Infrapatellar Fat Pad Stem Cells: From Developmental Biology to Cell Therapy

The ideal cell type to be used for cartilage therapy should possess a proven chondrogenic capacity, not cause donor-site morbidity, and should be readily expandable in culture without losing their phenotype. There are several cell sources being investigated to promote cartilage regeneration: mature articular chondrocytes, chondrocyte progenitors, and various stem cells. Most recently, stem cells isolated from joint tissue, such as chondrogenic stem/progenitors from cartilage itself, synovial fluid, synovial membrane, and infrapatellar fat pad (IFP) have gained great attention due to their increased chondrogenic capacity over the bone marrow and subcutaneous adipose-derived stem cells. In this review, we first describe the IFP anatomy and compare and contrast it with other adipose tissues, with a particular focus on the embryological and developmental aspects of the tissue. We then discuss the recent advances in IFP stem cells for regenerative medicine. We compare their properties with other stem cell types and discuss an ontogeny relationship with other joint cells and their role on in vivo cartilage repair. We conclude with a perspective for future clinical trials using IFP stem cells

Ultrasound-triggered disruption and self-healing of reversibly cross-linked hydrogels for drug delivery and enhanced chemotherapy

Foldable photoelectronics and muscle-like transducers require highly stretchable and transparent electrical conductors. Some conducting oxides are transparent, but not stretchable. Carbon nanotube films, graphene sheets and metal-nanowire meshes can be both stretchable and transparent, but their electrical resistances increase steeply with strain <100%. Here we present highly stretchable and transparent Au nanomesh electrodes on elastomers made by grain boundary lithography. The change in sheet resistance of Au nanomeshes is modest with a one-time strain of ~160% (from ~21 Ω per square to ~67 Ω per square), or after 1,000 cycles at a strain of 50%. The good stretchability lies in two aspects: the stretched nanomesh undergoes instability and deflects out-of-plane, while the substrate stabilizes the rupture of Au wires, forming distributed slits. Larger ratio of mesh-size to wire-width also leads to better stretchability. The highly stretchable and transparent Au nanomesh electrodes are promising for applications in foldable photoelectronics and muscle-like transducers.Engineering and Applied Science

Physical structuring of injectable polymeric systems to controllably deliver nanosized extracellular vesicles

Extracellular vesicles (EVs) are emerging as a promising alternative approach to cell‐therapies. However, to realize the potential of these nanoparticles as new regenerative tools, healthcare materials that address the current limitations of systemic administration need to be developed. Here, two technologies for controlling the structure of alginate based microgel suspensions are used to develop sustained local release of EVs, in vitro. Microparticles formed using a shearing technique are compared to those manufactured using vibrational technology, resulting in either anisotropic sheet‐like or spheroid particles, respectively. EVs harvested from preosteoblasts are isolated using differential ultracentrifugation and successfully loaded into the two systems, while maintaining their structures. Promisingly, in addition to exhibiting even EV distribution and high stability, controlled release of vesicles from both structures is exhibited, in vitro, over the 12 days studied. Interestingly, a significantly greater number of EVs are released from the suspensions formed by shearing (69.9 ± 10.5%), compared to the spheroids (35.1 ± 7.6%). Ultimately, alterations to the hydrogel physical structures have shown to tailor nanoparticle release while simultaneously providing ideal material characteristics for clinical injection. Thus, the sustained release mechanisms achieved through manipulating the formation of such biomaterials provide a key to unlocking the therapeutic potential held within EVs

Physical structuring of injectable polymeric systems to controllably deliver nanosized extracellular vesicles

Extracellular vesicles (EVs) are emerging as a promising alternative approach to cell‐therapies. However, to realize the potential of these nanoparticles as new regenerative tools, healthcare materials that address the current limitations of systemic administration need to be developed. Here, two technologies for controlling the structure of alginate based microgel suspensions are used to develop sustained local release of EVs, in vitro. Microparticles formed using a shearing technique are compared to those manufactured using vibrational technology, resulting in either anisotropic sheet‐like or spheroid particles, respectively. EVs harvested from preosteoblasts are isolated using differential ultracentrifugation and successfully loaded into the two systems, while maintaining their structures. Promisingly, in addition to exhibiting even EV distribution and high stability, controlled release of vesicles from both structures is exhibited, in vitro, over the 12 days studied. Interestingly, a significantly greater number of EVs are released from the suspensions formed by shearing (69.9 ± 10.5%), compared to the spheroids (35.1 ± 7.6%). Ultimately, alterations to the hydrogel physical structures have shown to tailor nanoparticle release while simultaneously providing ideal material characteristics for clinical injection. Thus, the sustained release mechanisms achieved through manipulating the formation of such biomaterials provide a key to unlocking the therapeutic potential held within EVs

Biomaterial based modulation of macrophage polarization: a review and suggested design principles

Macrophages have long been known for their phagocytic capabilities and immune defence; however, their role in healing is being increasingly recognized in recent years due to their ability to polarize into pro-inflammatory and anti-inflammatory phenotypes. Historically, biomaterials were designed to be inert to minimize the host response. More recently, the emergence of tissue engineering and regenerative medicine has led to the design of biomaterials that interact with the host through tailored mechanical, chemical and temporal characteristics. Due to such advances in biomaterial functionality and an improved understanding of macrophage responses to implanted materials, it is now possible to identify biomaterial design characteristics that dictate the host response and contribute to successful tissue integration. Herein, we begin by briefly reviewing macrophage cell origin and the key cytokine/chemokine markers of macrophage polarization and then describe which responses are favorable for both replacement and regenerative biomaterials. The body of the review focuses on macrophage polarization in response to inherent cues directly provided by biomaterials and the consequent cuesthat result from events related to biomaterial implantation. To conclude, a section on potential design principles for both replacement and regenerative biomaterials is presented. An in depth understanding of biomaterial cues to selectively polarize macrophages may prove beneficial in the design of a new generation of ‘immuno-informed’ biomaterials that can positively interact with the immune system to dictate a favorable macrophage response following implantation

Special collection: closing the gaps in skin wound healing

Skin is the largest and most accessible organ in the body and any compromise in its integrity results in a healing cascade. Often, underlying pathologies hamper these cascades. A tissue-engineering approach has the potential to attenuate healing in these compromised wounds. Solutions for dermal wound healing has direct clinical impact in addressing other compromised wounds in other clinical targets where matrix deposition, fibrosis or angiogenesis needs to be modulated

Engineering, science and medicine: transforming healthcare

The treatment of disease is being revolutionised by the increasing use and capabilities of intelligent medical devices. Currently, there is a translational drive from basic research into clinical realisation, with multidisciplinary teams responsible for this synergistic effort. This work is forming the era of biomedical engineering, which is manifested in many aspects of medicine at both the bench and the bedside. Here, we focus on two different categories: imaging and medical robotics; and, tissue engineering. We introduce the underlying tenets on which these fields are built before discussing current research and the possibilities for tomorrow’s practice.</p

The Use of Extracorporeal Shock Wave-Stimulated Periosteal Cells for Orthotopic Bone Generation

The cambium cells of the periosteum, which are known osteoprogenitor cells, have limited suitability for clinical applications of tissue engineering in their native state due to their low cell number (2–5 cells thick). Extracorporeal shock waves (ESWs) have been shown to cause rapid periosteal cambium cell proliferation and subsequent periosteal osteogenesis. This work investigates a novel strategy for orthotopic bone generation: applying ESW therapy as a noninvasive, inexpensive, and rapid method for stimulating cambium cell proliferation, and combining these cells with a bioactive scaffold for bone growth. ESWs applied to the rabbit medial tibia resulted in a significant 2.7-fold increase in cambium cell number and a 4-fold increase in cambium cell thickness at 4 days post-ESW. ESW-stimulated, or nontreated control, periosteal cells were elevated in situ and overlaid on an anorganic bovine bone scaffold to interrogate their ability to form bone. At 2 weeks post-surgery, there was a significant increase in all key outcome variables for the ESW-stimulated group when compared with controls: a 4-fold increase in osseous tissue in the upper half of the scaffold underlying the periosteum; a 12-fold increase in osseous tissue overlying the scaffold; and a 2-fold increase in callus size. These results successfully demonstrated the efficacy of ESW-stimulated periosteum for orthotopic bone generation

DNA Origami: Folded DNA-Nanodevices That Can Direct and Interpret Cell Behavior.

DNA origami is a DNA-based nanotechnology that utilizes programmed combinations of short complementary oligonucleotides to fold a large single strand of DNA into precise 2D and 3D shapes. The exquisite nanoscale shape control of this inherently biocompatible material is combined with the potential to spatially address the origami structures with diverse cargoes including drugs, antibodies, nucleic acid sequences, small molecules, and inorganic particles. This programmable flexibility enables the fabrication of precise nanoscale devices that have already shown great potential for biomedical applications such as: drug delivery, biosensing, and synthetic nanopore formation. Here, the advances in the DNA-origami field since its inception several years ago are reviewed with a focus on how these DNA-nanodevices can be designed to interact with cells to direct or probe their behavior

The economic impact of pressure ulcers among patients in intensive care units : a systematic review

Background: The incidence and prevalence of pressure ulcers in critically ill patients in intensive care units (ICUs) remain high, despite the wealth of knowledge on appropriate prevention strategies currently available. Methods: The primary objective of this systematic review was to examine the economic impact of pressure ulcers (PU) among adult intensive care patients. A systematic review was undertaken, and the following databases were searched; Medline, Embase, CINAHL, and The Cochrane Library. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was used to formulate the review. Quality appraisal was undertaken using the Consensus on Health Economic Criteria (CHEC)-list. Data were extracted using a pre-designed extraction tool, and a narrative analysis was undertaken. Results: Seven studies met the inclusion criteria. Five reported costs associated with the prevention of pressure ulcers and three explored costs of treatment strategies. Four main PU prevention cost items were identified: support surfaces, dressing materials, staff costs, and costs associated with mobilisation. Seven main PU treatment cost items were reported: dressing materials, support surfaces, drugs, surgery, lab tests, imaging, additional stays and nursing care. The overall validities of the studies varied between 37 and 79%, meaning that there is potential for bias within all the included studies. Conclusion: There was a significant difference in the cost of PU prevention and treatment strategies between studies. This is problematic as it becomes difficult to accurately evaluate costs from the existing literature, thereby inhibiting the usefulness of the data to inform practice. Given the methodological heterogeneity among studies, future studies in this area are needed and these should use specific methodological guidelines to generate high-quality health economic studies