Preface

*"Experimentation and clinical tests have shown that for the graft to take root, not only should it be as viable as possible, but from the very beginning it should have a strong relationship with the host" Vittorio Putti 1912 [1].*

Bone has an efficient ability to regenerate. But the critically large defects in bone, either postsurgical or after trauma, progress to nonunion and instability in 10% of patients and therefore require implantation of a bone graft [2]. In the USA alone about half a million bone grafting surgeries are done annually [3]. Furthermore, the rate of bone grafting procedures is expected to rise due to the constantly advancing techniques of bone grafting.

Autologous bone grafting is the gold standard for the reconstruction of critical bone defects. However, autologous grafts have several significant disadvantages, such as donor site morbidity and limited availability. The alternative use of allografts or xenografts is limited due to the risks of rejection, infection, and high nonunion rates. Progress in bone tissue engineering is essential to provide an unlimited source for autologous-like bone grafting source. There is an indication that the method to generate autologous bone-like material, as live autologous bone tissue, originating from patientspecific osteoblast-like cells, grown from bone marrow on β-tricalcium phosphate supporting three-dimensional matrix under optimal biomechanical conditions, is possible (**Figure 1**) [4, 5].

But meanwhile other methods for effective bone grafting are under ongoing development aiming to achieve optimal osteoconductivity and osteoinductivity similar to the autologous bone graft material. Thus, the potential of the newly developed tissue engineering methods for bone grafting is discussed in this book. According to the ongoing research, progress of the methods to create readily available autologous-like bone grafting material that doesn't cause additional surgical morbidity, is anticipated to evolve. Naturally, these methods are expected to fulfill the regulatory requirements, including clinical studies, that will allow the start of widespread clinical use. For this purpose, a thorough understanding of bone regeneration control in vivo by systemic humoral and local factors is essential. In this book, several such factors are presented and discussed.

The classic method of local bone regeneration by means of distraction osteogenesis, which is based on mechanical stimulation at the bone deficient site is presented by Domingos et al. This widespread effective clinical method requires a good understanding of the optimal mechanical and humoral factors – those are presented in the chapter.

#### **Figure 1.**

**II**

**Section 3**

Thyroid Disorders and Osteoporosis

Relation between Vitamin K and Osteoporosis

Metabolic Disorders in Patients with Chronic Osteomyelitis:

*by Archil Tsiskarashvili, Nikolay Zagorodny, Svetlana Rodionova* 

*by Olga Viktorovna Berdyugina and Kirill Alexandrovich Berdyugin*

*by Stevo Najman, Jelena Najdanović and Vladimir Cvetković*

MicroRNAs as Next Generation Therapeutics in Osteoporosis

*by Taruneet Kaur, Rajeev Kapila and Suman Kapila*

Immunological Monitoring of Osteogenesis Disorder

*by Ayotunde Oladunni Ale*

Etiology and Pathogenesis

*and Dmitry Gorbatyuk*

**Section 4**

Defects

*by Sawsan Jaghsi*

Bone-Related Diseases **111**

**Chapter 7 113**

**Chapter 8 125**

**Chapter 9 137**

**Chapter 10 155**

Biologicals for Bone Tissue Regeneration **177**

**Chapter 11 179**

**Chapter 12 209**

Application of Adipose-Derived Stem Cells in Treatment of Bone Tissue

 *A- micrograph (HE staining) of a critical bone gap in rat calvarium, 6 weeks after the creation of the gap. No evidence of bone bridging. B- micrograph (HE staining) of bridging of the critical bone gap by young woven bone, 6 weeks after implantation with in vitro generated bone-like tissue.*

Berdyugina OV and Berdyugin KA present the immunological aspects related to bone regeneration. Those are not always apparent to the clinicians who are involved in the treatment of bone deficiencies.

The microRNAs control the proliferation and differentiation of osteoblasts and osteoclasts, which influences bone formation, and this is described in the chapter by Kaur T et al. This rarely addressed subject might become an important therapeutic tool in the treatment of bone related disabilities.

The additional important issue of systemic effect of bone damage due to osteomyelitis is reviewed by Tsiskarashvili A et al. The systemic metabolic changes that occur in that situation are crucial for understanding the treatment of bone deficiencies due to osteomyelitis.

The maintenance of bone remodeling is governed by the thyroid hormone. The relationship between thyroid impairment, and bone mass, especially in the aged population, is discussed in the chapter by Ayotunde Oladunni Ale.

The biological effect of vitamin K and bone maintenance is not widely apparent but in the dedicated chapter by Sawsan Jaghsi, this subject is discussed aiming to open an additional niche for possible pharmacological intervention in bone metabolism.

These chapters address the less discussed aspects of bone regeneration and maintenance, therefore the reader may find new areas of interest when approaching the deep understanding of the fascinating area of bone regeneration control.

> **Mike Barbeck** University Hospital Hamburg-Eppendorf, Germany

#### **Nahum Rosenberg**

Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

> **Patrick Michael Rider** Botiss Biomaterials GmbH, Germany

> > **Željka Perić Kačarević** University of Osijek, Croatia

> > > **V**

[1] Donati D, Zolezzi C, Tomba P, Vigano A. Bone grafting: historical and conceptual review, starting with old an old manuscript by Vittorio Putti. Acta

[2] Alexander PG, Hofer HR, Clark KL, Tuan RS: Mesenchymal Stem Cells in Musculoskeletal Tissue Engineering. In Principles of Tissue Engineering. 4th edition. Edited by Lanza R, Langer R, Vacanti J. Waltham, MA, USA: Elsevier;

[3] Mauffrey C, Madsen M, Bowles RJ, Seligson D: Bone graft harvest site options in orthopaedic trauma: a prospective in vivo quantification study.

Injury 2012,**43**:323-326. 4

[4] Rosenberg N, Rosenberg O.

Extracorporeal human bone-like tissue generation. Bone and Joint Research

[5] Rosenberg N, Rosenberg O. Safety and efficacy of in vitro generated bone-like material for in vivo bone regeneration – a feasibility study. Heliyon (CellPress) 2020;**6**:1-7

Ortop 2007;**78**(1):19-25

**References**

2014:1171-1200

(BJR) 2012;**1**:1-7

**Ole Jung** Department of Dermatology and Venereology, University Medical Center Rostock, Germany
