Human amniotic membrane modulates collagen production and deposition in vitro.

Pathological fibrosis is a significant complication of surgical procedures resulting from the accumulation of excess collagen at the site of repair which can compromise the tissue architecture and severely impede the function of the affected tissue. Few prophylactic treatments exist to counteract this process; however, the use of amniotic membrane allografts has demonstrated promising clinical outcomes. This study aimed to identify the underlying mechanism of action by utilizing relevant models that accurately represent the pathophysiology of the disease state.

PURION processed human amnion chorion membrane allografts retain material and biological properties supportive of soft tissue repair.

The reparative properties of amniotic membrane allografts are well-suited for a broad spectrum of specialties. Further enhancement of their utility can be achieved by designing to the needs of each application through the development of novel processing techniques and tissue configurations. As such, this study evaluated the material characteristics and biological properties of two PURION processed amniotic membrane products, a lyophilized human amnion, intermediate layer, and chorion membrane (LHACM) and a dehydrated human amnion, chorion membrane (DHACM).

CD46 and CD59 inhibitors enhance complement-dependent cytotoxicity of anti-CD38 monoclonal antibodies daratumumab and isatuximab in multiple myeloma and other B-cell malignancy cells.

Multiple myeloma (MM) is an incurable malignancy of the B-cell lineage. Remarkable progress has been made in the treatment of MM with anti-CD38 monoclonal antibodies such as daratumumab and isatuximab, which can kill MM cells by inducing complement-dependent cytotoxicity (CDC). We showed that the CDC efficacy of daratumumab and isatuximab is limited by membrane complement inhibitors, including CD46 and CD59, which are upregulated in MM cells.

In vivo HSC prime editing rescues sickle cell disease in a mouse model.

Sickle cell disease (SCD) is a monogenic disease caused by a nucleotide mutation in the β-globin gene. Current gene therapy studies are mainly focused on lentiviral vector-mediated gene addition or CRISPR/Cas9-mediated fetal globin reactivation, leaving the root cause unfixed. We developed a vectorized prime editing system that can directly repair the SCD mutation in hematopoietic stem cells (HSCs) in vivo in a SCD mouse model (CD46/Townes mice).

In vivo base editing by a single i.v. vector injection for treatment of hemoglobinopathies.

Individuals with β-thalassemia or sickle cell disease and hereditary persistence of fetal hemoglobin (HPFH) possessing 30% fetal hemoglobin (HbF) appear to be symptom free. Here, we used a nonintegrating HDAd5/35++ vector expressing a highly efficient and accurate version of an adenine base editor (ABE8e) to install, in vivo, a -113 A>G HPFH mutation in the γ-globin promoters in healthy CD46/β-YAC mice carrying the human β-globin locus. Our in vivo hematopoietic stem cell (HSC) editing/selection strategy involves only s.

Dehydrated Human Amniotic Membrane Inhibits Myofibroblast Contraction through the Regulation of the TGFβ‒SMAD Pathway In Vitro.

Excessive fibrosis affects more than 100 million patients yearly, leading to the accumulation of extracellular matrix that compromises tissue architecture and impedes its function. Intrinsic properties of the amniotic membrane have alluded to its potential to inhibit excessive fibrosis; therefore, this study aimed to investigate the effects of dehydrated human amnion/chorion membrane (dHACM) on dermal fibroblasts and their role in fibrotic pathways. Human dermal fibroblasts were stimulated with TGFβ1, triggering myofibroblast-like characteristics in vitro.

Dehydrated human amniotic membrane regulates tenocyte expression and angiogenesis in vitro: Implications for a therapeutic treatment of tendinopathy.

Tendon injuries are among the most common ailments of the musculoskeletal system. Prolonged inflammation and persistent vasculature are common complications associated with poor healing. Damaged tendon, replaced with scar tissue, never completely regains the native structural or biomechanical properties.

Human amniotic membrane modulates Wnt/β-catenin and NF-κβ signaling pathways in articular chondrocytes .

Objective: Inflammation, catabolism, and hypertrophy in chondrocytes play a central role in osteoarthritis (OA). The Wnt/β-catenin and NF-κβ pathways contribute to these degradative processes. This study evaluates the inhibitory effect of a novel therapeutic, micronized dehydrated human amnion/chorion membrane (μdHACM), as a potential treatment to offset elevated Wnt/β-catenin and NF-κβ signaling.

Dehydrated human amniotic membrane modulates canonical Wnt signaling in multiple cell types in vitro.

Canonical Wnt signaling is a major pathway known to regulate diverse physiological processes in multicellular organisms. Signaling is tightly regulated by feedback mechanisms; however, persistent dysregulation of this pathway is implicated in the progression of multiple disease states. In this study, proteomic analysis identified endogenous Wnt antagonists in micronized dehydrated human amnion/chorion membrane (μdHACM); thereby, prompting a study to further characterize the intrinsic properties of μdHACM as it relates to Wnt activity, in vitro.

Evaluation of dehydrated human umbilical cord biological properties for wound care and soft tissue healing.

Chronic wounds are a significant health care problem with serious implications for quality of life because they do not properly heal and often require therapeutic intervention. Amniotic membrane allografts have been successfully used as a biologic therapy to promote soft tissue healing; however, the umbilical cord, another placental-derived tissue, has also recently garnered interest because of its unique composition but similar placental tissue origin. The aim of this study was to characterize PURION® PLUS Processed dehydrated human umbilical cord (dHUC) and evaluate the biological properties of this tissue that contribute to healing.

Identification of Extracellular Matrix Components and Biological Factors in Micronized Dehydrated Human Amnion/Chorion Membrane.

The use of bioactive extracellular matrix (ECM) grafts such as amniotic membranes is an attractive treatment option for enhancing wound repair. In this study, the concentrations, activity, and distribution of matrix components, growth factors, proteases, and inhibitors were evaluated in PURION Processed, micronized, dehydrated human amnion/chorion membrane (dHACM; MiMedx Group, Inc.).

Type I and II Diabetic Adipose-Derived Stem Cells Respond to Dehydrated Human Amnion/Chorion Membrane Allograft Treatment by Increasing Proliferation, Migration, and Altering Cytokine Secretion.

Human amniotic membranes have been shown to be effective for healing diabetic foot ulcers clinically and to regulate stem cell activity and ; however, diabetic stem cells may be impaired as a sequela of the disease. In this study, dehydrated human amnion/chorion membrane (dHACM) allografts (EpiFix; MiMedx Group) were evaluated for their ability to regulate diabetic stem cells . Human adipose-derived stem cells (ADSCs) from normal, type I diabetic, and type II diabetic donors were treated with soluble extracts of dHACM and evaluated for proliferation after 3 days by DNA assay, chemotactic migration after 1 day by transwell assay, cytokine secretion after 3 days by multiplex ELISA, and gene expression after 5 days by reverse transcription-polymerase chain reaction.

Dehydrated human amnion/chorion membrane regulates stem cell activity in vitro.

Human-derived placental tissues have been shown in randomized clinical trials to be effective for healing chronic wounds, and have also demonstrated the ability to recruit stem cells to the wound site in vitro and in vivo. In this study, PURION(®) Processed dehydrated human amnion/chorion membrane allografts (dHACM, EpiFix(®) , MiMedx Group, Marietta, GA) were evaluated for their ability to alter stem cell activity in vitro. Human bone marrow mesenchymal stem cells (BM-MSCs), adipose derived stem cells (ADSCs), and hematopoietic stem cells (HSCs) were treated with soluble extracts of dHACM tissue, and were evaluated for cellular proliferation, migration, and cytokine secretion.

Cell recruitment by amnion chorion grafts promotes neovascularization.

Background: Nonhealing wounds are a significant health burden. Stem and progenitor cells can accelerate wound repair and regeneration. Human amniotic membrane has demonstrated efficacy in promoting wound healing, though the underlying mechanisms remain unknown.

Cytokines in single layer amnion allografts compared to multilayer amnion/chorion allografts for wound healing.

Human amniotic membrane allografts have proven effective at improving healing of cutaneous wounds. The mechanism of action for these therapeutic effects is poorly understood but is thought to involve the resident growth factors present in near term amniotic tissue. To determine the relative cytokine contribution of the amnion and chorion in amniotic allografts, the content of 18 cytokines involved in wound healing were measured in samples of PURION® Processed dehydrated amnion, chorion, and amnion/chorion membrane (dHACM) grafts by multiplex enzyme-linked immunosorbent assay array.

Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration.

Background: Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis.

Properties of dehydrated human amnion/chorion composite grafts: Implications for wound repair and soft tissue regeneration.

PURION(®) processed dehydrated human amnion/chorion membrane (dHACM; MiMedx Group, Marietta, GA) tissue products were analyzed for the effectiveness of the PURION(®) process in retaining the native composition of the amniotic membrane and preserving bioactivity in the resulting products. dHACM was analyzed for extracellular matrix (ECM) composition through histological staining and for growth factor content via multiplex ELISA arrays. Bioactivity was assessed by evaluating endogenous growth factor production by human dermal fibroblasts in response to dHACM and for thermal stability by mechanical tests and in vitro cell proliferation assays.

Cyclic tension promotes fibroblastic differentiation of human MSCs cultured on collagen-fibre scaffolds.

Mesenchymal stem cells (MSCs) have been suggested as a potential cell source for tendon/ligament tissue engineering. Extrinsic cues, such as the chemical and physical properties of scaffolds, as well as external forces, play an important role in fibroblastic differentiation of these cells. In this study, we employed a collagen-fibre scaffold that mimics the chemical and fibrous structure and mechanical properties of tendon/ligament, and studied how imparting cyclic tension to these fibrous collagen scaffolds affects tendon/ligament fibroblastic differentiation of MSCs.

Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing.

Human amnion/chorion tissue derived from the placenta is rich in cytokines and growth factors known to promote wound healing; however, preservation of the biological activities of therapeutic allografts during processing remains a challenge. In this study, PURION® (MiMedx, Marietta, GA) processed dehydrated human amnion/chorion tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for the presence of growth factors, interleukins (ILs) and tissue inhibitors of metalloproteinases (TIMPs). Enzyme-linked immunosorbent assays (ELISA) were performed on samples of dHACM and showed quantifiable levels of the following growth factors: platelet-derived growth factor-AA (PDGF-AA), PDGF-BB, transforming growth factor α (TGFα), TGFβ1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), placental growth factor (PLGF) and granulocyte colony-stimulating factor (GCSF).

Minimum 5-year wear analysis of first-generation highly cross-linked polyethylene in patients 65 years and younger.

The purpose of this study was to analyze wear rates of highly cross-linked polyethylene comparing the Martell and the Roman methods in 112 total hip arthroplasties in patients 65 years and younger, with a mean follow-up of 5.7 years. The mean wear rates in the Martell and Roman methods were 0.

Properties of the patient administered questionnaires: new scales measuring physical and psychological symptoms of hip and knee disorders.

The Patient Administered Questionnaires (PAQ) incorporate physical and psychological symptoms into one scale and permit more comprehensive self-reports for hip and knee disorders. We tested the psychometric properties of the PAQ-Hip and PAQ-Knee. Correlations between baseline PAQ-Hip and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were .

Early reactive synovitis and osteolysis after total hip arthroplasty.

Background: Little is known about intraarticular pathology following THA prior to the radiographic appearance of osteolysis, primarily due to imaging limitations. MRI has recently been applied to imaging the postarthroplasty hip with the ability to detect periarticular bony and soft tissue pathology; specifically, it is able to detect abnormal synovial patterns and focal bone loss well before the radiographic appearance of osteolysis.

Questions/purposes: We therefore used MRI to determine the incidence of early reactive synovitis and osteolysis in asymptomatic patients after THA, and whether there is an association between these MRI findings and clinical outcomes or radiographic wear measurements at this early stage.

A novel porous collagen scaffold around an implantable biosensor for improving biocompatibility. I. In vitro/in vivo stability of the scaffold and in vitro sensitivity of the glucose sensor with scaffold.

A new 3D porous and biostable collagen scaffold has been developed to improve the biocompatibility of implantable glucose sensors by minimizing tissue reactions while stimulating angiogenesis around the sensors. The novel collagen scaffold was crosslinked using nordihydroguaiaretic acid (NDGA) to enhance biostability. NDGA-treated collagen scaffolds were stable without physical deformation in the subcutaneous tissue of rats for 4 weeks.

Low strain nanomechanics of collagen fibrils.

The high stiffness of collagenous tissues such as tendon and ligament is derived in large part from the mechanics and geometries of the constituent collagen's hierarchical forms. The primary structural unit in connective tissues is the collagen fibril for which there exists little direct mechanical or deformational study. Therefore, the current understanding of the mechanisms involved is extrapolated from whole tissue data.