Balancing biological and biomechanical performance in intervertebral disc repair: a systematic review of injectable cell delivery biomaterials

Discogenic back pain is a common condition without approved intervertebral disc (IVD) repair therapies. Cell delivery using injectable biomaterial carriers offers promise to restore disc height and biomechanical function, while providing a functional niche for delivered cells to repair degenerated tissues. This systematic review advances the injectable IVD cell delivery biomaterials field by characterising its current state and identifying themes of promising strategies. Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines were used to screen the literature and 183 manuscripts met the inclusion criteria. Cellular and biomaterial inputs, and biological and biomechanical outcomes were extracted from each study. Most identified studies targeted nucleus pulposus (NP) repair. No consensus exists on cell type or biomaterial carrier, yet most common strategies used mesenchymal stem cell (MSC) delivery with interpenetrating network/co-polymeric (IPN/CoP) biomaterials composed of natural biomaterials. All studies reported biological outcomes with about half the studies reporting biomechanical outcomes. Since the IVD is a load-bearing tissue, studies reporting compressive and shear moduli were analysed and two major themes were found. First, a competitive balance, or ‘seesaw’ effect, between biomechanical and biological performance was observed. Formulations with higher moduli had inferior cellular performance, and vice versa. Second, several low-modulus biomaterials had favourable biological performance and matured throughout culture duration with enhanced extracellular matrix synthesis and biomechanical moduli. Findings identify an opportunity to develop next-generation biomaterials that provide high initial biomechanical competence to stabilise and repair damaged IVDs with a capacity to promote cell function for long-term healing.

Intervertebral Disc Repair: Current Concepts

Study Design: Review article. Objective: A review of the literature on current strategies utilized in intervertebral regeneration and repair efforts. Methods: A review of the literature and analysis of the data to provide an updated review on current concepts of intervertebral disc repair and regeneration efforts. Results: Multiple regenerative strategies for intervertebral disc regeneration are being employed to reduce pain and improve quality of life. Current promising strategies include molecular therapy, gene therapy, cell-based therapy, and augmentation with biomaterials. Multiple clinical trials studying biologic, cell-based, and scaffold-based injectable therapies are currently being investigated. Conclusion: Low back pain due to intervertebral disc disease represents a significant health and societal burden. Current promising strategies include molecular therapy, gene therapy, cell-based therapy, and augmentation with biomaterials. To date, there are no Food and Drug Administration–approved intradiscal therapies for discogenic back pain, and there are no large randomized trials that have shown clinically significant improvement with any investigational regenerative treatment. Multiple clinical trials studying biologic, cell-based, or scaffold-based injectable therapies are being currently investigated.

Intervertebral Disc Nucleus Repair: Hype or Hope?

Chronic back pain is a common disability, which is often accredited to intervertebral disc degeneration. Gold standard interventions such as spinal fusion, which are mainly designed to mechanically seal the defect, frequently fail to restore the native biomechanics. Moreover, artificial implants have limited success as a repair strategy, as they do not alter the underlying disease and fail to promote tissue integration and subsequent native biomechanics. The reported high rates of spinal fusion and artificial disc implant failure have pushed intervertebral disc degeneration research in recent years towards repair strategies. Intervertebral disc repair utilizing principles of tissue engineering should theoretically be successful, overcoming the inadequacies of artificial implants. For instance, advances in the development of scaffolds aided with cells and growth factors have opened up new possibilities for repair strategies. However, none has reached the stage of clinical trials in humans. In this review, we describe the hitches encountered in the musculoskeletal field and summarize recent advances in designing tissue-engineered constructs for promoting nucleus pulposus repair. Additionally, the review focuses on the effect of biomaterial aided with cells and growth factors on achieving effective functional reparative potency, highlighting the ways to enhance the efficacy of these treatments.