Bone marrow-derived vasculogenesis leads to scarless regeneration in deep wounds with periosteal defects

Abstract

Deep skin wounds with periosteal defects, frequently caused by traffic accidents or radical dissection, are refractory. Transplant surgery is frequently performed, but patients are subjected to stress for long operation periods, the sacrifice of donor regions, or several complications, such as flap necrosis or intractable ulcers. Even if the defects are covered, a scar composed of fibrous tissue remains in the body, which can cause itching, dysesthesia, or repeated ulcers because of the lack of distribution of peripheral nerves or hair follicles. Thus, treatments with the aim of regenerating lost tissue for deep wounds with periosteal defects are needed. Here, we show that the use of gelatin sponges (GS), which have been used as haemostatic materials in clinical practice, allowed the regeneration of heterogeneous tissues, including periosteum, skin, and skin appendages, when used as scaffolds in deep wounds with periosteal defects in rats. Bone marrow transplantation in rats revealed the mechanism by which the microenvironment provided by GS enabled bone marrow-derived cells (BMDCs) to form a vascular niche, followed by regeneration of the periosteum, skin, or skin appendages such as hair follicles by local cells. Our findings demonstrated that vascular niche formation provided by BMDCs is crucial for heterogeneous tissue regeneration.

Plasticity of bone marrow-derived cell differentiation depending on microenvironments in the skin

“…Nevertheless, scaffolds without seeding cells or growth factors are still an attractive tool, considering that they can be more easily and quickly applied to patients than cell-incorporated scaffolds. For example, we recently demonstrated the unexpected result that the use of a gelatin sponge as a scaffold led to tissue regeneration in deep injuries with periosteal defects in the calvariae of rats ( Shirai et al, 2022 ). Surprisingly, gelatin sponges allowed periosteum regeneration as well as skin appendages such as hair follicles or peripheral nerves, whereas the defects were encrusted in wounds without gelatin sponges.…”

Exploring Localized Provoked Vulvodynia: Insights from Animal Model Research

“…Protein gene product 9.5 (PGP9.5) Pan axonal marker Peripheral nerve fiber identification [38] Calcitonin gene-related peptide (CGRP) Amino acid peptide Found in sensory fibers; usually found in perivascular localization and has sensory and efferent functions [39] Vesicular monoamine transporter 2 (VMAT2) Presynaptic protein Regulates dopamine and monoamine release into synapse [40] Substance P (SP) Neuropeptide Overexpressed in nociception and chronic pain; histamine release from mast cells [41,42] Neuropeptide Y (NPY) Peptide Present in CNS *, PNS *, peripheral tissues, and blood vessels [43,44] Vasoactive intestinal polypeptide (VIP) Neuropeptide…”