Table 5.

Scaffold-based regeneration of the dentin-pulp complex (cell homing strategies).

Scaffold	Indications/Mechanism/Results	Ref.
Intracanal blood clot	It induces apical bleeding, leading to delivery of SCAP to root canal space; it is an autologous scaffold with growth factors, is clinically efficient, and is economical; and it can be an unstable and unreliable movement of stem cells within the canal space after revascularization.	[88,89,90,91]
Platelet-rich plasma (PRP)	Autologous injectable scaffold: it can be delivered via collagen sponges; platelet elevation results in increased production and secretion of growth factors PDGF, TGF-b, Insulin-like growth factor (IGF), epidermal growth factor (EGF), and epithelial cell growth factor (ECGF), leading to improved angiogenesis and cell proliferation	[88,92]
Alginate	Natural polysaccharides from cell walls and seaweeds: stem cells can be incorporated during scaffold processing; it supports 3-D printing in combination with proteins like DMPs; it includes easy diffusion of nutrients and waste debris due to porous structure; it is highly biocompatible, has low immune reactions, is economic, and is easy to fabricate; and has low mechanical strength of the scaffold when used alone.	[93,94]
Hyaluronic acid (HA)and derivatives	Glycosaminoglycans which mimic ECM components: it interacts with stem cell receptors and drives them towards the area of regeneration; it is shown to have a role in dentin matrix and pulp tissue development; it exhibits good biocompatibility, biodegradability, and bioactivity; HA derivatives induce proangiogenic factors release; it improves stem cell mineralisation and odontogenic differentiation; it has low mechanical strength and needs combination with growth factors to improve regenerative potential; and it may cause hypersensitivity reactions.	[90,94,95,96,97]
Chitosan derivatives	Linear amino polysaccharide mimics ECM structure and composition: it is easy to fabricate, is highly porous, and allows easy migration of cells and growth factors; when fabricated as nanoparticles, it improved properties due to increased surface area, has better mechanical strength, and is resistant to enzymatic degradation; it allows the controlled release of growth factors and improves stem cell or SCAP adhesion, viability, and differentiation; and it is highly biocompatible, has controlled biodegradation, and has low cytotoxicity with antibacterial properties.	[98,99,100]
Gelatin	Consists of proteins from hydrolysis of hard and soft tissue-derived collagen; they are biocompatible and biodegradable, elicits no immune responses, and is cost-efficient; they can be modified with RBDs (receptor binding motifs), which promotes cell attachment and allows chemical modifications to improve the scaffold’s physiochemical properties; it is used as a drug delivery medium or in 2D and 3D cultures; and the use of FGF-2 with gelatin shows the formation of osteo-dentin-like calcified tissue for dentin pulp complex regeneration.	[101,102]
Cellulose	Naturally occurring scaffold obtained from green plants and algae: they are not biodegradable due to the absence of cellulase enzymes in humans; they possess high tensile strength, high crystallinity, fine fibrous structure, and good formability and is biocompatible; they have higher chances of immune response; and they are used mostly in target-specific drug delivery or growth factor release in dental tissue engineering.	[103,104]
Collagen	It is a natural biomaterial, is easily adapted to root canal morphology, and mimics ECM; the most used is type I, suitable for DPSCs proliferation and mineralisation; it is biocompatible, provides bioactivity by facilitating adhesion and attachment of stem cells, and induces signalling pathways that promote differentiation; the highly porous structure allows easy cell seeding for site-specific delivery; and commercially available SynnOss (bovine type 1 collagen) in conjunction with revascularization forms mineralised cementum-like tissues.	[105,106,107,108,109]
Self-assembling peptide hydrogels -Puramatrix	Synthetic, biocompatible, biodegradable, nontoxic, 3D matrix gel available as a liquid phase, which solidifies when in contact with a physiologic salt environment: in vitro studies show pure matrix support DPSC cell proliferation and viability when evaluated over three weeks within tooth slices; puramatrix showed better in vitro results in terms of cell viability and odontogenic differentiation when used with a co-culture of DPSC/HUVEC (human umbilical vein endothelial cells).	[110,111,112,113]
Poly L- Lactic acid (PLLA) nanofibrous microspheres	Injectable scaffold with integrated BMP-2, when combined with polylactic acid (PLA) and polyglycolic acid (PGA), significantly improving the properties and half-life of the PLLA and prolonged BMP-2 release: it is easily adapts to root canal shape and is biodegradable; it can incorporate drugs/growth factors and is conductive for cells, including DPSC and SHED; it has favourable viscosity and porosity; it does not elicit any adverse immune response; it is cheap and reproducible; the regenerated dentin structure may be disorganized and may not replicate the natural tooth architecture; and degradation metabolites might cause unfavourable conditions for surrounding cells but can be excreted to urine without complications.	[114,115,116]
Poly (lactide-co gylcolide)-polyethylene glycol (PLGA-PE) NP	It has better conductivity for dental pulp fibroblasts proliferation; it is clinically biodegradable, has fast setting, has low toxicity, has good biocompatibility, and has low immunogenicity; but, it lacks intrinsic signalling abilities and is more expensive than other synthetic scaffolds.	[106,117]