New Perspectives in Cell Delivery Systems for Tissue Regeneration: Natural-derived Injectable Hydrogels

Abstract

Natural polymers, because of their biocompatibility, availability, and physico-chemical properties have been the materials of choice for the fabrication of injectable hydrogels for regenerative medicine. In particular, they are appealing materials for delivery systems and provide sustained and controlled release of drugs, proteins, gene, cells, and other active biomolecules immobilized.In this work, the use of hydrogels obtained from natural source polymers as cell delivery systems is discussed. These materials were investigated for the repair of cartilage, bone, adipose tissue, intervertebral disc, neural, and cardiac tissue. Papers from the last ten years were considered, with a particular focus on the advances of the last five years. A critical discussion is centered on new perspectives and challenges in the regeneration of specific tissues, with the aim of highlighting the limits of current systems and possible future advancements.

Advancing the cellular and molecular therapy for intervertebral disc disease

“…For this reason, and because of the potential for tailoring its mechanical and degradation behaviour, HA has widely been considered as biological vehicle for the delivery of therapeutic cells [104].…”

Effect of lactoferrin-impregnated porous poly(lactide-co-glycolide) (PLGA) microspheres on osteogenic differentiation of rabbit adipose-derived stem cells (rADSCs)

“…The main advantage of injectable scaffolds compared to 3D porous scaffolds for orthopedic procedures is that they can be administered using 10-16-gauge needles at the bone defect site [17]. In addition, injectable scaffolds loaded with osteoinductive agents or therapeutic drugs minimize patient discomfort, scarring, operation time, and risk of infections from bone regeneration as a clinical treatment [18]. As injectable scaffolds, microspheres have been used as good delivery vehicles for the sustained release of many kinds of drugs or proteins.…”

The past, present and future in scaffold-based tendon treatments

“…However, direct cell injections have failed to deliver in a consistent manner in humans due to poor cell localisation [218][219][220][221], triggering an extensive investigation into the optimal cell carrier for tendon repair [1]. The ideal carrier system should prevent cell membrane rupture during the injection process; create increased tissue integration through fast in situ self-assembly; facilitate long-term cell survival and functionality maintenance; and allow spatiotemporal release of the cargo [222][223][224][225][226][227][228][229][230][231]. Preclinical data using either collagen [232] or fibrin [233] hydrogels have demonstrated improved mechanical properties, histological scores, tissue integration and restored functionality using TCs and various stem cell populations [234,235], however clinical use of injectable cell/hydrogel systems is still to be realised.…”