Actuation-Mediated Compression of a Mechanoresponsive Hydrogel by Soft Robotics to Control Release of Therapeutic Proteins.

Therapeutic proteins, the fastest growing class of pharmaceuticals, are subject to rapid proteolytic degradation in vivo, rendering them inactive. Sophisticated drug delivery systems that maintain protein stability, prolong therapeutic effects, and reduce administration frequency are urgently required. Herein, a mechanoresponsive hydrogel is developed contained within a soft robotic drug delivery (SRDD) device.

Exploring therapy transport from implantable medical devices using experimentally informed computational methods.

Implantable medical devices that can facilitate therapy transport to localized sites are being developed for a number of diverse applications, including the treatment of diseases such as diabetes and cancer, and tissue regeneration after myocardial infraction. These implants can take the form of an encapsulation device which encases therapy in the form of drugs, proteins, cells, and bioactive agents, in semi-permeable membranes. Such implants have shown some success but the nature of these devices pose a barrier to the diffusion of vital factors, which is further exacerbated upon implantation due to the foreign body response (FBR).

Intermittent actuation attenuates fibrotic behaviour of myofibroblasts.

The foreign body response (FBR) to implanted materials culminates in the deposition of a hypo-permeable, collagen rich fibrotic capsule by myofibroblast cells at the implant site. The fibrotic capsule can be deleterious to the function of some medical implants as it can isolate the implant from the host environment. Modulation of fibrotic capsule formation has been achieved using intermittent actuation of drug delivery implants, however the mechanisms underlying this response are not well understood.

Towards a Whole Sample Imaging Approach Using Diffusion Tensor Imaging to Examine the Foreign Body Response to Explanted Medical Devices.

Analysing the composition and organisation of the fibrous capsule formed as a result of the Foreign Body Response (FBR) to medical devices, is imperative for medical device improvement and biocompatibility. Typically, analysis is performed using histological techniques which often involve random sampling strategies. This method is excellent for acquiring representative values but can miss the unique spatial distribution of features in 3D, especially when analysing devices used in large animal studies.

Design and Verification of a Novel Perfusion Bioreactor to Evaluate the Performance of a Self-Expanding Stent for Peripheral Artery Applications.

Endovascular stenting presents a promising approach to treat peripheral artery stenosis. However, a significant proportion of patients require secondary interventions due to complications such as in-stent restenosis and late stent thrombosis. Clinical failure of stents is not only attributed to patient factors but also on endothelial cell (EC) injury response, stent deployment techniques, and stent design.

Manufacturing, characterization, and degradation of a poly(lactic acid) warp-knitted spacer fabric scaffold as a candidate for tissue engineering applications.

Three-dimensional bioabsorbable textiles represent a novel technology for the manufacturing of tissue engineering scaffolds. In the present study, 3D bioabsorbable poly(lactic acid) (PLA) spacer fabric scaffolds are fabricated by warp-knitting and their potential for tissue engineering is explored . Changes in physical properties and mechanical performance with different heat setting treatments are assessed.

Medical devices, smart drug delivery, wearables and technology for the treatment of Diabetes Mellitus.

Diabetes mellitus refers to a group of metabolic disorders which affect how the body uses glucose impacting approximately 9% of the population worldwide. This review covers the most recent technological advances envisioned to control and/or reverse Type 1 diabetes mellitus (T1DM), many of which will also prove effective in treating the other forms of diabetes mellitus. Current standard therapy for T1DM involves multiple daily glucose measurements and insulin injections.

Assessing the Effects of VEGF Releasing Microspheres on the Angiogenic and Foreign Body Response to a 3D Printed Silicone-Based Macroencapsulation Device.

Macroencapsulation systems have been developed to improve islet cell transplantation but can induce a foreign body response (FBR). The development of neovascularization adjacent to the device is vital for the survival of encapsulated islets and is a limitation for long-term device success. Previously we developed additive manufactured multi-scale porosity implants, which demonstrated a 2.

Developing a morphomics framework to optimize implant site-specific design parameters for islet macroencapsulation devices.

Delivering a clinically impactful cell number is a major design challenge for cell macroencapsulation devices for Type 1 diabetes. It is important to understand the transplant site anatomy to design a device that is practical and that can achieve a sufficient cell dose. We identify the posterior rectus sheath plane as a potential implant site as it is easily accessible, can facilitate longitudinal monitoring of transplants, and can provide nutritive support for cell survival.

A versatile technique for high-resolution three-dimensional imaging of human arterial segments using microcomputed tomography.

Background: Quantitative methods for evaluating microstructure of arterial specimens typically rely on histologic techniques that involve random sampling, which cannot account for the unique spatial distribution of features in three dimensions.

Methods: To overcome this limitation, we demonstrate a nondestructive method for three-dimensional imaging of intact human blood vessels using microcomputed tomography (microCT). Human artery segments were dehydrated and stained in an iodine solution then imaged with a standard laboratory microCT scanner.

The Foreign Body Response to an Implantable Therapeutic Reservoir in a Diabetic Rodent Model.

Advancements in type 1 diabetes mellitus treatments have vastly improved in recent years. The move toward a bioartificial pancreas and other fully implantable systems could help restore patient's glycemic control. However, the long-term success of implantable medical devices is often hindered by the foreign body response.

Additive Manufacturing of Multi-Scale Porous Soft Tissue Implants That Encourage Vascularization and Tissue Ingrowth.

Medical devices, such as silicone-based prostheses designed for soft tissue implantation, often induce a suboptimal foreign-body response which results in a hardened avascular fibrotic capsule around the device, often leading to patient discomfort or implant failure. Here, it is proposed that additive manufacturing techniques can be used to deposit durable coatings with multiscale porosity on soft tissue implant surfaces to promote optimal tissue integration. Specifically, the "liquid rope coil effect", is exploited via direct ink writing, to create a controlled macro open-pore architecture, including over highly curved surfaces, while adapting atomizing spray deposition of a silicone ink to create a microporous texture.

Design Considerations for Macroencapsulation Devices for Stem Cell Derived Islets for the Treatment of Type 1 Diabetes.

Stem cell derived insulin producing cells or islets have shown promise in reversing Type 1 Diabetes (T1D), yet successful transplantation currently necessitates long-term modulation with immunosuppressant drugs. An alternative approach to avoiding this immune response is to utilize an islet macroencapsulation device, where islets are incorporated into a selectively permeable membrane that can protect the transplanted cells from acute host response, whilst enabling delivery of insulin. These macroencapsulation systems have to meet a number of stringent and challenging design criteria in order to achieve the ultimate goal of reversing T1D.

Enhancing delivery of small molecule and cell-based therapies for ovarian cancer using advanced delivery strategies.

Ovarian cancer is the most lethal gynecological malignancy with a global five-year survival rate of 30-50%. First-line treatment involves cytoreductive surgery and administration of platinum-based small molecules and paclitaxel. These therapies were traditionally administered via intravenous infusion, although intraperitoneal delivery has also been investigated.

Pre-culture of mesenchymal stem cells within RGD-modified hyaluronic acid hydrogel improves their resilience to ischaemic conditions.

The incorporation of the RGD peptide (arginine-glycine-aspartate) into biomaterials has been proposed to promote cell adhesion to the matrix, which can influence and control cell behaviour and function. While many studies have utilised RGD modified biomaterials for cell delivery, few have examined its effect under the condition of reduced oxygen and nutrients, as found at ischaemic injury sites. Here, we systematically examine the effect of RGD on hMSCs in hyaluronic acid (HA) hydrogel under standard and ischaemic culture conditions, to elucidate under what conditions RGD has beneficial effects over unmodified HA and its effectiveness in improving cell viability.

Development of a nanomedicine-loaded hydrogel for sustained delivery of an angiogenic growth factor to the ischaemic myocardium.

The 5-year mortality rate for heart failure borders on 50%. The main cause is an ischaemic cardiac event where blood supply to the tissue is lost and cell death occurs. Over time, this damage spreads and the heart is no longer able to pump efficiently.

A bioresorbable biomaterial carrier and passive stabilization device to improve heart function post-myocardial infarction.

The limited regenerative capacity of the heart after a myocardial infarct results in remodeling processes that can progress to congestive heart failure (CHF). Several strategies including mechanical stabilization of the weakened myocardium and regenerative approaches (specifically stem cell technologies) have evolved which aim to prevent CHF. However, their final performance remains limited motivating the need for an advanced strategy with enhanced efficacy and reduced deleterious effects.

An injectable alginate/extra cellular matrix (ECM) hydrogel towards acellular treatment of heart failure.

As treatments for myocardial infarction (MI) continue to improve, the population of people suffering from heart failure (HF) is rising significantly. Novel treatment strategies aimed at achieving long-term functional stabilisation and improvement in heart function post MI include the delivery of biomaterial hydrogels and myocardial matrix-based therapies to the left ventricle wall. Individually alginate hydrogels and myocardial matrix-based therapies are at the most advanced stages of commercial/clinical development for this potential treatment option.

Advanced Material Catheter (AMCath), a minimally invasive endocardial catheter for the delivery of fast-gelling covalently cross-linked hyaluronic acid hydrogels.

Injectable hydrogels that aim to mechanically stabilise the weakened left ventricle wall to restore cardiac function or to deliver stem cells in cardiac regenerative therapy have shown promising data. However, the clinical translation of hydrogel-based therapies has been limited due to difficulties injecting them through catheters. We have engineered a novel catheter, Advanced Materials Catheter (AMCath), that overcomes translational hurdles associated with delivering fast-gelling covalently cross-linked hyaluronic acid hydrogels to the myocardium.

Hydrogels in adipose tissue engineering-Potential application in post-mastectomy breast regeneration.

Current methods of breast reconstruction are associated with significant shortcomings, including capsular contracture, infection, rupture, the need for reoperation in implant-based reconstruction, and donor site morbidity in autologous reconstruction. These limitations result in severe physical and psychological issues for breast cancer patients. Recently, research has moved into the field of adipose tissue engineering to overcome these limitations.

The development and mechanical characterisation of a novel reinforced venous conduit that mimics the mechanical properties of an arterial wall.

Venous grafts have been used to bypass stenotic arteries for many decades. However, this "gold standard" treatment is far from optimal, with long-term vein graft patency rates reported to be as low as 50% at >15 years. These results could be a result of the structural and functional differences of veins compared to arteries.