https://www.oarsijournal.com/article/S1063-4584(02)90801-0/pdf

Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects.

Commensal and pathogenic microorganisms must resist the deleterious actions of bile in order to survive in the human gastrointestinal tract. Herein we review the current knowledge on the mechanisms by which Gram-positive and Gram-negative bacteria contend with bile stress. We describe the antimicrobial actions of bile, assess the variations in bile tolerance between bacterial genera and examine the interplay between bile stress and other stresses. The molecular mechanisms underlying bile tolerance are investigated and the relationship between bile and virulence is examined. Finally, the potential benefits of bile research are briefly discussed.

The interaction between bacteria and bile

https://www.exphem.org/article/S0301-472X(00)00482-3/pdf

Mesenchymal stem cells: Biology and potential clinical uses

https://www.cell.com/trends/biotechnology/pdf/S0167-7799(09)00015-8.pdf

Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF).

We demonstrate the additive manufacturing of complex three-dimensional (3D) biological structures using soft protein and polysaccharide hydrogels that are challenging or impossible to create using traditional fabrication approaches. These structures are built by embedding the printed hydrogel within a secondary hydrogel that serves as a temporary, thermoreversible, and biocompatible support. This process, termed freeform reversible embedding of suspended hydrogels, enables 3D printing of hydrated materials with an elastic modulus <500 kPa including alginate, collagen, and fibrin. Computer-aided design models of 3D optical, computed tomography, and magnetic resonance imaging data were 3D printed at a resolution of ~200 μm and at low cost by leveraging open-source hardware and software tools. Proof-of-concept structures based on femurs, branched coronary arteries, trabeculated embryonic hearts, and human brains were mechanically robust and recreated complex 3D internal and external anatomical architectures.

Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels.

Background
Full-thickness chondral defects and early osteoarthritis continue to present major challenges for the patient and the orthopaedic surgeon as a result of the limited healing potential of articular cartilage. The use of bioactive growth factors is under consideration as a potential therapy to enhance healing of chondral injuries and modify the arthritic disease process.

The Role of Growth Factors in Cartilage Repair

Platelet concentrates such as platelet-rich plasma (PRP) have gained popularity in sports medicine and orthopaedics to promote accelerated physiologic healing and return to function. Each PRP product varies depending on patient factors and the system used to generate it. Blood from some patients may fail to make PRP, and most clinicians use PRP without performing cell counts on either the blood or the preparation to confirm that the solution is truly PRP. Components in this milieu have bioactive functions that affect musculoskeletal tissue regeneration and healing. Platelets are activated by collagen or other molecules and release growth factors from alpha granules. Additional substances are released from dense bodies and lysosomes. Soluble proteins also present in PRP function in hemostasis, whereas others serve as biomarkers of musculoskeletal injury. Electrolytes and soluble plasma hormones are required for cellular signaling and regulation. Leukocytes and erythrocytes are present in PRP and function in inflammation, immunity, and additional cellular signaling pathways. This article supports the emerging paradigm that more than just platelets are playing a role in clinical responses to PRP. Depending on the specific constituents of a PRP preparation, the clinical use can theoretically be matched to the pathology being treated in an effort to improve clinical efficacy.

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Platelet-rich plasma: a milieu of bioactive factors.

Background: Previous studies of bioactive molecules in platelet-rich plasma (PRP) have documented growth factor concentrations that promote tissue healing. However, the effects of leukocytes and inflammatory molecules in PRP have not been defined.Hypothesis: The hypothesis for this study was that the concentration of growth factors and catabolic cytokines would be dependent on the cellular composition of PRP.Study Design: Controlled laboratory study.Methods: Platelet-rich plasma was made from 11 human volunteers using 2 commercial systems: Arthrex ACP (Autologous Conditioned Plasma) Double Syringe System (PRP-1), which concentrates platelets and minimizes leukocytes, and Biomet GPS III Mini Platelet Concentrate System (PRP-2), which concentrates both platelets and leukocytes. Transforming growth factor-β1 (TGF-β1), platelet-derived growth factor–AB (PDGF-AB), matrix metalloproteinase-9 (MMP-9), and interleukin-1β (IL-1β) were measured with enzyme-linked immunosorbent assay (ELISA).Results: The PRP-1 syste...

/pdf/growth-factor-and-catabolic-cytokine-concentrations-are-4imqiuas7o.pdf

Growth Factor and Catabolic Cytokine Concentrations Are Influenced by the Cellular Composition of Platelet-Rich Plasma:

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jor.20278

Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons

Background: The purpose of this study was to compare the outcomes of treatment with bone marrow aspirate concentrate, a simple, one-step, autogenous, and arthroscopically applicable method, with the outcomes of microfracture with regard to the repair of full-thickness cartilage defects in an equine model.

Methods: Extensive (15-mm-diameter) full-thickness cartilage defects were created on the lateral trochlear ridge of the femur in twelve horses. Bone marrow was aspirated from the sternum and centrifuged to generate the bone marrow concentrate. The defects were treated with bone marrow concentrate and microfracture or with microfracture alone. Second-look arthroscopy was performed at three months, and the horses were killed at eight months. Repair was assessed with use of macroscopic and histological scoring systems as well as with quantitative magnetic resonance imaging.

Results: No adverse reactions due to the microfracture or the bone marrow concentrate were observed. At eight months, macroscopic scores (mean and standard error of the mean, 9.4 ± 1.2 compared with 4.4 ± 1.2; p = 0.009) and histological scores (11.1 ± 1.6 compared with 6.4 ± 1.2; p = 0.02) indicated improvement in the repair tissue in the bone marrow concentrate group compared with that in the microfracture group. All scoring systems and magnetic resonance imaging data indicated that delivery of the bone marrow concentrate resulted in increased fill of the defects and improved integration of repair tissue into surrounding normal cartilage. In addition, there was greater type-II collagen content and improved orientation of the collagen as well as significantly more glycosaminoglycan in the bone marrow concentrate-treated defects than in the microfracture-treated defects.

Conclusions: Delivery of bone marrow concentrate can result in healing of acute full-thickness cartilage defects that is superior to that after microfracture alone in an equine model.

Clinical Relevance: Delivery of bone marrow concentrate to cartilage defects has the clinical potential to improve cartilage healing, providing a simple, cost-effective, arthroscopically applicable, and clinically effective approach for cartilage repair.

Lisa A. Fortier

Papers

The Role of Growth Factors in Cartilage Repair

Platelet-rich plasma: a milieu of bioactive factors.

Growth Factor and Catabolic Cytokine Concentrations Are Influenced by the Cellular Composition of Platelet-Rich Plasma:

Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons

Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model.