Natural Polymeric Scaffolds in Bone Regeneration

Abstract

Despite considerable advances in microsurgical techniques over the past decades, bone tissue remains a challenging arena to obtain a satisfying functional and structural restoration after damage. Through the production of substituting materials mimicking the physical and biological properties of the healthy tissue, tissue engineering strategies address an urgent clinical need for therapeutic alternatives to bone autografts. By virtue of their structural versatility, polymers have a predominant role in generating the biodegradable matrices that hold the cells in situ to sustain the growth of new tissue until integration into the transplantation area (i.e., scaffolds). As compared to synthetic ones, polymers of natural origin generally present superior biocompatibility and bioactivity. Their assembly and further engineering give rise to a wide plethora of advanced supporting materials, accounting for systems based on hydrogels or scaffolds with either fibrous or porous architecture. The present review offers an overview of the various types of natural polymers currently adopted in bone tissue engineering, describing their manufacturing techniques and procedures of functionalization with active biomolecules, and listing the advantages and disadvantages in their respective use in order to critically compare their actual applicability potential. Their combination to other classes of materials (such as micro and nanomaterials) and other innovative strategies to reproduce physiological bone microenvironments in a more faithful way are also illustrated. The regeneration outcomes achieved in vitro and in vivo when the scaffolds are enriched with different cell types, as well as the preliminary clinical applications are presented, before the prospects in this research field are finally discussed. The collection of studies herein considered confirms that advances in natural polymer research will be determinant in designing translatable materials for efficient tissue regeneration with forthcoming impact expected in the treatment of bone defects.

Keywords: bone tissue; natural polymer; regeneration; scaffold; tissue engineering.

Figure 1

Bone tissue composition and hierarchical morphology. Bone tissue composition: cell types present in the bone tissue (top), and hierarchical structure (bottom) of the cortical (compact) and trabecular (cancellous) bone. The various structural elements are represented, ranging from the mesostructures (i.e., osteons/lamellar packets) to the sub-nanostructures (i.e., collagen molecule).

Figure 2

Principles of bone tissue engineering. Principles of bone tissue engineering useful in the design of scaffolds serving as functional bone substitutes. TE combines cells, signaling molecules and biocompatible materials to design bioactive scaffolds and achieve successful reinstate of a variety of tissues. The criteria to be considered in the choice of the basal material to manufacture the matrix (yellow), the cell type (green), and the inductive signals (purple) to promote bone healing and formation are recalled by keywords in the respective sections of the diagram.

Figure 3

Biodegradable polymers for biomedical applications. Classification of biodegradable polymers commonly used in biomedical applications based on the origin of their source (natural, synthetic, or semi-synthetic). GAGs, Glycosaminoglycans; PHA, Poly(hydroxyalkanoates); PBAT, Poly(butylene adipate-co-terephthalate); MC, Methyl-cellulose; EC, Ethyl-cellulose; PBS, Poly(butylene succinate); PLA, Poly(lactic acid); PVA, Poly(vinyl alcohol); PGA, Poly(glycolic acid); PBSA, Poly(butylene succinate-co-adipate); PHK, Poly(hydroxylketones); PCL, Poly-ε-caprolactone; PMMA, Poly(methyl methacrylate); PHB, Poly(hydroxybutyrates); PET, Poly(ethylene terephthalate); PHVB, Poly(hydroxybutyrate-co-hydroxyvalerate); PTMAT, Poly(methylene adipate/terephthalate).

Figure 4

Polymer processing techniques and different scaffold architectures. Polymers can be processed through conventional or advanced techniques in order to obtain scaffolds endowed with different architectures, including: hydrogels, porous sponges, fibrous scaffolds, micro/nanoparticles and membranes.