Clearing and replacing tissue-resident myeloid cells with an anti-CD45 antibody-drug conjugate.

Tissue-resident myeloid (TRM) cells in adults have highly variable lifespans, and may be derived from early embryonic yolk sac, fetal liver, or bone marrow. Some of these TRM cells are known pathogenic participants in congenital and acquired diseases. Myeloablative conditioning and hematopoietic stem cell transplantation can replace long-lived brain TRM cells, resulting in clinical improvements in metabolic storage diseases.

CD45-antibody-drug conjugate clears tissue resident myeloid cells from their niches enabling therapeutic adoptive cell transfer.

Tissue resident myeloid cells (TRM) in adults have highly variable lifespans and may be derived from early embryonic yolk sac, fetal liver or bone marrow. Some of these TRM are known pathogenic participants in congenital and acquired diseases. Myeloablative conditioning and hematopoietic stem cell transplant can replace long-lived brain TRM resulting in clinical improvements in metabolic storage diseases.

VEGF-A regulates angiogenesis during osseointegration of Ti implants via paracrine/autocrine regulation of osteoblast response to hierarchical microstructure of the surface.

Establishment of a patent vasculature at the bone-implant interface plays a significant role in determining overall success of orthopedic and dental implants. Osteoblasts produce vascular endothelial growth factor-A (VEGF-A), an important regulator of angiogenesis during bone formation and healing, and the amount secreted is sensitive to titanium (Ti) surface microtopography and surface energy. The purpose of this study was to determine if surface properties modulate cellular response to VEGF-A.

Effects of Tunable Keratin Hydrogel Erosion on Recombinant Human Bone Morphogenetic Protein 2 Release, Bioactivity, and Bone Induction.

Recombinant human bone morphogenetic protein 2 (rhBMP-2) delivery from collagen sponges for bone formation is an important clinical example of growth factors in tissue engineering. Side effects from rhBMP-2 burst release and rapid collagen resorption have led to investigation of alternative carriers. Here, keratin carriers with tunable erosion rates were formulated by varying disulfide crosslinking via ratios of oxidatively (keratose) to reductively (kerateine) extracted keratin.

Role of Wnt11 during Osteogenic Differentiation of Human Mesenchymal Stem Cells on Microstructured Titanium Surfaces.

Successful osseointegration of an endosseous implant involves migration and differentiation of mesenchymal stem cells (MSCs) on the implant surface. Micro-structured, hydrophilic titanium surfaces direct MSCs to undergo osteoblastic differentiation in vitro, in the absence of media additives commonly used in cultures grown on tissue culture polystyrene (TCPS). This process involves non-canonical Wnt5a, in contrast to canonical Wnt3a typically credited with osteoblastic differentiation on TCPS.

MicroRNA Contents in Matrix Vesicles Produced by Growth Plate Chondrocytes are Cell Maturation Dependent.

Chondrocytes at different maturation states in the growth plate produce matrix vesicles (MVs), membrane organelles found in the extracellular matrix, with a wide range of contents, such as matrix processing enzymes and receptors for hormones. We have shown that MVs harvested from growth zone (GC) chondrocyte cultures contain abundant small RNAs, including miRNAs. Here, we determined whether RNA also exists in MVs produced by less mature resting zone (RC) chondrocytes and, if so, whether it differs from the RNA in MVs produced by GC cells.

Surface modification of bulk titanium substrates for biomedical applications via low-temperature microwave hydrothermal oxidation.

Micro-to-nanoscale surface topographies of orthopaedic and dental implants can affect fluid wetting and biological response. Nanoscale features can be superimposed on microscale roughness of titanium (Ti) surfaces at high temperatures, resulting in increased osteoblast differentiation. However, high temperatures can compromise mechanical properties of the bulk material.

Inhibition of angiogenesis impairs bone healing in an in vivo murine rapid resynostosis model.

Biologics can improve bone formation, but may diffuse away from sites of therapeutic need. We developed a click-chemistry hydrogel that rapidly polymerizes in situ to control delivery of biologics during post-suturectomy resynostosis in 21-day-old male mice. Here, we used this model to determine the role of angiogenesis in post-suturectomy resynostosis and examine whether controlled release of angiogenesis inhibitors could delay bone regeneration.

Laser Sintered Porous Ti-6Al-4V Implants Stimulate Vertical Bone Growth.

The objective of this study was to examine the ability of 3D implants with trabecular-bone-inspired porosity and micro-/nano-rough surfaces to enhance vertical bone ingrowth. Porous Ti-6Al-4V constructs were fabricated via laser-sintering and processed to obtain micro-/nano-rough surfaces. Male and female human osteoblasts were seeded on constructs to analyze cell morphology and response.

Bone Morphogenetic Protein 2 Alters Osteogenesis and Anti-Inflammatory Profiles of Mesenchymal Stem Cells Induced by Microtextured Titanium In Vitro.

Objectives: Microtextured titanium (Ti) induces osteoblast differentiation of mesenchymal stem cells (MSCs) in the absence of exogenous osteogenic factors; and high-energy surface modifications speed healing of microrough Ti implants. Bone morphogenetic protein 2 (BMP2) is used clinically to improve peri-implant bone formation and osseointegration but can cause inflammation and bone-related complications. In this study, we determined whether BMP2 alters human MSC differentiation, apoptosis, and inflammatory factor production when grown on Ti implants with different surface properties.

Substrate Stiffness Controls Osteoblastic and Chondrocytic Differentiation of Mesenchymal Stem Cells without Exogenous Stimuli.

Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs) could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte.

Effects of low-frequency ultrasound treatment of titanium surface roughness on osteoblast phenotype and maturation.

Objective: Low-frequency ultrasound is widely used in the treatment of chronically infected wounds. To investigate its feasibility as a method for in situ restoration of metal implant surfaces in cases of peri-implantitis, we evaluated how low-frequency ultrasound affected surface properties of and response of human osteoblast-like MG63 cells to titanium (Ti).

Material And Methods: Three Ti surfaces [hydrophobic/smooth (pretreatment, PT); hydrophobic/rough (sandblasted/acid-etched, SLA); and hydrophilic/rough (SLA processed and stored hydrophilicity, mSLA)] were subjected to 25 kHz ultrasound for 10 min/cm .

24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.

Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] accumulates in articular cartilage following injection of [3H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health.

Hydrogels derived from cartilage matrices promote induction of human mesenchymal stem cell chondrogenic differentiation.

Unlabelled: Limited supplies of healthy autologous or allogeneic cartilage sources have inspired a growing interest in xenogeneic cartilage matrices as biological scaffolds for cartilage tissue engineering. The objectives of this study were to determine if shark and pig cartilage extracellular matrix (ECM) hydrogels can stimulate chondrocytic differentiation of mesenchymal stem cells (MSCs) without exogenous growth factors and to determine if the soluble factors retained by these ECM hydrogels are responsible. Human MSCs cultured on hydrogels from shark skull cartilage, pig articular cartilage, and pig auricular cartilage ECM had increased expression of chondrocyte markers and decreased secretion of angiogenic factors VEGF-A and FGF2 in comparison to MSCs cultured on tissue culture polystyrene (TCPS) at one week.

Comparable responses of osteoblast lineage cells to microstructured hydrophilic titanium-zirconium and microstructured hydrophilic titanium.

Objectives: Although titanium (Ti) is commonly used for dental implants, Ti alloy materials are being developed to improve their physical material properties. Studies indicate that osteoblast differentiation and maturation of human mesenchymal stem cells (MSCs) and normal human osteoblasts (NHOsts) respond to microstructured Ti and titanium-aluminum-vanadium (Ti6Al4V) surfaces in a similar manner. The goal of this study was to determine whether this is the case for osteoblast lineage cells grown on microstructured TiZr surfaces and whether their response is affected by surface nanotexture and hydrophilicity.

Characterization of osteoarthritic human knees indicates potential sex differences.

Background: The prevalence of osteoarthritis is higher in women than in men in every age group, and overall prevalence increases with advancing age. Sex-specific differences in the properties of osteoarthritic joint tissues may permit the development of sex-specific therapies. Sex hormones regulate cartilage and bone development and homeostasis in a sex-dependent manner.

Role of integrin α7β1 signaling in myoblast differentiation on aligned polydioxanone scaffolds.

Unlabelled: The aligned structural environment in skeletal muscle is believed to be a crucial component in functional muscle regeneration. Myotube formation is increased on aligned biomaterials, but we do not fully understand the mechanisms that direct this enhanced fusion. Previous studies indicate that the α7 integrin subunit is upregulated during myoblast differentiation, suggesting that signaling via α7β1 mediates the effect of alignment.

Novel hydrophilic nanostructured microtexture on direct metal laser sintered Ti-6Al-4V surfaces enhances osteoblast response in vitro and osseointegration in a rabbit model.

The purpose of this study was to compare the biological effects in vivo of hierarchical surface roughness on laser sintered titanium-aluminum-vanadium (Ti-6Al-4V) implants to those of conventionally machined implants on osteoblast response in vitro and osseointegration. Laser sintered disks were fabricated to have micro-/nano-roughness and wettability. Control disks were computer numerical control (CNC) milled and then polished to be smooth (CNC-M).

Selective enrichment of microRNAs in extracellular matrix vesicles produced by growth plate chondrocytes.

Matrix vesicles (MVs) are membrane organelles found in the extracellular matrix of calcifying cells, which contain matrix processing enzymes and regulate the extracellular environment via action of these enzymes. It is unknown whether MVs are also exosomic mediators of cell-cell communication via transfer of RNA material, and specifically, microRNA (miRNA). We investigated the presence of RNA in MVs isolated from cultures of costochondral growth zone chondrocytes.

Differential spatial regulation of BMP molecules is associated with single-suture craniosynostosis.

OBJECTIVE The aim of this study was to examine messenger RNA (mRNA) levels of bone morphogenetic protein (BMP) ligands, receptors, and soluble inhibitors in cells isolated from single-suture synostoses from fused coronal, metopic, sagittal, and lambdoid sutures. METHODS Cells were isolated from bone collected from patients undergoing craniotomies at Children's Healthcare of Atlanta. Real-time polymerase chain reaction was used to examine mRNA levels in cells isolated from fused sutures or patent sutures in comparison with levels in normal bone from the same patient.

Dental implant surface chemistry and energy alter macrophage activation in vitro.

Objectives: To determine the effects of dental implant surface chemistry and energy on macrophage activation in vitro.

Materials And Methods: Disks made from two clinically used implant materials (titanium [Ti], titanium zirconium alloy [TiZr]) were produced with two different surface treatments (sandblast/acid-etch [SLA], hydrophilic-SLA [modSLA]). Surface roughness, energy, and chemistry were characterized.

Titanium surface characteristics, including topography and wettability, alter macrophage activation.

Unlabelled: Biomaterial surface properties including chemistry, topography, and wettability regulate cell response. Previous studies have shown that increasing surface roughness of metallic orthopaedic and dental implants improved bone formation around the implant. Little is known about how implant surface properties can affect immune cells that generate a wound healing microenvironment.

Spag17 deficiency results in skeletal malformations and bone abnormalities.

Height is the result of many growth and development processes. Most of the genes associated with height are known to play a role in skeletal development. Single-nucleotide polymorphisms in the SPAG17 gene have been associated with human height.

Regulation of Osteoblast Differentiation by Acid-Etched and/or Grit-Blasted Titanium Substrate Topography Is Enhanced by 1,25(OH)2D3 in a Sex-Dependent Manner.

This study assessed contributions of micron-scale topography on clinically relevant titanium (Ti) to differentiation of osteoprogenitor cells and osteoblasts; the interaction of this effect with 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3); and if the effects are sex-dependent. Male and female rat bone marrow cells (BMCs) were cultured on acid-etched (A, R a = 0.87 μm), grit-blasted (GB, R a = 3.