**3. Biomaterials**

The development of scaffolds is a major aspect in bone tissue engineering research. On one hand, these scaffolds should be rigid and resilient since they function as the main supporting frame work of bone graft. On the other hand, they should also be porous, biocompatible, osteoinductive and osteoconductive so that bone tissue can regenerate within the scaffolds [55]. In addition, a relatively slow degradation rate is crucial to provide mechanical support prior to complete native bone regeneration. The scaffolds can be made of natural, synthetic materials or suitable composites.

#### **3.1. Natural materials**

Natural materials applied to bone tissue engineering include biological polymers (such as collagen and hyaluronic acid), as well as inorganic materials (such as hydroxyapatite and tricalcium phosphate). Intuitively, naturally occurring materials in native bone, such as collagen, are favoured as the possess the innate biological cues that favour cell attachment and promote chemotactic response when being implanted in vivo [56]. When used as grafts implanted in vivo, those polymers are readily remodelled by the resident cells to the internal environment. Besides, the fibrous property of polymers allows manipulation during scaffold fabrication, so that the scaffold's structure and porosity can be easily controlled [57, 58]. However, the telopeptide within these polymers may be immunogenic, and some of the polymer's nature (poor inherent rigidity and high degradation rate) limit their application in bone repair.

The main minerals in bone matrix, hydroxyapatite (HA) and tri-calcium phosphate (TCP), are other candidates for bone scaffolds. Their mechanical properties are able to provide the mechanical support at the defect area after transplantation. However, these minerals are inherently brittle, and may perform poorly in response to impact. Currently, they are usually combined with polymer materials with higher fracture toughness to achieve optimized performance in bone tissue engineering application [59].

#### **3.2. Synthetic materials**

**2.4. Conclusion**

604 Regenerative Medicine and Tissue Engineering

cell sources.

**Cell origin**

Adult bone

Embryonic

Fetal bone

**3. Biomaterials**

materials or suitable composites.

**3.1. Natural materials**

**Proliferation rate**

**Osteogenic capacity**

stem cell High Medium High Non-specific

Cord blood Medium High Low Autograft

marrow High Very high Very high Autograft

**Table 1.** A comparison of stem cell sources based on comparative studies

Stem cell sources for bone tissue engineering have been widely explored recently, and several studies have been conducted to compare the different cell sources [21, 29, 30, 44, 54]. Table 1 below summarizes some of these studies and compares the main properties of different stem

> **Mineral deposition**

marrow Low Medium Medium Limited efficiency Autograft

Adipose Low Low Low Low efficiency Autograft

Periosteum High High High Less resource Autograft

The development of scaffolds is a major aspect in bone tissue engineering research. On one hand, these scaffolds should be rigid and resilient since they function as the main supporting frame work of bone graft. On the other hand, they should also be porous, biocompatible, osteoinductive and osteoconductive so that bone tissue can regenerate within the scaffolds [55]. In addition, a relatively slow degradation rate is crucial to provide mechanical support prior to complete native bone regeneration. The scaffolds can be made of natural, synthetic

Natural materials applied to bone tissue engineering include biological polymers (such as collagen and hyaluronic acid), as well as inorganic materials (such as hydroxyapatite and tricalcium phosphate). Intuitively, naturally occurring materials in native bone, such as collagen, are favoured as the possess the innate biological cues that favour cell attachment and promote chemotactic response when being implanted in vivo [56]. When used as grafts implanted in vivo, those polymers are readily remodelled by the resident cells to the internal environment. Besides, the fibrous property of polymers allows manipulation during scaffold fabrication, so

**Main Limitations Key Advantages**

non-accessibility Highest efficiency

differentiation

non-accessibility

accessibility

accessibility

accessibility

Least mature, highest potential

High potential, good efficiency As compared to natural materials, synthetic materials may be designed and customised for highly specified chemical and physical properties. These properties contribute to controllable mechanical properties of the scaffolds, including tensile strength, resiliency and degradation rate and to tailor desirable biological outcomes, such as reducing risks of toxicity, immuno‐ genicity and infectionscan [60].Synthetic materials, however, lack bioactive properties such as biocompatibility, osteoinductivity and osteoconductivity, necessitating further modification prior to use.

The most often used synthetic materials for three dimensional scaffolds are saturated poly-αhydroxy esters, including poly lactic acid (PLA), poly glycolic acid (PGA), poly lactic-coglycolic acid (PLGA), and poly caprolactone (PCL) [60]. They can be processed by techniques such as gas forming, phase separation, fused deposition, and 3D printing [61-64]. The choice of polymers and fabrication techniques for three dimensional scaffolds used in tissue engi‐ neering are a major aspect in material science, and much progress in this field has been made in the last few decades [65].

As most materials alone showed some form of limitations, now researchers mostly design and fabricate composite materials that combine polymers and inorganic minerals, to let the different nature of materials complement each other, and attain optimal and controllable degradation rate and mechanical properties. The combination can be varies and the fabrication methods are diverse [66].
