Biomaterial Delivery Systems Research Articles

Cutting-Edge Biomaterials in Intervertebral Disc Degeneration Tissue Engineering.

Intervertebral disc degeneration (IVDD) stands as the foremost contributor to low back pain (LBP), imposing a substantial weight on the world economy. Traditional treatment modalities encompass both conservative approaches and surgical interventions; however, the former falls short in halting IVDD progression, while the latter carries inherent risks. Hence, the quest for an efficacious method to reverse IVDD onset is paramount. Biomaterial delivery systems, exemplified by hydrogels, microspheres, and microneedles, renowned for their exceptional biocompatibility, biodegradability, biological efficacy, and mechanical attributes, have found widespread application in bone, cartilage, and various tissue engineering endeavors. Consequently, IVD tissue engineering has emerged as a burgeoning field of interest. This paper succinctly introduces the intervertebral disc (IVD) structure and the pathophysiology of IVDD, meticulously classifies biomaterials for IVD repair, and reviews recent advances in the field. Particularly, the strengths and weaknesses of biomaterials in IVD tissue engineering are emphasized, and potential avenues for future research are suggested.

Application of Antioxidant Compounds in Bone Defect Repair.

Bone defects caused by trauma, tumor resection, and infections are significant clinical challenges. Excessive reactive oxygen species (ROS) usually accumulate in the defect area, which may impair the function of cells involved in bone formation, posing a serious challenge for bone repair. Due to the potent ROS scavenging ability, as well as potential anti-inflammatory and immunomodulatory activities, antioxidants play an indispensable role in the maintenance and protection of bone health and have gained increasing attention in recent years. This narrative review aims to give an overview of the main research directions on the application of antioxidant compounds in bone defect repair over the past decade. In addition, the positive effects of various antioxidants and their biomaterial delivery systems in bone repair are summarized to provide new insights for exploring antioxidant-based strategies for bone defect repair.

De Novo Self-Assembling Peptides Mediate the Conversion of Temozolomide and Delivery of a Model Drug into Glioblastoma Multiforme Cells

Glioblastoma multiforme (GBM) is the most aggressive central nervous system tumor, and standard treatment, including surgical resection, radiation, and chemotherapy, has not significantly improved patient outcomes over the last 20 years. Temozolomide (TMZ), the prodrug most commonly used to treat GBM, must pass the blood–brain barrier and requires a basic pH to convert to its active form. Due to these barriers, less than 30% of orally delivered TMZ reaches the central nervous system and becomes bioactive. In this work, we have developed a novel biomaterial delivery system to convert TMZ to its active form and that shows promise for intracellular TMZ delivery. Self-assembling peptides were characterized under several different assembly conditions and evaluated for TMZ loading and conversion. Both solvent and method of assembly were found to affect the supramolecular and secondary structure of peptide assemblies. Additionally, as peptides degraded in phosphate-buffered saline, TMZ was rapidly converted to its active form. This work demonstrates that peptide-based drug delivery systems can effectively create a local stimulus during drug delivery while remaining biocompatible. This principle could be used in many future biomedical applications in addition to cancer treatment, such as wound healing and regenerative medicine.

Hydrogel-Embedded Poly(Lactic-co-Glycolic Acid) Microspheres for the Delivery of hMSC-Derived Exosomes to Promote Bioactive Annulus Fibrosus Repair.

ObjectiveIntervertebral disk degeneration is a prevalent postoperative complication after discectomy, underscoring the need to develop preventative and bioactive treatment strategies that decelerate degeneration and seal annulus fibrosus (AF) defects. Human mesenchymal stem cell–derived exosomes (MSC-Exos) hold promise for cell-free bioactive repair; however, their ability to promote AF repair is poorly understood. The objective of this study was to evaluate the ability of MSC-Exos to promote endogenous AF repair processes and integrate MSC-Exos within a biomaterial delivery system.DesignWe characterize biophysical and biochemical properties of normoxic (Nx) and hypoxic (Hx) preconditioned MSC-Exos from young, healthy donors and examine their effects on AF cell proliferation, migration, and gene expression. We then integrate a poly(lactic-co-glycolic acid) microsphere (PLGA µSphere) delivery platform within an interpenetrating network hydrogel to facilitate sustained MSC-Exo delivery.ResultsHx MSC-Exos led to a more robust response in AF cell proliferation and migration than Nx MSC-Exos and was selected for a downstream protection experiment. Hx MSC-Exos maintained a healthy AF cell phenotype under a TNFα challenge in vitro and attenuated catabolic responses. In all functional assays, AF cell responses were more sensitive to Hx MSC-Exos than Nx MSC-Exos. PLGA µSpheres released MSC-Exos over a clinically relevant timescale without affecting hydrogel modulus or pH upon initial embedment and µSphere degradation.ConclusionsThis MSC-Exo treatment strategy may offer benefits of stem cell therapy without the need for exogenous stem cell transplantation by stimulating cell proliferation, promoting cell migration, and protecting cells from the degenerative proinflammatory microenvironment.

Advances in Stem Cell Therapies for Rotator Cuff Injuries.

Rotator cuff injury is a common upper extremity musculoskeletal disease that may lead to persistent pain and functional impairment. Despite the clinical outcomes of the surgical procedures being satisfactory, the repair of the rotator cuff remains problematic, such as through failure of healing, adhesion formation, and fatty infiltration. Stem cells have high proliferation, strong paracrine action, and multiple differentiation potential, which promote tendon remodeling and fibrocartilage formation and increase biomechanical strength. Additionally, stem cell-derived extracellular vesicles (EVs) can increase collagen synthesis and inhibit inflammation and adhesion formation by carrying regulatory proteins and microRNAs. Therefore, stem cell-based therapy is a promising therapeutic strategy that has great potential for rotator cuff healing. In this review, we summarize the advances of stem cells and stem cell-derived EVs in rotator cuff repair and highlight the underlying mechanism of stem cells and stem cell-derived EVs and biomaterial delivery systems. Future studies need to explore stem cell therapy in combination with cellular factors, gene therapy, and novel biomaterial delivery systems.

Altering Antigen Charge to Control Self-Assembly and Processing of Immune Signals During Cancer Vaccination.

Biomaterial delivery systems offer unique potential to improve cancer vaccines by offering targeted delivery and modularity to address disease heterogeneity. Here, we develop a simple platform using a conserved human melanoma peptide antigen (Trp2) modified with cationic arginine residues that condenses an anionic toll-like receptor agonist (TLRa), CpG, into polyplex-like nanoparticles. We reasoned that these structures could offer several useful features for immunotherapy – such as tunable loading, co-delivery of immune cues, and cargo protection – while eliminating the need for synthetic polymers or other complicating delivery systems. We demonstrate that Trp2/CpG polyplexes can readily form over a range of Trp2:CpG ratios and improve antigen uptake by primary antigen presenting cells. We show antigen loading can be tuned by interchanging Trp2 peptides with defined charges and numbers of arginine residues. Notably, these polyplexes with greater antigen loading enhance the functionality of Trp-2 specific T cells and in a mouse melanoma model, decrease tumor burden and improve survival. This work highlights opportunities to control the biophysical properties of nanostructured materials built from immune signals to enhance immunotherapy, without the added complexity or background immune effects often associated with synthetic carriers.

Impact of Release Kinetics on Efficacy of Locally Delivered Parathyroid Hormone for Bone Regeneration Applications.

Characterizing the release profile for materials-directed local delivery of bioactive molecules and its effect on bone regeneration is an important step to improve our understanding of, and ability to optimize, the bone healing response. This study examined the local delivery of parathyroid hormone (PTH) using a thiol-ene hydrogel embedded in a porous poly(propylene fumarate) (PPF) scaffold for bone regeneration applications. The aim of this study was to characterize the degradation-controlled in vitro release kinetics of PTH from the thiol-ene hydrogels, in vivo hydrogel degradation in a subcutaneous implant model, and bone healing in a rat critical size bone defect. Tethering PTH to the hydrogel matrix eliminated the early timepoint burst release that was observed in previous in vitro work where PTH was free to diffuse out of the matrix. Only 8% of the tethered PTH was released from the hydrogel during the first 2 weeks, but by day 21, 80% of the PTH was released, and complete release was achieved by day 28. In vivo implantation revealed that complete degradation of the hydrogel alone occurred by day 21; however, when incorporated in a three-dimensional printed osteoconductive PPF scaffold, the hydrogel persisted for >56 days. Treatment of bone defects with the composite thiol-ene hydrogel-PPF scaffold, delivering either 3 or 10 μg of tethered PTH 1-84, was found to increase bridging of critical size bone defects, whereas treatment with 30 μg of tethered PTH resulted in less bone ingrowth into the defect area. Continued development of this biomaterial delivery system for PTH could lead to improved therapies for treatment of nonunion fractures and critical size bone defects.

Biomaterial Based Strategies for Engineering New Lymphatic Vasculature.

The lymphatic system is essential for tissue regeneration and repair due to its pivotal role in resolving inflammation, immune cell surveillance, lipid transport, and maintaining tissue homeostasis. Loss of functional lymphatic vasculature is directly implicated in a variety of diseases, including lymphedema, obesity, and the progression of cardiovascular diseases. Strategies that stimulate the formation of new lymphatic vessels (lymphangiogenesis) could provide an appealing new approach to reverse the progression of these diseases. However, lymphangiogenesis is relatively understudied and stimulating therapeutic lymphangiogenesis faces challenges in precise control of lymphatic vessel formation. Biomaterial delivery systems could be used to unleash the therapeutic potential of lymphangiogenesis for a variety of tissue regenerative applications due to their ability to achieve precise spatial and temporal control of multiple therapeutics, direct tissue regeneration, and improve the survival of delivered cells. In this review, the authors begin by introducing therapeutic lymphangiogenesis as a target for tissue regeneration, then an overview of lymphatic vasculature will be presented followed by a description of the mechanisms responsible for promoting new lymphatic vessels. Importantly, this work will review and discuss current biomaterial applications for stimulating lymphangiogenesis. Finally, challenges and future directions for utilizing biomaterials for lymphangiogenic based treatments are considered.

Iloprost-treated dendritic cells promote antigen-specific regulatory T cell differentiation in mice

Abstract Iloprost, a stable prostaglandin I2 (PGI2) analog, can inhibit allergic inflammation in an OVA-induced asthma model via inhibition of airway dendritic cell (DC) function. However, the underlying mechanism of PGI2 signaling-mediated immunosuppression remains unclear. This study explored whether iloprost-treated DCs can suppress inflammation by promoting antigen-specific regulatory T cell (Treg) differentiation. We established an allergic lung inflammation model using a hydrogel biomaterial delivery system and observed that iloprost significantly suppressed OVA-induced Th2 lung inflammation and increased the frequency of OVA-specific Tregs in vivo. We further observed that iloprost-treated DCs displayed tolerogenic characteristics, including low inflammatory cytokine (IL-12p70, TNF-α, IL-6, IL-23) expression levels, high anti-inflammatory cytokine (IL-10) production, and a semimature phenotype. In addition, iloprost-treated DCs increased OVA-specific CD4+Foxp3+ T cell differentiation from naïve T cells in vitro and in vivo. Blocking experiments showed that iloprost-treated DCs promoted Treg differentiation, at least in part, through PD-L1. Furthermore, iloprost treatment suppressed DC-mediated airway inflammation and increased the frequency of OVA-specific Tregs through PD-L1 in vivo. Taken together, these results show that PGI2 signaling in DCs may lead to immune tolerance, suggesting that the PGI2 analog has the potential to be applied therapeutically for tolerogenic DC immunotherapy in autoimmune diseases or allergic asthma.

Dendritic cells treated with a prostaglandin I2 analog, iloprost, promote antigen-specific regulatory T cell differentiation in mice

Iloprost, a stable prostaglandin I2 (PGI2) analog, can inhibit allergic inflammation in an ovalbumin (OVA)-induced asthma model via inhibition of airway dendritic cell (DC) function. However, the underlying mechanism of PGI2 signaling-mediated immunosuppression remains unclear. This study explored whether iloprost-treated DCs can suppress inflammation by promoting antigen-specific regulatory T cell (Treg) differentiation through PGI2-G-protein-coupled receptor (IP). We established an allergic lung inflammation model using a hydrogel biomaterial delivery system and observed that iloprost significantly suppressed OVA-induced Th2 lung inflammation and increased the frequency of OVA-specific Tregs in vivo. We further observed that iloprost-treated DCs displayed tolerogenic characteristics, including low inflammatory cytokine (IL-12, TNF-α, IL-6, IL-23) expression levels, high anti-inflammatory cytokine (IL-10) production, and a semimature phenotype. In addition, iloprost-treated DCs increased OVA-specific CD4+Foxp3+ T cell differentiation from naïve T cells in an IP-dependent pathway in vitro and in vivo. Blocking experiments showed that iloprost-treated DCs promoted Treg differentiation, at least in part, through programmed death ligand 1 (PD-L1), whereas iloprost-induced PD-L1 expression in DCs was through the IP receptor. Furthermore, iloprost treatment suppressed DC-mediated airway inflammation and increased the frequency of OVA-specific Tregs through PD-L1 in vivo. Taken together, these results show that PGI2-IP signaling mediated by iloprost in DCs may lead to immune tolerance, suggesting that the PGI2 analog has the potential to be applied therapeutically for tolerogenic DC immunotherapy in autoimmune diseases or allergic asthma.

Harnessing the Potential of Biomaterials for Brain Repair after Stroke

Stroke is a devastating disease for which no clinical treatment exists to regenerate lost tissue. Strategies for brain repair in animal models of stroke include the delivery of drug or cell-based therapeutics; however, the complex anatomy and functional organization of the brain presents many challenges. Biomaterials may alleviate some of these challenges by providing a scaffold, localizing the therapy to the site of action, and/or modulating cues to brain cells. Here, the challenges associated with delivery of therapeutics to the brain and the biomaterial strategies used to overcome these challenges are described. For example, innovative hydrogel delivery systems have been designed to provide sustained trophic factor delivery for endogenous repair and to support transplanted cell survival and integration. Novel treatments, such as electrical stimulation of transplanted cells and the delivery of factors for the direct reprogramming of astrocytes into neurons, may be further enhanced by biomaterial delivery systems. Ultimately, improved clinical translation will be achieved by combining clinically relevant therapies with biomaterials strategies.

Bioactive glasses as delivery systems for antimicrobial agents.

Most biomaterial-associated infections are caused by opportunistic pathogens and bacteria that are regularly found within the microflora of the implant site. In addition, a biomaterial implant or device remains at risk of infection by hematogenous spread of bacteria disseminated from infections elsewhere in the body or from infected peri-implant tissue in revision surgery. The resulting infections are frequently accompanied by patient morbidity and discomfort and can lead to surgical replacement of the implant after lengthy, unsuccessful attempts to mitigate infections with antibiotic treatments. Therefore, extensive study is aiming to find new infection-resistant antimicrobial biomaterials and coatings for implants and devices to effectively reduce the incidence of biomaterial-associated infections. An overview of the invitro and invivo antimicrobial efficacies of the numerous biomaterials currently available is beyond the scope of this review. Herein, we provide a comprehensive review of bioactive glasses as biomaterial delivery systems for antimicrobial agents.

RETRACTED: Recent advances in cardiac regeneration: Stem cell, biomaterial and growth factors.

Myocardial infarction has been reported to be responsible for about 7.3 million deaths each year globally. Present treatments for myocardial infarction have been more palliative rather than curative. Over the past few years, stem cells have demonstrated its potency in regenerating damaged cardiac tissue, especially after myocardial infarction. However, limited short half-life of the protein and cell therapy and low transplanted cell survival rate as demonstrated via several clinical trials have lead to development of more potent and novel delivery systems like biomaterial delivery system and the use of various growth factors. In this review, we will be enumerating and discussing the recent advances in cardiac regeneration with focus on stem cell, biomaterial and growth factors.

Drug delivery systems for wound healing.

Protein, gene, and small molecule therapies hold great potential for facilitating comprehensive tissue repair and regeneration. However, their clinical value will rely on effective delivery systems which maximize their therapeutic benefit. Significant advances have been made in recent years towards biomaterial delivery systems to satisfy this clinical need. Here we summarize the most outstanding advances in drug delivery technology for cutaneous wound healing.

Biocompatibility of a coacervate-based controlled release system for protein delivery to the injured spinal cord

The efficacy of protein-based therapies for treating injured nervous tissue is limited by the short half-life of free proteins in the body. Affinity-based biomaterial delivery systems provide sustained release of proteins, thereby extending the efficacy of such therapies. Here, we investigated the biocompatibility of a novel coacervate delivery system based on poly(ethylene argininylaspartate diglyceride) (PEAD) and heparin in the damaged spinal cord. We found that the presence of the [PEAD:heparin] coacervate did not affect the macrophage response, glial scarring or nervous tissue loss, which are hallmarks of spinal cord injury. Moreover, the density of axons, including serotonergic axons, at the injury site and the recovery of motor and sensorimotor function were comparable in rats with and without the coacervate. These results revealed the biocompatibility of our delivery system and supported its potential to deliver therapeutic proteins to the injured nervous system.

Thermally Triggered Injectable Hydrogel Carrier System for Mesenchymal Stem Cell Delivery to Promote Intervertebral Disc Regeneration

Introduction Instability of the motion segment as a result of intervertebral disc (IVD) degeneration is well known as a major cause of low back pain. Several tissue engineering and stem cell approaches have been investigated to attempt to regenerate the degenerate IVD. However, many of the proposed therapies would entail lengthy/risky operations to “implant” the tissue regeneration scaffold. Our vision is to develop a novel, injectable biomaterial delivery system which can deliver mesenchymal stem cells (MSCs) to the degenerate nucleus pulposus (NP) to stimulate regeneration, together with inhibitors of degeneration if required and provide mechanical support to the motion segment enabling regeneration to take place. Materials and Methods Here, we investigated a novel hydrogel system, which can be maintained as a liquid ex vivo and can be injected into the IVD where body temperature triggers in situ solidification. Human MSCs were incorporated into hydrogel systems and cell viability, migration characteristics, SEM, gene expression for NP markers, and matrix production investigated to determine differentiation capacity of incorporated MSCs. Mechanical properties of hydrogel systems were determined using dynamic mechanical analysis and compared with native NP tissue. Microparticles incorporation to provide delivery of inhibitors of degeneration were also investigated. Results Viability of MSCs was maintained within hydrogel systems for the 6 weeks investigated, where they were shown to migrate through the hydrogel system, deposit matrix within and differentiate toward NP cells with a switch in matrix gene expression from collagen type I to type II, and deposition of GAGs with immunopositivity seen for aggrecan following 4 weeks in culture. DMA analysis demonstrated hydrogel systems containing 10% hyaluronic acid displayed similar mechanical properties to native NP cells. Hydrogel systems were injected via 26-gauge needles into collagenase digested bovine caudal discs, which was maintained during loading of the bovine motion segments. In addition, microparticles were successfully incorporated into hydrogel systems in the liquid state before thermal triggered solidification. Conclusion Here, we have developed a hydrogel system with the potential to deliver MSCs via minimally invasive injection using small bore needles which decreases the chance of inducing damage to the annulus fibrosus. Hydrogel systems were nontoxic, support MSC growth and differentiation, and show potential to provide mechanical support to the motion segment while regeneration takes place. Such a therapy combined with inhibition of degeneration could show great promise for early and mid-stages of degeneration. Disclosure of Interest None declared

Monitoring the biological effect of BMP-2 release on bone healing by PET/CT

Bone morphogenetic protein-2 (BMP-2) releasing scaffolds are routinely used in bone tissue engineering to accelerate regeneration. Thus, assessing growth factor activity, and tissue regeneration around a biomaterial delivery system is extremely important to optimize the stages of bone healing. Such assessment commonly relies on histology. A non-invasive method would allow longitudinal monitoring of the regeneration process. The present study sought to explore the feasibility of Positron Emission Tomography (PET) as a non-invasive method to monitor the osteogenic potential of a BMP-2 releasing calcium phosphate cement (CPC) bone substitute. In a calvarial defect model in rats, 18F-Fluoride PET was used to quantify 18F-Fluoride uptake around the BMP-2/CPC material. As controls, non-loaded porous CPC, dense CPC and autograft samples were used. PET was performed every two weeks, during a period of 8weeks post-implantation. In parallel, computed tomography (CT) imaging was performed for anatomical reference. Four specimens were evaluated per group per time point. The highest 18F-Fluoride signal intensity was measured in the BMP-2 group (approximately 5 times higher than the baseline value), followed by the controls in the order, from high to low, porous, dense and autograft. The same trend was maintained during the entire experimental period. Histology and measurements of the bone volume percentage confirmed the significantly higher new bone formation in the BMP-2 releasing group (about 25%), compared to the controls. Moreover, 18F-Fluoride PET uptake showed a statistically significant positive correlation (r=0.6038, P=0.0171) with the newly formed bone volume. In conclusion, our results support the use of a PET/CT method for the longitudinal monitoring of BMP-2 releasing scaffolds, in vivo.

Recovery from hind limb ischemia enhances rhBMP-2-mediated segmental bone defect repair in a rat composite injury model

Although severe extremity trauma is often inclusive of skeletal and vascular damage in combination, segmental bone defect repair with concomitant vascular injury has yet to be experimentally investigated. To this end, we developed a novel rat composite limb injury model by combining a critically-sized segmental bone defect with surgically-induced hind limb ischemia (HLI). Unilateral 8mm femoral defects were created alone (BD) or in combination with HLI (BD+HLI), and all defects were treated with rhBMP-2 via a hybrid biomaterial delivery system. Based on reported clinical and experimental observations on the importance of vascular networks in bone repair, we hypothesized that HLI would impair bone regeneration. Interestingly, the BD+HLI group displayed improved radiographic bridging, and quantitative micro-CT analysis revealed enhanced bone regeneration as early as week 4 (p<0.01) that was sustained through week 12 (p<0.001) and confirmed histologically. This effect was observed in two independent studies and at two different doses of rhBMP-2. Micro-CT angiography was used to quantitatively evaluate vascular networks at week 12 in both the thigh and the regenerated bone defect. No differences were found between groups in total blood vessel volume in the thigh, but clear differences in morphology were present as the BD+HLI group possessed a more interconnected network of smaller diameter vessels (p<0.001). Accordingly, while the overall thigh vessel volume was comparable between groups, the contributions to vessel volume based on vessel diameter differed significantly. Despite this evidence of a robust neovascular response in the thigh of the BD+HLI group, differences were not observed between groups for bone defect blood vessel volume or morphology. In total, our results demonstrate that a transient ischemic insult and the subsequent recovery response to HLI significantly enhanced BMP-2-mediated segmental bone defect repair, providing additional complexity to the relationship between vascular tissue networks and bone healing. Ultimately, a better understanding of the coupling mechanisms may reveal important new strategies for promoting bone healing in challenging clinical scenarios.

Delivery of Growth Factors for Tissue Regeneration and Wound Healing

Growth factors are soluble secreted proteins capable of affecting a variety of cellular processes important for tissue regeneration. Consequently, the self-healing capacity of patients can be augmented by artificially enhancing one or more processes important for healing through the application of growth factors. However, their application in clinics remains limited due to lack of robust delivery systems and biomaterial carriers. Interestingly, all clinically approved therapies involving growth factors utilize some sort of a biomaterial carrier for growth factor delivery. This suggests that biomaterial delivery systems are extremely important for successful usage of growth factors in regenerative medicine. This review outlines the role of growth factors in tissue regeneration, and their application in both pre-clinical animal models of regeneration and clinical trials is discussed. Additionally, current status of biomaterial substrates and sophisticated delivery systems such as nanoparticles for delivery of exogenous growth factors and peptides in humans are reviewed. Finally, issues and possible future research directions for growth factor therapy in regenerative medicine are discussed.

Injectable Hydrogel for Mesenchymal Stem Cell and Protein Delivery to the Degenerate Intervertebral Disk

IntroductionInstability of the motion segment as a result of intervertebral disk degeneration is well known as a major cause of lower back pain. In recent years, a number of tissue engineering and stem cell approaches have been investigated in an attempt to regenerate the degenerate IVD. However, many of the proposed therapies would entail lengthy/risky operations to “implant” the tissue regeneration scaffold. Our vision is to develop a novel, injectable biomaterial delivery system which will deliver mesenchymal stem cells (MSCs) to the degenerate nucleus pulposus (NP) to stimulate regeneration, it will also deliver inhibitors of degeneration, while providing mechanical support to the motion segment during this process. Here, we investigate a novel hydrogel system, which can be maintained as a liquid ex vivo and can potentially be injected into the IVD where it will gel in situ. Materials and MethodsHuman MSCs were labelled with a green fluorescent membrane dye to enable visualization before culture within or on hydrogel systems. Effects on cell viability, migration characteristics, matrix production, and differentiation capacity of MSCs were investigated. Additionally, the feasibility of injection through narrow bore needles, into a model degenerate IVDs using collagenase digested bovine caudal disks, was investigated. In addition, effects of the degenerate tissue niche were investigated on MSC behavior to determine whether inhibitors of degeneration would need to be codelivered. MSC were treated with IL-1beta and induction of matrix degrading enzymes and expression of IL-1 family genes investigated. ResultsViability of MSCs were unaffected by coculture with hydrogel systems, or following growth on or in such systems over time periods of up to 6 weeks. MSCs adhered to the hydrogel systems and were shown to migrate through the system when applied to the upper surface of a preset hydrogel system. Additionally, MSCs mixed with liquid hydrogel before setting and maintained at 37°C for up to 4 weeks, survived, proliferated, synthesized collagen type II and aggrecan matrix (Fig. 1) similar to that seen within the NP including aggrecan, gene expression analysis demonstrated expression of key genes. Liquid hydrogel was successfully injected into degenerated bovine disks where it fill both the large voids and the smaller branches induced by collagenase digestion. MSC treated with IL-1 induced expression of IL-1, IL-1Ra, MMP3 and MMP13 were also upregulated. IL-Ra was successfully incorporated into the hydrogel system. ConclusionWe have developed a hydrogel system with the potential to deliver MSCs via minimally invasive injection via narrow bore needles, decreasing the risk of damage to the annulus fibrosus. The system is nontoxic, supports MSC growth, differentiation and shows potential to provide mechanical support to the motion segment while regeneration takes place. Such a therapy combined with inhibition of degeneration shows immense potential for early and midstages of spinal degeneration.I confirm having declared any potential conflict of interest for all authors listed on this abstractYesDisclosure of InterestNone declared