A Comparative Study of the Resorption and Immune Response for Two Starch-Based Hemostat Powders.

Introduction: Powder hemostats are valuable adjuncts to minimize intraoperative and postoperative complications. In addition to promotion of rapid coagulation, resorption, and biocompatibility are desirable attributes. Plant starch-based polysaccharide hemostat powders are effective and widely used hemostatic agents, however their source and/or processing can affect characteristics such as in vivo degradability.

Mesenchymal Stem Cell Delivery via Topographically Tenoinductive Collagen Biotextile Enhances Regeneration of Segmental Tendon Defects.

Background: Successful management of massive rotator cuff (RC) tendon tears represents a treatment challenge because of the limited intrinsic healing capacity of native tendons and the risk of repair failure. Biologic augmentation of massive RC tears utilizing scaffolds-capable of regenerating bulk tendon tissue to achieve a mechanically functional repair-represents an area of increasing clinical interest.

Purpose: To investigate the histological and biomechanical outcomes after the use of a novel biologic scaffold fabricated from woven electrochemically aligned collagen (ELAC) threads as a suture-holding, fully load-bearing, defect-bridging scaffold with or without mesenchymal stem cells (MSCs) compared with direct repair in the treatment of critically sized RC defects using a rabbit model.

PMMA Bone Cement Composite Functions as an Adjuvant Chemotherapeutic Platform for Localized and Multi-Window Release during Bone Reconstruction.

Primary bone tumor resections often result in critical size defects, which then necessitate challenging clinical management approaches to reconstruct. One such intervention is the Masquelet technique, in which poly(methyl methacrylate) (PMMA) bone cement is placed as a spacer temporarily while adjuvant chemotherapeutics are administered systemically. The spacer is later removed and replaced with bone autograft.

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections .

While orthopedic implant-associated infections are rare, revision surgeries resulting from infections incur considerable healthcare costs and represent a substantial research area clinically, in academia, and in industry. In recent years, there have been numerous advances in the development of antimicrobial strategies for the prevention and treatment of orthopedic implant-associated infections which offer promise to improve the limitations of existing delivery systems through local and controlled release of antimicrobial agents. Prior to translation to orthopedic implant-associated infection models, the properties (, degradation, antimicrobial activity, biocompatibility) of the antimicrobial materials can be evaluated in subcutaneous implant models.

Characterization of Inflammatory and Fibrotic Encapsulation Responses of Implanted Materials with Bacterial Infection.

Medical device infections are costly, while preclinical assessment of antimicrobial properties for new materials is time intensive and imperfect at capturing the interrelated aspects of infection response and wound resolution. Herein, we developed an in vivo model for quantification of inflammatory and biocompatibility responses in the presence of a sustained implant-associated infection. The antimicrobial effectiveness of commercially available polymer materials was compared to that of thermoplastic polyurethane (TPU) materials modified with putative antimicrobial strategies as example test materials.

Modified Cyclodextrin Microparticles to Improve PMMA Drug Delivery Without Mechanical Loss.

Antibiotic-loaded poly(methyl methacrylate) (PMMA) cement is commonly used as a local delivery system to treat and prevent orthopedic infections associated with arthroplasties in load-bearing applications. However, these delivery systems are inefficient as release rate sharply declines to subinhibitory levels. Prior studies have shown that by adding in drug-filled cyclodextrin (CD) microparticles into PMMA cement, a more consistent release is observed, and antibiotic refilling through simulated implantation can be achieved.

Poly(methyl methacrylate) Bone Cement Composite Can Be Refilled with Antibiotics after Implantation in Femur or Soft Tissue.

While periprosthetic joint infections (PJIs) result in a small percentage of patients following arthroplasties, they are challenging to treat if they spread into bone and soft tissue. Treatment involves delivering antibiotics using poly(methyl methacrylate) (PMMA) bone cement. However, antibiotic release is insufficient for prolonged infections.

Antibiotic Refilling, Antimicrobial Activity, and Mechanical Strength of PMMA Bone Cement Composites Critically Depend on the Processing Technique.

Antibiotic-laden poly(methyl methacrylate) (PMMA) bone cement is used in a variety of applications including temporary spacers for load-bearing arthroplasties and non-load bearing orthopedic revision procedures and antibiotic beads to treat infections. Depending upon the surgical preparation technique, properties of PMMA can widely vary. The primary objective of this work was to perform an in-depth structure-function analysis regarding how processing of PMMA impacted material and structural properties (i.

A Polymeric Delivery System Enables Controlled Release of Genipin for Spatially-Confined In Situ Crosslinking of Injured Connective Tissues.

An emerging approach toward repair of connective tissues applies exogenous crosslinkers to mechanically augment injured structures in vivo. One crosslinker that has been explored for this purpose is the plant-derived small molecule genipin. However, genipin's high reactivity to primary amines in proteins, small size, and high diffusion coefficient necessitate localizing and controlling its delivery to avoid off-target or adverse effects.

Nonthermal plasma treatment of polymers modulates biological fouling but can cause material embrittlement.

Plasma-based treatment is a prevalent strategy to alter biological response and enhance biomaterial coating quality at the surfaces of biomedical devices and implants, especially polymeric materials. Plasma, an ionized gas, is often thought to have negligible effects on the bulk properties of prosthetic substrates given that it alters the surface chemistry on only the outermost few nanometers of material. However, no studies to date have systematically explored the effects of plasma exposure on both the surface and bulk properties of a biomaterial.

Combination Antibiotic Delivery in PMMA Provides Sustained Broad-Spectrum Antimicrobial Activity and Allows for Postimplantation Refilling.

Antibiotics are commonly added to poly(methyl methacrylate) (PMMA) by surgeons to locally treat infections such as in bone cement for joint replacement surgeries, as well as implantable antimicrobial "beads". However, this strategy is of limited value in high-risk patients where infections can be recurrent or chronic and otherwise hard to treat. Also, when only one drug is incorporated and applied toward polymicrobial infections (multiple bacterial species), there is a high risk that bacteria can develop antibiotic resistance.

Contribution of proteasome-catalyzed peptide -splicing to viral targeting by CD8 T cells in HIV-1 infection.

Peptides generated by proteasome-catalyzed splicing of noncontiguous amino acid sequences have been shown to constitute a source of nontemplated human leukocyte antigen class I (HLA-I) epitopes, but their role in pathogen-specific immunity remains unknown. CD8 T cells are key mediators of HIV type 1 (HIV-1) control, and identification of novel epitopes to enhance targeting of infected cells is a priority for prophylactic and therapeutic strategies. To explore the contribution of proteasome-catalyzed peptide splicing (PCPS) to HIV-1 epitope generation, we developed a broadly applicable mass spectrometry-based discovery workflow that we employed to identify spliced HLA-I-bound peptides on HIV-infected cells.

Ancient Introgression between Two Ape Malaria Parasite Species.

The Laverania clade comprises the human malaria parasite Plasmodium falciparum as well as at least seven additional parasite species that infect wild African apes. A recent analysis of Laverania genome sequences (Otto TD, et al. 2018.

High multiplicity infection following transplantation of hepatitis C virus-positive organs.

Highly effective direct-acting antivirals against Hepatitis C virus (HCV) have created an opportunity to transplant organs from HCV-positive individuals into HCV-negative recipients, since de novo infection can be routinely cured. As this procedure is performed more widely, it becomes increasingly important to understand the biological underpinnings of virus transmission, especially the multiplicity of infection. Here, we used single genome sequencing of plasma virus in four genotype 1a HCV-positive organ donors and their seven organ recipients to assess the genetic bottleneck associated with HCV transmission following renal and cardiac transplantation.

Use of affinity allows anti-inflammatory and anti-microbial dual release that matches suture wound resolution.

Surgical sutures are vulnerable to bacterial infections and biofilm formation. At the suture site, pain and undesirable, excess inflammation are additionally detrimental to wound healing. The development of a polymerized cyclodextrin (pCD) coated surgical suture introduces the capability to locally deliver both anti-inflammatory and anti-microbial drugs throughout the phases of acute and chronic healing.

CD4 receptor diversity in chimpanzees protects against SIV infection.

Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells. Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions. Testing the replication fitness of SIVcpz strains in CD4 T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.

HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.

Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being explored. We used neutralization data from four large virus panels to comprehensively map viral signatures associated with bNAb sensitivity, including amino acids, hypervariable region characteristics, and clade effects across four different classes of bNAbs. The bNAb signatures defined for the variable loop 2 (V2) epitope region of HIV-1 Env were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines.

Woven collagen biotextiles enable mechanically functional rotator cuff tendon regeneration during repair of segmental tendon defects in vivo.

Despite advancements in surgical techniques and materials for rotator cuff repair procedures, primary repair failures remain common. This study examines the use of electrochemically aligned collagen (ELAC) threads woven into biotextile scaffolds as grafts to repair critical infraspinatus tendon defects in New Zealand White rabbits. Three surgical treatment groups were evaluated: rabbits undergoing direct repair as operative controls, rabbits receiving ELAC scaffolds alone, and rabbits treated with mesenchymal stem cell (MSC)-seeded ELAC scaffolds.

Broadly Neutralizing Antibody Mediated Clearance of Human Hepatitis C Virus Infection.

The role that broadly neutralizing antibodies (bNAbs) play in natural clearance of human hepatitis C virus (HCV) infection and the underlying mechanisms remain unknown. Here, we investigate the mechanism by which bNAbs, isolated from two humans who spontaneously cleared HCV infection, contribute to HCV control. Using viral gene sequences amplified from longitudinal plasma of the two subjects, we found that these bNAbs, which target the front layer of the HCV envelope protein E2, neutralized most autologous HCV strains.

Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.

Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition. Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth. To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.

An Additive to PMMA Bone Cement Enables Postimplantation Drug Refilling, Broadens Range of Compatible Antibiotics, and Prolongs Antimicrobial Therapy.

Poly(methyl methacrylate) (PMMA) bone cement is used in several biomedical applications including as antibiotic-filled beads, temporary skeletal spacers, and cement for orthopedic implant fixation. To mitigate infection following surgery, antibiotics are often mixed into bone cement to achieve local delivery. However, since implanted cement is often structural, incorporated antibiotics must not compromise mechanical properties; this limits the selection of compatible antibiotics.

Evolutionary history of human revealed by genome-wide analyses of related ape parasites.

Wild-living African apes are endemically infected with parasites that are closely related to human , a leading cause of malaria outside Africa. This finding suggests that the origin of was in Africa, even though the parasite is now rare in humans there. To elucidate the emergence of human and its relationship to the ape parasites, we analyzed genome sequence data of strains infecting six chimpanzees and one gorilla from Cameroon, Gabon, and Côte d'Ivoire.