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

Abstract

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.

From Mechanobiology to Mechanical Repair Strategies: A Bibliometric Analysis of Biomechanical Studies of Intervertebral Discs

“…The second relevant citer provided a systematic review of injectable cell delivery biomaterials used in IVD repair. 36 Therefore, the actual interests of the citing articles were consistent with the suboptimal label of clusters #6, "annulus fibrosus repair".…”

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration

“…NP repair restores the motion characteristics and physical properties of the target segments by NP tissue rehydration or NP replacement [ 6 ]. Biomaterials for NP replacement have focused mainly on injectable synthetic or biologically based hydrogels [ [7] , [8] , [9] ]. These hydrogels are mainly derived from non-degradable polyacrylates and polyacrylamides [ 10 , 11 ] and degradable hyaluronic acid, collagen in the extracellular matrix and chitosan [ 8 , 12 ].…”

Single‐cell RNA‐sequencing atlas of bovine caudal intervertebral discs: Discovery of heterogeneous cell populations with distinct roles in homeostasis

“…The etiology of chronic back pain is multifactorial and complex 3 ; however, 39%–42% of back pain cases involve the intervertebral disc (IVD) 4 . This strong association between IVD pathology and back pain highlights the importance of developing regenerative IVD therapies 5,6 . However, advances in regenerative IVD therapies are limited by a poor understanding of IVD biology and lack of consensus regarding the cell types that support IVD health and homeostasis.…”

“…4 This strong association between IVD pathology and back pain highlights the importance of developing regenerative IVD therapies. 5,6 However, advances in regenerative IVD therapies are limited by a poor understanding of IVD biology and lack of consensus regarding the cell types that support IVD health and homeostasis. This information is critical for developing therapies that can stimulate endogenous cell populations to heal the IVD or choosing appropriate cell sources for exogenous cell delivery strategies.…”