**2. Allografts**

Allograft (also called homograft) is a tissue/organ graft from one individual to another of the same species with a different genotype [6]. It has been successfully used in various medical procedures for more than 150 years. Approximately 1500000 allografts are transplanted each year for a variety of life-saving and life-enhancing surgeries. For example, skeletal grafts for patients with bone defects from cancer or traffic accidents; cornea transplants to help restore sight; heart valves to replace damaged heart tissues; skin grafts to save the lives of burn vic‐ tims, and tendon replacements to help people with more active lives [7].

injury, blood–material interactions, provisional matrix formation, acute inflammation, chronic inflammation, granulation tissue development, foreign body reaction, and fibrosis/ fibrous capsule development [2]. There are numerous types of host responses to a broad

When considering a biomaterial for implantation or medical use, the first and most impor‐ tant requirement is nontoxic, nonimmunogenic, chemically inert/active, and acceptable by the human body. Biocompatible in most cases means that the biomaterials must not form thrombi in the blood system, result in tumors in the surround tissues, or be immediately at‐ tacked, encapsulated, or rejected by the body [3]. According to the host responses to im‐ plantable biomaterials, there are many different kinds of biocompatibilities, including local tissue responses, such as necrosis, repulsion, infection, inflammation, calcification, scar, cyst, amalgamation, thrombus, tumor, cancer, and whole body responses, such as fever, toxicity, circulation impediment, nerve anesthesia, malformation, etc. The overall biocompatibilities including cyto-compatibility, hemo-compatibility, and tissue-compatibility, are often evalu‐ ated using histological sections, cell markers, and metabolite measurements. Sometimes, polymers with similar chemical characteristics behave differently in certain situations. For example, polyethylene and ultrahigh molecular weight polyethylene behave differently as orthopedic biomaterials for knee and hip replacement [4]. Until present, most of the im‐ plantable biomaterials trigger acute or/and chronic inflammatory responses in the body. These reactions can totally black a biomaterial and even lead to huge disasters or personal misfortunes. Among the numerous types of host responses, early interactions between im‐ plants and inflammatory cells are probably mediated by a layer of host proteins on the bio‐ material surface. Franz and coworkers have described several typical host responses of implantable biomaterials (Figure 1) [5]. This model can be used as a reference for evaluation

In this chapter, I will focus on the *in vivo* host responses about twenty common used bioma‐ terials which cover nearly every tissue and organ in human body. Advanced biologic techni‐ ques have been employed in determining the mechanisms behind observed macroscopic or microscopic responses. An understanding of the molecular and cellular events which occur in response to implantable biomaterials may allow us to manipulate responses and design more biocompatible, bioactive and functional biomaterials for clinical applications, such as

Allograft (also called homograft) is a tissue/organ graft from one individual to another of the same species with a different genotype [6]. It has been successfully used in various medical procedures for more than 150 years. Approximately 1500000 allografts are transplanted each year for a variety of life-saving and life-enhancing surgeries. For example, skeletal grafts for patients with bone defects from cancer or traffic accidents; cornea transplants to help restore sight; heart valves to replace damaged heart tissues; skin grafts to save the lives of burn vic‐

tims, and tendon replacements to help people with more active lives [7].

of an implantable biomaterial when it is implanted shortly *in vivo*.

regenerative medicine and controlled releasing drugs.

**2. Allografts**

spectrum of biomaterials.

112 Advances in Biomaterials Science and Biomedical Applications

**Figure 1.** Immune response toward biomaterials. (A) Adsorption of blood proteins and activation of the coagulation cas‐ cade, complement and platelets result in the priming and activation of polymorphonuclear leukocytes (PMNs), monocytes and resident macrophages. (B) Danger signals (alarmins) released from damaged tissue additionally prime the immune cells for enhanced function via pattern recognition receptor (PRR) engagement. (C) The acute inflammatory response is dominated by the action of PMNs. PMNs secrete proteolytic enzymes and reactive oxygen species (ROS), corroding the bio‐ material surface. Interleukin (IL)-8 released from PMNs enhances PMN influx and priming. In the transition from acute to chronic inflammation, PMNs stop secreting IL-8 in favor of cytokines promoting immigration and activation of monocytes and macrophages. (D) Macrophages are the driving force of chronic inflammation. Constant release of inflammatory me‐ diators like tumor-nekrose-faktor alpha (TNFα), IL-6, and monocyte chemotactic protein (MCP)-1 results in permanent acti‐ vation of macrophages. Fusion-inducing stimuli like IL-4 and IL-13 promote the fusion of macrophages to foreign body giant cells (FBGCs,) which form a highly degradative environment on the biomaterial surface. Furthermore, FBGC promote extracellular matrix (ECM) remodeling and fibroblast activation resulting in excessive fibrosis and biomaterial encapsula‐ tion. (E) Macrophage-derived cytokines and pattern recognition receptor engagement activate dendritic cells (DCs) on the biomaterial surface. Depending on the nature of the stimulus, DCs mature to either immunogenic or tolerogenic subtypes, amplifying or suppressing the inflammatory response [5].

Compared with autografts which come from the same bodies and are only available in limit‐ ed amounts, allografts are more readily available and accompany with less risk and postop‐ erative morbidity. The healing times is therefore shorter and less painful for a patient with no second surgical site is required (as there is when an autograft is utilised). Currently, the use of allograft tissues is increasingly popular all over the world, with widespread orthopae‐ dic surgeons and debilitating musculoskeletal conditions. Nearly one tissue/organ donor can save or improve the lives of up to 60 people. Especially, Musculoskeletal Transplant Foundation, the world's largest tissue bank, provides allograft tissue and biologic solutions for ligament reconstruction [8]. Meanwhile bone and soft tissue allografts from the Steri‐ Graft™ line has been in existence for over 13 years and has helped doctors and their patients with over one hundred thousand successful transplantations. Before transplantation, a blood sample from the donor is normally tested in case any infected diseases, such as hu‐ man immunodeficiency virus (HIV), Hepatitis, and Syphilis [9].

Specially, decellularized tissue/organ matrices derived from allografts have been used since the 1940s to support tissue repair and replacement. Their popularity has grown sharply dur‐ ing the last decade with the advent of tissue engineering [10]. At present, decellularized tis‐ sues/organs have been successfully used in a variety of tissue/organ regenerative medicines. The efficiency of cell removal from a tissue/organ is dependent on the origin of the tissue/ organ and the specific physical, chemical, and enzymatic methods that are used. Each of these treatments affects the biochemical composition, tissue ultrastructure, and mechanical behavior of the remaining extracellular matrix (ECM) scaffold, which in turn, affect the host response to the material [11].
