosa with an average ZOI of (16.33 ± 2.22 [average ± SD] mm). NS-PHE had a small but statistically significant difference (17.83 ± 3.189 mm) between NS-OXY-kids (14.67 ± 1.033 mm); 0.0125% BKC had a smaller (p < 0.05) ZOI of 10.5 ± 0.837 mm. Solutions containing solely OXY (0.025%, 0.05%) and PHE (0.2%, 1%) demonstrated no bactericidal activity but had a slight bacteriostatic inhibition in the broth inhibition assay. The commercial OTC formulations of NS-PHE and NS-OXY-kids needed to be diluted 1:10 to have near 50% metabolic activity of hDPSCs normalized to untreated control cells. CONCLUSIONS:NS-PHE and NS-OXY (both original and kids) had antimicrobial activity toward R. dentocariosa and comparable biocompatibility with hDPSCs. SNS may have both hemostatic and antimicrobial properties if used as pulpal medicaments.

This study evaluated the antibacterial properties of a potential pulpal medicament, a nasal solution with oxymetazoline (NS-OXY, 0.05

Abstract Orthopedic and dental implant failure continues to be a significant concern due to localized bacterial infections. Previous studies have attempted to improve implant surfaces by modifying their texture and roughness or coating them with antibiotics to enhance antibacterial properties for implant longevity. However, these approaches have demonstrated limited effectiveness. In this study, we attempted to engineer the titanium (Ti) alloy surface biomimetically at the nanometer scale, inspired by the cicada wing nanostructure using alkaline hydrothermal treatment (AHT) to simultaneously confer antibacterial properties and support the adhesion and proliferation of mammalian cells. The two modified Ti surfaces were developed using a 4 h and 8 h AHT process in 1 N NaOH at 230 °C, followed by a 2-hour post-calcination at 600 °C. We found that the control plates showed a relatively smooth surface, while the treatment groups (4 h & 8 h AHT) displayed nanoflower structures containing randomly distributed nano-spikes. The results demonstrated a statistically significant decrease in the contact angle of the treatment groups, which increased wettability characteristics. The 8 h AHT group exhibited the highest wettability and significant increase in roughness 0.72 ± 0.08 µm (P < 0.05), leading to more osteoblast cell attachment, reduced cytotoxicity effects, and enhanced relative survivability. The alkaline phosphatase activity measured in all different groups indicated that the 8 h AHT group exhibited the highest activity, suggesting that the surface roughness and wettability of the treatment groups may have facilitated cell adhesion and attachment and subsequently increased secretion of extracellular matrix. Overall, the findings indicate that biomimetic nanotextured surfaces created by the AHT process have the potential to be translated as implant coatings to enhance bone regeneration and implant integration. Graphical Abstract

The design of biomaterials to regenerate bone is likely to increasingly require modifications that reduce bacterial attachment and biofilm formation as infection during wound regeneration can significantly impede tissue repair and typically requires surgical intervention to restart the healing process. Further, much research on infection prevention in bone biomaterials has focused on modeling of non-resorbable metal alloy materials, whereas an expanding direction of bone regeneration has focused on development of bioresorbable materials. This represents a need for the prevention and understanding of infection in resorbable biomaterials. Here, we investigate the ability of a mineralized collagen biomaterial to natively resist infection and examine how the addition of manuka honey, previously identified as an antimicrobial agent, affects gram positive and negative bacterial colonization and mesenchymal stem cell osteogenesis and vasculature formation. We incorporate manuka honey into these scaffolds via either direct fabrication into the scaffold microarchitecture or via soaking the scaffold in a solution of manuka honey after fabrication. Direct incorporation results in a change in the surface characteristics and porosity of mineralized collagen scaffolds. Soaking scaffolds in honey concentrations higher than 10% had significant negative effects on mesenchymal stem cell metabolic activity. Soaking or incorporating 5% honey had no impact on endothelial cell tube formation. Although solutions of 5% honey reduced metabolic activity of mesenchymal stem cells, MSC-seeded scaffolds displayed increased calcium and phosphorous mineral formation, osteoprotegerin release, and alkaline phosphatase activity. Bacteria cultured on mineralized collagen scaffolds demonstrated surfaces covered in bacteria and no method of preventing infection, and using 10 times the minimal inhibitory concentration of antibiotics did not completely kill bacteria within the mineralized collagen scaffolds, indicating bioresorbable scaffold materials may act to shield bacteria from antibiotics. The addition of 5% manuka honey to scaffolds was not sufficient to prevent P. aeruginosa attachment or consistently reduce the activity of methicillin resistant staphylococcus aureus, and concentrations above 7% manuka honey are likely necessary to impact MRSA. Together, our results suggest bioresorbable scaffolds may create an environment conducive to bacterial growth, and potential trade-offs exist for the incorporation of low levels of honey in scaffolds to increase osteogenic potential of osteoprogenitors while high-levels of honey may be sufficient to reduce gram positive or negative bacteria activity but at the cost of reduced osteogenesis.

Emerging multifunctional nanoparticulate formulations take advantage of nano-meter scale size and surface chemistry to work as a therapeutic delivery agent and a diagnostic tool for non-invasive real-time monitoring using imaging technologies. Here, we evaluate the selective uptake of 18 nm and 80 nm sized gold nanoparticles (AuNPs) by SKOV3 (4 times higher) ovarian cancer (OC) cells (compared to OVCAR5) in vitro, quantified by inductively coupled plasma (ICP) and MARS spectral photon-counting CT imaging (MARS SPCCT). Based on in vitro analysis, pristine AuNPs (18 nm) and surface modified AuNPs (18 nm) were chosen as a contrast agent for MARS SPCCT. The chemical analysis by FTIR spectroscopy confirmed the luteinizing hormone-releasing hormone (LHRH) conjugation to the AuNPs surface. For the first time, LHRH conjugated AuNPs were used for in vitro and selective in vivo OC targeting. The ICP-MS analysis confirmed preferential uptake of LHRH modified AuNPs by organs residing in the abdominal cavity with OC nodules (pancreas: 0.46 ng mg-1, mesentery: 0.89 ng mg-1, ovary: 1.43 ng mg-1, and abdominal wall: 2.12 ng mg-1) whereas the MARS SPCCT analysis suggested scattered accumulation of metal around the abdominal cavity. Therefore, the study showed the exciting potential of LHRH conjugated AuNPs to target ovarian cancer and also as a potential contrast agent for novel SPCCT imaging technology.

The limitations of current treatment strategies for cancer management have prompted a significant shift in the research and development of new effective strategies exhibiting higher efficacy and acceptable side effects. In this direction, nanotheranostics has gained significant interest in recent years, combining the diagnostic and therapeutic capabilities of nanostructures for efficient disease diagnosis, treatment, and management. Such nano-assisted platforms permit the site-specific release of bioactive cargo in a controlled fashion while permitting non-invasive real-time in situ monitoring. A plethora of materials has been developed as pharmacologically relevant nanoformulations for theranostic applications ranging from metallic to lipid and polymer-based composite systems, with each offering potential opportunities and its own limitations. To improve advancements with better clarity, the main focus of this review is to highlight the recent developments focusing on using different noble metal nanoparticles (noble MNPs) as cancer nanotheranostic agents, highlighting their properties, advantages, and potential modifications for their successful utilization in personalized medicine. The advantage of using noble metals (not all, but those with an atomic number ≥76) over metal NPs is their tendency to provide additional properties, such as X-ray attenuation and near-infrared activity. The combination of these properties translates to noble MNPs for therapeutic and diagnostic applications, independent of the need for additional active molecules. Through this review, we highlighted the potential application of all noble MNPs and the limited use of osmium, iridium, palladium, rhodium, and ruthenium metal NSs, even though they express similar physicochemical characteristics. The literature search was limited by PubMed, full-text availability, and studies including both in vitro and in vivo models.

Spectral CT imaging (multi-energy detection) is a promising imaging technique that can benefit from the use of high atomic number (high- Z ) based nanoparticles (NPs) as contrast agents.

Abstract Orthopedic and dental implant failure continues to be a significant concern due to localized bacterial infections. Although previous studies have attempted to improve implant surfaces by modifying their texture and roughness or coating them with antibiotics to enhance antibacterial properties for implant longevity. However, these approaches have demonstrated limited effectiveness. In this study, we attempted to engineer the titanium (Ti) alloy surface biomimetically at the nanometer scale, inspired by the cicada wing nanostructure using alkaline hydrothermal treatment (AHT). The two modified surfaces of Ti plates were developed using 4 and 8-Hr AHT at 230oC. We found that the control plates showed a relatively smooth surface, with few artifacts on the surface. The results demonstrated a statistically significant decrease in the contact angle of the treated groups, which increased wettability characteristics. The 8-hour AHT group exhibited the highest wettability and significant increase in roughness 1.50 x 10-1 ± 0.029 µm (P<0.05), leading to more osteoblast cell attachment, reduced cytotoxicity effects, and enhanced relative survivability. The alkaline phosphatase activity measured in all different groups indicated that the 8-hour AHT group exhibited the highest activity, suggesting that the surface roughness and wettability of the treatment groups may have facilitated cell adhesion and attachment and subsequently increased secretion of extracellular matrix. Overall, the findings indicate that biomimetic nanotextured surfaces created by the AHT process have the potential to be translated as implant coatings or surface nano-texturing to enhance bone regeneration and implant integration.

Dental implant−associated infection is a clinical challenge which poses a significant healthcare and socio−economic burden. To overcome this issue, developing antimicrobial surfaces, including antimicrobial peptide coatings, has gained great attention. Different physical and chemical routes have been used to obtain these biofunctional coatings, which in turn might have a direct influence on their bioactivity and functionality. In this study, we present a silane−based, fast, and efficient chemoselective conjugation of antimicrobial peptides (Cys−GL13K) to coat titanium implant surfaces. Comprehensive surface analysis was performed to confirm the surface functionalization of as−prepared and mechanically challenged coatings. The antibacterial potency of the evaluated surfaces was confirmed against both Streptococcus gordonii and Streptococcus mutans, the primary colonizers and pathogens of dental surfaces, as demonstrated by reduced bacteria viability. Additionally, human dental pulp stem cells demonstrated long−term viability when cultured on Cys−GL13K−grafted titanium surfaces. Cell functionality and antimicrobial capability against multi−species need to be studied further; however, our results confirmed that the proposed chemistry for chemoselective peptide anchoring is a valid alternative to traditional site−unspecific anchoring methods and offers opportunities to modify varying biomaterial surfaces to form potent bioactive coatings with multiple functionalities to prevent infection.

In the growing field of dentistry research, there is significant scope for investigating novel and high-performance functional biomaterials for dental care, mainly to combat oral health diseases. Considering the growing economic burden on dental care, there is an urgent need to investigate affordable and biologically acceptable functional antibacterial nanostructures capable of exhibiting desired pharmacological properties. Although a wide range of materials has been investigated for dentistry applications, their acceptability and scaling-up clinical acceptance remain a challenge to cytotoxicity and alterations in cellular function. To address these challenges, nanolipids are emerging as potential materials to develop the next generation of treatment modalities for dental care and oral diseases. However, there is a need to cover the knowledge gap between developing good quality nanolipid formulations, their introduction in dental research, establishing a track from laboratory to clinical application, exploring associated risks, and proposing step-by-step systematic research to obtain FDA approval for recommending nanolipids for next-generation systems for dentistry applications. This study also summarizes the outcomes of the literature carefully and critically to provide a clear view about selecting an appropriate nanolipid system to manage a targeted dental issue. These programmable nanolipids can be designed and developed using optimized chemistry and pharmacology to be used in a controlled manner by manipulating their responsiveness according to the demand of targeted disease management, i.e., a programmable system. The future of this research, keeping clinical adaptability as a focus, is also discussed in this review, along with the possible challenges and possible alternative approaches.

Biodegradable polymers are a rapidly growing field driven by increasing concerns about plastic waste and its environmental impact. Polymers prepared from inexpensive and renewable raw materials might be the perfect alternative to plastics, and the properties like biodegradability and biocompatibility make them suitable for various biomedical applications. The biodegradability of the polymers is controllable by altering the monomer concentration and adding hydrolytically degradable groups in the polymeric backbone. These biopolymers can provide a safe and effective way of preparing devices/implantable materials for various biomedical applications. This chapter discusses biodegradable polymers, their synthesis, biodegradability, biocompatibility, along with their advantages and disadvantages for various biomedical applications, including drug delivery and tissue engineering.

Correction for 'LHRH conjugated gold nanoparticles assisted efficient ovarian cancer targeting evaluated via spectral photon-counting CT imaging: a proof-of-concept research' by Dhiraj Kumar et al., J. Mater. Chem. B, 2023, 11, 1916-1928, https://doi.org/10.1039/D2TB02416K.

Current resin composites have favorable handling and upon polymerization initial physical properties that allow for efficient material replacement of removed carious tooth structure. Dental resin composites have long term durability limitations due to the hydrolysis of ester bonds within the methacrylate based polymer matrix. This article outlines the importance of ester bonds positioned internal to the carbon-carbon double bond in current methacrylate monomers. Water and promiscuous salivary/bacterial esterase activity can initiate ester bond hydrolysis that can sever the polymer backbone throughout the material. Recent studies have custom synthesized, with the latest advances in modern organic chemical synthesis, a novel molecule named ethylene glycol bis (ethyl methacrylate) (EGEMA). EGEMA was designed to retain the reactive acrylate units. Upon intermolecular polymerization of vinyl groups, EGEMA ester groups are positioned outside the backbone of the polymer chain. This review highlights investigation into the degradation resistance of EGEMA using buffer, esterase, and microbial storage assays. Material samples of EGEMA had superior final physical and mechanical properties than traditional ethylene glycol dimethacrylate (EGDMA) in all degradation assays. Integrating bioinformatics-based biodegradation predictions to the experimental results of storage media analyzed by LC/GC-MS revealed that hydrolysis of EGEMA generated small amounts of ethanol while preserving the strength bearing polymer backbone. Prior studies support investigation into additional custom synthesized methacrylate polymers with “flipped external” ester groups. The long term goal is to improve clinical durability compared to current methacrylates while retaining inherent advantages of acrylic based chemistry, which may ease implementation of these novel methacrylates into clinical practice.

Tissue engineering approaches for bone repair have rapidly evolved due to the development of novel bio-fabrication technologies, providing an opportunity to fabricate anatomically-accurate living implants with precise placement of specific cell types. However, limited availability of biomaterial inks, that can be 3D-printed with high resolution, while providing high structural support and the potential to direct cell differentiation and maturation towards the osteogenic phenotype, remains an ongoing challenge. Aiming towards a multifunctional biomaterial ink with high physical stability and biological functionality, this work describes the development of a nanocomposite biomaterial ink (Mg-PCL) comprising of magnesium hydroxide nanoparticles (Mg) and poly-caprolactone (PCL) thermoplastic for 3D printing of strong and bioactive bone regenerative scaffolds. We characterised the Mg nanoparticle system and systematically investigated the cytotoxic and osteogenic effects of Mg supplementation to human mesenchymal stromal cells (hMSCs) 2D-cultures. Next, we prepared Mg-PCL biomaterial ink using a solvent casting method, and studied the effect of Mg over mechanical properties, printability and scaffold degradation. Furthermore, we delivered MSCs within Mg-PCL scaffolds using a gelatinmethacryloyl (GelMA) matrix, and evaluated the effect of Mg over cell viability and osteogenic differentiation. Nanocomposite Mg-PCL could be printed with high fidelity at 20 wt% of Mg content, and generated a mechanical reinforcement between 30%-400% depending on the construct internal geometry. We show that Mg-PCL degrades faster than standard PCL in an accelerated-degradation assay, which has positive implications towards in vivo implant degradation and bone regeneration. Mg-PCL did not affect MSCs viability, but enhanced osteogenic differentiation and bone-specific matrix deposition, as demonstrated by higher ALP/DNA levels and Alizarin Red calcium staining. Finally, we present proof of concept of Mg-PCL being utilised in combination with a bonespecific bioink (Sr-GelMA) in a coordinated-extrusion bioprinting strategy for fabrication of hybrid constructs with high stability and synergistic biological functionality. Mg-PCL further enhanced the osteogenic differentiation of encapsulated MSCs and supported bone ECM deposition within the bioink component of the hybrid construct, evidenced by mineralised nodule formation, osteocalcin (OCN) and collagen type-I (Col I) expression within the bioink filaments. This study demonstrated that magnesium-based nanocomposite bioink material optimised for extrusion-based 3D printing of bone regenerative scaffolds provide enhanced mechanical stability and bone-related bioactivity with promising potential for skeletal tissue regeneration.

To streamline the drug discovery pipeline, there is a pressing need for preclinical models which replicate the complexity and scale of native tumors. While there have been advancements in the formation of microscale tumor units, these models are cell-line dependent, time-consuming and have not improved clinical trial success rates. In this study, two methods for generating 3D tumor microenvironments are compared, rapidly fabricated hydrogel microspheres and traditional cell-dense spheroids. These modules are then bioassembled into 3D printed thermoplastic scaffolds, using an automated biofabrication process, to form tumor-scale models. Modules are formed with SKOV3 and HFF cells as monocultures and cocultures, and the fabrication efficiency, cell architecture, and drug response profiles are characterized, both as single modules and as multimodular constructs. Cell-encapsulated Gel-MA microspheres are fabricated with high-reproducibility and dimensions necessary for automated tumor-scale bioassembly regardless of cell type, however, only cocultured spheroids form compact modules suitable for bioassembly. Chemosensitivity assays demonstrate the reduced potency of doxorubicin in coculture bioassembled constructs and a ≈five-fold increase in drug resistance of cocultured cells in 3D modules compared with 2D monolayers. This bioassembly system is efficient and tailorable so that a variety of relevant-sized tumor constructs could be developed to study tumorigenesis and modernize drug discovery.

Musculoskeletal disorders are a significant burden on the global economy and public health. Hydrogels have significant potential for enhancing the repair of damaged and injured musculoskeletal tissues as cell or drug delivery systems. Hydrogels have unique physicochemical properties which make them promising platforms for controlling cell functions. Gelatin methacryloyl (GelMA) hydrogel in particular has been extensively investigated as a promising biomaterial due to its tuneable and beneficial properties and has been widely used in different biomedical applications. In this review, a detailed overview of GelMA synthesis, hydrogel design and applications in regenerative medicine is provided. After summarising recent progress in hydrogels more broadly, we highlight recent advances of GelMA hydrogels in the emerging fields of musculoskeletal drug delivery, involving therapeutic drugs (e.g., growth factors, antimicrobial molecules, immunomodulatory drugs and cells), delivery approaches (e.g., single-, dual-release system), and material design (e.g., addition of organic or inorganic materials, 3D printing). The review concludes with future perspectives and associated challenges for developing local drug delivery for musculoskeletal applications.

Developing multifunctional nanostructures that promote bone repair while fighting infection is highly desirable in bone regenerative therapies. Previous efforts have focused on achieving one property or another by altering the chemical makeup of nanostructures or using growth factors or antibiotics. We present nanostructures with several simultaneous functional attributes including positive effects of strontium on bone formation and pre-vention of osteoclast differentiation along with incorporation of antimicrobial peptides (AMP) to prevent infection. To form these multifunctional nanostructures, mesoporous calcium silicate (CaMSN) was modified with high levels of strontium. For this, CaMSNs were either partially substituted (20 wt% Ca) or completely replaced with strontium (Sr) to form Sr-CaMSN or SrMSN. The mesoporous nature of these bioactive silicate nanostructures rendered a configuration for substantial AMP loading as well as their effective delivery. The physico-chemical and structural characterization of synthesized MSNs confirmed the mesoporous nature of the synthesized MSNs and their total surface area, pore size, pore volume and SBF-mediated bioactivity remained unaltered with the incorporation of Sr. However, biological evaluation confirmed that synthesized SrMSN upregulated osteogenic differentiation of mesenchymal stromal cells and significantly downregulated osteoclast differentiation. Also, the AMP-loaded MSNs prevented formation and growth of methicillin resistant Staphylo-coccus aureus (MRSA) biofilms. Thus, high Sr-containing AMP-loaded SrMSNs may combat MRSA-associated infection while promoting bone regeneration. The controlled availability of therapeutic Sr and AMP release as SrMSN degrade enables its potential application in bone tissue regeneration.

Abstract Background Transdermal osseointegrated prosthesis have relatively high infection rates leading to implant revision or failure. A principle cause for this complication is the absence of a durable impervious biomechanical seal at the interface of the hard structure (implant) and adjacent soft tissues. This study explores the possibility of recapitulating an analogous cellular musculoskeletal-connective tissue interface, which is present at naturally occurring integumentary tissues where a hard structure exits the skin, such as the nail bed, hoof, and tooth. Methods Porcine mesenchymal stromal cells (pMSCs) were derived from nine different porcine integumentary and connective tissues: hoof-associated superficial flexor tendon, molar-associated periodontal ligament, Achilles tendon, adipose tissue and skin dermis from the hind limb and abdominal regions, bone marrow and muscle. For all nine pMSCs, the phenotype, multi-lineage differentiation potential and their adhesiveness to clinical grade titanium was characterized. Transcriptomic analysis of 11 common genes encoding cytoskeletal proteins VIM (Vimentin), cell–cell and cell–matrix adhesion genes (Vinculin, Integrin β1, Integrin β2, CD9, CD151), and for ECM genes (Collagen-1a1, Collagen-4a1, Fibronectin, Laminin-α5, Contactin-3) in early passaged cells was performed using qRT-PCR. Results All tissue-derived pMSCs were characterized as mesenchymal origin by adherence to plastic, expression of cell surface markers including CD29, CD44, CD90, and CD105, and lack of hematopoietic (CD11b) and endothelial (CD31) markers. All pMSCs differentiated into osteoblasts, adipocytes and chondrocytes, albeit at varying degrees, under specific culture conditions. Among the eleven adhesion genes evaluated, the cytoskeletal intermediate filament vimentin was found highly expressed in pMSC isolated from all tissues, followed by genes for the extracellular matrix proteins Fibronectin and Collagen-1a1. Expression of Vimentin was the highest in Achilles tendon, while Fibronectin and Col1agen-1a1 were highest in molar and hoof-associated superficial flexor tendon bone marrow, respectively. Achilles tendon ranked the highest in both multilineage differentiation and adhesion assessments to titanium metal. Conclusions These findings support further preclinical research of these tissue specific-derived MSCs in vivo in a transdermal osseointegration implant model.