1 Introduction
Guided bone regeneration (GBR) is a therapeutical strategy widely applied to promote new bone regeneration mainly in the maxillofacial region, especially in cases of periodontal and peri-implant bone defects [1]. As an important step in GBR procedures, a barrier membrane is inserted between the soft tissue defect and the bone defect to prevent ingrowth of competing epithelial and connective tissue [1, 2]. This creates a segregated space for slow-migrating progenitor cells and/or stem cells with osteogenic potential to colonize the defect site and ultimately achieve bone regeneration. Given the key role that the barrier membrane plays in GBR procedures, researchers have continued pursuing novel strategies to develop superior GBR membranes.
Periosteum is a thin vascularized connective tissue that covers the external surface of bone (with the exception of articular bone) and plays a key role in bone regeneration [3, 4]. Periosteum is known to be a niche of progenitor cells and local growth factors, as well as to serve as a natural scaffold for recruitment of cells and biological factors [5, 6]. Additionally, this tissue shows prominent smart material properties, such as direction- and flow rate-dependent permeability [3, 7, 8]. Based on the great potential of periosteum in bone tissue engineering applications, several attempts have been made to apply tissue engineering methods to develop an artificial periosteum that mimics native periosteum in structure and function [9, 10]. To date, however, no tissue engineering strategy has been able to recreate the unique three-dimensional (3D) microenvironment that fully recapitulates the periosteum-specific extracellular matrix (ECM) properties.
In recent years, in the fields of tissue engineering and regenerative medicine, tissue-derived ECM has become an increasingly popular biomaterial source [11-13]. It has been shown that the decellularization process efficiently removes antigenic cellular components while retaining the natural 3D ultrastructure complete with the native ECM composition. Studies have demonstrated the feasibility of preparing decellularized tissue ECM scaffolds and applied them in the repair of multiple types of tissues and organs with varying degrees of success [14-16]. Although tissue-derived ECM scaffolds are generally used for the repair of non-homologous anatomic sites, site-specific homologous tissue scaffolds have been shown to be more effective than non-site-specific tissue scaffolds in remodeling constructive tissue. Therefore, we speculated that decellularized periosteum, which provides the native ECM derived from periosteum, holds great potential as a GBR membrane. However, the related research is relatively scarce.
Based on the convergence of osteoimmunology and immunomodulation, osteoimmunomodulation has been proposed to be an essential ability of biomaterials for regulating bone regeneration [17, 18]. A fundamental principle underlying this concept is that biomaterials have immunomodulatory properties that are important for generating an osteoimmune environment that facilitates bone regeneration. With more detailed investigations of the interaction between host tissues and biomaterials, the immune response is considered a necessary element in membrane-mediated GBR procedures. Due to its “foreign body” nature, the barrier membrane will inevitably alter the local immune microenvironment and thereby influence the dynamics of bone regeneration [19-21]. Therefore, research efforts to develop improved barrier membranes must consider the osteoimmunomodulatory properties of the membrane material.
In the present study, cranial periosteum of mini-pig was harvested to fabricate decellularized periosteum (DP), which was then characterized. In vitro, we investigated the effect of DP on the inflammatory reaction and polarization of macrophages as well as its effect on osteogenesis. In vivo, we examined the effectiveness of DP in GBR in rat cranium critical defect model. Collectively, the findings of this study indicate that the DP possesses osteoimmunomodulatory properties and represents a promising membrane for GBR procedures.