Local Delivery Of Growth Factors Research Articles

Cryogel microcarriers for sustained local delivery of growth factors to the brain

Neurotrophic growth factors such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) have been considered as potential therapeutic candidates for neurodegenerative disorders due to their important role in modulating the growth and survival of neurons. However, clinical translation remains elusive, as their large size hinders translocation across the blood-brain barrier (BBB), and their short half-life in vivo necessitates repeated administrations. Local delivery to the brain offers a potential route to the target site but requires a suitable drug-delivery system capable of releasing these proteins in a controlled and sustained manner. Herein, we develop a cryogel microcarrier delivery system which takes advantage of the heparin-binding properties of GDNF and BDNF, to reversibly bind/release these growth factors via electrostatic interactions. Droplet microfluidics and subzero temperature polymerization was used to create monodisperse cryogels with varying degrees of negative charge and an average diameter of 20 μm. By tailoring the inclusion of 3-sulfopropyl acrylate (SPA) as a negatively charged moiety, the release duration of these two growth factors could be adjusted to range from weeks to half a year. 80% SPA cryogels and 20% SPA cryogels were selected to load GDNF and BDNF respectively, for the subsequent biological studies. Cell culture studies demonstrated that these cryogel microcarriers were cytocompatible with neuronal and microglial cell lines, as well as primary neural cultures. Furthermore, in vivo studies confirmed their biocompatibility after administration into the brain, as well as their ability to deliver, retain and release GDNF and BDNF in the striatum. Overall, this study highlights the potential of using cryogel microcarriers for long-term delivery of neurotrophic growth factors to the brain for neurodegenerative disorder therapeutics.

Precise Engineering of Growth Factor Presentation Using Extracellular Microenvironment-Mimicking Microfluidic Microparticles.

One of the main challenges in tissue engineering is finding a way to deliver specific growth factors (GFs) with precise spatiotemporal control over their presentation. Here, we report a novel strategy for generating microscale carriers with enhanced affinity for high content loading suitable for the sustained and localized delivery of GFs. Our developed microparticles can be injected locally and sustainably release encapsulated growth factors for up to 28 days. Fine-tuning of particles' size, affinity, microstructures, and release kinetics is achieved using a microfluidic system along with bioconjugation techniques. We also describe an innovative 3D micromixer platform to control the formation of core-shell particles based on superaffinity using a polymer-peptide conjugate for further tuning of release kinetics and delayed degradation. Chitosan shells block the burst release of encapsulated GFs and enable their sustained delivery for up to 10 days. The matched release profiles and degradation provide the local tissues with biomimetic, developmental-biologic-compatible signals to maximize regenerative effects. The versatility of this approach is verified using three different therapeutic proteins, including human bone morphogenetic protein-2 (rhBMP-2), vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1α). As in vivo morphogenesis is typically driven by the combined action of several growth factors, the proposed technique can be developed to generate a library of GF-loaded particles with designated release profiles.

An Update on Orthobiologics: Cautious Optimism

Orthobiologics are rapidly growing in use given their potential to augment healing for multiple musculoskeletal conditions. Orthobiologics consist of a variety of treatments including platelet-rich plasma and stem cells that provide conceptual appeal in providing local delivery of growth factors and inflammation modulation. The lack of standardization in nomenclature and applications within the literature has led to a paucity of high-quality evidence to support their frequent use. The purpose of this review was to describe the current landscape of orthobiologics and the most recent evidence regarding their use.

Efficacy of Ablative Fractional Carbon Dioxide Laser Alone and Combined with Platelet-Rich Plasma in the Treatment of Androgenetic Alopecia

Abstract Androgenetic alopecia (AGA) is a common form of hair loss in both men and women. In men, this condition is also known as male-pattern baldness. Fractional CO2 laser treatment has effectively induced hair regrowth through the wound-healing process. Platelet-rich plasma (PRP) ensures local delivery of growth factors, modification of the inflammatory response, and stimulation of cell proliferation and differentiation within the target tissue. PRP therefore showed a beneficial effect in treatment of AGA. Aim of the Study The aim of this study is to evaluate and compare the efficacy and safety of ablative carbon dioxide (CO2) fractional laser alone or combined with platelets rich plasma therapy in the treatment of Male Androgenetic Alopecia. Patients and Methods The study included 35 patients suffering from AGA. All patients will receive bilateral ablative fractional CO2 laser treatment on the alopecic scalp and the right or left side of the scalp will be randomly selected to be covered with platelet-rich plasma and the other half of the scalp will be covered with saline after the laser at the same session. Results Combined ablative fractional CO2 laser treatment and platelet-rich plasma showed statistically significant improvement compared to ablative fractional CO2 laser alone.

Transplantation of hybrid adipose-derived stem cell sheet with autologous peritoneum: An in vivo feasibility study

IntroductionIn regenerative medicine, cell sheet engineering has various advantages, including the retention of cells at the transplantation site for a longer period and the local delivery of growth factors and cytokines. Adipose-derived stem cell (ASC) is widely used owing to their various functions such as wound healing, immunomodulation, and nerve regeneration, in addition to their ability to differentiate into adipocytes, chondrocytes, and osteoblasts. ASC sheet generated using cell sheet engineering is considered effective in preventing anastomotic leakage, a serious postoperative complication in gastrointestinal surgery. However, the ASC sheet is too soft, thin, and brittle to handle with laparoscopic forceps during the operation. Therefore, we considered using the peritoneum, which is stiff and easy to collect while operating, as an alternative support. In this study, we explored the feasibility of using the peritoneum as a support for the precise transplantation of ASC sheets during surgery. MethodsASCs were isolated from the subcutaneous fat of the inguinal region of Sprague-Dawley (SD) transgenic rats expressing green fluorescent protein. ASCs were cultured until passage 3, seeded in temperature-responsive culture dishes, and the resulting ASC sheet was harvested at more than 80% confluency. Non-transgenic SD rats were used for transplant experiments. The wall peritoneum was harvested from SD rats following laparotomy, and hybrid adipose-derived stem cell (HASC) sheet was prepared by laminating the peritoneum with ASC sheet. The cell sheets were transplanted on the backs of SD rats following the incision. On post-transplantation days 3 and 7, the specimens were extracted. ASC and HASC sheets were then compared macroscopically and histopathologically. ResultsHASC sheet transplantation was macroscopically and histopathologically more effective than ASC sheet transplantation. The peritoneum provided sufficient stiffness as a support for precise transplantation. ConclusionThe newly developed HASC sheet, which combine the advantages of ASC sheet with those of the peritoneum, could be more useful for clinical application than the ASC sheet alone.

Dual growth factor entrapped nanoparticle enriched alginate wafer-based delivery system for suppurating wounds

We have investigated the wound healing efficiency of calcium alginate wafer embedded with growth factor entrapped PLGA nanoparticle. Herein, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) entrapped PLGA nanoparticles were synthesized and embedded in a sodium alginate gel by freeze-drying technique. The synthesized dressing exhibited a high degree of swelling and appropriate porosity. The scaffold was characterized by Scanning Electron Microscopy (SEM) showing a highly porous morphology. Also, incorporation of growth factor loaded nanoparticles in a wafer-based delivery system resulted in localized growth factor delivery at the site of the wound in a sustained manner. The biocompatibility of the scaffold was evaluated by MTT assay, which showed a higher cell proliferation in the proposed scaffold as compared to the control. In vivo wound healing efficiency of the scaffold was evaluated using a full thickness murine wound model, which showed improved re-epithelialization, collagen deposition, and angiogenesis. These results suggest the use of the scaffold as a promising wound dressing material.

Texturing Hierarchical Tissues by Gradient Assembling of Microengineered Platelet-Lysates Activated Fibers.

The heterogeneity of hierarchical tissues requires designing multipart engineered constructs as suitable tissue replacements. Herein, the incorporation of platelet lysate (PL) within an electrospun fiber core is proposed aiming for the fabrication of functionally graded 3D scaffolds for heterotypic tissues regeneration, such as tendon-to-bone interfaces. First, anisotropic yarns (A-Yarns) and isotropic threads with nanohydroxyapatite (I-Threads/PL@nHAp) are fabricated to recreate the tendon- and bone-microstructures and both incorporated with PL using emulsion electrospinning for a sustained and local delivery of growth factors, cytokines, and chemokines. Biological performance using human adipose-derived stem cells demonstrates that A-Yarns/PL induce a higher expression of scleraxis, a tenogenic-marker, while in I-Threads/PL@nHAp, higher alkaline phosphatase activity and matrix mineralization suggest an osteogenic commitment without the need for biochemical supplementation compared to controls. As a proof-of-concept, functional 3D gradient scaffolds are fabricated using a weaving technique, resulting in 3D textured hierarchical constructs with gradients in composition and topography. Additionally, the precise delivery of bioactive cues together with in situ biophysical features guide the commitment into a phenotypic gradient exhibiting chondrogenic and osteochondrogenic profiles in the interface of scaffolds. Overall, a promising patch solution for the regeneration of tendon-to-bone tissue interface through the fabrication of PL-functional 3D gradient constructs is demonstrated.

Multifunctional Thermoresponsive Microcarriers for High-Throughput Cell Culture and Enzyme-Free Cell Harvesting.

An effective treatment of human diseases using regenerative medicine and cell therapy approaches requires a large number of cells. Cultivation of cells on microcarriers is a promising approach due to the high surface-to-volume ratios that these microcarriers offer. Here, multifunctional temperature-responsive microcarriers (cytoGel) made of an interpenetrating hydrogel network composed of poly(N-isopropylacrylamide) (PNIPAM), poly(ethylene glycol) diacrylate (PEGDA), and gelatin methacryloyl (GelMA) are developed. A flow-focusing microfluidic chip is used to produce microcarriers with diameters in the range of 100-300 μm and uniform size distribution (polydispersity index of ≈0.08). The mechanical properties and cells adhesion properties of cytoGel are adjusted by changing the composition hydrogel composition. Notably, GelMA regulates the temperature response and enhances microcarrier stiffness. Human-derived glioma cells (U87) are grown on cytoGel in static and dynamic culture conditions with cell viabilities greater than 90%. Enzyme-free cell detachment is achieved at room temperature with up to 70% detachment efficiency. Controlled release of bioactive molecules from cytoGel is accomplished for over a week to showcase the potential use of microcarriers for localized delivery of growth factors to cell surfaces. These microcarriers hold great promise for the efficient expansion of cells for the industrial-scale culture of therapeutic cells.

Articular cartilage regeneration by activated skeletal stem cells

Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2–4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis5–7. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA. Endogenous skeletal stem cells are recruited to form cartilage in mice when stimulated by microfracture surgery together with localized delivery of growth factors, pointing to a new approach for treating cartilage defects.

Growth factor-loaded microspheres in mPEG-polypeptide hydrogel system for articular cartilage repair.

We developed an injectable hydrogel system with a sustained release of TGF-β3 through growth factor-loaded microsphere to mimic the cartilage-like microenvironment. Poly(lactic-co-glycolic acid) (PLGA) microspheres incorporated in three dimensional (3D) scaffolds were chosen because of its regulatory approval, good biodegradability, and acting as carriers with sustained release behavior. We evaluated sustained release of TGF-β3 by PLGA microspheres encapsulated in methoxy poly(ethylene glycol)-poly(alanine) (mPA) hydrogels and the resulting enhanced chondrogenic effects. We reported here the effect of the proposed system for sustained release of growth factors on chondrogenesis in cartilage regeneration. PLGA microspheres were used in our thermosensitive mPA hydrogel system with bovine serum albumin as a stabilizing and protecting agent for the emulsion and TGF-β3 enabling sustained release. Gelation, structural properties, and in-vitro release of this composite, that is, microspheres in hydrogel, system were investigated. Using PLGA microspheres to carry growth factors could complement the mPA hydrogel's ability to provide an excellent 3D microenvironment for the promotion of chondrogenic phenotype as compared the systems using mPA hydrogel or microspheres alone. Our study demonstrated that this synthesized composite hydrogel system is capable of modulating the biosynthetic and differentiation activities of chondrocytes. The sustained release of TGF-β3 in this novel hydrogel system could improve biomedical applicability of mPEG-polypeptide scaffolds. The distinctive local growth factor delivery system successfully combined the use of both polymers to be a suitable candidate for prolonged articular cartilage regeneration.

Vascularization Strategies in the Prevention of Nonunion Formation.

Delayed healing and nonunion formation are major challenges in orthopedic surgery, which require the development of novel treatment strategies. Vascularization is considered one of the major prerequisites for successful bone healing, providing an adequate nutrient supply and allowing the infiltration of progenitor cells to the fracture site. Hence, during the last decade, a considerable number of studies have focused on the evaluation of vascularization strategies to prevent or to treat nonunion formation. These involve (1) biophysical applications, (2) systemic pharmacological interventions, and (3) tissue engineering, including sophisticated scaffold materials, local growth factor delivery systems, cell-based techniques, and surgical vascularization approaches. Accumulating evidence indicates that in nonunions, these strategies are indeed capable of improving the process of bone healing. The major challenge for the future will now be the translation of these strategies into clinical practice to make them accessible for the majority of patients. If this succeeds, these vascularization strategies may markedly reduce the incidence of nonunion formation. Impact statement Delayed healing and nonunion formation are a major clinical problem in orthopedic surgery. This review provides an overview of vascularization strategies for the prevention and treatment of nonunions. The successful translation of these strategies in clinical practice is of major importance to achieve adequate bone healing.

The development of natural polymer scaffold-based therapeutics for osteochondral repair.

Due to the limited regenerative capacity of cartilage, untreated joint defects can advance to more extensive degenerative conditions such as osteoarthritis. While some biomaterial-based tissue-engineered scaffolds have shown promise in treating such defects, no scaffold has been widely accepted by clinicians to date. Multi-layered natural polymer scaffolds that mimic native osteochondral tissue and facilitate the regeneration of both articular cartilage (AC) and subchondral bone (SCB) in spatially distinct regions have recently entered clinical use, while the transient localized delivery of growth factors and even therapeutic genes has also been proposed to better regulate and promote new tissue formation. Furthermore, new manufacturing methods such as 3D bioprinting have made it possible to precisely tailor scaffold micro-architectures and/or to control the spatial deposition of cells in requisite layers of an implant. In this way, natural and synthetic polymers can be combined to yield bioactive, yet mechanically robust, cell-laden scaffolds suitable for the osteochondral environment. This mini-review discusses recent advances in scaffolds for osteochondral repair, with particular focus on the role of natural polymers in providing regenerative templates for treatment of both AC and SCB in articular joint defects.

Where do you want your drugs delivered?

Promoting bone repair and regeneration in bone fractures by local delivery of growth factors possessing osteoinductive activity has been extensively investigated with significant advancements. Meth...

Growth Factors, Carrier Materials, and Bone Repair.

This chapter provides an overview of the growth factors active in bone regeneration and healing. Both normal and impaired bone healing are discussed, with a focus on the spatiotemporal activity of the various growth factors known to be involved in the healing response. The review highlights the activities of most important growth factors impacting bone regeneration, with a particular emphasis on those being pursued for clinical translation or which have already been marketed as components of bone regenerative materials. Current approaches the use of bone grafts in clinical settings of bone repair (including bone grafts) are summarized, and carrier systems (scaffolds) for bone tissue engineering via localized growth factor delivery are reviewed. The chapter concludes with a consideration of how bone repair might be improved in the future.

Scaffold-Based Delivery of Nucleic Acid Therapeutics for Enhanced Bone and Cartilage Repair.

Recent advances in tissue engineering have made progress toward the development of biomaterials capable of the delivery of growth factors, such as bone morphogenetic proteins, in order to promote enhanced tissue repair. However, controlling the release of these growth factors on demand and within the desired localized area is a significant challenge and the associated high costs and side effects of uncontrolled delivery have proven increasingly problematic in clinical orthopedics. Gene therapy may be a valuable tool to avoid the limitations of local delivery of growth factors. Following a series of setbacks in the 1990s, the field of gene therapy is now seeing improvements in safety and efficacy resulting in substantial clinical progress and a resurgence in confidence. Biomaterial scaffold-mediated gene therapy provides a template for cell infiltration and tissue formation while promoting transfection of cells to engineer therapeutic proteins in a sustained but ultimately transient fashion. Additionally, scaffold-mediated delivery of RNA-based therapeutics can silence specific genes associated with orthopedic pathological states. This review will provide an overview of the current state-of-the-art in the field of gene-activated scaffolds and their use within orthopedic tissue engineering applications. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1671-1680, 2019.

Mechanically Defined Microenvironment Promotes Stabilization of Microvasculature, Which Correlates with the Enrichment of a Novel Piezo-1+ Population of Circulating CD11b+ /CD115+ Monocytes.

Vascularization is a critical step in the restoration of cellular homeostasis. Several strategies including localized growth factor delivery, endothelial progenitor cells, genetically engineered cells, gene therapy, and prevascularized implants have been explored to promote revascularization. But, long-term stabilization of newly induced vessels remains a challenge. It has been shown that fibroblasts and mesenchymal stem cells can stabilize newly induced vessels. However, whether an injected biomaterial alone can serve as an instructive environment for angiogenesis remains to be elucidated. It is reported here that appropriate vascular branching, and long-term stabilization can be promoted simply by implanting a hydrogel with stiffness matching that of fibrin clot. A unique subpopulation of circulating CD11b+ myeloid and CD11b+ /CD115+ monocytes that express the stretch activated cation channel Piezo-1, which is enriched prominently in the clot-like hydrogel, is identified. These findings offer evidence for a mechanobiology paradigm in angiogenesis involving an interplay between mechanosensitive circulating cells and mechanics of tissue microenvironment.

Efficient and cost-effective generation of hepatocyte-like cells through microparticle-mediated delivery of growth factors in a 3D culture of human pluripotent stem cells

Biomedical application of human pluripotent stem cell-derived hepatocyte-like cells (hPSC-HLCs) relies on efficient large-scale differentiation, which is commonly performed by a suspension culture of three-dimensional (3D) multicellular spheroids in bioreactors. However, this approach requires large amounts of growth factors (GFs) and the need to overcome limited diffusional transport posed by the inherent 3D structure of hPSC spheroids. Here, we have hypothesized that localized delivery of GFs by incorporation of GF-laden degradable polymeric microparticles (MPs) within the hPSC spheroids would circumvent such limitations. In this study, GFs for hepatocytic differentiation were encapsulated in gelatin-coated poly (l-lactic acid)/poly (DL-lactic-co-glycolic acid) (PLLA/PLGA) MPs which were subsequently incorporated into the hPSC spheroids. Gene expression analyses demonstrated that MP delivery of the GFs resulted in similar expression levels of hepatocytic markers despite the use of 10-fold less total GFs. The differentiated HLCs in the MP group exhibited ultrastructure and functional characteristics comparable with the conventional soluble GF group. The generated HLCs in the MP group were successfully engrafted in an acute liver injury mouse model and maintained hepatocytic function after implantation. These results suggested that sustained and localized delivery of GFs using MPs might offer a novel approach towards scalable technologies for hepatocytic differentiation and engineer a better 3D microenvironment for cells.

Calcium phosphate bone cement/mesoporous bioactive glass composites for controlled growth factor delivery.

Calcium phosphate (CaP) bone cements are widely used for the treatment of bone defects and have been proposed to serve as a delivery platform for therapeutic drugs, proteins and growth factors into the defect region. However, they lack sufficient porosity to allow immediate bone ingrowth and thus foster rapid integration into the bone tissue. In this study we investigated a composite prepared from a hydroxyapatite forming bone cement and mesoporous bioactive glass (MBG) granules as a potential carrier for biologically active proteins. The mechanical properties of the composite were not compromised by up to 10 wt% MBG granule addition, which can be attributed to the strong interface between the cement matrix and MBG particles, however this modification induced a significant increase in porosity within 3 weeks ageing in an aqueous liquid. The release profiles of two proteins, lysozyme and the vascular endothelial growth factor (VEGF), could be controlled when they were loaded onto MBG granules that were subsequently embedded into the cement when compared to direct loading into the cement precursor. Both proteins were also demonstrated to maintain their biologic activity during embedding and release from the composite. These findings suggest the CaP bone cement/MBG composite developed in this study as a potential delivery platform for growth factors or other bioactive substances.

Use of calcium phosphate- silver nanoparticles in chitosan coatings on titanium and for drug delivery

Event Abstract Back to Event Use of calcium phosphate- silver nanoparticles in chitosan coatings on titanium and for drug delivery Gillen Gonzales1, Joel D. Bumgardner1, Jegdish P. Babu2, Jessica A. Jennings1, Warren O. Haggard1, Hitesh Adhikari3, Diego V. Pulgarin1, Timothy B. Martin1, Vishnu P. Murali1 and Sanjay R. Mishra3 1 University of Memphis, Biomedical Engineering, United States 2 UTHCS, School of Dentistry, United States 3 University of Memphis, Department of Physics, United States Introduction: Calcium-phosphate (CaP) nanoparticles decorated with silver (Ag) have shown potential to kill infectious bacteria in vitro.[1] [2]A coating that localizes the antibacterial CaP- Ag nanoparticles using osteoconductive chitosan may provide a means to inhibit bacterial biofilm formation and subsequent infectious complications for these implants. This work evaluated antimicrobial, cytocompatibility, and protein delivery properties of CaP- Ag in chitosan coatings. Materials and Methods: Porous CaP nanospheres with 0, 15, 37, or 50% Ag were fabricated using a hydrothermal synthesis of CaP followed by microwave heating of CaP-AgNO3 for Ag decoration on CaP. [1] Chitosan (82 DDA) coatings with 30wt% CaP-Ag particles were made via silane-solution casting on to cpTi and sterilized using ethylene oxide gas. Coated and uncoated cpTi coupons (n=3/group) were incubated with 3ml of bacteria (5X106 colony forming units) under anaerobic conditions for common dental pathogens (P. gingivalis, ATC BAA-388; P. denticola, ATCC 35308) and aerobic conditions for orthopedic pathogens (P. aeruginosa: ATCC 15442; S. aureus, ATCC 25923, and S. epidermidis, ATCC 700576). Percent viability of bacteria was determined using MTT Bacterial Viability Assay (Roche Lab) using culture plastic controls. Coated and uncoated cpTi coupons were incubated with 2X104 NIH 3T3 cells for 24 hrs and viability determined using CellTitre-Glo Assay (Promega). For protein release, 20mg of CaP-Ag particles (n=4/group) were incubated in 3mL of 1mg/mL α-chymotrypsin (MW = 25kDa, pI ~ 9.1), used as an analogue to BMP-2 (MW = 26kDa, pI ~8.2), for 24 hrs at 37C under gentle rocking. After 24hrs, supernatant was collected for determining protein loading by subtraction. Samples were incubated in 3mL PBS at 37C and eluates were collected with complete PBS every 2 days for 3 weeks. Protein concentration was determined using Quant-iT Protein Kit (Mol. Probe). Size and Zeta potential of particles was determined using Delsa™ Nano Submicron Particle Size and Zeta Potential Particle Analyzer (Beckmann Coulter). Result:Uncoated cpTi, plain chitosan and chitosan coatings with CaP-0%Ag particles had minimal effect on viability of bacteria (Figure 1). There was a significant and dose-related decrease in viability of all bacteria with increasing Ag content on CaP nanoparticles with the CaP-50%Ag particles having the largest antibacterial properties (p<0.05). There were some differences in the sensitivity of bacteria to the coatings with S. epidermidis showing the highest sensitivity. Figure1: Viability of bacteria on chitosan with CaP- Ag coatings The total loading and percent release of protein was not different for the different CaP-Ag particles (Figure 2). This may be due to the similarly large negative Zeta potential of the particles (Table). Protein release pattern was also similar for the different CaP-Ag particles showing an initial burst release followed by a sustained release of approximately10 ng/µl from day 3 to 21. Figure2: Protein release from CaP- Ag particles in PBS Discussion: There was no difference in the viability of the fibroblasts on the uncoated cpTi, plain chitosan and chitosan coatings with CaP-0%Ag particles. However, cell viability was reduced 100-fold on all chitosan coatings incorporating CaP-Ag particles regardless of the %Ag in the particles (data not shown). Part of reduced viability of the fibroblasts may be due to early release of Ag from particles due to the acetic acid used in the coating process. Previous studies showed that CaP-Ag particles alone had little effect on cell viability.[1] Conclusion: Increasing concentration of Ag in CaP particles in chitosan coatings exhibited a dose dependent antibacterial effect on 5 implant pathogens in vitro. However, low cell viability to CaP-Ag particles in the coatings needs to be addressed. The CaP-Ag particles exhibited high protein loading and sustained protein release profile that may be advantageous for the local delivery of growth factors or other agents that require low and extended release profiles. FedEx Institute of Technology, Memphis USA

Does Platelet-Rich Plasma Increase Tendon Metabolism?

Acute and overuse tendon disorders are frequently observed in the middle-aged active population. Tendon overuse injuries are currently designated as "tendinopathy". Histopathological studies have shown that chronic tendinopathy is frequently characterised by degenerative changes, such as decreased organisation of collagen, altered cell distribution and neovascularisation. In the recent years, scientific research and technology in the field of regenerative medicine has provided a new perspectives on managing chronic tendinopathy. An initiation of tissue healing can be attempted by local delivery of growth factors. Nowadays, platelet-rich plasma (PRP) is a commonly applied approach to achieve this. Platelet degranulation leads to a release of various growth factors and cytokines. There is a classification system to define the different forms of PRP. In the past decade, a number of studies have been published on the effects of PRP in different basic science studies. These studies suggest that PRP modulates some aspects of tendon metabolic activity. This is one of the reasons why PRP is increasingly used by many clinicians as treatment option for tendinopathy in daily clinical practice. There is, however, evidence from the literature that it does not lead to improved outcome on imaging findings and on patient-reported outcomes. This questions the role of PRP injections as regular treatment for tendinopathy. Moreover, it results in a broader discussion on the required effects that need to occur for tendon healing and symptom relieve.