Biomaterials for In Situ Tissue Regeneration: A Review

Abstract

This review focuses on a somewhat unexplored strand of regenerative medicine, that is in situ tissue engineering. In this approach manufactured scaffolds are implanted in the injured region for regeneration within the patient. The scaffold is designed to attract cells to the required volume of regeneration to subsequently proliferate, differentiate, and as a consequence develop tissue within the scaffold which in time will degrade leaving just the regenerated tissue. This review highlights the wealth of information available from studies of ex-situ tissue engineering about the selection of materials for scaffolds. It is clear that there are great opportunities for the use of additive manufacturing to prepare complex personalized scaffolds and we speculate that by building on this knowledge and technology, the development of in situ tissue engineering could rapidly increase. Ex-situ tissue engineering is handicapped by the need to develop the tissue in a bioreactor where the conditions, however optimized, may not be optimum for accelerated growth and maintenance of the cell function. We identify that in both methodologies the prospect of tissue regeneration has created much promise but delivered little outside the scope of laboratory-based experiments. We propose that the design of the scaffolds and the materials selected remain at the heart of developments in this field and there is a clear need for predictive modelling which can be used in the design and optimization of materials and scaffolds.

Keywords: biomaterials; in situ tissue engineering; natural polymers; synthetic polymers.

Figure 1

Pathways for tissue regeneration.

Figure 2

Examples of different pore sizes, shapes, and biomaterials for scaffolds for tissue engineering. (a) Titanium (Ti6Al4V), (b) Starch poly(ε-caprolactone) (SPCL), (c) poly(lactide-co-glycolide) (PLGA), (d) Bioactive glass (BG), (e) poly(propylene fumarate) (PPF), (f) collagen-apatite, (g) Mesoporous bioactive glass (MBG), and (h) Silk fibroin (SF). Reproduced from [39], CC BY 3.0 license.

Figure 3

Schematic illustration to show (a) the radially oriented pores scaffold, O-PLGA and (b) its implantation in an osteochondral defect in a rabbit model. The blue and red arrows in (b) refer to the bioactive interflow from neighbor cartilage and subchondral bone layers, respectively. PLGA—poly(lactide-co-glycolide). With permission [48].

Figure 4

Assessment of the osteochondral defects regeneration using (a) O-PLGA and (b) R-PLGA for 12 weeks, respectively. (a1,b1) Gross view of the scaffold in the osteochondral bone, (a2,b2) hematoxylin and eosin staining images, and (b3,b3) periodic acid Schiff staining of glycosaminoglycans. Immunohistochemical staining of collagen Type II (a4,b4), collagen Type I (a5,b5), and collagen Type X (a6,b6), respectively. The black arrows in the images are used to indicate the edges of the defects, while the white arrows highlight debris of in the PLGA scaffold. Safranine O and fast green staining of glycosaminoglycans (red) and collagen (green) of O-PLGA (c1) and R-PLGA (d1) respectively. Reproduced with permission from [48].

Figure 5

Photomicrographs of hematoxylin and eosin staining for the decalcified sections of porous Calcium Phosphate-based ceramics implanted into the thigh muscles of mice for 45 and 90 days. Yellow markers indicate the newly formed bone. Bar, 200 µm, reproduced with permission from [148].