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.